case study of phineas gage summary

Phineas Gage: His Accident and Impact on Psychology

Olivia Guy-Evans, MSc

Associate Editor for Simply Psychology

BSc (Hons) Psychology, MSc Psychology of Education

Olivia Guy-Evans is a writer and associate editor for Simply Psychology. She has previously worked in healthcare and educational sectors.

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Saul Mcleod, PhD

Editor-in-Chief for Simply Psychology

BSc (Hons) Psychology, MRes, PhD, University of Manchester

Saul Mcleod, PhD., is a qualified psychology teacher with over 18 years of experience in further and higher education. He has been published in peer-reviewed journals, including the Journal of Clinical Psychology.

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Key Takeaways

In 1848, 25-year-old Phineas Gage survived an accident where an iron rod was propelled through his left cheek and skull. He made an improbable recovery and lived for 12 more years.

Examination of Gage’s exhumed skull in 1867 revealed the probable trajectory of the tamping iron through left frontal lobe structures, offering insight into his improbable survival and selective changes in behavior following this massive traumatic brain injury.

Gage’s case is famous in psychology as it shows the resilience of the human brain and profoundly influenced early understanding of cerebral localization.

What happened to Phineas Gage?

Phineas Gage was an American railroad construction foreman born in 1823 near Lebanon, New Hampshire.

On September 13, 1848, when Gage was 25 years old, he was working in Cavendish, Vermont, leading a crew preparing a railroad bed for the Rutland and Burlington Railroad by blasting away rock using explosives.

Around 4:30 pm, as Gage was using a 43-inch-long, 13-pound iron tamping rod to pack the explosive powder into a hole in the rock, the powder detonated unexpectedly.

The tamping iron launched from the hole and entered the left side of Gage’s face from the bottom up.

The iron rod entered Gage’s left cheek near the lower jaw hinge, passing behind his left eye socket, penetrating the base of his skull, traversing the left frontal lobe upwards at an angle, and exiting through the top frontal portion of his skull before landing about 25-30 yards behind him.

After the incident, Gage was thrown onto his back from the force of the iron rod and had some brief convulsions of the arms and legs.

Within minutes, however, assisted by his crew, Gage could stand, speak, and walk to an oxcart to be transported nearly a mile to the inn where he resided in Cavendish village.

Dr. Edward H. Williams arrived about an hour later to examine Gage. In his 1848 report, Williams noted visible pulsations of Gage’s exposed brain through an inverted funnel-shaped opening at the top of his skull from which brain tissue protruded.

Williams claimed that Gage was recounting his injuries to bystanders, and he did not initially believe the story, thinking that Gage was ‘deceived.’

Apparently, Gage had greeted Williams by angling his head at him and saying, ‘Here’s business enough for you.’

During repeated episodic vomiting, Williams observed additional small amounts of Gage’s brain matter expelled onto the floor through the frontal exit wound, as the cerebral tissue had likely detached from the skull during the passage of the tamping iron.

From Harlow’s written account, Gage was considered to be fully recovered and felt fit enough to reapply for his previous role as a foreman.

After an arduous early recovery, Gage eventually regained physical health, though his personality was markedly altered. He lived another 11 years before dying from severe epilepsy in 1860 at age 36.

How Did Phineas Gage’s Personality Change?

The descriptions of Gage’s personality and behavior before the accident are limited.

Before his accident, 25-year-old Gage was described by his railroad employers as a capable and efficient foreman, displaying a strong work ethic, drive, and dependability in overseeing his crews.

However, after surviving passage of the tamping iron through his frontal lobe in 1848, significant changes in Gage’s personality emerged during his physical recovery.

The contractors, who had regarded Gage as ‘efficient and capable’ before the accident, could no longer offer him work due to considerable changes in Gage’s personality.

In medical reports by Dr. John Martyn Harlow in 1848 and 1868, Gage is depicted as struggling with volatility, profanity, little deference for others, impatience, obstinance, unpredictability, and devising plans hastily abandoned.

Harlow wrote that Gage’s equilibrium between intellectual faculties and animal propensities was destroyed, reverting to childlike mental capacity regarding self-restraint and social appropriateness.

Though the specific neuroanatomical links were unclear at the time, Friends and colleagues felt Gage was “no longer Gage” after the traumatic brain injury, unable to process emotions or control impulsive behavior like his pre-accident self.

The shocking changes aligned with emerging localization theories that the frontal lobes regulate personality.

Marlow (1868) described Gage as follows:

“The equilibrium or balance, so to speak, between his intellectual faculties and animal propensities, seems to have been destroyed. He is fitful, irreverent, indulging at times in the grossest profanity (which was not previously his custom), manifesting but little deference for his fellows, impatient of restraint or advice when it conflicts with his desires, at times pertinaciously obstinate, yet capricious and vacillating, devising many plans of future operations, which are no sooner arranged than they are abandoned in turn for others appearing more feasible. A child in his intellectual capacity and manifestations, he has the animal passions of a strong man.”

“Previous to his injury, though untrained in the schools, he possessed a well-balanced mind, and was looked upon by those who knew him as a shrewd, smart business man, very energetic and persistent in executing all his plans of operation. In this regard his mind was radically changed, so decidedly that his friends and acquaintances said he was ‘no longer Gage.”

Through Harlow’s reports, it can be suggested that Gage’s personality changed due to the accident he endured.

The accounts imply that the injury led to a loss of social inhibition, meaning that Gage would behave in ways that were considered inappropriate.

Accuracy of Sources

In his 1848 and 1868 reports, Dr. Harlow provides a limited description of Gage’s pre-accident, stating he was “temperate inhabit, of great energy of character, possessed of considerable stamina of both brain and body” and was “a great favorite” with his men (Harlow, 1848, 1868).

However, later accounts add exaggerated positive traits not found in Harlow’s description. For example, Suinn (1970) describes Gage as enjoying “the respect as well as the favor of his men,” while Myers (1998) calls him “soft-spoken,” and Lahey (1992) says he was “polite and reasonable.”

Other sources paint him as friendly, affable, dependable, conscientious, and happy (Macmillan, 2000).

Similarly, post-accident descriptions often emphasize Gage’s negative qualities while ignoring any positive traits he retained.

Harlow documents personality changes but notes Gage remained employable for a period as a long-distance stagecoach driver in Chile (Harlow, 1868).

However, many accounts focus solely on traits like aggression, unreliability, or aimlessness (Macmillan, 2000). Damasio goes so far as to describe him as behaving violently with no self-control (Blakeslee, 1994).

In this way, later accounts tend to polish Gage’s pre-accident image as an upstanding citizen while presenting an almost cartoonishly perturbed version post-injury – neither in keeping with Harlow’s more nuanced clinical descriptions.

This likely reflects enthusiasm for fitting Gage’s case to localization theories. Macmillan (2000) argues that we must cautiously analyze such embellished personality descriptions when assessing Phineas Gage’s legacy.

Severity of Gage’s Brain Damage

When Gage died in 1861, no autopsies were performed until his skull was later recovered by Harlow years later. The brain damage that caused the significant personality changes was presumed to have involved the left frontal region of the brain.

It was not until 1994 that complex computer-based methods to examine brain damage could be used to investigate whether other areas of the brain were affected.

Phineas Gage brain image from Damasio et al. (1994)

Damasio et al. (1994) used measurements from Gage’s skull and neuroimaging techniques to determine the exact placement of the entry and exit point of the iron rod on a replica model (see Fig. 1).

They found that the damage caused by the rod involved both the left and right prefrontal cortices.

The left and right cortices are responsible for emotional processing and rational decision-making; therefore, it can be assumed that Gage had deficits in these areas.

Phineas Gage brain image from Ratiu et al., (2004)

A later study by Ratiu et al. (2004) also investigated Gage’s injury and the location of where the iron rod entered and exited the head. They used Gage’s actual skull rather than a model of it, as Damasio et al. (1994) had used.

Ratiu et al. (2004) generated three-dimensional reconstructions of the skull using computed tomography scans (CAT) and found that the extent of the brain injury was limited to the left frontal lobe only and did not extend to the right lobe (see Fig. 2).

Phineas Gage MRI brain image from Van Horn et al., (2012)

More recently, Van Horn et al. (2012) used a CAT scan of Gage’s skull as well as magnetic resonance imaging (MRI) data obtained from male participants of a similar age to Gage at the time (aged 25-36).

Their results supported Ratiu et al. (2004) in that they always concluded that the rod only damaged the left lobe and not the right.

Van Horn, however, went a step further in their research and investigated the potential levels of white and grey matter damaged due to Gage’s injury. White matter is deep in the brain and provides vital connections around the brain, essential to normal motor and sensory function.

Grey matter in the brain is essential to many areas of higher learning, including attention, memory, and thought.

The research by Van Horn proposed that Gage lost about 11% of his white matter and about 4% of his grey matter. White matter has the ability to regenerate, so this could explain why Gage recovered as well as he did.

Van Horn et al. (2012) compared Gage’s white matter damage to the damage that is caused by neurogenerative diseases such as Alzheimer’s.

This is supported by other studies that have found that changes in white matter is significantly associated with Alzheimer’s disease (Nasrabady, Rizvi, Goldman & Brickman, 2018; Kao, Chou, Chen & Yang, 2019).

It could be suggested that Gage’s apparent change in personality could have been the result of an early onset of Alzheimer’s.

However, as Dr. Harlow, who examined Gage, only reported on Gage’s behaviors shortly after his accident, rather than months or years later when Alzheimer’s symptoms may have emerged, we cannot be certain whether Gage actually had this condition.

All studies investigating the brain damage suffered by Gage is essentially all speculation as we cannot know for certain the extent of the accident’s effects.

We know that some brain tissue got destroyed, but any infections Gage may have suffered after the accident may have further destroyed more brain tissue.

We also cannot determine the exact location where the iron rod entered Gage’s skull to the millimeter. As brain structure varies from person to person, researchers cannot ever know for certain what areas of Gage’s brain were destroyed.

What Happened to Phineas Gage After the Brain Damage?

Dr. John Martyn Harlow took over Gage’s case soon after. Harlow (1848) reported that Gage was fully conscious and recognized Harlow immediately but was tired from the bleeding.

In the next couple of days, Harlow observed that Gage spoke with some difficulty but could name his friends, and the bleeding ceased. Gage then spent September 23rd to October 3rd in a semi-comatose state but was able to take steps out of bed by October 7th.

By October 11th, Harlow claimed Gage’s intellectual functioning began to improve. He recognized how much time had passed since the accident and could describe the accident clearly.

Four years after his injury, Gage moved to Chile and worked taking care of horses and being a stagecoach driver.

Harlow noted emerging personality changes in this period, with Gage becoming more erratic in behavior and responsibility.

In 1860, Gage moved to San Francisco to live near family but began suffering epileptic seizures – likely related to scar tissue and injury sequelae.

The convulsions worsened over months, and on May 21, 1861, almost 13 years after his shocking accident, Gage died at age 38 from complications of severe epilepsy.

How did Phineas Gage die?

On May 21st, 1861, twelve years after his accident, Gage died after having a series of repeated epileptic convulsions.

In 1867, Harlow arranged an exhumation of Gage’s body, claiming his skull and tamping iron for medical study.

These historic artifacts remain on display at the Harvard School of Medicine.

Though Gage initially survived, it was the secondary long-term effects of this massive brain injury that ultimately led to his premature death over a decade later.

Why Is Phineas Gage Important to Psychology?

Gage’s case is important in the field of neuroscience . The reported changes in his behavior post-accident are strong evidence for the localization of brain function , meaning that specific brain areas are associated with certain functions.

Neuroscientists have a better understanding of the function of the frontal cortex today. They understand that the frontal cortex is associated with language, decision-making, intelligence, and reasoning functions. Gage’s case became one of the first pieces of evidence suggesting that the frontal lobe was directly involved in personality.

It was believed that brain lesions caused permanent deficits in a person. However, Gage was proven to have recovered remarkably and lived a mostly normal life despite his injury. It was even suggested by a psychologist called Malcolm Macmillan that Gage may have relearned lost skills.

People with damage to their frontal lobes tend to have trouble completing tasks, get easily distracted, and have trouble planning.

Despite this damage to his frontal lobe, Gage was reported to have worked as a coach driver which would have involved Gage being focused and having a routine, as well as knowing his routes and multitasking.

Macmillan (2002), therefore, suggests that Gage’s damage to the frontal lobe could have somewhat repaired itself and recovered lost functions. The ability of the brain to change in this way is called brain plasticity .

Over time, Gage’s story has been retold, and this has sometimes led to a lot of exaggeration as to the personality changes of Gage.

Some popular reports described him as a hard-working, kind man prior to the accident and then described him as an aggressive, dishonest, and drunk man who could not hold down a job and died pennilessly.

Gage’s story seemed to take on a life of its own, and some even went as far as to say that Gage became a psychopath after his accident, without any facts behind this.

From the actual reports from the people in contact with Gage at the time, it appears that his personality change was nowhere near as extreme and that Gage was far more functional than some reports would have us believe (Macmillan, 2002).

Blakeslee, S. (1994, July 6). A miraculous recovery that went wrong . New York Times.

Damasio, H., Grabowski, T., Frank, R., Galaburda, A. M., & Damasio, A. R. (1994). The return of Phineas Gage: clues about the brain from the skull of a famous patient . Science, 264 (5162), 1102-1105.Harlow J. M. (1848). Passage of an iron rod through the head. Boston Medical and Surgical Journal, 39 , 389–393.

Harlow, J. M. (1868). Recovery from the Passage of an Iron Bar through the Head . Publications of the Massachusetts Medical Society. 2 (3), 327-347.

Kao, Y. H., Chou, M. C., Chen, C. H., & Yang, Y. H. (2019). White matter changes in patients with Alzheimer’s disease and associated factors . Journal of Clinical Medicine, 8 (2), 167.

Lahey, B. B. (1992). Psychology: An introduction . Wm. C. Brown Publishers.

Macmillan, M. (2000). Restoring Phineas Gage: A 150th retrospective. Journal of the History of the Neurosciences, 9 (1), 46-66.

Macmillan, M. (2002). An odd kind of fame: Stories of Phineas Gage. MIT Press.

Myers, D. G. (1998). Psychology (5th ed.). Worth Publishers.

Nasrabady, S. E., Rizvi, B., Goldman, J. E., & Brickman, A. M. (2018). White matter changes in Alzheimer’s disease: a focus on myelin and oligodendrocytes. Acta neuropathologica communications, 6 (1), 1-10.

Ratiu, P., Talos, I. F., Haker, S., Lieberman, D., & Everett, P. (2004). The tale of Phineas Gage, digitally remastered . Journal of neurotrauma, 21 (5), 637-643.

Suinn, R. M. (1970). Fundamentals of behavior pathology. Wiley.

Van Horn, J. D., Irimia, A., Torgerson, C. M., Chambers, M. C., Kikinis, R., & Toga, A. W. (2012). Mapping connectivity damage in the case of Phineas Gage . PloS one, 7(5) , e37454.

If a person suffers from a traumatic brain injury in the prefrontal cortex, similar to that of Phineas Gage, what changes might occur?

A traumatic brain injury to the prefrontal cortex could result in significant changes in personality, emotional regulation, and executive function. This region is vital for impulse control, decision-making, and moderating social behavior.

A person may exhibit increased impulsivity, poor judgment, and reduced ability to plan or organize. Emotional volatility and difficulty in interpersonal relationships may also occur.

Just like the case of Phineas Gage, who became more impulsive and less dependable, the injury could dramatically alter one’s character and abilities.

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Phineas Gage: His Accident and Impact on Psychology

Kendra Cherry, MS, is a psychosocial rehabilitation specialist, psychology educator, and author of the "Everything Psychology Book."

Emily is a board-certified science editor who has worked with top digital publishing brands like Voices for Biodiversity, Study.com, GoodTherapy, Vox, and Verywell.

Author unknown / Wikimedia Commons

Phineas Gage's Accident
Change in Personality
Severity of Brain Damage
Impact on Psychology

What Happened to Phineas Gage After the Brain Damage?

Phineas Gage is often referred to as the "man who began neuroscience." He experienced a traumatic brain injury when an iron rod was driven through his skull, destroying much of his frontal lobe .

Gage miraculously survived the accident. However, his personality and behavior were so changed as a result of the frontal lobe damage that many of his friends described him as an almost different person entirely. The impact that the accident had has helped us better understand what the frontal lobe does, especially in relation to personality .

At a Glance

In 1848, Phineas Gage had a workplace accident in which an iron tamping rod entered and exited his skull. He survived but it is said that his personality changed as a result, leading to a greater understanding of the brain regions involved in personality, namely the frontal lobe.

Phineas Gage's Accident

On September 13, 1848, 25-year-old Gage was working as the foreman of a crew preparing a railroad bed near Cavendish, Vermont. He was using an iron tamping rod to pack explosive powder into a hole.

Unfortunately, the powder detonated, sending the 43-inch-long, 1.25-inch-diameter rod hurling upward. The rod penetrated Gage's left cheek, tore through his brain , and exited his skull before landing 80 feet away.

Gage not only survived the initial injury but was able to speak and walk to a nearby cart so he could be taken into town to be seen by a doctor. He was still conscious later that evening and able to recount the names of his co-workers. Gage even suggested that he didn't wish to see his friends since he would be back to work in "a day or two" anyway.

The Recovery Process

After developing an infection, Gage spent September 23 to October 3 in a semi-comatose state. On October 7, he took his first steps out of bed, and, by October 11, his intellectual functioning began to improve.

Descriptions of Gage's injury and mental changes were made by Dr. John Martyn Harlow. Much of what researchers know about the case is based on Harlow's observations.

Harlow noted that Gage knew how much time had passed since the accident and remembered clearly how the accident occurred, but had difficulty estimating the size and amounts of money. Within a month, Gage was well enough to leave the house.

In the months that followed, Gage returned to his parent's home in New Hampshire to recuperate. When Harlow saw Gage again the following year, the doctor noted that while Gage had lost vision in his eye and was left with obvious scars from the accident, he was in good physical health and appeared recovered.

Theories About Gage's Survival and Recovery

The type of injury sustained by Phineas Gage could have easily been fatal. While it cannot be said with certainty why Gage was able to survive the accident, let alone recover from the injury and still function, several theories exist. They include:

The rod's path . Some researchers suggest that the rod's path likely played a role in Gage's survival in that if it had penetrated other areas of the head—such as the pterygoid plexuses or cavernous sinus—Gage may have bled to death.
The brain's selective recruitment . In a 2022 study of another individual who also had an iron rod go through his skull—whom the researchers referred to as a "modern-day Phineas Gage"—it was found that the brain is able to selectively recruit non-injured areas to help perform functions previously assigned to the injured portion.
Work structure . Others theorize that Gage's work provided him structure, positively contributing to his recovery and aiding in his rehabilitation.

How Did Phineas Gage's Personality Change?

Popular reports of Gage often depict him as a hardworking, pleasant man before the accident. Post-accident, these reports describe him as a changed man, suggesting that the injury had transformed him into a surly, aggressive heavy drinker who was unable to hold down a job.

Harlow presented the first account of the changes in Gage's behavior following the accident. Where Gage had been described as energetic, motivated, and shrewd prior to the accident, many of his acquaintances explained that after the injury, he was "no longer Gage."

Severity of Gage's Brain Damage

Since there is little direct evidence of the exact extent of Gage's injuries aside from Harlow's report, it is difficult to know exactly how severely his brain was damaged. Harlow's accounts suggest that the injury did lead to a loss of social inhibition, leading Gage to behave in ways that were seen as inappropriate.

In a 1994 study, researchers utilized neuroimaging techniques to reconstruct Phineas Gage's skull and determine the exact placement of the injury. Their findings indicate that he suffered injuries to both the left and right prefrontal cortices, which would result in problems with emotional processing and rational decision-making .

Another study conducted in 2004 used three-dimensional, computer-aided reconstruction to analyze the extent of Gage's injury. It found that the effects were limited to the left frontal lobe.

In 2012, new research estimated that the iron rod destroyed approximately 11% of the white matter in Gage's frontal lobe and 4% of his cerebral cortex.

Some evidence suggests that many of the supposed effects of the accident may have been exaggerated and that Gage was actually far more functional than previously reported.

Why Is Phineas Gage Important to Psychology?

Gage's case had a tremendous influence on early neurology. The specific changes observed in his behavior pointed to emerging theories about the localization of brain function, or the idea that certain functions are associated with specific areas of the brain.

In those years, neurology was in its infancy. Gage's extraordinary story served as one of the first sources of evidence that the frontal lobe was involved in personality.

Today, scientists better understand the role that the frontal cortex has to play in important higher-order functions such as reasoning , language, and social cognition .

After the accident, Gage was unable to continue his previous job. According to Harlow, Gage spent some time traveling through New England and Europe with his tamping iron to earn money, supposedly even appearing in the Barnum American Museum in New York.

He also worked briefly at a livery stable in New Hampshire and then spent seven years as a stagecoach driver in Chile. He eventually moved to San Francisco to live with his mother as his health deteriorated.

After a series of epileptic seizures, Gage died on May 21, 1860, almost 12 years after his accident. Seven years after his death, Gage's body was exhumed. His brother gave his skull and the tamping rod to Dr. Harlow, who subsequently donated them to the Harvard University School of Medicine. They are still exhibited in its museum today.

Bottom Line

Gage's accident and subsequent experiences serve as a historical example of how case studies can be used to look at unique situations that could not be replicated in a lab. What researchers learned from Phineas Gage's skull and brain injury played an important role in the early days of neurology and helped scientists gain a better understanding of the human brain and the impact that damage could have on both functioning and behavior.

Sevmez F, Adanir S, Ince R. Legendary name of neuroscience: Phineas Gage (1823-1860) . Child's Nervous System . 2020. doi:10.1007/s00381-020-04595-6

Twomey S. Phineas Gage: Neuroscience's most famous patient . Smithsonian Magazine.

Harlow JM. Recovery after severe injury to the head . Bull Massachus Med Soc . 1848. Reprinted in Hist Psychiat. 1993;4(14):274-281. doi:10.1177/0957154X9300401407

Harlow JM. Passage of an iron rod through the head . 1848. J Neuropsychiatry Clin Neurosci . 1999;11(2):281-3. doi:10.1176/jnp.11.2.281

Itkin A, Sehgal T. Review of Phineas Gage's oral and maxillofacial injuries . J Oral Biol . 2017;4(1):3.

de Freitas P, Monteiro R, Bertani R, et al. E.L., a modern-day Phineas Gage: Revisiting frontal lobe injury . The Lancet Regional Health - Americas . 2022;14:100340. doi:10.1016/j.lana.2022.100340

Macmillan M, Lena ML. Rehabilitating Phineas Gage . Neuropsycholog Rehab . 2010;20(5):641-658. doi:10.1080/09602011003760527

O'Driscoll K, Leach JP. "No longer Gage": An iron bar through the head. Early observations of personality change after injury to the prefrontal cortex . BMJ . 1998;317(7174):1673-4. doi:10.1136/bmj.317.7174.1673a

Damasio H, Grabowski T, Frank R, Galaburda AM, Damasio AR. The return of Phineas Gage: Clues about the brain from the skull of a famous patient . Science . 1994;264(5162):1102-5. doi:10.1126/science.8178168

Ratiu P, Talos IF. Images in clinical medicine. The tale of Phineas Gage, digitally remastered . N Engl J Med . 2004;351(23):e21. doi:10.1056/NEJMicm031024

Van Horn JD, Irimia A, Torgerson CM, Chambers MC, Kikinis R, Toga AW. Mapping connectivity damage in the case of Phineas Gage . PLoS One . 2012;7(5):e37454. doi: 10.1371/journal.pone.0037454

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Shelley B. Footprints of Phineas Gage: Historical beginnings on the origins of brain and behavior and the birth of cerebral localizationism . Archives Med Health Sci . 2016;4(2):280-6. doi:10.4103/2321-4848.196182

By Kendra Cherry, MSEd Kendra Cherry, MS, is a psychosocial rehabilitation specialist, psychology educator, and author of the "Everything Psychology Book."

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Lessons of the brain: The Phineas Gage story

Harvard Correspondent

In 1848, an iron bar pierced his brain, his case providing new insights on both trauma and recovery

Imagine the modern-day reaction to a news story about a man surviving a three-foot, 7-inch, 13½-pound iron bar being blown through his skull — taking a chunk of his brain with it.

Then imagine that this happened in 1848, long before modern medicine and neuroscience. That was the case of Phineas Gage.

Whether the Vermont construction foreman, who was laying railroad track and using explosives at the time of the industrial accident, was lucky or unlucky is a judgment that Warren Anatomical Museum curator Dominic Hall puzzles over to this day.

“It is an impossible question, because he was extraordinarily unlucky to have an iron bar borne through his skull, but equally lucky to have survived, on such a low level of care,” said Hall. “We are lucky, to have him.”

Gage’s skull, along with the tamping iron that bore through it, are two of the approximately 15,000 artifacts and case objects conserved at the Warren, which is a part of the Center for the History of Medicine in Harvard’s Francis A. Countway Library of Medicine .

The resultant change in Gage’s personality — when he went from being well-liked and professionally successful to being “fitful, irreverent, and grossly profane, showing little deference for his fellows” and unable to keep his job — is widely cited in modern psychology as the textbook case for post-traumatic social disinhibition.

But as the years have gone by and we’ve learned more about his life, argued Hall, the teachings have changed.

“In 1848, he was seen as a triumph of human survival. Then, he becomes the textbook case for post-traumatic personality change. Recently, people interpret him as having found a form of independence and social recovery, which he didn’t get credit for 15 years ago.”

When Gage died 12 years after the accident, following epileptic seizures, his body was exhumed, while his skull and tamping iron were sent to the physician who had cared for him since the accident, John Harlow. Harlow later donated the items to the Warren, where they have remained for 160 years.

“In many ways, I see Gage similarly to how you would see a portrait of one of the famous professors hanging on the wall — he’s an important part of Harvard Medical School’s identity,” said Hall. “By continually reflecting on his case, it allows us to change how we reflect on the human brain and how we interact with our historical understanding of neuroscience.”

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Uncovering the Impact of Phineas Gage’s Accident on Psychology

Phineas Gage is a name that has become synonymous with studying psychology. His case has greatly interested researchers and students alike for years. Gage experienced a traumatic brain injury in 1848 when an iron rod was driven through his skull, destroying much of his frontal lobe. Despite the severity of his injury, Gage survived the accident, and his story has contributed significantly to our understanding of the brain and its functions.

Gage’s case is unique because it is one of the first recorded instances of a person surviving a severe brain injury. The accident profoundly impacted Gage’s personality, behavior, and cognitive abilities. Before the accident, Gage was described as a responsible and hard-working man. However, after the injury, he became impulsive, inconsistent, and unable to plan for the future. His case has been a subject of much debate and speculation, and it has contributed significantly to our understanding of the brain and its functions.

This article will explore Phineas Gage’s accident and its impact on psychology. We will examine his life before and after the injury, his personality and behavior changes, and the significance of his psychology case. We will also discuss how Gage’s case has contributed to our understanding of the brain and its functions.

The Life of Phineas Gage

Phineas Gage was born on July 9, 1823, in Grafton County, New Hampshire. He was the first of five children born to Jesse Eaton Gage and Hannah Trussell Gage. According to records, Phineas was a healthy and intelligent child who enjoyed playing outdoors and was well-liked by his peers.

Early Years

Phineas grew up in a modest household and attended school until he was 12. He then began working on his family’s farm, where he gained experience working with animals and machinery. In his late teens, he moved to Vermont to work as a farmhand and eventually found employment as a stagecoach driver.

Career as a Railroad Construction Foreman

In 1848, at 25, Phineas worked as a railroad construction foreman for the Rutland and Burlington Railroad Company. On September 13 that year, he suffered a traumatic brain injury when an iron rod measuring 43 inches long and 1.25 inches in diameter was accidentally driven through his skull. The rod entered below his left cheekbone and exited through the top of his head, destroying much of his frontal lobe.

Despite the severity of his injury, Phineas survived and could walk and talk within minutes of the accident. However, his personality and behavior were dramatically altered. He became impulsive, irritable, and unable to plan or make decisions. He also struggled with memory loss and had difficulty with social interactions.

After the accident, Phineas worked odd jobs and traveled around the country, becoming a celebrity due to his survival story. He eventually settled in San Francisco, where he worked as a longshoreman until his death on May 21, 1860.

Phineas Gage: The Accident

The incident.

We have all heard of Phineas Gage, who survived a devastating brain injury that changed his personality forever. But what exactly happened to him? In 1848, Gage was a 25-year-old railroad construction foreman working in Vermont. On September 13 that year, he was using a tamping iron to pack explosive powder into a hole when the powder ignited, sending the iron rocketing through his skull.

The iron, 43 inches long and weighing over 13 pounds, entered Gage’s head just below his left cheekbone and exited through the top of his skull, landing several yards away. Miraculously, Gage remained conscious throughout the ordeal and was able to speak within minutes of the accident.

Immediate Aftermath

The immediate aftermath of the accident was chaotic. Gage’s coworkers rushed to his aid and found him sitting up, blood pouring from his head. They took him to a nearby hotel, where a physician named Edward H. Williams examined him. Williams later described the scene: “I first noticed the wound upon the head before I alighted from my carriage, the brain pulsations being very distinct. Mr. Gage, during the time I was examining this wound, was relating how he was injured to the bystanders. I did not believe Mr. Gage’s statement then but thought he was deceived.”

Despite Williams’ skepticism, Gage’s account of the accident was accurate. He was eventually taken to his boarding house, where Dr. John Martyn Harlow attended. Harlow later wrote that “the iron entered the left side of the face, shattering the upper jaw, and passing back of the left eye, tearing the left lobe of the brain, and passing out at the top of the head, carrying with it a portion of the brain and other substances.”

Gage’s survival was miraculous, but it came at a significant cost. The iron had destroyed much of his left frontal lobe, which regulates emotions, personality, and decision-making. Gage’s behavior changed dramatically in the aftermath of the accident, and he became irritable, impulsive, and unpredictable. His story would become one of the most famous case studies in psychology and neuroscience, and it continues to fascinate researchers and laypeople today.

Medical and Psychological Impact

Phineas Gage’s accident had significant medical and psychological consequences. This section will discuss his injury’s physical consequences, behavioral changes, and long-term effects.

Physical Consequences

The iron rod that went through Phineas Gage’s skull damaged much of his frontal lobe, resulting in significant physical consequences. He lost his left eye and partially lost vision in his right eye. Additionally, he suffered from seizures and chronic headaches.

Behavioral Changes

Phineas Gage’s injury also resulted in significant behavioral changes. He became impulsive, irritable, and lacked empathy. He struggled with decision-making and planning, and his personality underwent a complete transformation. His friends and family reported that he was no longer the person he was before the accident.

Long-Term Effects

The long-term effects of Phineas Gage’s injury were significant. He could not return to his previous job as a railroad construction foreman and struggled to maintain employment. He became a circus attraction, traveling around the country as a living example of the effects of brain injury.

Phineas Gage’s case profoundly impacted the field of psychology, as it was one of the first documented cases of the link between brain damage and behavior. It helped researchers understand the role of the frontal lobe in decision-making, planning, and personality.

Significance in Psychology

Phineas Gage’s accident and its aftermath have significantly impacted the field of psychology. It has provided valuable insight into brain function, influenced neuropsychology development, and had implications for personality theory.

Insights into Brain Function

Gage’s injury provided a unique opportunity to study the relationship between the brain and behavior. It demonstrated that damage to specific brain areas can result in profound changes in personality and behavior. It also highlighted the importance of the prefrontal cortex in regulating social behavior, decision-making, and emotional regulation.

Influence on Neuropsychology

Gage’s case was one of the first documented cases of brain injury resulting in significant changes in behavior. It influenced the development of neuropsychology, a field that focuses on the relationship between brain function and behavior. Neuropsychologists use a variety of tests to assess cognitive function, including memory, attention, and language skills. They also use brain imaging techniques like magnetic resonance imaging (MRI) to study the brain’s structure and function.

Implications for Personality Theory

Gage’s case challenged the prevailing view of personality as fixed and unchanging. It demonstrated that brain injury can alter personality and that different parts of the brain are responsible for various aspects of personality. For example, damage to the prefrontal cortex can result in impulsivity, poor judgment, and emotional instability. This has led to theories that emphasize personality’s dynamic nature and the brain’s importance in shaping behavior.

Overall, Phineas Gage’s case has had a lasting impact on psychology. It has provided valuable insights into brain function, influenced neuropsychology development, and challenged prevailing views of personality.

Public Response and Legacy

Public perception.

After Phineas Gage’s accident, his story quickly spread throughout the public. People were fascinated by the idea that a simple iron rod could cause such a dramatic change in a person’s personality. However, the public’s understanding of Gage’s case was often oversimplified and exaggerated. Many people believed that Gage’s accident had turned him into a completely different person when, in reality, the changes were more subtle and complex.

Over time, Gage’s story became a cautionary tale about the dangers of head injuries. It was used to warn people about the potential consequences of traumatic brain injuries and to encourage them to take precautions to protect their heads.

Legacy in Science and Popular Culture

Phineas Gage’s case profoundly impacted the field of psychology and neuroscience. It was one of the first documented cases of a person with a brain injury that affected their personality and behavior. Gage’s case helped to establish the idea that different parts of the brain are responsible for various functions and that damage to these areas can cause specific changes in behavior.

Gage’s story has also had a lasting impact on popular culture. It has been referenced in countless books, movies, and TV shows and has become a symbol of the strange and mysterious workings of the human brain. In recent years, Gage’s case has even been used to promote the idea of neuroplasticity, which suggests that the brain can change and adapt throughout a person’s life.

Overall, Phineas Gage’s accident and its aftermath have left a lasting legacy in both the scientific and popular realms. While the public’s understanding of Gage’s case may be oversimplified, his story’s impact on psychology and neuroscience must be considered.

Frequently Asked Questions

Did phineas gage lose his eye.

No, Phineas Gage did not lose his eye in the accident. However, the iron rod that went through his skull damaged his left eye and caused him to lose vision in that eye.

When did Phineas Gage’s accident happen?

Phineas Gage’s accident happened on September 13, 1848. He was working on a railroad construction crew in Vermont when the iron rod he was using to tamp down blasting powder accidentally ignited the powder, causing the rod to shoot through his skull.

How long did Phineas Gage live after the accident?

Phineas Gage lived for another 12 years after the accident. He suffered from seizures and personality changes due to the damage to his brain, but he could continue living a relatively everyday life until he died in 1860.

How did Phineas Gage survive?

Phineas Gage’s survival is considered a medical miracle. The iron rod that went through his skull destroyed much of his frontal lobe, responsible for many essential functions such as decision-making, personality, and social behavior. However, the fact that the rod went through his brain in a relatively straight line and did not damage other vital areas likely contributed to his survival.

Why did Phineas Gage not feel pain?

It is unclear why Phineas Gage did not feel pain immediately after the accident. Some speculate that the damage to his brain may have affected his ability to perceive pain, while others believe that his body went into shock and he did not feel the pain at the time.

What happened to Phineas Gage, and how did it impact the field of psychology?

Phineas Gage’s accident and subsequent personality changes profoundly impacted the field of psychology. His case was one of the first to suggest a link between brain function and behavior, and it helped to establish the field of neuropsychology. Gage’s story also highlighted the importance of the frontal lobe in regulating personality and decision-making, and it continues to be studied by psychologists and neuroscientists today.

Phineas Gage: Neuroscience’s Most Famous Patient

An accident with a tamping iron made Phineas Gage history’s most famous brain-injury survivor

Steve Twomey

Jack and Beverly Wilgus, collectors of vintage photographs, no longer recall how they came by the 19th-century daguerreotype of a disfigured yet still-handsome man. It was at least 30 years ago. The photograph offered no clues as to where or precisely when it had been taken, who the man was or why he was holding a tapered rod. But the Wilguses speculated that the rod might be a harpoon, and the man’s closed eye and scarred brow the result of an encounter with a whale.

So over the years, as the picture rested in a display case in the couple’s Baltimore home, they thought of the man in the daguerreotype as the battered whaler.

In December 2007, Beverly posted a scan of the image on Flickr, the photo-sharing Web site, and titled it “One-Eyed Man with Harpoon.” Soon, a whaling enthusiast e-mailed her a dissent: that is no harpoon, which suggested that the man was no whaler. Months later, another correspondent told her that the man might be Phineas Gage and, if so, this would be the first known image of him.

Beverly, who had never heard of Gage, went online and found an astonishing tale.

In 1848, Gage, 25, was the foreman of a crew cutting a railroad bed in Cavendish, Vermont. On September 13, as he was using a tamping iron to pack explosive powder into a hole, the powder detonated. The tamping iron—43 inches long, 1.25 inches in diameter and weighing 13.25 pounds—shot skyward, penetrated Gage’s left cheek, ripped into his brain and exited through his skull, landing several dozen feet away. Though blinded in his left eye, he might not even have lost consciousness, and he remained savvy enough to tell a doctor that day, “Here is business enough for you.”

Gage’s initial survival would have ensured him a measure of celebrity, but his name was etched into history by observations made by John Martyn Harlow, the doctor who treated him for a few months afterward. Gage’s friends found him“no longer Gage,” Harlow wrote. The balance between his “intellectual faculties and animal propensities” seemed gone. He could not stick to plans, uttered “the grossest profanity” and showed “little deference for his fellows.” The railroad-construction company that employed him, which had thought him a model foreman, refused to take him back. So Gage went to work at a stable in New Hampshire, drove coaches in Chile and eventually joined relatives in San Francisco, where he died in May 1860, at age 36, after a series of seizures.

In time, Gage became the most famous patient in the annals of neuroscience, because his case was the first to suggest a link between brain trauma and personality change. In his book An Odd Kind of Fame: Stories of Phineas Gage , the University of Melbourne’s Malcolm Macmillan writes that two-thirds of introductory psychology textbooks mention Gage. Even today, his skull, the tamping iron and a mask of his face made while he was alive are the most sought-out items at the Warren Anatomical Museum on the Harvard Medical School campus.

Michael Spurlock, a database administrator in Missoula, Montana, happened upon the Wilgus daguerreotype on Flickr in December 2008. As soon as he saw the object the one-eyed man held, Spurlock knew it was not a harpoon. Too short. No wooden shaft. It looked more like a tamping iron, he thought. Instantly, a name popped into his head: Phineas Gage. Spurlock knew the Gage story well enough to know that any photograph of him would be the first to come to light. He knew enough, too, to be intrigued by Gage’s appearance, if it was Gage. Over the years, accounts of his changed character had gone far beyond Harlow’s observations, Macmillan says, turning him into an ill-tempered, shiftless drunk. But the man in the Flickr photogragh seemed well-dressed and confident.

It was Spurlock who told the Wilguses that the man in their daguerreotype might be Gage. After Beverly finished her online research, she and Jack concluded that the man probably was. She e-mailed a scan of the photograph to the Warren museum. Eventually it reached Jack Eckert, the public-services librarian at Harvard’s Center for the History of Medicine. “Such a ‘wow’ moment,” Eckert recalls. It had to be Gage, he determined. How many mid-19th-century men with a mangled eye and scarred forehead had their portrait taken holding a metal tool? A tool with an inscription on it?

The Wilguses had never noticed the inscription; after all, the daguerreotype measures only 2.75 inches by 3.25 inches. But a few days after receiving Spurlock’s tip, Jack, a retired photography professor, was focusing a camera to take a picture of his photograph. “There’s writing on that rod!” Jack said. He couldn’t read it all, but part of it seemed to say, “through the head of Mr. Phi...”

In March 2009, Jack and Beverly went to Harvard to compare their picture with Gage’s mask and the tamping iron, which had been inscribed in Gage’s lifetime: “This is the bar that was shot through the head of Mr. Phinehas P. Gage,” it reads, misspelling the name.

Harvard has not officially declared that the daguerreotype is of Gage, but Macmillan, whom the Wilguses contacted next, is quite certain. He has also learned of another photograph, he says, kept by a descendant of Gage’s.

As for Spurlock, when he got word that his hunch was apparently correct, “I threw open the hallway door and told my wife, ‘I played a part in a historical discovery!’ ”

Steve Twomey is based in New Jersey. He wrote about map and document thieves for the April 2008 issue of Smithsonian .

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Why Brain Scientists Are Still Obsessed With The Curious Case Of Phineas Gage

Jon Hamilton

Cabinet-card portrait of brain-injury survivor Phineas Gage (1823–1860), shown holding the tamping iron that injured him. Wikimedia hide caption

Cabinet-card portrait of brain-injury survivor Phineas Gage (1823–1860), shown holding the tamping iron that injured him.

It took an explosion and 13 pounds of iron to usher in the modern era of neuroscience.

In 1848, a 25-year-old railroad worker named Phineas Gage was blowing up rocks to clear the way for a new rail line in Cavendish, Vt. He would drill a hole, place an explosive charge, then pack in sand using a 13-pound metal bar known as a tamping iron.

But in this instance, the metal bar created a spark that touched off the charge. That, in turn, "drove this tamping iron up and out of the hole, through his left cheek, behind his eye socket, and out of the top of his head," says Jack Van Horn , an associate professor of neurology at the Keck School of Medicine at the University of Southern California.

Gage didn't die. But the tamping iron destroyed much of his brain's left frontal lobe, and Gage's once even-tempered personality changed dramatically.

"He is fitful, irreverent, indulging at times in the grossest profanity, which was not previously his custom," wrote John Martyn Harlow, the physician who treated Gage after the accident.

This sudden personality transformation is why Gage shows up in so many medical textbooks, says Malcolm Macmillan, an honorary professor at the Melbourne School of Psychological Sciences and the author of An Odd Kind of Fame: Stories of Phineas Gage.

"He was the first case where you could say fairly definitely that injury to the brain produced some kind of change in personality," Macmillan says.

And that was a big deal in the mid-1800s, when the brain's purpose and inner workings were largely a mystery. At the time, phrenologists were still assessing people's personalities by measuring bumps on their skull.

Gage's famous case would help establish brain science as a field, says Allan Ropper , a neurologist at Harvard Medical School and Brigham and Women's Hospital.

One Account Of Gage's Personality Shift

Dr. John Harlow, who treated Gage following the accident, noted his personality change in an 1851 edition of the American Phrenological Journal and Repository of Science.

One doctor's account of the personality shift in Phineas Gage following the accident.

"If you talk about hard core neurology and the relationship between structural damage to the brain and particular changes in behavior, this is ground zero," Ropper says. It was an ideal case because "it's one region [of the brain], it's really obvious, and the changes in personality were stunning."

So, perhaps it's not surprising that every generation of brain scientists seems compelled to revisit Gage's case.

For example:

In the 1940s, a famous neurologist named Stanley Cobb diagrammed the skull in an effort to determine the exact path of the tamping iron.
In the 1980s, scientists repeated the exercise using CT scans.
In the 1990s, researchers applied 3-D computer modeling to the problem.

And, in 2012, Van Horn led a team that combined CT scans of Gage's skull with MRI scans of typical brains to show how the wiring of Gage's brain could have been affected .

"Neuroscientists like to always go back and say, 'we're relating our work in the present day to these older famous cases which really defined the field,' " Van Horn says.

And it's not just researchers who keep coming back to Gage. Medical and psychology students still learn his story. And neurosurgeons and neurologists still sometimes reference Gage when assessing certain patients, Van Horn says.

"Every six months or so you'll see something like that, where somebody has been shot in the head with an arrow, or falls off a ladder and lands on a piece of rebar," Van Horn says. "So you do have these modern kind of Phineas Gage-like cases."

Two renderings of Gage's skull show the likely path of the iron rod and the nerve fibers that were probably damaged as it passed through. Van Horn JD, Irimia A, Torgerson CM, Chambers MC, Kikinis R, et al./Wikimedia hide caption

Two renderings of Gage's skull show the likely path of the iron rod and the nerve fibers that were probably damaged as it passed through.

There is something about Gage that most people don't know, Macmillan says. "That personality change, which undoubtedly occurred, did not last much longer than about two to three years."

Gage went on to work as a long-distance stagecoach driver in Chile, a job that required considerable planning skills and focus, Macmillan says.

This chapter of Gage's life offers a powerful message for present day patients, he says. "Even in cases of massive brain damage and massive incapacity, rehabilitation is always possible."

Gage lived for a dozen years after his accident. But ultimately, the brain damage he'd sustained probably led to his death.

He died on May 21, 1860, of an epileptic seizure that was almost certainly related to his brain injury.

Gage's skull, and the tamping iron that passed through it, are on display at the Warren Anatomical Museum in Boston, Mass.

Brain research
neuroscience
Brain injuries

Phineas Gage

In this post

You may have already heard of Phineas Gage, such is his infamous history with psychology. He was working on a railway line in the USA when there was an explosion, which resulted in an iron rod being fired through his head. He survived the accident even though there were serious injuries to his face and brain but it was soon discovered that in terms of his personality, he was completely different after the accident than he was before it.

Before the accident he was described as a very calm man who was very popular, but afterwards he was considered to be rude and irresponsible.

Gage died 12 years after the accident and after hearing of his death, his doctor, John Harlow, who had worked with him at the time of his accident, asked for his body to be exhumed so that he could look at his skull and try to identify how this caused the change in his personality.

Many years later, Damasio and her colleagues were able to make use of much better technology to further investigate the damage that had been caused to Phineas Gage’s brain and the effects that this had on his personality.

Damasio et al. aimed to build a replica model of Gage’s skull (using the actual skull as a guide) so that they could show exactly where the iron rod entered and exited Gage’s head.

A 3D representation of the skull and the injuries it received meant that it was much clearer which parts of his brain would have been affected by the accident and Damasio et al. wanted to see if any other areas of the brain had also been damaged.

Pictures and measurements of Gage’s skull were taken
A 3D replica model was built based on the information from the skull
Information was also taken from the iron rod (which had been buried with Gage!)
Information from the rod and the skull together meant that the trajectory of the iron rod could be accurately mapped
Altogether 20 different points of entry and 16 points of exit were identified and the five most likely paths were chosen
Each of these five paths were explored to map out which areas of Gage’s brain would have been damaged by each path.

It was thought that damage to both the left and right hemispheres of the brain were likely and that no other area than the frontal lobe would have been affected.

The iron rod would have gone through Gage’s left eye socket and then upwards in its trajectory. This means that rather than affecting the right frontal lobe, only the white matter (tissue containing nerve fibres) in the brain’s left hemisphere would have been affected. However, this meant that neural messages in this area of the brain would not have been transmitted because white matter is where neurons pass messages along axon fibres.

The findings from the 3D model and its implications for the parts of the brain that were thought to be damaged were compared to reports of the changes in Gage’s personality. It was concluded that a specific area of the frontal lobe (the ventromedial area) is responsible for making controlled decisions, regulating impulses and urges and dealing with emotions in a proper way.

These findings were compared to 12 other individuals who had experienced similar brain injuries and the same problems with control and impulse were found, showing that it is likely possible to predict the behaviour of people who have sustained this kind of brain injury.

Strengths of the study

Modern-day technology is very reliable and therefore the 3D model that was created would have been very accurate and information could be ‘seen’ rather than just guessed at from written reports
Predictions can now be made about people’s behaviour when they have experienced injuries in specific areas of the brain; this can help people to adjust to new lifestyles and may help in treating them as well.

Weaknesses of the study

Information about the change in Gage’s personality were gleaned from details written more than a century ago, meaning its accuracy is questionable
As this was a case study, it is difficult to generalise the findings to a wider population so predictions about possible changes in behaviour may not be applicable to everyone.

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The Oxford Handbook of the History of Clinical Neuropsychology

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41 Phineas Gage: A Neuropsychological Perspective of a Historical Case Study

Alan G. Lewandowski, Clinical Neuropsychologist, Neuropsychology Associates

Joshua D. Weirick, Post-Doctoral Research Fellow, Department of Speech, Language and Hearing Sciences, Purdue University

Caroline A. Lewandowski, Private Practice

Jack Spector, Clinical Neuropsychologist, Independent Practice

Published: 07 May 2020
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The case of Phineas Gage is one of the most frequently cited cases from 19th century medical literature and represents the first of a series of famous cases involving the brain and behavior. While many reiterations of Gage’s case have been published, it remains important to modern neuroscience due to its unique historical significance, ongoing clinical relevance, and the insights it offers neuropsychology into the functional effects of brain injury on thinking, emotions, and behavior. This chapter revisits the critical aspects of this landmark case from a contemporary clinical perspective and discusses the implications of injury to the prefrontal cortex and pathways.

Introduction

On Wednesday, September 13, 1848, a construction crew working for the Rutland and Burlington Railroad near Duttonsville, Vermont, was excavating rock to prepare the ground for track that was soon to be laid. In charge of the crew was a 25-year-old foreman named Phineas Gage, who was using an iron bar to pack black powder into a hole that had been drilled into the rock. For an unknown reason, a spark ignited the black powder and the ensuing explosion propelled the metal rod through the left side of Gage’s face, entering at a slight angle below his zygomatic arch. It passed behind his left eye, through the left frontal lobe, and exited the skull anterior to the juncture of the sagittal and coronal sutures, landing about one hundred feet behind him. Incredibly, Gage endured the injuries and lived another eleven and a half years. Due to his survival of an accident of this magnitude, he entered into the annals of scientific and historical literature as a frequently cited example of a frontal cortical injury.

One week after the accident, on September 21, 1848, the Free Soil Union newspaper in Ludlow, Vermont, published the following account:

Horrible Accident—As Phineas P. Gage, a foreman on the railroad in Cavendish, was yesterday engaged in tamkin [sic] for a blast, the powder exploded, carrying an iron instrument through his head an inch and a fourth in circumference, and three feet and eight inches in length, which he was using at the time. The iron entered on the side of his face, shattering the upper jaw, and passing back of the left eye, and out at the top of his head. The most singular circumstance connected with this melancholy affair is, that he was alive at two o’clock this afternoon, and in full possession of his reason, and free from pain. (Macmillan, 2000a , p. 12)

A review of the medical notes kept by the John Harlow, the physician who treated Gage immediately after his injury are not fully consistent with this newspaper account, especially with regard to the patient having been “free from pain.” Interestingly, 161 years later in July 2009, the Los Angeles Times published an article titled “A piercing image of Phineas Gage” (Maugh, 2009 ), which described the discovery of “the only known image of legendary brain-injury patient Phineas Gage” in a daguerreotype image. The LA Times account claims that “it [the bar] was successfully removed” and “contemporary accounts suggest that Gage’s personality was dramatically altered because he was disfigured in the accident” (Maugh, 2009 ). Unfortunately, but perhaps not surprisingly, more than a century and a half later the complexities of the case continue to pose challenges.

Phineas Gage, his treating physicians, the witnesses to the accident, and Cavendish, Vermont: the characters and setting of this story are, individually, unremarkable. Yet united by the circumstances of a remarkable event, they have contributed uniquely to the development of neuropsychology and continue to be relevant to modern psychological practice. Gage’s case is a story of the right projectile, at the right speed and the right distance, passing through the right area of the brain, of the right patient, who was treated by the right doctor, at the right time in history (Lewandowski, 2003 ). The result is that his injury, treatment, and long-term recovery continue to lend interest and relevance to contemporary neuroscientists across a broad range of medical and psychological disciplines.

Although birth documentation for Gage is lacking, he was probably born on September 9, 1823, in Lebanon, New Hampshire, and was named after his paternal grandfather. Genealogy records confirm that his father was Jesse Gage and his mother was Hannah Swetland, who married on April 27, 1823. He was the oldest of five children: his siblings Laura and Roswell were born in 1826, Dexter was born in 1831, and Phoebe was born in 1832 (Macmillan, 1986 ).

At the time of the injury Gage was 25 years old, and was described as “a perfectly healthy, strong and active young man” prior to the accident, standing “five feet six inches in height” with an “average weight one hundred and fifty pounds.” He possessed “an iron frame” and a “muscular system unusually well developed,” thus indicating that he was in excellent physical health (Harlow, 1868 , p. 330).

Gage’s premorbid psychological and cognitive status is also portrayed in very positive terms. He was reportedly of “well balanced mind,” and “was looked upon by those who knew him as a shrewd, smart businessman, very energetic and persistent in executing all his plans of operation.” In addition, he was of “considerable energy of character” (Harlow, 1868 , p. 340), and was regarded by his employers as “the most efficient and capable in their employ” (Harlow, 1868 , p. 399). Harlow observed that Gage possessed “an iron will” and a “nervo bilious temperament” (Harlow, 1868 , p. 330). His use of the term “nervo bilious” is a subtle indicator of phrenology’s influence on Harlow, as bilious (fibrous) and nervous are two of the four phrenological temperaments (Combe, 1830 , pp. 42–34).

Interestingly, Gage is described as having been “untrained in the schools” (Harlow, 1868 , p. 340); however, considering he could read and write (which may have assisted him in securing employment in a supervisory position as a railroad foreman), Macmillan ( 2000a ) suggests that this description refers to a lack of secondary education.

Cavendish past and present

Gage’s accident occurred outside Duttonsville, Vermont, which was a small village in the township of Cavendish, incorporated in 1761 (at present, however, “Cavendish” is the name of both the township and village). It is located east of the Green Mountains range of the Appalachians in Windsor County, approximately 25 miles southeast of Killington, Vermont (Cavendish Connects, n.d.) . As shown in Figure 41.1 , if one were to compare a historical map of Cavendish to a current topographical map, little change would be noted (Chase, 1856 ). The railroad bed that Gage and his construction crew were preparing is located approximately ¾ of a mile south of Main Street and to the east of Depot Street (Macmillan, 2000c ).

To fully appreciate the circumstances leading to Gage’s accident, it behooves one to have some familiarization with the state of transportation in the United States at that time in history. Prior to the development of railways in the early 1800s, the only available methods of travel or transporting goods in the northeast was limited to walking or using horses or pack animals attached to carriages or wagons when roads were available or the terrain permitted. Whereas transportation by steamer, canal boat, or barge offered an alternative, movement was restricted by the location and direction of the river or waterway and still required some land travel at the point of disembarking. As a result, the movement of people and their possessions across land remained very slow, inefficient, and cumbersome until John Stevens, the father of American railroads, sought to improve the speed and efficiency of transportation by proposing a rail line between New York and Lake Erie in 1815 (Winchester, 2014 ), generally following the Erie Canal. Stevens built a steam locomotive that he demonstrated at his New Jersey estate in an attempt to secure funding from local legislators. While he never lived to see this project completed, his efforts proved the viability of railway transportation such that, by the first half of the 1800’s, railroad construction exploded. The meager 20 miles of railroad track that had existed in 1828, expanded to almost 3000 miles by 1836 (Winchester, 2014 ).

Initially railroads were designed to connect major ports and their surrounding communities, but by 1870 rapid expansion resulted in the railroad industry becoming the nation’s second largest employer of men organized by innumerable work crews responsible for preparing the ground and laying track (Winchester, 2014 ). Over time railways developed to connect cities and therefore the ground required preparation by either excavation or filling in low areas. This drive to expand railway transportation to increase the efficiency of commerce is ultimately why Gage and his crew were engaged in the foothills outside of Duttonsville in 1848.

Gage was employed by the Rutland and Burlington railroad as a foreman of a construction crew. At the time of the accident he and his crew were excavating rock approximately ¾ mile southeast of Duttonsville in order to prepare the ground for track. This task, on its surface, seems relatively simple: Gage and his crew drilled holes in the to-be-excavated rock and filled those holes with gunpowder. The charges were then detonated, and the fragmented rock could be removed or placed in low-lying areas to level the grade. However, with the inherent risks in excavating rock by using explosives and the rudimentary equipment available, the danger and complexity of this type of work should not be underestimated. In order to fully grasp the planning, organization, and complexity required of Gage to execute these tasks, a cursory understanding of drilling and blasting with 19th century technology is necessary.

In the 1800s the method for drilling blasting holes in solid rock involved the use of a team of men working in close proximity and in concert to strike an iron drill bit with sledge hammers. One member of the gang was assigned the position of holding a drill bit, while one or two other members of the crew struck the head of the bit with a hammer. The force of the blow drove the bit into the rock, and the worker holding the bit turned it with each blow. The accrued rock dust was then removed by pouring small amounts of water into the hole to create a mud that stuck to the bit and was periodically removed by tapping the bit against a rock or wiping it clean with the worker’s hand. The bit was then replaced in the hole and the process continued, substituting bits of greater length as the hole deepened.

One can only speculate as to the skill and precision required of Gage and his crew as his men alternated hammer blows in a rhythmic manner, while one turned the bit with one or both hands. Holes approximately 2 yards deep could be bored into granite in about 5 to 6 hours, and several holes would be “drilled” across the area of rock to be excavated. Once the rock was loosened by the blast, a derrick crane and boom were used to load the rock onto animal- drawn carts for removal or placement into low-lying areas to level the ground for the rails (Lynch & Rowland, 2005 ).

After drilling, holes were packed with explosive powder. While some Gage citations have suggested the use of dynamite or blasting powder, the process of removing rock in the early 1800s involved the use of black powder. Dynamite was not yet invented and would not be available until Alfred Nobel introduced it to the United States in 1868 (Schuck & Sohlman, 1929 , p. 101).

Blasting powder uses detonation from the Latin word “de-tonare,” meaning to (expend) thunder, and therefore creates a supersonic combustion through shock compression that splits rock. In contrast, black powder, more commonly known as gunpowder, occurs through deflagration from the Latin word “de-flagrare,” meaning to burn down. The combination of heat and gas result in an effective propellant, as was the case in Gage’s tamping iron. As a result, black powder creates a subsonic combustion that occurs through thermal conductivity that heaves rock (Lynch, 2002 , p. 168).

Black powder is an inherently unstable chemical that combines proportionate measures of sulphur, potassium nitrate (saltpeter) and charcoal. While sulphur and charcoal act as the fuel, saltpeter acts as an oxidizer (Lynch, 2002 ). Its advantage (and danger) lies in the fact that it is relatively easy to ignite. A small spark is sufficient to set it off, as can be seen in the use of muzzle-loading weapons that use either flint or a percussion cap to ignite the powder packed into a breech. The force of the blast depends on a number of variables that include the amount of powder, the size of the grains, and the pressure under which the blast is initiated. Pressure and combustion are obtained by the ratio of fuel to the oxidizing agent and how tightly the powder is packed into a receptacle such as the breech of a gun, or in this case, the hole that Gage was drilling into solid rock (Krehl, 2009 ).

Blasting rock is done by placing black powder into a deep hole of fairly narrow diameter with a fuse positioned to the same depth. The fuse is then trailed onto the ground and of sufficient length to allow the person who ignites the fuse time to move a safe distance away. Layered in the hole on top of the black powder is a collection of aggregate such as sand or soft clay. Sand was commonly used because it is a readily available, easily obtainable, inexpensive, and can be compacted tightly to fill up the small spaces in a hole. As a result, pressure is created by trapping expanding gases, thus leading to combustion sufficient to heave rock (Ihlseng & Wilson, 1907 ). The process of drilling and tamping is demonstrated in Figure 41.2 .

Drilling blasting holes

Another variable that added to the danger of Gage’s work was the fuse. In the early 1800s fuses were known as “coils” or “quills” and were hand made by filling quills or straw with black powder, by covering lengths of hemp of varying thickness with tar and black powder, or by wrapping hemp around a core of powder-filled straw and coating the resulting fuse in tar to protect it from moisture (U.S. Department of the Army, 1984 ). Because of variability in their individual manufacture, fuses lacked uniformity and it was difficult to estimate their burn rate. Safety fuses were not introduced to civil engineering until 1831 when William Bickford introduced a half-inch “coil” to the British mining industry. Safety fused were probably uncommon among railroad workers in America at the time of Gage’s accident (Smith, 1909 , pp. 112–117).

Given the instability of black powder combined with the unreliable fuses, it is easy to see the inherent danger in Gage’s work during a period when explosives technology was in its infancy. At the time of Gage’s accident, railroading in general was a very dangerous profession. Although railroad worker fatalities were not reliably documented until the late 1800s, Aldrich ( 2006 ) found that nearly 4000 workers were killed in 1845 as a result of various railroad construction accidents, although the actual deaths were likely to have been higher than recorded.

The missile that caused the injury was an iron bar measuring 3 feet 7 inches long and weighing 13 ¼ pounds (shown in Figure 41.3 ). It is described as a “tamping iron,” named for its purpose. A tamper is a device used to compact or flatten aggregate to increase compression. Gage’s iron was used to “tamp” or pack down the loose sand that was placed on top of black powder during the process of blasting rock.

The terms “tamper” and “tamping” are derived from the Middle English “tampion,” which is a type of plug placed in a gun or cannon muzzle in order to protect it from dirt or moisture in the environment. “Tampion” itself may be a borrowing from Old French “tapon,” which referred to a piece of cloth used for plugging a hole (Tamp, n.d.) .

Tamping refers to the use of a “tamper” or, as in Gage’s work, a tool designed to compress aggregate. Typically, sand is placed over explosive powder and packed tightly in order to increase compression of gases to render a more powerful blast. In his 1850 publication, Bigelow describes that the iron was “forged by a neighboring blacksmith” and that it was “unlike any other having been made to please the fancy of the owner” (p. 14), indicating that Gage probably had his tamping iron custom made.

Gage’s tamping iron

An inspection of the tamping iron reveals that it is about 1¼ inch in diameter and roughly speaking the width of a common broom or mop handle. The texture is smooth and one end of the bar is gradually shaped to a point (Lewandowski, 2001 ). This is this end that was propelled into Gage’s lower left face and through his head.

It may be questioned as to why the bar was designed to be pointed at one end, when its primary purpose was packing aggregate. Tools, and particularly farm implements, are most often designed to serve multiple purposes. Consider a hammer that is designed to drive as well as remove nails, or a wrench with both open and closed ends). It is not unreasonable to assume that Gage instructed the blacksmith who forged the tamping iron to shape the end to a gradual point, as was common among miners, who often referred to this type of tool as a “needle” (Lewandowski, 2003 ). The tapered shape allowed for the tool to be used for holes of different diameters, for shaping a hole, or as a wedge or lever that could be used for dislodging split rock (Ihlseng & Wilson, 1907 ).

The Accident Site

Navigating to the accident site from the center of modern-day Cavendish would involve traveling down Main Street until Depot Street is reached, and then following Depot Street to the south. A set of railroad tracks will be encountered. The accident occurred east of this area near the first bend of the track heading to the south (Lewandowski, 1998 ; Macmillan, 2000c ; Pate, 1999 ).

More important than the exact site of the accident, which is not precisely known, is the topography of the immediate area (Lewandowski, 2001 ). The railroad bed where Gage was injured is nested in a corridor between two vertical walls of rock of about 30 feet in height and of considerable length (as shown in Figure 41.4 ).

Railroad track and rock near the accident site

The Accident

Gage’s accident occurred on September 13, 1848 at approximately 4:30 in the afternoon. The account is well documented by John Harlow, the local physician who treated Gage, and to whom it can be assumed Gage provided details during his period of recovery. Harlow ( 1868 ) recounts the accident as follows:

He was engaged in charging a hole drilled in the rock, for the purpose of blasting, sitting at the time upon a shelf of rock above the hole. His men were engaged in the pit, a few feet behind him, loading rock upon a platform car, with a derrick. The powder and fuse had been adjusted in the hole, and he was in the act of ‘tamping it in,’ as it was called, previous to pouring the sand. While doing this, his attention was attracted by his men in the pit behind him. Averting his head and looking over his right shoulder, at the same instant dropping the iron upon the charge, it struck fire upon the rock, and the explosion followed, which projected the iron obliquely upwards, in a line of its axis, passing completely through his head, and high into the air, falling to the ground several rods behind him, where it was afterwards picked up by his men, smeared with blood and brain. The missile entered by is pointed end, the left side of the face, immediately anterior to the angle of the lower jaw and passing obliquely upwards, and obliquely backwards, emerged in the median line, at the back part of the frontal bone, near the coronal suture. (Harlow, 1868 , p. 331)

After the accident Gage reportedly suffered “a few convulsive motions of the extremities,” but was soon conscious and able to speak (p. 331). Astonishingly there are no reports of Gage having lost consciousness or experiencing post-traumatic amnesia. His men carried him approximately 10 yards to the road where he was placed in a sitting position in a cart and transported about ¾ of a mile to Adams’s Inn. Gage left the cart with only a little assistance from bystanders and made his way to a chair on the porch where he awaited medical assistance from the local physician. During this time documents support that he remained alert and oriented.

Eyewitness Accounts

One of the first witnesses to Gage’s condition after the accident was Joseph Adams, the proprietor of the local tavern where some of the railway workers boarded. This is the hotel to which witnesses refer and where Gage was taken after the injury. In addition to being the local tavern owner, Adams was also the local Justice of the Peace who provided an affidavit for Harlow at the request of Henry Bigelow who also examined Gage months after the accident (Bigelow, 1850 ).

It is understandable that many did not believe that a person could survive such a devastating injury and therefore his public position and testimony lent credibility in the subsequent documentation. The notification of a local cabinet maker named Winslow who owned a shop about four buildings down from the tavern provides a good example. Winslow was told of the accident and subsequently measured Gage in order to begin work on a coffin for his anticipated death (Macmillan, 2000a ).

In his affidavit Adams testifies as follows:

This is to certify that P.P. Gage had boarded in my house for several weeks previous to his being injured upon the railroad, and that I saw him and conversed with him soon after the accident, and am of opinion that he was perfectly conscious of what was passing around him. He rode to the house, three-quarters of a mile, sitting in a cart, and walked from the cart into the piazza, and thence upstairs, with but little assistance. I noticed the state of the left eye, and know, from experiment, that he could see with it for several days though not distinctly. In regard to the elevated appearance of the wound, and the introduction of the finger into it, I can fully confirm the certificate of my nephew, Washington Adams, and others, and would add that I repeatedly saw him eject matter from the mouth similar in appearance to that discharged from the head. (Bigelow, 1850 , p. 14)

Adams, along with others, presented a compelling picture of Gage’s physical condition immediately after the injury. In addition, he must have recognized the importance of the tool, as he went searching for the bar the following day:

The morning subsequent to the accident I went in quest of the bar, and found it at a smith’s shop, near the pit in which he was engaged. The men in his pit asserted that ‘they found the iron, covered with blood and brains,’ several rods behind where Mr. Gage stood, and that they washed it in the brook, and returned it with the other tools; which representation was fully corroborated by the greasy feel and look of the iron, and the fragments of the brain which I saw upon the rock where it fell (Bigelow, 1850 , pp. 14–15).

A second and equally important witness was a local Protestant minister who observed Gage as he was taken out of the cart and assisted onto a porch chair. Reverend Joseph Freeman spoke with Gage, discussed the incident with some of his crew, and inspected the accident site and the tamping tool that was taken to the blacksmith’s shop. Because of his position in the community, Reverend Freeman also provided an affidavit and further verified the facts of the incident. On December 14, 1849 he testified as follows:

I was home on the day Mr. Gage was hurt; and seeing an Irishman ride rapidly up to your door, I stepped over to ascertain the cause, and then went immediately to meet those who I was informed were bringing him to our village. I found him in a cart, sitting up without aid, with his back against the fore board. When we reached his quarters, he rose to his feet without aid, and walked quick, though with an unsteady step, to the hind end of the cart, when two of his men came forward and aided him out, and walked with him, supporting him to the house. I then asked his men how he came to be hurt? The reply was, ‘The blast went off when he was tamping it, and the tamping-iron passed through his head.’ I said, ‘That is impossible.’ Soon after this, I went to the place where the accident happened. As I came up to them, they pointed me to the iron, which has since attracted so much attention, standing outside the shop-door. They said they found it covered with brains and dirt, and had washed it in the brook. The appearance of the iron corresponded with this story. It had a greasy appearance, and was so to the touch. (Bigelow, 1850 , p. 15)

Dr. Edward Williams, who spoke with Gage and collaborated with Harlow immediately after Gage’s injury, also provided an affidavit. In a letter dated December 4, 1849, from his home in Northfield, Vermont he wrote:

Dr. Bigelow: Dear Sir—Dr. Harlow having requested me to transmit to you a description of the appearance of Mr. Gage at the time I first saw him after the accident, which happened to him in September 1848, I now hasten to do so with pleasure. Dr. Harlow being absent at the time of the accident, I was sent for, and was the first physician who saw Mr. G., some twenty-five or thirty minutes after he received the injury; he at that time was sitting in a chair upon the piazza of Mr. Adams’s hotel, in Cavendish. (Bigelow, 1850 , pp. 14–16)

Williams’s contribution was in detailing Gage’s appearance and his examination findings.

First Responder

Dr. John Harlow, the physician best known for his treatment of Gage, was not immediately available when Gage was brought to Adams’s Inn. As a result, Dr. Edward Higginson Williams, another local physician, was summoned in his stead, and it was Williams who was the first to evaluate Gage’s injury and render immediate assistance. In a sense, he was ex post facto the emergency physician who first attended Gage, and the portico of the Adams’s Inn was his de facto emergency and trauma bay where he began his assessment.

Williams was a twenty-four-year-old graduate of Vermont Medical School when he attended to Gage. His obituary in the New York Times , appearing in December 1899, notes that he practiced as a physician for only a short period of time before he left medicine to work in the railroad industry, eventually securing part ownership of the Baldwin Locomotive Works (New York Times, 1899 ). Although a young physician at the time he treated Gage, he had sufficient medical experience to begin addressing the penetrating head wound, verify the presenting history and mechanism by which the injury occurred, confirm the symptoms, and do what he could to stabilize the patient until Harlow arrived.

Most students of psychology, neuroscience, and medicine are very familiar with the quotation attributed to Gage’s family and friends that, “He was no longer Gage” (Harlow, 1868 ); however, Williams provides a quote from Gage himself that, while lesser-known, is equally compelling. Consider the circumstances under which he and Gage were introduced: the patient had just suffered a horrific injury that should have killed him. He was then transported back to town on an oxcart three quarters of a mile to a local tavern where he sat in a chair on a veranda waiting for half an hour for a physician to arrive. When Dr. Williams arrived in his carriage, Gage addressed him. Williams recalled, “When I drove up he said, ‘ Doctor, here is business enough for you .’ ” This simple statement by Gage confirms his self-reliant character and offers marvelous insight into his personality.

Dr. Williams’ comments about Gage’s injuries suggest that he was in disbelief of the circumstances of the injury. He was decisively convinced following a personal examination in addition to the confirmatory comments of the railroad crew members who were present at the time of the accident (Figure 41.5 ):

I first noticed the wound upon the head before I alighted from my carriage the pulsations of the brain being very distinct; there was also an appearance which before I examined the head, I could not account for: the top of the head appeared somewhat like an inverted funnel; this was owing, I discovered, to the bone being fractured about the opening for a distance of about two inches in every direction. I ought to have mentioned above that the opening through the skull and integuments was not far from one and a half inch in diameter; the edges of this opening were everted and the whole wound appeared as if some wedge-shaped body had passed from below upward. (Bigelow, 1850 , p. 16)

Williams’ initial observations of Gage’s behavior may be of interest to neurological clinicians. Recall that his examination took place within an hour of the traumatic brain injury. Gage was probably in shock, but had not yet succumbed to infection, hence delirium had not yet set in. Retrospectively, Williams’s interactions with Gage provide behavioral observations that could be considered a rudimentary mental status examination. He was able to establish that Gage was oriented to person, place, time, and purpose. In addition, Williams’s observations of visual, verbal, and motor responding, which are supported by affidavits, establish that Gage’s eyes were open, he conversed normally, and he obeyed commands. By today’s emergency and trauma standards for head injury evaluation, one could speculate that Gage demonstrated a normal Glasgow Coma Scale score of 15 (Teasdale & Jennett, 1974 ), which would lend some support to a positive outcome from his traumatic brain injury.

Gage’s skull

Williams continues:

At the time I was examining this wound, he was relating the manner in which he was injured to the bystanders; he talked so rationally and was so willing to answer questions, that I directed my inquiries to him in preference to the men who were with him at the time of the accident and who were standing about at this time. Mr. G. then related to me some of the circumstances as he has since done; and I can safely say that neither at that time nor any subsequent occasion, save once, did I consider him to be other than perfectly rational. The one time to which I allude was about a fortnight after the accident, and then he persisted in calling me John Kirwin; yet he answered all my questions correctly.

Despite being the first physician to directly assess Gage’s injury, Williams nonetheless remained skeptical. In an affidavit to Bigelow he reported:

I did not believe Mr. Gage’s statement at that time, but thought he was deceived; I asked him where the bar entered, and he pointed to the wound on his cheek, which I had not before discovered; this was a slit running from the angle of the jaw forward about one and a half inch; it was very much stretched laterally, and was discolored by powder and iron rust, or at least appeared so. Mr. Gage persisted in saying that the bar went through his head.

The Treating Physician

Dr. John Martyn Harlow arrived at Adams’s Inn at approximately 6 p.m., and was clearly taken by Gage’s presentation: “the picture presented was, to one unaccustomed to military surgery, truly terrific; but the patient bore his sufferings with the most heroic firmness.” At that point both physicians combined their medical skill to stabilize Gage’s condition. He walked up a flight of stairs to an upper bedroom “with a little assistance” (Harlow, 1848 , p. 390) and was placed in a bed so that Harlow could begin a more detailed examination. In this sense, Harlow actions were similar to those of a modern-day trauma surgeon.

Harlow found Gage’s wound so significant and complete that he “passed in the index finger its whole length without the least resistance, in the direction of the wound in the cheek, which received the other finger in like manner” (Harlow, 1848 , p. 390). Although this procedure may seem alarming by modern standards, it should be recalled that at the time, an understanding of pathogens and infectious disease (germ theory) was not yet commonplace in American medicine. In fact, many physicians educated in the 19th century continued to debate the Miasma theory of disease transmission (Halliday, 2001 ; Last, 2007 ). Consider that Lister’s use of phenol in aseptic surgical techniques would not be introduced until 1867 and not widely accepted into clinical practice until the late 1800s (Greenwood, 1998 ; Lister, 1867 , 1868 ).

While Harlow and Williams dressed the wound, Gage’s behavior was compliant and cooperative, and he was “perfectly conscious, answering all questions, and calling his friends by name as they came into the room.” At the same time, however, he was observed to be losing a significant amount of blood “both externally and internally,” vomited several times, and began to fatigue. Gage’s pulse was weak at 60, but Harlow does not report where he palpated his patient. Harlow reports that “he was getting exhausted from the hemorrhage, which was very perfuse both exterally [sic] and internally, the blood finding its way into the stomach, which rejected it as often as every 15 or 20 minutes.” The blood loss was clearly significant, as Harlow reports that, “His person, and the bed on which he was laid, were literally one gore of blood” (p. 390). Given this description, it seems likely that the effects of hypovolemic shock were occurring as Gage’s hemoglobin was decreasing.

Williams and Harlow then shaved Gage’s head, removed the dried blood and a very small sharp piece of bone, and resected “a portion of the brain which hung by a pedicle” (p. 390). Larger pieces of the frontal bone were replaced as close to their original position as possible, the scalp was closed with “adhesive straps,” and a compression dressing was applied, over which they placed a night cap. This concluded the initial resuscitation and stabilization of the patient, and, in a cursory sense, it was not too dissimilar to that of contemporary protocols exercised by emergency room physicians and trauma surgeons.

Historically, injuries to the brain were more often than not fatal due to the trauma itself, intracerebral infection, and herniation from increased intracranial pressure, blood loss, etc. (Bollet, 2002 ; Cronyn, 1871 ; Karger, Sudhues, & Brinkmann, 2001 ). It was not until Percivall Pott’s publication of Observations on the nature and consequences of those injuries to which the head is liable from external violence in 1768 that physicians would be offered clear guidance on the medical management of acceleration and deceleration head injuries, not just injury to the skull, but to the treatment of the brain (Pott, 1768 ). Pott addressed cerebral contusions, skull fractures, concussions, and the management of pus (McCrory, 2001 ), and his writings were recognized in the 19th century as revolutionary in the treatment of head wounds (Butler, 1851 , p. 99). Thus, his medical treatises would have been well known to Harlow’s professors at Jefferson Medical College.

Interestingly, in his report, Harlow is somewhat defensive when he addresses the issue of “probing” the brain, noting that he had later been questioned as to why he did not do so. He presents his rationale as follows: “I think no surgeon of discretion would have upheld me in the trial of such a foolhardy experiment, in the risk of disturbing lacerated vessels from which the hemorrhage was near being staunched [sic], and thereby rupturing the attenuated thread, by which the sufferer still held life” (Bigelow, 1850 , p. 17; Harlow, 1848 , p. 390).

Probes in the 19th century were essentially long stiff metal wires with porcelain tips used to extract skull and bone fragments from the brain after penetrating head injuries. Such an instrument was used by US Surgeon General Dr. Joseph Barnes, who attended to President Lincoln after his assassination. Accompanying Barnes were Lincoln’s personal civilian physician, Dr. Robert Stone, and other US Army physicians who included Dr. Anderson Abbott, the first African-Canadian doctor, and Dr. Charles Crane, Assistant Surgeon General. As the ranking officer, Barnes directed the trauma treatment and, with the assistance of U.S. Army surgeon Dr. Charles Leale, probed Lincoln’s brain first with his (nonsterile) fingers and then with a Nelaton probe. Given the absence of modern neuroimaging, the use of a probe was judged necessary to discern the location and trajectory of the bullet (Trunkey & Farjah, 2005 , pp. 977–978). This porcelain tipped medical instrument was used to explore the wound and break blood clots, which likely increased the loss of blood and in doing so may have expedited Lincoln’s death (Bollet, 2002 ; Trunkey and Farjah, 2005 ). (An excellent example of this type of probe can be found on display at the Armed Forces Institute of Pathology museum in Washington, D.C., which displays the actual probe Barnes and Leale used, alongside fragments of the President’s skull and the 41 caliber lead ball fired from Booth’s derringer.)

Harlow’s treatment of Gage was guided by having been taught to avoid probing a brain (Harlow, 1848 , p. 390). In his medical education at Jefferson Medical College in Philadelphia (now Thomas Jefferson University) he had the benefit of being trained by several famous faculty members who historically have been referred to as the “faculty of ‘41” (Aptowicz, 2014 , p. 83; Elliot, 1911 ; Macmillan, 2001 ).

One of Harlow’s professors was Thomas Dent Mutter, a pioneer of reconstructive surgery, who was known for advocating for antiseptic techniques, replacing bone fragments, allowing for wound drainage, treating with purgatives and cathartics, and never probing. His influence is clearly seen in Harlow’s detailed description of his treatment of Gage (Harris, 1994 ). Further medical insight pertinent to this particular type of injury came from Professor Joseph Pancoast. Pancoast is still well known to surgeons today, and, like Mutter, he pioneered a number of procedures particularly with early reconstructive techniques. He authored A Treatise on Operative Surgery (Pancoast, 1844 ) in which he addresses the treatment of intracerebral pus, and chaired both the Departments of Surgery and Anatomy (Radbill, 1986 ). Lastly, Professor Robley Dunglison was Thomas Jefferson’s private physician who immigrated from England to establish the medical school at the University of Virginia (Gemmill, 1972 ). He published books on health, hygiene, morals, and intellect (Dunglison, 1835 ); human physiology and the history of medicine; and the medicinal use of marijuana (Dunglison, 1846 , p. 153). Known as the father of American Physiology (The National Cyclopaedia of American Biography, 1909, p. 270) Dunglison chaired Jefferson Medical College’s Department of Medicine and was best known for his publication Human Physiology , in which he addressed human temperament and idiosyncrasies, individual and cultural differences, and phrenology (Dunglison, 1832 , pp. 445–479). In addition to these accomplishments, perhaps equally important to Gage’s survival were his extensive prescriptions for multiple medical conditions (Dunglison, 1846 , 1833 ).

Harlow’s Physical Medicine and Rehabilitation

From the time of his arrival at bedside about 6 p.m. on Wednesday, September 13 until Saturday, November 18, 1848, Harlow made detailed observations of his treatment (Bigelow, 1850 , 1900 ; Harlow, 1848 , 1868 ). A review of his medical record indicates that he managed Gage’s medical trauma in a manner commensurate with prevailing medical practice and is rightfully credited with Gage’s stabilization and ultimate recovery. In addition, however, the circumstances of Gage’s wound and his preinjury status may have contributed to his survival. As the noted neurologist Charles Symonds declared, “It is not only the kind of injury that matters, but the kind of head” (Richardson, 2013 , p. 168).

Both Bigelow and Harlow report in some detail about Gage’s pre-injury status (Bigelow, 1850 , 1900 ; Harlow, 1848 , 1868 ), as this was pertinent in their discussion of his subsequent survival and later changes in demeanor. Recall that Gage was described by those who knew him as healthy, strong, active, muscular, physically well developed, shrewd, and intelligent. One can assume, then, that Gage’s premorbid physical and mental condition was not complicated by any significant known or documented premorbid disease, insults, or injuries. This is entirely consistent with Harlow’s ( 1868 ) report that Gage “had scarcely a day’s illness from his childhood to the date of this injury (p. 330). As a result, Gage’s state of health at the time the accident likely contributed positively to his chances of recovery.

A second variable that has not been previously discussed is the effects of the skull fracture that occurred as the tamping iron exited Gage’s cranium. It is very likely that Harlow’s efforts to stabilize his patient were inadvertently aided by the shattering of his skull resulting in a de facto decompressive craniectomy.

A decompressive craniectomy is a neurosurgical procedure sometimes employed in cases of severe brain trauma to allow for brain expansion where swelling occurs as the result of increased intracranial pressure within the skull vault. If left untreated, the interruption of the autoregulation of normal cerebral blood flow can result in increased cerebral perfusion pressure causing marked intracranial edema and ultimately leading to herniation and death (Aarabi et al., 2006 ; Reitan & Wolfson, 1986 ). The energy expended from the acceleration force drove the iron under Gage’s zygomatic arch, through the brain and dura, and exited the calvarium, resulting in bone loss that in turn, allowed for a natural expansion of the brain. Although Harlow and Williams replaced the pieces of bone available, all of the fragments were not recovered and part of the exit wound remained uncovered. This is apparent when examining any photograph or drawing of the skull or when viewing Gage’s life mask. Harlow ( 1868 ) observed that, “The fragments of bone being lifted up, the brain protruding from the opening and hanging in shreds upon the hair, it was evident that the opening in the skull was occasioned by some force acting from below.” He specifically describes how the frontal bone “was extensively fractured, leaving an irregular oblong opening in the skull of two by three and one-half inches” and goes on to report that “the pulsations of the brain were distinctly seen and felt” (p. 332).

After dressing the wound with Williams, Harlow stayed with Gage until 10 p.m., noting that “sensorial powers remain as yet unimpaired” (p. 391). Gage remained fully oriented as evidenced by his ability to name his friends and their residences. His unfaltering and committed character is reflected in his statement to Harlow that he expected to return to work in one or two days, even though he continued to hemorrhage for the next 48 hours.

The next morning Gage’s face became quite swollen and, although in pain, he was able to speak and was noted to be rational. Day two post injury (the 15th) his hemorrhaging stopped, but he began to show signs of delirium and was observed to be “disconnected and incoherent.” At this point Harlow recorded a prescription of “vin. Colchicum ℥ 3 ss every six hours until it purges him” (p. 391). Following the Apothecaries’ system of pharmacy common to 19th century United States at that time (Hasegawa, 2006 ), Harlow administered one half dram, or about 2 ml of colchicine, which in high doses is a toxic alkaloid derived from the corms of the autumn crocus (Colchicum autumnale). This flower extract was frequently used by physicians at that time for its pain-relieving, sedative, and anti-inflammatory properties. In small to moderate doses it produces gastrointestinal side effects that can be used as a sedative, cathartic, diuretic, and emetic (Kyle, et al., 1997 ; Rodnan & Benedek, 1970 ). Because its side effects include gastrointestinal movement, Harlow used it to induce bowel evacuation.

Day three post injury Harlow ( 1848 ) reported a discharge of foul smelling and thin watery pus intermixed with brain material and a fungus at the outside corner where the upper and lower eyelids of the left (injured) eye meet. Gage described the feeling of the left side of his head as “banked up” (p. 391) and had not yet had a bowel movement. Harlow applied ice water to Gage’s eye and head to address the inflammation and prescribed “sulph. magnesia ℥, repeated every four hours until it operates” (p. 391), hence an ounce of magnesium sulfate that was used as a laxative to initiate bowel motility.

Day four post injury, Harlow ( 1848 ) recorded the success of the laxative, noting that Gage “purged freely,” experienced some remission from his delirium, and that he was “rational and knows his friends.” While his facial wounds were healing, Gage’s abscess increased in volume, became foul smelling, and was described by Harlow as “very foetid and sanous” (p. 391).

Day five post injury Harlow ( 1848 ) observed that Gage slept throughout the night and showed preference for lying on his right side, probably because of pain and discomfort. His tongue was described as “red and dry” and his breath as “foetid,” suggesting probable dehydration. Harlow’s interventions that day included probing the skull at its base “without giving pain,” prescribing a cathartic “which operated freely,” and applying cold to the wound. While Gage remained psychologically optimistic and reported to Harlow that “he shall recover,” he continued to experience delirium marked by periods of coherence (p. 391).

Day six through day eight post injury, Gage’s mental and physical condition remained compromised but stable. Harlow ( 1848 ) recorded symptoms of restlessness, dry hot skin, red tongue, and excessive thirst over these three days, as well as impaired mental status marked by “talking incoherently with himself, and directing his men” (p. 391). By this description, Gage clearly continued to suffer from acute confusion, ongoing infection, and dehydration.

Gage’s impaired mental status continued through the morning of the 9th day post injury when he reported “he shall not live long.” His physical agitation and behavioral noncompliance now complicated the clinical picture as evidenced by Harlow’s ( 1848 ) description that his patient “Throws his hands and feet about, and tries to get out of bed.” Harlow described fever (“head hot”) and prescribed “a cathartic of calomel and rhubarb, to be followed by castor oil, if it does not operate in six hours” (p. 391).

Harlow’s use of medications to regularly purge Gage was consistent with 19th century “heroic medicine.” This philosophy advocated alleviating nerve and blood overstimulation that were assumed to cause all disease. Common treatments to restore health included blistering, bloodletting, vomiting, and purging (Duffy, 1990 ; Stavrakis, 1997 ). Harlow’s choice of Calomel is understandable as it was a commonly prescribed therapeutic in the 1800s. In its pharmaceutical form, it is an odorless powder that was commonly prescribed for internal use to treat multiple medical conditions such as constipation, infectious disease, fever, cholera, pleurisy, dropsy, gout, worms, and eclampsia (Weatherall, 2006 ). Externally its use was intended as a disinfectant to treat smallpox sores, syphilitic ulcers, and warts (Risse, 1973 ). Calomel is mercury chloride and therefore is no longer used as a therapeutic agent. Consistent with standards of practice at that time, Harlow used it with Gage in small does as a stool softener and laxative, and in larger does as a purgative.

For the next 11 days (Saturday September 23 through Tuesday October 3) Harlow’s records indicate that Gage remained semi-comatose, “seldom speaking unless spoken to, and then answering only in monosyllables” and that he lost vision in his injured eye (p. 392). Harlow treated the fungal brain and orbit abscess with cold compresses to the head and silver nitrate. Prior to the advent of modern antibiotics, silver nitrate was used medicinally as an antimicrobial. It can be assumed that Harlow applied the antiseptic to Gage’s wounds to treat the infection and prevent sepsis and further tissue decomposition. Gage’s dressings were changed every 8 hours and laxatives were administered regularly. Nevertheless, during this time an infection occurred in the occipitofrontalis muscle that Harlow punctured to drain about 8 ounces of pus.

Twenty-two through 24 days post injury Harlow observed wound discharge, which he referred to as “laudable pus” (p. 392), which, at the time, was thought to be associated with healing (Alexander, 1985 ). Gage’s improvement was also evidence by his ability to raise his head. During this time Harlow also prescribed that Gage sit up at bedside for five minutes at a time before returning to bed, a practice not dissimilar from modern rehabilitation methods used on intensive care units.

Twenty-eight days post injury Harlow recorded Gage’s responses to that which constituted brief mental status questions. While he had already documented that Gage was oriented to person, he was now able to establish orientation to place, time, and purpose. That is, when asked about the date of injury, Gage confirmed accurately that the accident occurred “four weeks this afternoon at 4 ½ o’clock” (p. 392). Given the severity of the brain trauma, the contemporary neuropsychologist or physician might assume significant anterograde and retrograde amnesia. Surprisingly, this was not the case, as Gage was able to recall how the accident took place and his transport to Adam’s Inn. In addition, he kept an accurate account of the day and recognized most of his visitors. In fact, Harlow described Gage’s memory as being “perfect as ever.” However, Gage is also described as being unable to perform some simple activities of daily living, which included estimating “size or money” or “exchanging $1000 for a few pebbles” (p. 392), suggesting limitations to executive reasoning. In contrast, his physical condition showed progressive improvement as the abscess in the posterior part of his mouth continued to diminish with the topical use of silver nitrate.

At thirty-seven days post injury Gage was able to get out of bed independently and sit up at bedside for 30 minutes at a time; however, he was noted to be “very childish” and asked Harlow to allow him to return to his home in New Hampshire. Considering his physical condition, his request probably reflected an early indication of his lack of insight. Two months after the injury on November 8, Gage was no longer confined to his bed. Harlow kept him on a “low diet” and noted normal appetite, sleep, digestive, and bowel patterns. Gage’s increased physical activity included sitting up “most of the time during the day,” ambulating about the stairs and porch of Adams’s Inn, and walking in the street. Given his apparent stable mental and physical status, Harlow left for a week and instructed his patient “to avoid excitement and exposure” (p. 392).

In spite of his directives, when Harlow returned a week later he was told that Gage was reportedly “in the street every day except Sunday” and that “his desire to be out and to go home to Lebanon has been uncontrollable by his friends, and he has been making arrangements to that effect” (p. 392). At one point, Gage walked half a mile to a store in the cold wet weather without benefit of a coat or proper footwear. When Harlow checked on him, Gage was in bed and described as “depressed and very irritable” with “hot and dry skin,” thirsty, constipated, and complained of stabbing pain on the left side of his face. Harlow’s use of the term “rigors” suggests that Gage’s symptoms included high fever, cold, sweating, and shivering. His treatment included a cold compress to treat the fever and prescribing a “black dose” every six hours. This historical pharmaceutical was compounded by combining elixir of senna (black figs), currants, coriander, and cream of tartar every six hours as a remedy for constipation (Beringer & Griffith, 1921 ). Of equal interest to Harlow was a needle-like piece of bone in the back of Gage’s mouth that he ejected “within a few days” (Harlow, 1848 , p. 393).

The following day, Gage’s physical condition had not improved much. As a result, Harlow appears to have become more aggressive in his treatment, bleeding him about 16 ounces and prescribing 650 mg of calomel, 130 mg of ipecac, and a dose of castor oil. He notes that Gage responded to this intervention and in the evening added 195 mg of “r. Antim. Et potassa tart” (tartar emetic) and 180 ml of simple syrup administered every four hours, likely to address the fever.

Over the next two days, between November 17 and 18, Gage reported “feeling better in every respect.” He was now nine weeks and two days’ post injury, without head pain, and able to ambulate. As a result, Harlow perceived him medically stable, although he clearly had reservations regarding Gage’s psychological condition, as evidenced by his final entry into the medical record that Gage “appears to be in a way of recovering if he can be controlled ” (emphasis added; Harlow, 1848 , p. 393). Harlow provided additional behavioral observations on Gage’s change in mental status in his republication of the case in 1868. However, of particular interest to neuropsychologists is that he signed off in the medical record by noting, “I think the case presents one fact of great interest to the practical surgeon, and, taken as a whole, is exceedingly interesting to the enlightened physiologist and intellectual philosopher ” (emphasis added; Harlow, 1848 , p. 393).

Status Post Discharge

Harlow ( 1868 ) ended his acute care on November 18, which was two months and ten days’ post injury. His last entry into the medical record suggests that his patient was sufficiently physically recovered. Having been released from Harlow’s care, Gage returned to his home in Lebanon, New Hampshire on November 25.

The following week, Harlow traveled the 30 miles for a home visit to Gage and “found him going on well” (p. 338). He also notes a recheck on January 1, now almost 16 weeks after the injury from which Harlow concluded further healing, noting “the opening in the top of his head was entirely closed, and the brain shut out from view, though every pulsation could be distinctly seen and felt” (Harlow, 1868 , p. 338).

Gage remained at home in New Hampshire over the next 12 weeks and continued to recover throughout the winter months. Harlow ( 1868 ) documents that in the spring, he returned to Cavendish and applied for his previous position as a foreman but was not afforded reemployment due to the significant change in his behavior and comportment. Given the convenience of his return, Harlow took the opportunity to reexamine his patient.

Harlow’s Reexamination

Upon his return to Cavendish, Gage was about seven months into his recovery. Harlow’s assessment included observations of Gage’s appearance, physical findings, and behavior, with inferences about his psychological functioning that retrospectively constitute a fairly thorough examination of his physical, behavioral, and psychological status.

Harlow described Gage’s physical status as generally normal, noting the following:

General appearance good; stands quite erect, with his head inclined slightly towards the right side; his gait in walking is steady; his movements rapid, and easily executed. The left side of the face is wider than the right side, the left malar bone being more prominent than its fellow. There is a linear cicatrix near the angle of the lower jaw, an inch in length. Ptosis of the left eyelid; the globe considerably more prominent than its fellow, but not as large as when I last saw him. Can adduct and depress the globe, but cannot move it in other directions; vision lost. A linear cicatrix, length two and one-half inches, from the nasal protuberance to the anterior considerably more prominent than its fellow, but not as large as when I last saw him. Can adduct and depress the globe, but cannot move it in other directions; vision lost. A linear cicatrix, lengths two and one-half inches, from the nasal protuberance to the anterior edge of the raised fragment of the frontal bone, is quite unsightly. Upon the top of the head, and covered with hair, is a large unequal depression and elevation-a quadrangular fragment of bone, which was entirely detached from the frontal and extending low down upon the forehead, being still raised and quite prominent. Behind this is a deep depression, two inches by one and one-half inches wide, beneath which the pulsations of the brain can be perceived. Partial paralysis of the left side of face. His physical health is good, and I am inclined to say that he has recovered.

Harlow’s remarks suggest that Gage’s overall appearance was generally unremarkable, the exception being the ptosis of his left eyelid which can clearly be seen in the daguerreotype discovered in 2009. Harlow also documented apparent changes in Gage’s personality:

Has no pain in the head, but says it has a queer feeling which he is not able to describe. Applied for his situation as foreman, but is undecided whether to work or travel. His contractors, who regarded him as the most efficient and capable foreman in their employ previous to his injury, considered the change in his mind so marked that they could not give him place again. The equilibrium or balance, so to speak, between his intellectual faculties and animal propensities seems to have been destroyed. He is fitful, irreverent, indulging at times in the grossest profanity (which was not previously his custom), manifesting but little deference for his fellows, impatient of restraint or advice when it conflicts with his desires, at times pertinaciously obstinate, yet capricious and vacillating, devising many plans of future operation, which are no sooner arranged than they are abandoned in turn for others appearing more feasible. A child in his intellectual passions of a strong man. Previous to his injury, though untrained in the schools, he possessed a well-balanced mind, and was looked upon by those who knew him as a shrewd, smart business man, very energetic and persistent in executing all his plans of operation. In this regard his mind was radically changed, so decidedly that his friends and acquaintances said he was ‘no longer Gage.’ (Harlow, 1868 , pp. 338–340)

After Harlow published his initial report in December 1848, he was contacted by Dr. Henry Bigelow, a prominent Boston surgeon and Harvard professor. Bigelow ( 1850 ) acknowledged having been verbally informed of the accident but was highly skeptical as to the facts of the case. Using Harlow as an intermediary, he provided funds for Gage to travel to Boston for an examination. Given Harlow’s determination that his patient was now “quite well” (p. 330), Gage accepted Bigelow’s offer.

Dr. Henry Bigelow: A Second Opinion

Henry Bigelow, M.D. is perhaps one of the most interesting individuals with whom Gage interacted. Bigelow was a prominent surgeon at Massachusetts General Hospital and a professor of surgery at Harvard University who was instrumental in bringing Gage’s accident to medical prominence. To fully appreciate how his involvement was necessary in validating Gage’s injuries and treatment to the skeptical medical community at that time, one must understand Bigelow’s social background and medical training that allowed him to lend gravitas to Harlow’s report (Schatzki, 1994 ).

Bigelow was the eldest son of an affluent Massachusetts family whose father was a renowned surgeon and Harvard Medical School professor who was socially well connected in Boston society. He entered Harvard at age 15 intent on following his father’s medical career. His memoirs suggest an egotistical individual, self-described as having “personal magnetism,” being a “brilliant operator,” and to those who observed his surgical technique “was to recognize a master” (Bigelow, 1894 , pp. 37–38).

In spite of these self-described laudable attributes, Bigelow’s actual behavior was in many circumstances otherwise. While at Harvard, he was reprimanded for noise violations after disturbing the college with a trumpet he made from a tin coffee pot. He also made nitrous oxide for the Rumford student chemistry club and compromised his health from multiple binges. Perhaps as an early indication of his fascination with anesthesia, he rationalized his abuse of the inhalant as being one of his “most important investigations.” While these pranks were tolerated by Harvard’s administration, he was eventually expelled in 1834 along with five freshmen and the entire sophomore class for taking part in a three-month student rebellion. Although he dismissed damages from the uprising by describing it as a “stirring incident,” the revolt included burning a classroom, exploding a device in Holden Chapel, assaulting two watchmen, and using gunpowder to burn the Harvard’s president, Quincy, in effigy (McCaughey, 1970 ). Compounding the group’s vandalism, Bigelow was personally sanctioned for having three muskets in his dorm room at Hollis Hall that he discharged multiple times into a wooden post (pp. 10–12) and for nearly wounding a fellow student named James Elliot Cabot “by the accidental discharge of a gun” (Bigelow, 1894 , pp. 9–13).

After his expulsion he studied anatomy and physiology at Dartmouth College with Oliver Wendell Holmes, visited Cuba for a period of months to remedy his respiratory difficulties (allegedly from his nitrous abuse), spent time in Italy, Egypt, Paris, and London, where he studied with Longet and reportedly “mastered” auscultation with the stethoscope under Sir James Paget. He finally returned to the Boston, where he eventually he received his medical degree from Harvard in 1841 (Bigelow, 1894 pp. 24–25).

Historically Bigelow is best known for being the first physician to publish on the surgical application of ether, having first watched Morton and Warren demonstrate its use with two cases. in October 1846 (Morton & Woodbury, 1895 ). He used the inhalant on one of his own cases a month later and published his account, thereby circumventing publication by the actual pioneers of the discovery. In doing so was given credit for establishing its medical importance, which contributed to his surgical appointment that same year at Massachusetts General Hospital. Interestingly, he also addressed the anesthetic properties of kerosene after experimenting with self-inhalation of its vapor (Bigelow, 1846 , 1894 ).

Having established his medical credentials, it is not surprising that Bigelow was highly skeptical of the occurrence of Gage’s accident and his survival. The injury as described with the limited loss of function was so inconceivable that many in the medical community were highly doubtful and thought that the facts were misunderstood. In Bigelow’s published remarks, he noted that “A physician who holds in his hand a crowbar, three feet and a half long, and more than thirteen pounds in weight, will not readily believe that it has been driven with a crash through the brain of a man who is still able to walk off, talking with composure and equanimity of the hole in his head” (Bigelow, 1850 , p. 19).

In January 1850, Bigelow secured Gage’s presence and exhibited him to Boston’s medical community for a number of weeks during which Gage was subject to multiple examinations that confirmed the case facts as described by Harlow. Having presented him as a case study in medical rounds, Bigelow reported, “I have been able to satisfy myself as well of the occurrence and extent of the injury as of the manner of its infliction” (Bigelow, 1850 , p. 13). Bigelow demonstrated the injury to colleagues by recreating the path of the tamping iron through an anatomical (cadaver) skull and in doing so verified how the bar could enter, pass through, and exit the cranium without inflicting a fatal lesion. As a result, he wrote, “This is the sort of accident which happens in the pantomime at the theatre, but not elsewhere. Yet there is every reason for supposing it in this case literally true. Being at first wholly skeptical, I have been personally convinced; and this has been the experience of many medical gentlemen who, having first heard of the circumstances, have had a subsequent opportunity to examine the evidence” (Bigelow, 1850 , p. 13).

Bigelow’s importance in Gage’s case lies in his establishing a second opinion and, given his position of prominence in Boston medical society and his reputation, to corroborate Harlow’s findings. In addition, his recapitulation of Harlow’s treatment provided an additional source of documentation in a highly-respected medical publication, The American Journal of the Medical Sciences . In doing so, he afforded the case broader public exposure to the medical community of the northeast United States, which other physicians then began to cite (Butler, 1851 ). Of equal importance to Bigelow’s gravitas was his successful obtainment of a collection of affidavits by those who either witnessed the accident or saw Gage afterwards. Through letters to Harlow, he collected critical documents that formally affirmed the facts of the case, and included these accounts in his 1850 publication. By doing so, he resolved the doubts or reservations held by his medical colleagues who subsequently supported his opinion. “This is no fancy picture drawn to task credulity, but a well authenticated fact” (Butler, 1851 , p. 99).

Gage’s Change in Mental Status: Frontal Cortical Injury

Gage is often cited as an example of a frontal cortical injury with subsequent changes in personality or comportment (Mesulam, 1985 ; Prigatano, 1992 ; Suchy, 2016 ). It has been suggested that there are three principal frontal-subcortical circuits involved in cognitive, emotional, and behavioral processes: dorsolateral, ventromedial, and orbitofrontal, each corresponding to areas of the prefrontal cerebral cortex.

The dorsolateral frontal cortex mainly projects to the dorsolateral head of the caudate nucleus and has been linked to executive functions, such as those measured on tests of mental flexibility, planning, abstraction, and deductive reasoning. It was this link between dorsolateral structures and executive reasoning that led to early conclusions that the frontal lobes were the seat of executive reasoning, so much so that such tasks were described as tests of “frontal lobe functioning.”

The ventromedial circuit projects from the anterior cingulate gyrus to the nucleus accumbens in the basal forebrain. Ventromedial lesions are associated with apathy, amotivational states, social withdrawal, reduced initiation, and motor slowing (Herman, et al., 1992 ; Herman & Cullinan, 1997 ).

It has been proposed that the anterior cingulate cortex (ACC) can be further sectioned into anatomically and functionally distinct subdivisions, based upon its connections to other frontal lobe regions, notably a supracallosal region of the ACC. This area projects to dorsolateral frontal areas and subcallosal portions of the ACC, which then connect to the posterior orbitofrontal regions. While supracallosal ACC lesions are associated with executive impairment and related cognitive inefficiencies, subcallosal ACC lesions are associated with control of respiration, blood pressure, and other autonomic functions (Herman & Cullinan, 1997 ).

The orbitofrontal cortex projects to the ventromedial caudate nucleus and is linked to socially inappropriate behaviors, such as disinhibition, impulsivity, and anti-social behaviors, behavioral inconsistency, and unreliability (Cullinan, et al., 1995 ). These are the behaviors described by Harlow ( 1868 ) in the aftermath of Gage’s injury.

Advances in neuroimaging and modeling technology have led to refined hypotheses as to the likely path of the tamping iron that produced Gage’s brain injury. Based upon magnetic resonance imaging (MRI) data and three dimensional modeling, Damasio and associates (1994) concluded that Gage’s brain lesion involved the anterior half of the left orbital-frontal context, the polar and anterior mesial frontal cortices, and the anterior-most portions of the anterior cingulate gyrus. That is, his lesion affected the ventromedial region of both frontal lobes while sparing the dorsolateral regions. They further concluded that “Gage … fits a neuroanatomical pattern we have identified within a group of individuals with frontal damage. Their ability to make rational decisions in personal and social matters is invariably compromised and so is their processing of emotion.”

More recently, Van Horn and associates (2012) employed diffusion weighted imagery (DWI) and MRI modeling and determined that considerable cortical and subcortical damage to white matter tracts was localized to the left frontal lobe. In their modeling, it was estimated that the tamping iron damaged approximately 11% of the white matter in the frontal lobe and approximately 4% of the cerebral cortex. They hypothesized that damage occurred to the superior longitudinal fasciculus, which connects all lobes in both hemispheres, and the uncinated fasciculus, which links the limbic system to parts of the frontal lobe. As such, some brain structures affected were quite remote from the site of impact, but nonetheless contributed to Gage’s changes in behavior and comportment in the aftermath of his brain injury.

According to Bigelow ( 1850 ), these mental status changes were fairly marked. He described Gage as “fitful” and “irreverent”; he demonstrates “but little deference for his fellows” (a far cry from the Gage who was a “great favorite” of his men) and is “at times pertinaciously obstinate, yet capricious and vacillating”; he employs “the grossest profanity,” which was not typical pre-injury. Harlow also seems to imply that Gage had an unwillingness to carry out his plans, writing that they were “no sooner arranged than they are abandoned in turn for others appearing more feasible” (p. 340). This characterization seems to contrast sharply with Harlow’s descriptions of Gage’s pre-injury mental status, when he was “persistent in executing all his plans of operation” (p. 340) and possessed “an iron will” (p. 330). The Rutland and Burlington railroad company, who previously employed Gage and regarded him as highly capable and dependable, now “considered the change in his mind so marked that they could not give him his place again” (p. 339).

Long-Term Recovery

Harlow ( 1868 ) provided an account of Gage’s long-term recovery, as relayed by Gage’s mother. According to Harlow, sometime after his examination in 1850, Gage traveled throughout New England, including to Boston and New York. While in New York, that Gage spent some time “at Barnum’s,” apparently in reference to P. T. Barnum’s famous New York museum (Bigelow, 1894 , pp. 119–123).

Barnum’s autobiography (Barnum, 1855 ) contains no mention of Gage (an observation also noted by Macmillan, 2000a ), and a review of the Barnum’s Museum Illustrated Guide from 1850 similarly does not mention him (The Lost Museum Archive, n.d.) ; however, there is also some evidence to support Harlow’s assertion that Gage participated in public exhibition. Macmillan and Lena ( 2010 ) describe first a letter by Henry Bigelow which also states that Gage appeared at Barnum’s museum. Second, they describe two advertisements for appearances by Gage, one for an appearance in Concord, New Hampshire, and another for Montpelier, Vermont. While it is unclear if Gage’s stay at Barnum’s was extended or quite brief, he clearly seems to have appeared at the museum for a time and also participated in other public appearances, possibly independent of the museum and possibly under his own management (Macmillan & Lena, 2010 ).

Harlow reports that Gage took a job in the livery stable of Jonathan Currier in 1851, apparently abandoning exhibition due to lack of public interest (Macmillan & Lena, 2010 ). After working in Currier’s stable for “nearly a year and a half” (Harlow, 1868 , p. 340), Gage travelled to Valparaiso, Chile, with an acquaintance who planned to establish a horse drawn coach business to transport passengers from the coastal region to Santiago.

At this point there is evidence that the dates in Harlow’s report become somewhat less accurate; for example, while he ends by stating that Gage died in 1861, records list his burial date as May 23, 1860, making Harlow’s history inaccurate by a year in this regard. Gage likely remained in Chili until 1859, at which time he travelled to San Francisco, home to his mother and sister, reportedly due to failing health. Gage briefly worked on a farm in Santa Clara although “did not remain there long,” and approximately three months before his death suffered seizures, described as “a fit,” followed by “two or three fits in succession” (p. 341). He then suffered a “severe convulsion” the day before his death, followed by repeated convulsions until his time of death at approximately 10 p.m. the following day.

Gage’s Final Resting Place

Gage was first interred at Lone Mountain Cemetery (renamed Laurel Hill in 1864) on May 23, 1860; however, he would not finally lie undisturbed until nearly eight decades later. Gage’s body was exhumed in 1867 at the request of John Harlow. Because no autopsy of Gage was performed upon his death, Harlow requested that Gage’s mother give him possession of the skull and tamping iron for the benefit of the historical record (Harlow, 1868 ). The skull and tamping iron were retrieved and sent to Harlow, who subsequently donated them to the Museum of the Medical Department of Harvard University (now the Warren Anatomical Museum), where they are still on display in the Countway Library of Medicine. The remainder of Gage’s body was reinterred and would remain at Laurel Hill. But unstoppable urban progress prompted San Francisco supervisors to prohibit new burials in the city and eventually declare the city’s old cemeteries a public nuisance. Heated debate over what do with the cemeteries’ tens of thousands of occupants, as well as the many ornate and expensive monuments, prevented any action from being taken for a number of years. By the early 1900s Laurel Hill was in a lamentable state of disrepair:

At Laurel Hill Cemetery high weeds obstructed the once stylish paths and avenues. Statues were overturned and carried off. Scavengers methodically pillaged vaults. Coffins were hacked open and bones strewn about. Entire skeletons were stolen (Svanevik & Burgett, 1992 , p. 28).

Fortunately, Gage was not among the many dead who had their final resting place desecrated by vandals. In 1937 the city of San Francisco ordered the transfer of remains from Laurel Hill to Cypress Lawn in Colma, California (Svanevik & Burgett, 1992 ). Gage’s transfer slip (Figure 41.6 ) indicates his remains were transferred from Laurel Hill on May 17, 1940, and interned in vault 962 of the Pioneer Monument, located in Cypress Lawn Memorial Park (H. Lopez, personal communication, May 21, 1996).

Why Study Gage?

What contemporary significance does the case study of Gage’s injury hold for neuropsychology? The detailed descriptions of his injury and meticulous notes recording his changes in physical and cognitive status during and after recovery lend the case a uniqueness that is unparalleled by most medical case studies of the period. In this sense, Gage’s case provides at least four compelling reasons for ongoing study by clinicians interested in brain-behavior relationships. First, it is of historical importance to neuropsychology. Second, it remains clinically relevant to students, psychologists, physicians, and scientists in the fields of neuroscience, physical medicine, and rehabilitation, particularly for those interested in brain injuries, localization, and the frontal lobes (Macmillan, 1994 ). In addition, most reiterations in texts and scholarly articles contain errors, and lastly, the mechanism of injury and accompanying historical facts continue to maintain a high level of interest that is referenced by multiple medical and scientific disciplines.

Gage’s transfer slip

Historical Importance

The historical importance of Gage’s case can be found in the influence it had on 19th century thinking about the brain and behavior. It was one of the first in a series of single-case medical studies published in the 1800s and early 1900s that provided a foundation for understanding the brain’s function and mental status changes following disease, insult, or injury to the central nervous system.

Following publication of Gage’s injury, Paul Broca ( 1861 ) published his famous case of the patient Leborgne, known as “Tan,” who experienced language deficits associated with a left frontal lesion as the result of syphilis (Lazar & Mohr, 2011 ). In 1880 Josef Breuer presented Bertha Pappenheim, “Anna O.,” to the medical community as an example of psychogenic paralysis of vision and speech, hence an early example of conversion disorder (Breuer & Freud, 2000 ). Sigmund Freud ( 1909 ) published his famous case of severe anxiety of horses of Herbert Graf or “Little Hans,” titled “Analysis of a Phobia in a Five-year-old Boy.” Lastly, in the 1920s Alexander Luria presented his synesthesia case of the journalist Solomon Shereshevsky to describe how stimulation of one sensory pathway leads to automatic, involuntary experiences in a second sensory or cognitive pathway (Luria, 1966 ).

Clinical Relevance

Gage’s injury is significant to neuroscience and neuropsychology, in particular, because his attending doctor, John Harlow, conducted the first detailed documentation of frontal cortical damage altering emotional regulation and behavior. Not surprisingly, many who learned of the accident doubted the mechanism of injury, assuming that survival from a traumatic impalement of the brain of this magnitude was inconceivable. Even the Reverend Joseph Freeman, who saw Gage immediately after the accident, responded with disbelief upon being told that the tamping iron passed through his head, simply stating “That is impossible” (Bigelow, 1850 , p. 15).

Though many are commonly met with skepticism or disbelief, there are a number of historical references to the treatment of traumatic brain injuries (Chaucer, 2005 , p. 770; Cronyn, 1871 ; Karger, 2001 ; Leny, 1793 ). Most describe military surgical interventions following impalement by projectiles such as spears, javelins, lances, and arrows (Bollet, 2002 ). One of the oldest examples is the ancient Egyptian medical text known as the Edwin Smith Papyrus (1600 bce ), which categorized trauma by organ, including brain injuries classified by scalp lacerations, penetration of the skull, and injury to the brain (Nunn, 1996 ; Reitan & Wolfson, 2000 ; Wilkins, 1992 ).

It is understandable that a lack of knowledge about brain functioning led to a simplistic approach to the treatment of brain trauma. For example, in his medical writings Hippocrates addressed head injuries by focusing on consequences of insults to the skull (Wilkins, 1972 ), whereas Galen concentrated on the ventricles and their association with psychic pneuma and the rational soul to explain changes in consciousness (Finger, 1994 ). Ganz ( 2013 ) writes that this approach continued until the 1700s, when French, English, Irish, and Scottish surgeons began to more accurately identify alterations in mental status subsequent to traumatic brain injury to the cerebral cortex. Specifically, he identifies Henri-Francois Le Dran, Percival Pott, James Hill, Sylvester O’Halloran, William Dease, and John Abernethy as being seminal figures in the development of surgical interventions of the brain.

One of the most famous historical examples similar to Gage’s injury is that of Henry V who, as a prince, was wounded in 1403 on the battlefield in Cheshire, England. After a massive barrage of arrows was launched, the future king was struck in the face by an arrow that entered below his eye and to the left side of his nose, penetrating six inches into his skull (Strickland & Hardy, 2011 ). He survived the injury and was treated at Kenilworth castle by John Bradmore, who described in detail his removal of the arrowhead with a mechanical extraction device and the use of resin, wax, herbs, and honey, which served as crude antiseptics, noted to be “good for chilled nerves and sinews” (Cole & Lang, 2003 , p. 97).

Even in the 1800s Gage’s case was not the first to document personality change as a result of frontal lobe injury. Benson and Blumer ( 1975 ) report on a 16-year-old male who suffered a self-inflicted gunshot wound with a black powder pistol which extensively damaged the medial-orbital frontal lobe (de Nobele, 1835 ). Prior to the injury, the adolescent was said to exhibit withdrawn, depressed behavior. Post-injury, his personality seemed markedly changed; he was described as being “happy, vivacious, and jocular” (Stuss & Benson, 1984 , p. 19), despite suffering blindness as a result of the injury. As exemplified here, while Gage’s injury may be the most widely known, frontal lobe injuries due to war, riding or draft animals, hunting, farming, and work accidents were documented long before Gage (Harris, 1847 ; Heustis, 1829 ; Leny, 1793 ) and after his injury (Bird, 1865 ; Cronyn, 1871 ; Fitch, 1852 ; Folsom, 1868 ; Noyes, 1882 ).

Gage’s case however, is unique from other historical examples of traumatic brain injury because of its contribution to our understanding of the role of the frontal lobes. Previously, it had been thought that the frontal lobes had little influence on behavior and cognition, until the absence of executive functioning became apparent following their impairment (Suchy, 2016 ). David Ferrier cited Gage as a primary example of how a frontal lobe injury can alter personality without sensory or motor findings (Neylan, 1999 ) and used Gage’s injury to explain inhibitory and attentional changes in primates and humans. He associated attention with higher cortical functioning and described “its relation to the anatomical substrata of the prefrontal lobes” (Ferrier, 1878 , p. 447). Although he later changed his position, in his first edition of The Functions of the Brain , Ferrier ( 1876 ) proposed a frontal-inhibitory-motor function of the brain and also advocated for cerebral localization using Harlow’s clinical observations to support focal mapping of cerebral functions (Ferrier, 1878 ). Damasio, Grabowski, Frank, Galaburda, and Damasio ( 1994 ) stated that Gage’s case perhaps should have signaled the beginning of the study of the biological basis of behavior, placing Harlow’s observations on par with those of Broca and Wernicke. It is no wonder that most students of neuroscience, medicine, and psychology have been taught about Gage’s change in behavior following cortical damage and the subsequent implication for personality change.

Most Reiterations Contain Errors

It is difficult to find a reiteration of Gage’s case in scholarly articles or texts without finding errors. This is particularly evident in introductory psychology textbooks that discuss Gage’s post-accident recovery and mental status changes (Macmillan, 2000b ); Griggs, 2015 ). Was the instrument of destruction a crowbar or tamping iron (Barker, 1995 )? Did the bar pass through his head or did his physician remove it (Maugh, 2009 )? Did he recover his “faculties of body and mind” (Bigelow, 1850 , p. 14) and retain “in a perfect degree his mental powers” such that “at no time during his recovery was his mind seriously affected” (Butler, 1851 , p. 99) or did he in fact not fully recover his mental faculties, as the American Phrenological Journal claimed after the injury (“Remarkable case of injury,” 1851)? Could he only “briefly sustain work as a stable hand” (Lyketsos, Rosenblatt, & Rabins, 2004 , p. 250) or did he maintain consistent employment after his recovery? After the injury was he rational? Did he demonstrate a lack of foresight (Harlow, 1868 ) or was his disfigurement so traumatic that it altered his personality (Kotowicz, 2007 )? Did Gage’s injury inspire the development of 19th century neurosurgical interventions for brain lesions or the frontal lobotomy procedure (Macmillan, 2000a; Starr, 1848)? The point to be made is that even though the original documents are now easily accessible to researchers and a comprehensive analysis of the case exists (Macmillan, 2000a ), even academic researchers continue to perpetuate errors and get the facts of this case wrong.

In his work, An Odd Kind of Fame: Stories of Phineas Gage , Malcolm Macmillan ( 2000a ) presents what is likely to be the most extensive research of Gage’s injury ever written. Macmillan hypothesized that errors or misrepresentations present in summaries of Gage’s injury, recovery, and subsequent behavioral changes could be the result of later authors’ ignoring some or all of Harlow’s description of Gage’s recovery and life post-injury. This is likely to lead to largely accurate descriptions of the basic facts of the case (date, time, and nature of the accident; the physical properties of the tamping iron; etc.) but vague, incomplete, inaccurate, or exaggerated descriptions of Gage’s behavioral changes and employment—the story becoming less clear as it moves away from its climax. Macmillan suggests that further exaggerations of Gage’s altered behavior may be the result of generalizations or the over-simplification of damage to the frontal lobe from other, similar case studies that may have been projected onto Gage’s history after the fact.

Numerous examples can be found in the literature that inaccurately cite the Gage case to illustrate a particular character trait such as wantonness, virulence, and immorality following damage to this area of the cortex. Inconsistent with Harlow’s behavioral observations, which were also supported by Bigelow’s affidavits collected from eyewitnesses, Biever and Karinch ( 2012 ) describe Gage as having become “sexually promiscuous and hostile” and “totally disinhibited,” and therefore conclude that “Phineas Gage’s limbic brain was apparently destroyed, but his cognitive brain survived intact” (p. 42). To paraphrase what Macmillan has said on a number of occasions (e.g., Kean, 2014 ; Lewandowski, 1998 ; Macmillan, 2000a , p. 333), the initial reports by Harlow and Bigelow come closest to accurately capturing the facts surrounding Gage’s accident, treatment, and recovery, and they should be treated as the primary sources for facts.

Uniqueness and Interest

Lastly, Gage’s injury and his recovery are very interesting. The patient and his attending doctor were very unremarkable people who were brought into the annals of science and history by this one remarkable event (Lewandowski, 2018 ). The mechanism of injury is a source of fascination that has somewhat of a carnival side-show quality. Gage is one of the most frequently cited cases from 19th century medical literature. Harlow himself said in his 1868 publication that Gage was “the man for the case,” that the iron’s smoothness reduced damage to concussion/compression, and that the area of the brain compromised “was the best fitted of any part of the cerebral substance to sustain the injury” (p. 344). As a result, the case of Phineas Gage continues to lend great interest and contemporary relevance to neuroscientists across a broad range of psychological and medical specialties.

Phineas Gage’s improbable survival from the blast that caused a tamping iron to pass through his head occurred during a time when survival from catastrophic brain injury was quite rare. The unique circumstances of the case—including the advantageous size, shape, and texture of Gage’s tamping iron, the limited concussive/compressive damage secondary to the force of impact, and the sequence of techniques employed by Harlow during Gage’s acute treatment—contributed to his survival and the implications of the case for the medical science of the time. Moreover, it occurred at a time when the particular functions associated with the cerebral cortex were for the most part unknown and thought to be unknowable. Because those very few individuals who suffered penetrating brain injuries and sustained pre-frontal trauma survived, it was assumed that these portions of the brain were behaviorally silent.

The Gage case was the first to extensively document that changes in such complex and seemingly inherent qualities such as judgment, impulse control, demeanor, and temperament were not only associated with the brain, but with particular regions within it. It challenged the medical community to begin to question if temperament could be subject to external influences and therefore amenable to scientific principles such as modification, prediction, and clinical treatment.

Gage’s injury occurred at a time when surgical advances and the treatment of infection had progressed to the point where at least some severely traumatically injured patients could survive long enough to be clinically observed and where individuals so injured would be triaged in a manner that would permit them access to heroic care. This would not have occurred if mediums for the exchange of medical information had not reached a tipping point, such that case reports, procedures, and findings previously occurring in isolation could be posted, compared, and aggregated in recently established medical journals. Consider also that while Harlow did not have the resources of hospitals, medical schools, medical meetings, and apothecaries that his physician colleagues had in urban areas, he was prepared through clinical training by a group of renowned medical professors for this very complex traumatic brain injury that even he equated with a military injury.

Gage is among the first well-documented cases of brain-injury where the roles of the patient and the treating physician evolved into intertwined and extended friendships or stewardships, such that long-term follow-up was possible and the changing nature of brain injuries over time could be detailed and explicated. There are echoes of the relationship between Gage and Harlow in the cases of “S.” (Luria), “Tan” (Broca), and Lelong (Wernicke), through to that between Corkin and the amnest, “H.M.” Gage was the first case of which we are aware that offered rich and compelling descriptions of the effects of brain injury over time. In fact, the copious notes taken by Harlow immediately after the accident and throughout Gage’s treatment and recovery have largely (but not completely) precluded the case from accusations of exaggeration and frank invention that haunt mid-19th century medical scholarship.

This, then, may be the reason that the case of Phineas Gage continues to have an enduring influence on contemporary neuropsychology. Many of us were first drawn to neuropsychology because of our interest in the human consequences of brain injuries, in the ways in which the complex activities of normal people could be dramatically damaged by injuries to their brains, and the ways in which that knowledge could be used to help them adapt or recover. This may be the lasting legacy of the case of Phineas Gage: the degree to which the facts and mythology of this case have captured the imagination of generations of future neuropsychologists.

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v.14; 2022 Oct

E.L., a modern-day Phineas Gage: Revisiting frontal lobe injury

Pedro h.m. de freitas.

a Instituto de Ciências Biomédicas, CCS, Universidade Federal do Rio de Janeiro, RJ, 21941-902, Brazil

Ruy C. Monteiro

b Miguel Couto Municipal Hospital, Rio de Janeiro, RJ, 22430-160, Brazil

Raphael Bertani

Caio m. perret, pedro c. rodrigues, joana vicentini, tagore m. gonzalez de morais, stefano f.a. rozental.

c Vassar College, Poughkeepsie, NY, 12604, USA

Gustavo F. Galvão

Fabricio de mattos, fernando a. vasconcelos.

d Dept Neurocirurgia, HUGG, Universidade Federal do Estado do Rio de Janeiro (UNIRIO), RJ, 20270-004, Brazil

Ivan S. Dorio

Cintya y. hayashi.

e Dept Neurologia, Universidade do Estado de São Paulo, SP, 05402-000, Brazil

Jorge R.L. dos Santos

f Pontificia Universidade Catolica do Rio de Janeiro, RJ, 22451-000, Brazil

Guilherme L. Werneck

Carla t. ferreira tocquer.

g Centro de Neurologia da Cognição e do Comportamento Ltda, RJ, 22071-000, Brazil

Claudia Capitão

h Centro Universitario IBMR, RJ, 22631-002, Brazil

Luiz C. Hygino da Cruz, Jr

i MRI Clinica de Diagnostico por Imagem (CDPI/DASA), Rio de Janeiro, 22271-040, Brazil

Jaan Tulviste

j University of Tartu, Institute of Psychology, Tartu, Estonia

Mario Fiorani

k Instituto de Biofísica, Universidade Federal do Rio de Janeiro, RJ, 21941-902, Brazil

Marcos M. da Silva

l Dept Neurologia, HUCFF, Universidade Federal do Rio de Janeiro, RJ, 21941-902, Brazil

Wellingson S. Paiva

Kenneth podell.

m Neurological Institute, Houston Methodist, TX, 77030, USA

Howard J. Federoff

n Georgetown University, Washington, D.C., 20057, USA

Divyen H. Patel

o Genome Explorations, Memphis, TN, 38132, USA

p Northwell Health, Manhasset, NY, 11030, USA

Elkhonon Goldberg

q Dept Neurology, New York University, School of Medicine, NY, 10016, USA

Rodolfo Llinás

r Dept. Physiology and Neuroscience, New York University, School of Medicine, NY, 10016, USA

Michael V.L. Bennett

s Dept Neuroscience, Albert Einstein Coll Medicine, Bronx, NY, 10461, USA

Renato Rozental

t Centro Desenvolvimento Tecnológico (CDTS), FIOCRUZ, Rio de Janeiro, 21040-361, Brazil

Associated Data

Extended FIG. 1 (a) 3D CT reconstruction of the iron bar trajectory through E.L.’s skull. (b,c) View of the large craniotomy allowing for a pterional-type approach to the iron bar within the intracranial cavity, exposing brain laceration and the perforated bone flap. (b) Note the path drilled by the iron bar in bone as it passed through the skull. (d,e) Lateral section MRI images depicting the path of the iron bar, pointing the entry- and exit-points with white arrow and arrowhead , respectively. (f) Coronal section MRI scan depicting direct damage to the right side of the nose and right frontal sinus secondary to the passage of the iron bar. (g,h) Lateral and axial images from a follow-up MRI scan performed 18 months later help propose a right frontal lobe disconnection (white arrows). R (right hemisphere), L (left hemisphere).

Movie #1. Supplementary movie S1.

E.L.’s challenge: finger-to-thumb movement performed simultaneously by both hands.

3D rendering of a T1-weighted MRI anatomical scan of E.L.’s brain.

3D rendering of a T1-weighted MRI anatomical scan of E.L.’s Corpus callosum.

How the prefrontal cortex (PFC) recovers its functionality following lesions remains a conundrum. Recent work has uncovered the importance of transient low-frequency oscillatory activity (LFO; < 4 Hz) for the recovery of an injured brain. We aimed to determine whether persistent cortical oscillatory dynamics contribute to brain capability to support ‘normal life’ following injury.

In this 9-year prospective longitudinal study (08/2012-2021), we collected data from the patient E.L., a modern-day Phineas Gage, who suffered from lesions, impacting 11% of his total brain mass, to his right PFC and supplementary motor area after his skull was transfixed by an iron rod. A systematic evaluation of clinical, electrophysiologic, brain imaging, neuropsychological and behavioural testing were used to clarify the clinical significance of relationship between LFO discharge and executive dysfunctions and compare E.L.´s disorders to that attributed to Gage (1848), a landmark in the history of neurology and neuroscience.

Selective recruitment of the non-injured left hemisphere during execution of unimanual right-hand movements resulted in the emergence of robust LFO, an EEG-detected marker for disconnection of brain areas, in the damaged right hemisphere. In contrast, recruitment of the damaged right hemisphere during contralateral hand movement, resulted in the co-activation of the left hemisphere and decreased right hemisphere LFO to levels of controls enabling performance, suggesting a target for neuromodulation. Similarly, transcranial magnetic stimulation (TMS), used to create a temporary virtual-lesion over E.L.’s healthy hemisphere, disrupted the modulation of contralateral LFO, disturbing behaviour and impairing executive function tasks. In contrast to Gage, reasoning, planning, working memory, social, sexual and family behaviours eluded clinical inspection by decreasing LFO in the delta frequency range during motor and executive functioning.

Interpretation

Our study suggests that modulation of LFO dynamics is an important mechanism by which PFC accommodates neurological injuries, supporting the reports of Gage´s recovery, and represents an attractive target for therapeutic interventions.

Fundação de Amparo Pesquisa Rio de Janeiro (FAPERJ), Universidade Federal do Rio de Janeiro (intramural), and Fiocruz/Ministery of Health (INOVA Fiocruz).

Research in context

Evidence before this study.

The historical case of Phineas Gage (1848) is an integral part of medical folklore, illustrating the resilience of the human brain and the involvement of the frontal lobes in problem solving, spontaneity, memory, initiation, judgement, impulse control, and social and sexual behavior. However, the dynamics of damaged frontal lobe continue to be the subject of controversy, and functional recovery has remained a matter of debate since Gage's accident. On a parallel track, sustained high amplitude low-frequency oscillations (LFO) generated in dysfunctional cortical networks has been suggested to have a high correlation with cortical dysfunction and as a marker of cortical disconnection.

Added value of this study

Our study suggests that modulation of LFO dynamics is an important mechanism by which PFC accommodates neurological injuries, supporting the reports of Gage´s recovery and represents an attractive target for therapeutic interventions.

Implications of all the available evidence

Modulation of LFO dynamics is an important mechanism by which PFC accommodates neurological injuries, representing an attractive new target for therapeutic interventions after frontal lobe injury.

Alt-text: Unlabelled box

Introduction

Today, some 170 years after the landmark case of Phineas Gage, who exhibited significant changes in personality as a result of frontal lobe damage, the so-called ‘riddle of the frontal lobes’ has yet to be solved. 1 The characterization that ‘Gage was no longer Gage’, 2 albeit poorly documented, was consonant with the rise of cortical localizationist theories of brain functioning in the mid-to late 19 th century, setting out the context of the ‘localization debate’ for the nascent science of the ‘brain and mind’. 1 Split-brain studies with sectioned corpus callosum ( CC ), the major neural pathway that connects homologous cortical areas of the cerebral hemispheres, provided evidence for the view of hemispheric asymmetries and specialization 3 and afforded insights into neural mechanisms. These studies also unveiled areas of the CC dedicated to the transfer of visual, somatosensory and motor information, which are stronger for handedness than for footedness. 4 These ideas bring us to the current view of a language-dominant left hemisphere while visuospatial (e.g., geometric forms) and other features show more lateralization in the right hemisphere. 5 The dynamics of damaged prefrontal cortices (PFC), however, critical for cognitive, asocial behavior, decision-making functions and moral judgment, continue to be the subject of controversy, and functional recovery has remained a matter of debate since 1848.

White matter (WM) change is central to a range of neurological conditions, including traumatic brain injury (TBI), psychiatric disorders and in healthy aging. 6 , 7 , 8 Consistent with neuropathological findings, neuroimaging and neuropsychological literature has focused on executive functioning decline in subjects who underwent brain signal processing by quantitative MRI measures such as lesion load, demyelination, WM integrity and altered gray matter (GM) volume. At the electroencephalographic level (EEG), sustained high amplitude low-frequency oscillations (LFO) (<4 Hz) generated in dysfunctional cortical networks in TBI patients, psychiatric disorders and aging, has been shown to have a high correlation with neuropsychological assessments in neurodegenerative processes 9 , 10 and it is regarded as a marker of cortical disconnection, leading to deafferentation of networks from their major input source. 11 Indeed, while an intact thalamus is required for proper brain function during both sleep and wakefulness in controls (CTRL), predisposing to declarative learning, memory 12 and sleep, 13 and thus improving cognitive performance, the sufficiency of the cortex for the generation of abnormal slow waves is supported by corticocortical connections following thalamectomy. 14 In turn, treatment-associated decreases in frontal LFO activity have been suggested to improve functional outcome and impaired attention in mental disorders. 15 However, no definitive explanation for how LFO interact with other recurring changes in excitability and is modulated in frontal lobe injury was provided so far.

The overarching goal of the current study, prompted by clinical, neuroimaging, neuropsychological and EEG evidence paired with TMS, is to provide clues as to how PFC accommodates to neurological insults and, in particular, to test the unsettled concept that down modulation of abnormal LFO has mechanistic implications for compensation on executive dysfunction. Identifying compensatory responses associated with LFO over the injured hemisphere may facilitate determination of the extent to which neural recruitment in injury represents reorganization or functional engagement of existing latent networks. Finally, while there is no question that, immediately following the accident there were changes in Gage's personality, other reports nevertheless state that Gage actually recovered and resumed something resembling a ‘normal life’ – a possibility that, if substantiated, could impact significantly our understanding of the brain's plasticity and treatment strategy.

LFO construct validity was performed by determining correlations among clinical examination, physiological recordings, commonly used imaging technology and neurobehavioral & sensorimotor tests of known frontal lobe vulnerabilities in controls and E.L. On the basis of the definition of multitasking, the group created a list of tasks to be tested on affective, cognitive and behavioral sub-domains. Magnetic stimulation, a technique that allows us to temporarily interfere with brain function, was aimed at proof-of-concept testing.

Because of the large amount of assays employed, materials, the following methods and well-established protocols are described in detail as “Supplementary Methods”: clinical exam, quantitative electroencephalography (qEEG), MRI image acquisition & segmentation (FreeSurfer), post-processing and volume measurements, 3D printed brain models, electrooculography (saccadic and antisacaddic tasks), oxcarbazepine (anticonvulsant) test and a set of neuropsychological and behavioral tests, including “apathy evaluation” and assessment of sexuality (BIQS).

Matched control sampling

The control sample consisted of consecutive healthy male participants, strictly right-handed, not taking any medications, with a mean age of 21.6 ± 0.9 (20-30 years) ( n = 5) (qEEG), 30 ± 1.3 years (20-35 years) ( n = 10) (TMS/ROFC), 33.4 ± 2.4 (20-45 years) ( n = 10) (Divided Attention), 26.7 ± 2.7 (20-35 years) ( n = 4) (TMS/EEG/apathy) and 21.6 ± 0.9 (20-30 years) ( n = 5) (EOG). In general, the participants were all volunteers made aware of the possibility of volunteering by a general notice, who responded to an advert in local recruitment flyers, University hospital flyers on volunteer opportunities or active recruitment approaches to take part in research on “neuropsychological testing”. Volunteers with incomplete junior high school were selected to match E.L. level of education ( Divided Attention ) (Supplementary Methods).

Transcranial magnetic stimulation (TMS). Neuronavigation

Patients underwent MRI using a 1.5 T SPREE (Siemens AG, Erlangen, Germany). T1-weighted images were acquired in the sagittal plane with a 3D magnetization prepared rapid acquisition gradient echo sequence (MPRAGE) (Supplementary Methods). The MRI images were recorded in Digital Imaging and Communications in Medicine format (DICOM). A neuronavigational device (BrainSight 2, Rogue Research Inc, Montreéal, QC, Canada) sensor was applied to guide the coil positioning, which allowed visualization of the angle of impact for the magnetic impulse onto the brain surface. Subsequently, a system was introduced that also facilitated elucidation of the exact strength and extent of the induced electrical field, depending on the depth of the area under the coil. For the TMS mapping, the patients were seated on a chair with a headrest. Focal single-pulse TMS was delivered to the motor cortex with a figure-of-eight magnetic stimulator (diameter 70 mm; 9 turns of the wire; peak magnetic − 2.2 T) (MagPro × 100; MagVenture A/S, Farum, Denmark). The magnetic coil was placed with navigation. We performed a co-registration of MRI for face recognition by points (glabella, nasion, right tragus, and left tragus). The motor cortex was identified, using TMS impulses in the cortex to produce movement in the contralateral hand. The motor threshold was considered as the lowest intensity of TMS single pulses required to induce a motor-evoked potential (MEP) with an amplitude ≥50 µV, in five out of ten consecutive trials.

Methods used to record EMG signals of the first dorsal interosseous muscle, to apply repetitive TMS stimulation (rTMS) of the dorsolateral PFC (dlPFC) and left Primary Motor Cortex (left PMC) and continuous theta-burst stimulation (cTBS) of the ventromedial PFC (vmPFC) are described in Supplementary Methods .

Neuropsychological testing

A comprehensive neuropsychological test battery to assess frontal lobe dysfunction was administered, comprising tests covering cognitive function, neuropsychological domain and sexual arousal. We aimed for a battery of tests, including the executive control battery, based on approaches and procedures developed by A. Luria and E. Goldberg, and other gold-standard tests of cognitive assessment, such as Iowa Gambling Task (IGT) (self-account measures), Cognitive Bias Test (CBT) (actor-centered decision making), Wisconsin Card Sorting Test (Nelson version) (WCST) (veridical decision making) and Rey-Osterrieth Complex Test (short- and long-term visuospatial memory). 16 The neuropsychological profile assessing each group of executive functioning is grouped in Table 1 , Extended Table 1 and described in Supplementary Methods.

E.L.: predicted difficulties and impairments in cognitive function and in neuropsychological domain on the basis of standard neuropsychological measures.

The executive control battery (ECB) – we included the bimanual (reciprocal) coordination. The test allows the eliciting of various types of motor perseverations, stereotypes, and other deficits of sequential motor organization. 16

Rey-Osterrieth Complex Figure (ROCF) (visuospatial memory). This test allows assessment of a variety of cognitive processes, including planning, problem-solving strategies, as well as perceptual, motor, and episodic memory functions. Participants were presented with a blank sheet of paper and were asked to make a copy of the figure with their right-hand (dominant hand) as carefully as possible. Subjects were allowed to rotate their drawings, which was aimed at maximizing the quality of their copies but were not allowed to rotate the figure. Erasing was allowed. Each subject delivered the copied figure within 5 min. After 3 min, the subjects were asked to reproduce the design from memory (3 min recall) and then again after a 30 min hiatus (30 min recall). Copy and reproductions of the ROCF were scored using original Scoring System by André Rey. 17

Statistics analyses

General statistical analysis.

Descriptive statistics (mean±SEM) were calculated with Excel (Microsoft) or GraphPad Prism (GraphPad Software). Mean±SEM was used to report statistics unless otherwise indicated. All statistical analyses were conducted using GraphPad Prism. A P value <0.05 was considered statistically significant.

EEG frequency power

Spectral power was averaged at all sensors, the time course of slow wave (SW) activity (0.5–4 Hz) was calculated and the open-source R program with "SingleCaseES" and "scan" packages was used to perform the Non-overlap of all pairs (NAP) method 18 to evaluate the changes in SW activity associated with the TMS-OFF (resting state) and the TMS-ON blocks within E.L. and CTRL ( n = 4), 26.7 ± 2.7 years (20-35 years) ( n = 4). Similar procedures were performed to evaluate SW activity during finger-tapping paradigm. dlPFC rTMS Rey-Osterrieth Complex Figure assay. E.L. single-case data analysis and comparison to a CTRL sample, 30 ± 1.3 years (20-35 years) ( n = 10) (TMS), were performed with the open source software Singlims ES using the Crawford and Howell's and the Crawford & Garthwaite´s methods, 19 supplemented by point and interval estimates of effect sizes tests if E.L's score was significantly below CTRL. This methodology provides a point estimate and percentage of the abnormality of the score, with the use of P value, and sets confidence limits on the abnormality of a patient's score using non-central t-distributions. CTRL sample sizes were chosen based on prior standards established in previous published studies in neuropsychology field to achieve 90% power in a one-tail test with α=0.05 and Z-CC ≥ 4. 19

Ethics committee

The present study was in strict accordance with the NIH Guide involving Human Subjects and approved by Institutional Ethics Committees (CAAE 96263418.0.0000.5279 – CONEP/Plataforma Brasil).

Role of the funding source

The sponsors of this study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. R. Rozental, M.V.L. Bennett and P.H.M. de Freitas had full access to all the data in the study and all authors had final responsibility for the decision to submit for publication.

History and physical examination: ‘replicating gage’

History repeated itself in August of 2012 (Gage vs E.L., Supplementary Clinical Case History). In 1848, Phineas Gage, a 25-year-old American construction foreman, sustained extensive frontal lobe damage after an iron bar - 31 mm in diameter, 1.06 meters long and weighing 6.1 kg - was propelled through the front part of his head. Gage reportedly experienced pronounced personality changes due to lesions from this accident that are presumed to have involved the left frontal region. 164 years later, at 9:30 am on August 15, 2012, E.L., a 24-year-old Brazilian man, who was kneeling on the ground floor at a construction site, experienced a similar accident; a round steel bar - 16 mm in diameter, 2.56 meters long and weighing 4 kg – fell from the 5th floor (15 m height), impaling his skull obliquely (superior-anterior) on the right side at an estimated velocity, at contact, of 17.32 m/sec (62.35 km/hr). The entry-point was about 1.5 cm posterolateral to bregma and the exit-path of the rod made contact with the glabella ( Figure 1 a,b, Extended Data Figure 1a,d,e). E.L. was discharged from hospital care on August 30th, 2012 and returned to work on a construction site in November, 2012 (Supplementary Clinical Case History). E.L. continued functioning normally for approximately 9 months after his return to work, until he experienced a tonic-clonic seizure. After the seizure, he stopped working, and began treatment with oxcarbazepine (OXC) (300 mg at 8-hr intervals), an anticonvulsant (AED). In the 94 months since beginning treatment with OXC, he experienced motor seizures 11 times (72% within the first 23 months of treatment), all lasting less than 1 min. Symptoms started on his left arm, while E.L. was fully aware of the surroundings, before losing consciousness and spreading to involve both sides of his body. All episodes, except for the first one, were due to medication noncompliance (Supplementary Clinical Case History).

Path of the iron bar through E.L.’s skull and its effects on white matter structure. (a) Lateral view of the transfixed skull with an iron bar on the CT scan reconstruction. (b) T1 weighted MRI reconstruction revealed the trajectory of the iron bar. Lateral (c) and transverse (d) sections (T2-weighted MRI images), 18 months after the accident, suggestive of a right frontal lobe disconnection; (e,g) FLAIR MRI spectroscopy (single-voxel) was applied to regions of interest (blue squares), indicated by blue arrows, on the anterior corpus callosum (CC). (f,h) An expected decrease in spectrum of resonances in N-acetyl-aspartate (NAA) (2ppm), marker of neuronal integrity, is illustrated. (i) Axial view of a tractography suggesting a difference in the volume of the association fiber tracts that connect temporo-parietal cortical regions with right frontal lobe (white arrow). (j) Fractional anisotropy (FA) map, a diffusion tensor imaging technique, revealed that the injured area was associated with greater anisotropy reduction in frontal right brain regions (white arrow). R (right hemisphere), L (left hemisphere).

Medical history (2012–2020)

E.L.'s medical history is otherwise unremarkable. E.L., who is right-handed, suffered traumatic injury (TBI) of the right frontal lobe, and now experiences post-traumatic epilepsy as his only notable symptom. Neurological examination shows only mild abnormalities: right-sided hyposmia as result of direct damage to the nose and sinus, injury to the anterior cranial fossa, and frontal lobe involvement. He exhibits subtle asymmetry of reflexes between left and right arms, mild incoordination with rapid alternating movements in the left hand, and difficulty maintaining left gaze, which is consistent with a lesion to the right frontal lobe including the right frontal eye fields, and evidence suggesting a grasp reflex in the left foot, a frontal release sign. Coordination testing showed normal symmetrical movements without dysmetria, or incoordination, on finger to nose testing, normal forearm and finger rolling tests using rapidly alternating movement, and on sequential active finger-to-thumb tapping, rapidly touching the thumb to each fingertip, during unimanual movements with either the left or right hand (Extended Data Figure 3) (Supplementary Clinical Case History - Neurological Examination). However, there was incoordination of sequential finger-to-thumb tapping movements in the left hand during bimanual movements suggestive of failure of compensatory mechanisms during multitasking (Supplementary Movie 1) (Supplementary Clinical Case History).

Functional magnetic resonance imaging (fMRI) – extent of cortical gray matter (GM) and white matter (WM) damage

A set of 5 MRI data collection from E.L. over the years, was used for this study. Cross-sectional, parasagittal and longitudinal MRI image scans (2012, 2013, 2014a,b and 2020) revealed an extensive right unilateral frontal lobe lesion affecting orbital, polar and anterior regions of the PFC. Figure 1 b-e,g, Extended Data Figure 1d-e,g-h, Extended Data Figure 2 illustrate the affected areas, involving the orbital frontal cortex (Brodmann´s cytoarchitectonic fields 11 and 12), the polar and anterior mesial frontal cortices (fields 8, 9, 10 and 32), the dorsolateral field 46 and the mesial aspect of field 6 (the supplementary [SMA] and the premotor [pre-SMA] areas). MRI scans over time have not detected enlarging lesions, atrophy or damage outside of the frontal lobe. The amount of right global hemisphere volume loss due to the iron bar was 11.2%, affecting regionally specific gray matter volume (4.6%), cerebrospinal fluid (CSF) and white matter (WM) volumes (6.6%), matching estimations of GM (up to 4%) and of WM (up to 11%) reported in Gage´s computational lesion studies. E.L. total intracranial volume (TIV) was 1,500.4 ml compared to the mean ± SEM CTRL 1,419.4 (23.7) ml ( n = 16 patients), and his estimated left lateral ventricle volume (LVV) was 56.6 ml compared to 64 ml of his contralateral one (right ventricle). Findings of hippocampal sclerosis were not suggested by long-term MRI scans (07/2020) ( Figure 5 d). Visualization of fully reconstructed E.L.’s 3D brain model in polyamide helped examine the extent of both cortical and subcortical lesions in close detail (Extended Data Figure 4) (Supplementary Movie 2) (Supplementary Methods).

rTMS influences short-term memory and behaviour in E.L., but not in CTRL, by modulating the frequency of slow waves. (a) depicts the position of the conventional TMS figure-of-eight coil with respect to E.L.’s scalp, over the left motor cortex (M1). (b-d) T2- weighted imaging of E.L.’s brain from 2020, 8 years since injury. (b,d) TBI did not result in progressive loss of E.L.’s brain tissue volume. Mesial temporal sclerosis was not detected with regard to hippocampal size and shape, fissure visualization and signal intensity (isotense) to cortical gray matter. (e-h) rTMS-EEG responses to stimulation in E.L. and in CTRL. (e) Topographic plots of the TMS-evoked responses. The extent to which increase in frequency and amplitude of SWs are higher contralateral than ipsilateral to the side of stimulation is illustrated by a train of rTMS at a frequency of 1 Hz (top panel). After rTMS, EEG SW responses were potentiated up to 40 min post 1 Hz (f,h) and up to 60 min post-Theta-burst stimulation (TBS) (g,h), followed by a complete return to background activity (e,h – top panel). (i,j) Subjects were asked to copy the Rey–Osterrieth figure (bottom left – ‘ template’), and then to reproduce it from memory 3–30 min later, prior and after TMS-treatment (1 Hz) applied to the DLPFC. The two groups drawing scores significantly differ between the retrieval rounds at 3 min (* P < 0.001) and at 30 min (* P < 0.001). rTMS scale (e): 0–500 µV².

Connectivity was damaged between the right PFC and other major lobes of the right hemisphere, in addition to the left frontal lobe. WM lack of integrity was identified in the following: superior longitudinal fasciculus (SLF), which connects bi-directionally the parietal, occipital and temporal lobes with ipsilateral frontal cortices; superior fronto-occipital fasciculus (SFOF), which connects frontal and occipital lobes; and, cingulum fasciculus (CF), which courses behind the splenium up to the frontal lobe, extending longitudinally above the C.C. - ( Figure 1 i,j; Extended Data Figure 5). Quantitative Diffusion Tensor Imaging (DTI) did not detect gross changes in volumetric imaging (total and regional) in E.L.’s C.C. , despite the nature of his frontal injury. There were no significant differences in midsagittal measures of anterior-posterior extent of C.C. between E.L. and CTRL ( n = 16), even though E.L.’s anterior segment (760.5 mm 3 ) was thinner while his central-posterior (453.8 mm 3 [mid-ant]; 469.6 mm 3 [central]; 483.6 mm 3 [mid-post]; and 878.2 mm 3 [post]) segments were thicker than the average for the matched CTRL ( n = 16)(868.3 ± 32.68 mm 3 [ant]; 433.6 ± 19.2 mm 3 [mid-ant]; 429.9 ± 18.43 mm 3 [central]; 397.3 ± 19.59 mm 3 [mid-post]; 991.2 ± 41.02 mm 3 [post]) (Supplementary Movie 3). The groups did not differ in total C.C. volume (3,045.6 mm 3 [E.L.] vs 3,120.3 ± 94.13 [matched-CTRL]).

Assessment of functional tasks performance and sexuality after right frontal lobe damage

E.L. and CTRL ratings on a measure of frontal cognitive, neuropsychological and sexual behaviour were assessed using standardized and gold-standard neuropsychological battery tests. Table 1 and Extended Table 1 display the abilities assessed by specific testing, including reading, language usage, attention, learning, processing speed, reasoning, remembering, problem-solving, mood and personality and more. No apparent direct relationship has been found between cognition, executive function or behavioural impairment in the clinical course of his injury during the last 9 years.

E.L. executive function and behaviour, for the most part, did not deteriorate since his accident. E.L. has not expressed neuropsychological problems in family, sexual, professional and social life and did not present attentional dysfunction. In general, he performed as well as CTRL in standard tests to assess TBI subjects, among them the WAIS-III (intelligence), Tower of London (planning ability), Boston Naming Test (BNT) (confrontation naming), the Wechsler Memory Scale (WMS) (auditory and visual memory; immediate and delayed memory), Rey-Osterrieth Complex Figure Test (RCFT) (visuospatial perception, skills and recognition memory), Mini-Mental State Examination (MMSE) (cognitive impairment), Beck Depression Inventory (BDI) (depression), Prospective Memory (PM) and tests to evaluate Divided Attention ( Table 1 ; Extended Table 1). Similarly, there was no detectable impairment by gold standard tests of cognitive assessment, such as, Iowa Gambling Task (IGT) (self-account measures), Cognitive Bias Test (CBT) (actor-centred decision making) and Wisconsin Card Sorting Test (Nelson version) (WCST) (veridical decision making). E.L. did, however, show deficits on episodic memory category (Ruche de Violon and Grober and Buschke Tests), visual memory (DMS-48), working memory (Corsi Blocks), color and word cognitive flexibility (Stroop) and attention and task switching (Trail Making Test) ( Table 1 ; Extended Table 1). Among them, on every subtest of the Wechsler Adult Intelligence Scale III (WAIS-III) and on the Divided Attention Test (DAT), tasks commonly thought to be sensitive to the integrity of the frontal cortex, E.L. showed abilities that were either average or superior to the averages for CTRL: 12 (WAIS), 88% (calculation task - DAT) and 17 (cancellation task – DAT). The results of the Wisconsin Card Sorting Test (WCST), the Stroop Colour Interference Test, the Iowa Gambling Test (Extended Data Figure 6) and the Cognitive Bias Task (CBT), regarded as the gold standards of neuropsychological frontal-lobe assessment in patients with lateralized lesions, were also favourable ( Table 1 ; Extended Table 1)

E.L. results were also within normal ranges in the assessment of sexual and behavioural functioning (described hereinafter) (Sexuality questionnaire – Extended Data Figure 7 a,b). We also did not learn of any problems related to higher brain dysfunction in E.L.’s family and/or social lives after his discharge from the hospital. The association of AED and abnormal slow electrographic activity with some cognitive deficits, however, cannot be ruled out (discussed hereinafter). E.L. returned to work with the same construction company and was able to handle a workload comparable to before his accident. There were no noticeable declines in his mental processing, moral reasoning, social behaviour, capacity to solve daily problems, ability to interact with his co-workers or ability to act efficiently (Social Interaction - Supplementary Clinical Case History).

In single task drawings, the phenomenon of spatial hemi-inattention, more common after right than after left hemisphere injuries, tends to be reflected in accuracy (e.g., size, shape, placement on the page) and in the omission of details on the left side of the drawing. Since spatial neglect is a complex disorder, subjects were also required to process information, to extrapolate and to think ahead using working memory in the PFC. 20 Within this context, no differences were found, between E.L. and normalized test data ( Figure 2 a-f) ( Table 1 ; Extended Table 1). However, univariate analyses suggested significant differences on a few measures involving working memory. E.L.’s attentional dysfunction was not identified and he performed within the upper range of CTRL ( n = 10) , in terms of both speed and drawing accuracy (placement, geometric forms and size), demonstrating: i) judgement of line length and orientation; ii) width of angles; iii) positioning of dots into geometrical figures; iv) pinpointing the location of a numeral in geometrical figures; v) mentally rotating figures; vi) recognition of nonsense shapes; vii) determining the number of cubes composing a complex 3D shape; and viii) mentally retrieving and reconstructing images. E.L.’s performance in the ‘clock drawing’ and in the Rey-Osterrieth Complex Figure (ROCF) (copy condition, immediate recall and delayed recall) tests, the most frequently used to assess nonverbal memory function, whose performance, needed for quotidian activities, was ranked in the top 10% of those elaborated among all subjects tested ( Figure 5 j E.L. TMS-untreated ).

E.L.: Figural fluency, emotional behaviour and EEG as a measure of right frontal lobe injury. This battery of tests was aimed at identifying dysfunction, such as attention and concentration, self-monitoring, personality, inhibition of behaviour and emotions, and with speaking or using expressive language. (a-d) Representative illustrations of memory for geometric designs, shapes, features and directional orientation. (a, top ) E.L. was asked to drawn R$ 5 cents, 25 cents and 1 Real coins from memory (i.e., draw-to-command). Coin measurements were compared to the respective official coins (a, bottom ). (e) The clock-drawing test did not confirm a diagnosis of cognitive deficits in E.L. Assessment focused on size of the clock, graphic difficulties, stimulus-bound response, conceptual deficit, spatial/planning deficit and perseveration. (f) context-dependence of emotions within text, illustrated by “Eu amo minha familia e meus pais” (“ I love my family and my parents ”). (g) Spontaneous EEG (four non-consecutive sec of the same recording session placed side by side). (i) Eye closure sensitivity: the awake EEG is characterized by a posterior dominant alpha rhythm (9-10Hz) and moderate voltage reactive to eye opening and closure. (ii) Awake, eyes-closed resting condition: there is frequent delta slowing seen in the right frontal region (Fp2-F4 and Fp2-F8). (iii) Hyperventilation (HV): HV showed a tendency to increase the focal slowing noted above. (iv) Photic Stimulation (PS): intermittent PS did not alter the background. Calibration bar: 100 µV.

Saccadic and antisaccadic tasks

E.L. and CTRL group, 21.6 ± 0.9 (20-30 years) ( n = 5), composed of male subjects of a similar age as E.L., performed saccadic and antisaccadic tasks under gap and overlap paradigms being quantified latencies of eye movements and tasks error (see Supplementary Methods and Extended Figure 8a-b and Extended Figure 9a-c). E.L. showed difference in prosaccadic and antisaccadic errors to single targets (Extended Figure 8c,d,e,f and Extended Figure 9). Similar trends, however, were not observed when the same CTRL group under oxcarbazepine-influence (OXC-CTRL) ( n = 5), compared to E.L. Accordingly, the OXC-treated group did not show difference in symmetry (right vs left) of prosaccadic-antisaccadic latency and velocity (Extended Data Figure 8) (Supplementary Methods).

Functional magnetic resonance imaging (fMRI) – dual tasks

Neurological (bimanual finger taps) test proved to be a valuable tool for unmasking functional limitations under dual tasks and paved the way for a strategic management of E.L.

On the day of E.L. scanning, the maximum number of index finger-to-thumb taps in 60 sec was obtained for both hands (unimanual movements). The mean number of finger taps for the left and right tasks were 40.7 ± 3 and 41 ± 2,5, respectively. During unilateral tasks, no detectable movements of the contralateral hand, i.e., mirror movements, occurred. Since E.L. was commanded to start the task, and required no decision making on his part, he was less likely to engage motor selection networks that show a bias towards left hemisphere activation. 21 In general, finger-tapping tasks activated the motor and premotor regions, including the primary motor (M1), ventral premotor (vPM) and dorsal premotor (dPM) cortex ( Figure 3 a-i). This task was performed with the right hand only, left hand only, and both hands simultaneously (Extended Data Figure 3c-f).

Functional BOLD MRI images (fMRI) of E.L.’s brain activation during sequential finger-to-thumb tapping movements using one hand alone or two hands simultaneously. Axial (a-c), sagittal (d-f) and coronal sections (g-i) offer the possibility of directly investigating cortical brain activation and connectivity during task performance using the right hand alone (a,d,g), left hand alone (b,e,h) or during bimanual movements (c,f,i). Of note, use of either the left hand alone or simultaneously both hands showed a similar trend of activation in the bilateral frontal and parietal regions, known to be involved in working memory. By contrast, for the right-hand alone movements, activation of the motor control regions was lateralized to the left hemisphere. Scale: Z score ranging from -40.95 to 40.95.

For the right-hand finger-tapping condition, there was robust contralateral (i.e., left hemisphere) activation in the supplementary motor area (SMA), overlying the primary motor (M1), as well as the ipsilateral cerebellum (i.e., right side). In contrast, during unilateral left hand tapping, there was robust bilateral (i.e., both hemispheres) activation in the SMA, M1, vPM and dPM and in the cerebellar hemisphere ipsilateral to the movements. Similar imagery activation patterns were observed for bilateral tapping, dPM activation extending superiorly to the dorsal convexity and vPM activation extending along the precentral gyrus ( Figure 3 a-i).

Characteristic of spontaneous EEG

A set of 5 EEG data collected from E.L. over the years (2014; 2015a,b; 2019; 2020) was used for this study. Each epoch was reviewed in two formats: raw EEG and quantitative EEG (qEEG)-only, in which the raw signal is converted into a digital colour form using derived measures. E.L.´s awake EEG at rest is characterized in all EEG datasets by increased asymmetrical right anterior slow dominant rhythm (delta and theta rhythms) of ≤ 4 Hz and of 4-7 Hz and by a symmetrical posterior alpha rhythm of 9-10 Hz, moderate voltage that is reactive to eye opening and closure. Low amplitude beta frequency activity and alpha waves were also present over the anterior head regions, predominantly in the right front central region. During drowsiness, there was attenuation of the awake background and an increase in background slowing. Hyperventilation showed a tendency to increase the focal slowing noted above. Photic stimulation did not alter the background ( Figure 2 g). A lateralized antero-to-posterior EEG spectral gradient (APSG), which had greater low frequency power from the right prefrontal, frontal lobe and occipital areas, emerged as the most prominent feature at rest associated with E.L. associated brain lesion. The APSG crossed over the genu (in 3 out of 4 runs) and body (in 4 out of 4 runs) of the C.C. to reach the contralateral hemisphere ( Figure 2 g; Figure 4 ).

Changes in slow wave amplitude of the quantitative EEG during active and passive (assisted) symmetric movement tasks. The topographic delta frequency band distribution in E.L. and CTRL (resting testing) (top row), during unimanual left/right and bimanual tasks (middle row) and during foot movements (bottom row) is illustrated. Significant differences from baseline for absolute amplitude (µV) in delta frequency were found only in E.L. right frontal region (Fp2) while performing active finger-to-thumb tapping movements – P < 0.05 baseline vs. left hand and P < 0.05 baseline vs. right hand. Changes in delta wave amplitude during active/passive hand or foot movements were neither documented for CTRL nor for E.L. during either active/passive foot and passive hand movements. Calibration (colour scale): 15-102 µV.

qEEG signals related to left/right hands and foot movements

Following execution of left-hand motor tasks, repeated measures of frequency of finger-tapping with the right hand alone showed no difference between E.L. and CTRLS ( Figure 4 ) (Supplementary Clinical Case History). In contrast, in the right PFC, delta waves outcome showed a significant increase in frequency to 104.4 ± 1.5 (µV)/epoch ( n = 3 assays) ( P < 0.05), while alpha, beta and theta values did not change during the execution of the motor task. A similar motor outcome by E.L. was evidenced during active dual-task performance executed simultaneously with the right- and left-hands ( Figure 4 ). However, during bimanual movements, the mean number of finger taps −1 dropped to 29 ± 3, achieving over 32% reduction as opposed to CTRL. In contrast, right foot and left foot alone or simultaneous bipedal movements executed by all subjects, passive or active, independent of the starting foot, did not change the frequency of EEG waves nor did it result in any change in the latency to start performing the task ( Figure 4 ).

Modulation of cortical network SW oscillatory dynamics by navigated transcranial magnetic stimulation (nTMS)

Mapping characteristics.

TMS was performed in E.L. and in CTRL ( n = 4), who were right-handed (age range: 30-35 years). Left Primary Motor Cortex (PMC), dlPFC and vmPFC were focally stimulated sequentially, during three consecutive days in all participants without technical problems or adverse events. Neuropsychological and behavioral performance were determined prior, during and after application of TMS protocols. TMS protocols applied directly on the right hemisphere were not considered because of the nature of E.L.’s frontal injury.

An MRI-guided navigation system was used to estimate in real time an accurate coil positioning on the surface of the skull of the subjects ( see Methods ). Optimal TMS stimulation parameters for modulating non-invasively brain SW activity, identified in the context of the motor system in left PMC (M1) ( day 1 ), were subsequently applied to higher level functions such as working memory ( day 2 ) and apathy behavior ( day 3 ), respectively, in the block design protocol applied in dlPFC and in vmPFC. Participants did not self-report any side effects of stimulation protocols, either excitatory (PMC) or inhibitory (PMC, dlPFC, vmPFC). No apparent abnormal seizure-like activity was detected on EEG recordings following TMS protocols.

Threshold of motor evoked potentials (MEPs) and left PMC repetitive transcranial magnetic stimulation (rTMS)

Resting- and active motor-thresholds were predetermined in all participants at about 50 µV and 200 µV in the left PMC, respectively, to produce liminal MEP at rest and during isometric contraction of hand muscles (in 50% of 10 trials – Supplementary Methods ). rTMS inhibitory protocol (1Hz) in left PMC induced high amplitude (> 80 µV) SWs, mostly detected on E.L.’s right-sided scalp ( Figure 5 e-g), contrasted sharply with the lower amplitude SW of the pre-TMS EEG. Lateralized SWs revealed an antero-to-posterior gradient along the right-sided scalp and, simultaneously, a rapid lateral spread to the left frontal region ( Figure 5 e). Moreover, in the right PFC, delta slow waves showed a significant increase in frequency and power to 284.56 ± 39.09 µV²/epoch ( n = 30) ( P < 0.001) (10 highest epoch: 532.08 ± 46.96 µV²/epoch), maintaining its power for at least 40min (total recording time = 60min). In the subsequent period, with the virtual lesion resolution ( see Methods), there was a decrease in delta power, with no significant difference ( P >0.05) from the resting state (73.86± 10.96 event µV²/epoch ( n = 30) - 10 highest epoch: 127.95 ± 25.51 µV²/epoch). Thus, cross-hemispheric high amplitude SW frontal propagation may rely on E.L.’s anterior C.C ., albeit expected but not evidently compromised functional integrity of this interhemispheric WM tract. Also, rTMS excitatory protocol (10Hz) in left PMC did not increase the SWs in E.L. ( P >0,05) 72.54 ± 5.58 µV²/epoch ( n = 30) (10 highest epoch: 105.3 ± 8.23 µV²/epoch) in comparison to the resting state – TMS-untreated 76.26 ± 10.15 event µV²/epoch ( n = 30) (10 highest epoch: 134.1 ± 20.21 µV²/epoch) ( Figure 5 e,h). The triggering of SWs in E.L. could be obtained reliably using inhibitory, not excitatory (10Hz), stimulating conditions at frequency of 1 Hz. In contrast, a similar protocol did not evoke SWs in the CTRL ( n = 4) ( Figure 5 e,h), regardless of stimulation site.

Left dlPFC contribution to E.L.’s working memory

Here, inhibitory TMS pulses (1 Hz) were used to create a ‘temporary lesion’ of a targeted cortical region, thereby disrupting dlPFC-mediated balance in visuospatial, perception, learning and short-term memory (retention) performance. E.L. apparent deficits on working memory, tailored the selection of the Rey-Osterrieth Figure (ROFC), one of the most frequently used tests for assessing executive dysfunction, to assess the TMS-treated participants. To preclude the possibility that impaired performance could be secondary to rTMS-mediated potential ‘loss of interest’ or ‘apathy’ ( see below), the intervention using dlPFC stimulation procedure was administered one day prior to that of vmPFC.

Prior to TMS treatment, no differences ( P >0,05) were found between E.L. and the CTRL ( n = 10) in the accuracy of the Rey-Osterrieth figural copy (5 min time limit set for the copy), in the immediate recall (IR) (3 min) (and in the delayed recall (DR) (30 min), indicated by Crawford & Garthwaite´s method for detecting the abnormality of a patient´s score. Details are illustrated in Figure 5 i,j. However, following TMS treatment, there was a significant difference between E.L. TMS-untreated/treated ratio in comparison with CTRL´s TMS-untreated/treated ratio at the IR ( P < 0.001 - E.L. 1.756 vs CTL 0.893 [0.02] - Effect Size (Z-CC) 10.128, as well as for the DR ( P < 0.001 - E.L. 1.619 vs CTL 0.877 [0.03] – Z-CC 6.523) ( Figure 5 i,j). TMS-treated E.L. reproduced the figure at both measurement points with fewer details and misplacement features. No TMS-mediated decreases in accuracy scores appeared for CTRL regarding IR and DR (mean score of 28.25 [2.06] vs 31.8 [2.18]), and of 28.6 [1.98] vs 32.3 [1.43], respectively).

rTMS-mediated left vmPFC triggering of slow waves and apathy is state-dependent

Here, a second inhibitory protocol of continuous Theta-Burst Stimulation (cTBS) was applied in left vmPFC, in which three 50-Hz pulses were applied at 5 Hz for 40 sec. E.L. presented increased frequency and power of SWs along with reduction of ‘goal-directed behavior’ (apathy) immediately following cTBS ( P < 0.001). In support of our main hypothesis following TBS applied to left vmPFC, neither SWs evoked in E.L.’s right hemisphere nor apathy were recorded in or manifested by CTRL. Figure 5 illustrates the results. Both CTRL and E.L. were previously assessed AES-C rating scale suggesting no apathy or apathy related symptoms. For CTRL, no SW pattern or significant behavioral changes (Scale for Assessment of Negative Symptoms (SANS) of 0 [ n = 4]), emerged following TBS-treatment. By contrast, for E.L., SANS changed from 0 to 45 units (range: 0-125 units), with the presentation of apathy related signs and symptoms 3-5 min after application of TBS protocol, including signs of affective flattening, poverty and increased latency of speech and inattentiveness, paralleling the increased frequency in SWs, and remained for up to 60 min. Return to basal behavioral state was paralleled by return of SWs to pre-TBS stimulation level, determined by EEG recordings ( Figure 5 e-h). Moreover, in the right PFC, there was a sustained increase in SWs to 184.45 ± 25.75 event (µV2)/epoch ( n = 30) ( P < 0.001) (10 highest epoch: 328.35 ± 46.99), maintaining its power for at least 60min (total recording time = 90min). In the subsequent period, with the virtual lesion resolution ( see Methods), there was a decrease in delta power, with no significant difference ( P >0.05) from the resting state (68.08± 5.68 event (µV2)/epoch ( n = 30) - 10 highest epoch: 103.41 ± 8.28).

We have documented the performance of a patient (E.L), a modern-day Gage, on tests of behavioural and executive functions, which were given during a period of 8 years. His severe transfixing frontal lobe damage, remarkably similar to that of Phineas Gage (1848) 22 (Supplementary Clinical Case), who attained a legendary status in the history of neuroscience and psychology, occurred against a background of largely intact cognitive, intellectual, perceptual, social and sexual functions. E.L. neither exhibited emotional and behavioral changes, including disinhibition, jocularity, and decline in social and occupational functioning, nor changes in higher-level cognitive and other executive functions associated with Gage's accident and “classical damage” to ventromedial- and dorsolateral prefrontal regions. Multitasking assessments and TMS-targeted protocols, however, unmasked compensatory mechanisms through modulation of slow wave oscillations under single task conditions, to maintain motor performance and executive functioning, eluding clinical detection and underlying brain capability to restore ‘normal life’ function after unilateral frontal lesions.

We selected tests for the most common neuropsychological functions sensitive to damage in the frontal lobe 16 ( Table 1 ; Extended Table 1). It is notable that E.L.’s decision-making impairments were not detected by gold standard tests of cognitive assessment, such as, IGT, CBT, WCST, and the ROCFT. 16 From a clinical perspective, we identified deficits in E.L. across working memory, including short-term memory, and using task switching tests, an executive function that involves the ability to unconsciously shift attention between dual-tasks. Similarly, we identified borderline performances on language (semantic [animals] and phonological [letter ‘p’]) tests ( Table 1 ; Extended Table 1). Although cognitive impairments are not always evident on Divided Attention and on Working Memory tests, previous studies reported that patients with right hemisphere damage exhibited a worse performance, 23 supporting the concept that the contribution of the right hemisphere is more pronounced than the left hemisphere for the processing of visuospatial short-term memory tasks. In agreement with this concept, E.L. showed working memory deficits, independent of a clear rising complexity level, and deficits on the spatial span, in agreement with previous reports on TBI patients. 24 However, several confounding variables must be taken into account. Among them, are the side effect of some symptomatic treatments with OXC - an anticonvulsant, which can impair performance in cognitive functions-, 25 intelligence, 26 age, and degree of education. Accordingly, no differences in anti-saccade task and eye tracking performance, manifested by subjects with a variety of neurological and psychiatric conditions, 27 were found on the OXC-treated CTRL and E.L. Thus, it remained unclear the extent to which a deficit in top-down inhibition in E.L. had functional significance.

Noting that dual-task interference effect may reflect the disruption of a central attention processor that uses limited resources to subordinate processing mechanisms for executing a task, 28 we decided to perform imaging and electrophysiological assays in conjunction with memory-guided simple sensorimotor decision tasks. E.L.’s performance on simultaneous bimanual movements is illuminated by his cortical activation patterns during functional neuroimaging assays, debunking misinterpretations and shedding light on resource allocation during task performance. In particular, E.L.’s movements revealed that right hand finger tasks induced most activation in the contralateral PMA, PFC and Supplementary Motor area (SMA) and ipsilateral cerebellum, in terms of total/relative voxels relative to his SMA. Previous studies reported that the primary sensory-motor cortex (SM1) is more activated by finger than toe movements, although the PMA and PFC are more activated by toe movements. 29 Therefore, different bold fMRI activation patterns are believed to be generated by movements of the arms or legs. On the other hand, we found that E.L.’s both unimanual finger movements (left hand) or bimanual movements induced similar patterns of activation in the bilateral frontal and parietal regions, known to be involved in working memory. 30 Previous research indicated that transcallosal inhibition from the contralateral to ipsilateral hemisphere in sensorimotor area, in response to voluntary extension/flexion of single hands, could account for modulation of neural activity on normal subjects 31 and that brain injured subjects presented abnormally increased transcallosal inhibition from the healthy hemisphere onto the injured side. 32 Nonetheless, the fact that reduced connectivity can reroute signal through more intact commissural fibers, thereby maintaining enough contralateral connectivity, 33 is consistent with previous results in context of how interhemispheric connectivity can be impaired without reducing cognitive or functional ability. 3 , 34 fMRI and TMS findings and qEEG for E.L. unveiled that interhemispheric connectivity via the use of the anterior or the posterior commissures in lieu of the C.C ., correlated with spontaneous brain activity or were measured in the presence of task demands, respectively. While some studies of typical interhemispheric coordination in neurologically intact subjects suggest entirely cortico-cortical connections, others implicate subcortical contributions. 35 Another possibility is that subcortical structures such as the thalamus or the superior colliculus play a greater role than previously thought in defining the flow of information between cortical regions. 36 , 37 This adjustment mechanism has been suggested in humans with agenesis of C.C . 34 In support of this view, interhemispheric functional synchronization in the absence of direct C.C. connectivity has also been reported in species that lack C.C . or have a small C.C. , such as song birds and cetaceans. 38

Although the same neuronal circuits may produce slow wave (SW) oscillation (1-4 Hz) in seizing brain and during sleep, 39 , 40 the two conditions seems to rely on differential activation of networks. Previous reports showed that SW activity is associated with increase fMRI-BOLD activation responses in a spatially related brain area. 41 However, while SW is thought to consolidate memory activity in normal subjects during deep sleep (NREM), 42 SW in the seizing brain is considered an epiphenomenon leading to dysfunction, including impairment of memory. The logic here has been that delta oscillation in lesioned and contralateral areas of E.L.’s brain may be not merely a marker of network dysfunction, 43 , 44 but, instead, an expression of signalling rearrangement enabling performance. 12 While E.L. presented a similar modulation of SW for passive/active foot movements, as predicted from previous work on Bold fMRI, 45 his active right finger movements, by engaging his left hemisphere, led to increased SW in his right frontal cortex as shown by EEG recordings. Subsequent, single-handed left finger movements, engaging both hemispheres, decreased SW on his injured right hemisphere. That is, while a decrease of frequency of irregular SW in the right damaged hemisphere, assumed as a non-epileptiform activity, facilitated E.L. to accomplish a number of cognitive and motor tasks, persistence/increase of delta waves became an indicator of impairment/dysfunction. Different patterns of anatomical activation induced by E.L's fingers or foot movements explain lack of modulation of frequency of SW by the latter. On the other side, although a similar pattern of brain representation is elicited by active or passive movements for upper limbs, during active movements only, activations of the basal ganglia and the cingulate gyrus were found. 46

TMS is increasingly used to create ‘virtual lesions’, with temporospatial resolution, in selected brain regions. 47 Thus, temporary disturbance of task-related neuronal activity mediated by a specific region should yield a decline in executive performance and behavior. We tested this prediction by applying rTMS pulses over the left PMC (motor), dlPFC (working memory) and vmPFC (behaviour) 48 and showed that it is possible to reliably trigger SWs in awake injured brain that resemble in all aspects spontaneously TMS-induced slow oscillations during NREM sleep (i.e., state-dependent). 49 Spatially, the TMS-treatment resulted in a substantial increase in SW oscillations that spread antero-to-posterior like a ‘water ripple wave’ across E.L.’s right hemisphere and laterally to his contralateral frontal lobe during wakefulness. In contrast to E.L. awake brain, however, the hot spot for TMS-triggered oscillations on CTRL sleep NREM brain corresponded closely to a hot spot for the origin of spontaneous SWs and their sensorimotor regions constituted a preferential site for triggering such SWs. 50 In contrast to E.L., TMS-triggered frontal SW oscillations in sleeping heathy brain are state-specific and displayed a sudden disappearance after transition from NREM to wakefulness. 49 Thus, lack of TMS-triggered SWs on our awake CTRL was not unexpected. By demonstrating these findings in awake injured brain, however, our study suggests that in contrast to the ‘sleeping mode’, 13 E.L.’s injured brain, active and reactive, does not lose its ability of entering integrated and differentiated states because of prompt modulation of frequency and amplitude of SW oscillations by the left contralateral hemisphere. Results from the present study support that such features are critical for performance of E.L. executive functions. It is important to note that, regardless of stimulation site, TMS pulses applied to E.L scalp area, were equally effective overlying PMC, dlPFC and vmPFC. Thus, in contrast to the sensorimotor cortex (precentral and postcentral gyri areas) on ‘sleeping brain’, 49 where activation of corticoreticulothalamocortical circuits by TMS primarily support triggering of SWs, evidence from our study support that, in injured E.L. awake brain, contralateral cortical reactivity is required to attenuate the frequency of irregular SW activity. Following the anticipated modulation criteria of contralateral SWs oscillation, the second criterion of successful compensation required disturbance of executive functioning and behaviour on selected regions, and a consequent decline in specific performance upon TMS-treatment. Temporary maintenance and processing of information, involving executive processes that manipulate the contents and retention of working memory, was explored assessing the ROCF task. Several studies give evidence for a role of the left dlPFC in working memory, but, no apparent deficits manifested by E.L. on any outcome measures (copy, IR and DR trials of ROCF test) were suggested prior to TMS-pulses as well as no effects were observed following unilateral stimulation of CTRL on any outcome measures. 51 We tested this prediction by probing the reactivity and executive functioning in E.L and CTRL brain after applying TMS pulses in left dlPFC at intensities commonly used in clinical practice. 52 As predicted, consolidation of the Rey-Osterrieth Complex Figure was disrupted at both 3 min (IR) and 30 min (DR) by stimulation selectively over E.L. dlPFC, without disruption of his motor skills or other aspects of motor function. Such strategy failed to find a similar disruption of executive functioning in the CTRL, suggesting that bilateral ‘lesions’ are required to impair short-memory consolidation and retrieval. In a third approach, an increase of SWs over the right hemisphere by means of TMS protocols applied to left vmPFC, used to interfere with motivation (i.e., apathy and asociality), disrupted E.L. willingness to engage in social interaction, similar to disorders secondary to bilateral frontal damage, 1 and produced indifference regarding interpersonal relationship. In contrast to E.L., the CTRL group did not manifest change in behaviour after TMS-treatment. Return to normal behaviour paralleled progressive reduction of SW activity over E.L. right hemisphere, within 60 min of TMS-stimuli.

Few cases in the history of neurosciences have been reported as frequently as the TBI case of Phineas Gage, which still lives as a part of neuroeducation. While great attention is given to executive dysfunction, one can merely speculate how Gage's brain injury actually affected his daily routine and feasibility of functional compensation. The current E.L. case, whose brain injury mirrored that of Gage's, sheds light on SW oscillatory dynamics following TBI, unveils compensatory mechanisms by which PFC may accommodate executive functional performance, which frequently elude clinical diagnosis, and provides an attractive target for therapeutic interventions on cortical circuits.

Contributors

R.C.M.S.F., F.A.V., I.S.D., R.M.B. and C.M.P. performed neurosurgical procedures. C.T.F.T., C.C., J.T., K.P. and E.G. selected neuropsychological batteries and performed testing and interpretations. L.C.H.C. Jr. performed diagnostic MRI. G.F.G. and F.M. applied BIQS testing. G.L.W. provided advice on statistical methods. M.F. and P.H.F. performed EOG testing. P.H.F., R.B., G.F.G., S.F.A.R., C.M.P. and R.R. developed the figures, table and movies; analysed data and revised the manuscript. W.S.P., C.Y.H., P.C.R. and P.H.F. conducted the T.M.S. assays. P.H.F., C.M.P., J.V., T.M.M.L., M.M.S., F.L., H.J.F. and R.R. performed neurological and neurophysiological assessments. J.R.L.S. developed the 3D brain modelling. D.H.P. performed diagnostics assays. R.L., M.V.L.B., P.H.F. and R.R. - conceived the study, structured its design, interpreted and integrated data and organized the general discussion. M.V.L.B. and R.R. - drafted and edited the main manuscript and proved the final version.

Declaration of interests

All authors declare that they have no conflicts of interest.

Acknowledgements

We thank Mr. M.B. da Silva (CDPI, Brazil), Dr. F. Tovar-Moll (IDOR, Brazil) and Dr. H. Werner (CDPI/DASA, Brazil) for MRI scans over the course of the study; Mr. M. Barroco and Mrs. C. Seixas (Zeike Medical Ltda, Brazil) for EEG measurements technical support; Dr M.S.Thome de Souza (USP, Brazil) for EEG/TMS monitoring; Dr C. Rego (HUCFF/UFRJ, Brazil) for video/EEG records; Mr E.M. de Souza (EMSA Equipamentos Médicos Ltda, Brazil) for qEEG (brain map); and Dr. S. Moshe (Einstein, NY) for valuable comments. We are grateful to Dr. O. Sacks † (NYU, NY) for his earlier insightful comments on E.L.’s right frontal lobe injury and for the assistance provided by Ms K. Edgar (‘The Oliver Sacks Foundation’, NY).

Supplementary material associated with this article can be found in the online version at doi: 10.1016/j.lana.2022.100340 .

Appendix. Supplementary materials

EXTENDED DATA

Extended FIG. 2. MRI follow-up of patient E.L. T2 weighted sequences suggesting the penetrating lesion extension. a, c – Scan sequences obtained 12 days after the transfixing traumatic brain insult, with overt perilesional edema (white arrow), without midline deviation. b, d – 18 months follow-up, with no visible edema, atrophy, or neurodegenerative signs. Axial (a, b) and coronal (c, d) sections, respectively.

Extended FIG. 3. E.L.: Failure of compensatory mechanisms during bimanual challenge. Coordination testing showed symmetrical movements without dysmetria, or incoordination, on finger to nose testing, normal forearm (a) and finger rolling tests (b), in which the subject rotates just the index fingers using rapidly alternating movement, and on sequential active finger-to-thumb tapping with the right hand alone (c) or with the left hand alone (d). However, there was incoordination of sequential finger-to-thumb tapping movements in the left hand during bimanual movements (e) low-magnification and (f) higher magnification. In the beginning, E.L. expressed surprise at the outcome to see that his left-hand fingers could end up paralyzed for a few sec upon the execution of bimanual movements.

Extended FIG. 4. 3D brain reconstruction from T1 MRI scan sequences helped unveil E.L.’s right frontal lobe dysfunction. Cortical surfaces reconstruction with sulcal identification output by FreeSurfer (inset) are illustrated (a,b). Life-size 3D view metrics of E.L brain morphology and the path that the transfixing iron bar followed through his right hemisphere (a,b in red colour), printed in polyamide (c), highlighted compromised regions and presented a detailed picture of the extent of the damage. R (right hemisphere), L (left hemisphere). Calibration bar (c): 2 cm.

Extended FIG. 5. Visual representation of major white matter fiber tracts tracked in E.L. Diffusion tensor tractography quantification of Uncinate Fasciculus (yellow), Cingulum bundle (blue) and Superior Longitudinal Fasciculus (SLF) (green), compromised in E.L. accident, and Corpus Callosum ( C.C. ) (red), are illustrated in lateral and axial scans (a-f). (c,d,e ). Axial and lateral views of a tractography suggested a difference in the volume of the association fiber tracts that connect temporo-parietal cortical regions with right frontal lobe (b,c,f – white arrows), but no difference in the volume of the C.C. association fiber tracts that connect the frontal lobes (c,e,f – red).

Extended FIG. 6. E.L.’s performance in Iowa Gambling Task (IGT), used to assess risk-based decision-making and impulsivity after TBI, is sensitive to behavioural deficits in subjects with PFC damage. The test consists of a card game where the risks and rewards vary by the decks chosen. (a) Percentage of cards selected from different decks. (b) Two of these decks (decks A [highest risk deck] and B) have higher short-term payoffs (‘high risk’) than the other two (decks C and D) (advantageous ‘safe’ decks), but over time (10 trials of the IGT) the decks with high immediate payoffs are disadvantageous, resulting in a long-term loss (net loss). (c,d) E.L.’s score based in safe vs. risky decks and numbers of cards selected (safe vs risky decks) over the course of the test. (e) reaction times (in sec) for each trial (total 100 trials) of the test (deck choice represented by colour patterns depicted in ‘a’). Total net IGT scores (100 trials per session) is analysed using methods of scoring risky decisions (Methods). Complex emotion based-learning remained intact in E.L.

Extended FIG. 7a,b. Assessment of sexuality following traumatic brain injury (TBI). The Brain Injury Questionnaire on Sexuality (BIQS), which is designed to account for temporal changes in sexual function, was applied in parallel to E.L. and to L., his wife (a, b), 31 months following E.L.’s TBI.

Extended FIG 8. The antisaccade task and the voluntary control of eye movement. Saccadic and antisaccadic eye movement tasks depend on the frontal/prefrontal cortex and related structures. (a) Schematic diagram of EOG test. A symbolic cue, such as a colour dot, instructs the subject to make a brief, rapid eye movement (a saccade) towards the stimulus (prosaccade) (green) or in the opposite direction (antisaccade) (red). (b) The schematics of the overlap (top layer) and gap (middle layer) tasks performed are displayed in msec. (Bottom) Reaction time latencies of eye movements during prosaccade and antisaccade commands. (c,d) Performance of a CTRL and E.L. during a gap task. (c) Eye position traces during prosaccades (left). (middle, right) Distribution of reaction times for each participant (histogram) – single test. (d) Antisaccade tasks . Correct responses are displayed in blue, corrected errors in red and anticipations or uncorrected errors in black – single test. (e,f) Overlap task % and gap task % distribution of EOG responses for the CTRL and E.L. Differing effects of prosaccades (Pro) and antisaccades (Anti) are illustrated by histograms correspondent to right (top) or left (bottom) stimuli.

Extended FIG. 9. Impaired antisaccades in oxcarbazepine-treated subjects. The comparison between the outcome of eye-tracking performance in oxcarbazepine (OXC)-treated E.L. and in OXC-treated/untreated CTRL ( n = 5). (a) The first row depicts latencies in saccade, prosaccade and antisaccade paradigms, presented randomly to the right or the left side. (b) The second row displays the performance (correct rate responses) of the OXC-treated subjects and CTRL. * - P ≤ 0.05. (b) Mean ±SEM values of prosaccade and antisaccade and latency of all groups. Of note, there were no differences in symmetry (right vs left, or up vs down) of prosaccadic-antisaccadic latency, velocity, or gain between E.L. and the OXC-treated CTRL. (c) E.L.’s therapeutic plasmatic levels of oxcarbazepine.

Extended TABLE 1. Neuropsychological battery performed in E.L. Abbreviations: MMSE: Mini Mental State Examination; BDI: Beck's Depression Inventory; WCST: Wisconsin Card Sorting Test (Modified Card Sorting Test. Nelson, 1976); PM 38: Standard Progressive Matrices 1938; RCFT: Rey – Osterreith Complex Figure Test; TMT: Trail Making Test; Stroop-W: word reading Stroop Task; Stroop-C: colour naming Stroop Task; Stroop CW: Colour-word interference Stroop Task; DMS-48: Delayed Matching to sample (Barbeau, 2004); CVLT: California Verbal Learning Test; BNT: Boston Naming test; Facial Recognition Test (Benton, 1983)

SUPPLEMENTARY MOVIES

Movie #2. Supplementary movie S2.

Movie #3. Supplementary movie S3.

Supplementary Clinical Case History.

Supplementary Methods.

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Phineas Gage

John Fleischman

Nonfiction | Biography | Adult | Published in 2002

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1.3: Connecting Biology to Behavior

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This page is a draft and under active development. Please forward any questions, comments, and/or feedback to the ASCCC OERI ( [email protected] ).

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Learning Objectives

Discuss the Case of Phineas Gage and its contribution to biological psychology.

While experiments are necessary to establish cause and effect relationships, in-depth studies of unique individuals or groups of people who share an experience can be used to inform our understanding of things that we can not study experimentally. Surgical errors, extreme mistreatment, and tragic accidents are impactful events that can alter individuals significantly, providing unique opportunities to study the effects of experiences which can not be ethically studied experimentally. There have been a number of these case studies which have revealed the role of different parts of the brain on our thinking and behavior. One such case is Phineas Gage. Gage lived 12 years after a rod pierced his skull, damaging his left frontal lobe. Researchers were able to gather information about his functioning before and observe his cognitive ability and personality after the accident. His case enabled the field to understand the role of frontal lobe in personality and mental processes.

The Tale of Phineas Gage

Phinease Cage after his accident, holding the rod that damaged his brain

The case of Phineas Gage is worthy of expanded coverage as his tragic accident establishes a clear connection between the brain and who we are. Gage, a 25-year-old man, was employed in railroad construction at the time of the accident. As the company's most capable employee, with a well-balanced mind and a sense of leadership, he was directing a rock-splitting workgroup while preparing the bed of the Rutland and Burlington Railroad south of Cavendish, Vermont, USA. At 4:30 PM on September 13, 1848, he and his group were blasting a rock, and Gage was assigned to put gunpowder in a deep hole inside it.

The moment he pressed the gunpowder into the hole with a bar, the friction caused sparks, and the powder exploded. The resulting blast projected the meter-long bar, which was 1.25 inches in diameter and weighed about 13.2 pounds, through his skull at high speed. The bar entered his left cheek, destroyed his eye, passed through the left front of his brain, and left his head at the top of the skull on the right side. Gage was thrown on his back and had some brief convulsions, but he woke up and spoke in a few minutes, walked with a little help, and sat in an ox cart for the 0.7-mile trip to where he was living.

About 30 minutes after the accident, a doctor arrived to provide medical care. Gage had lost a lot of blood, and the next days that followed were quite difficult. The wound became infected, and Phineas was anemic and remained semi-comatose for more than two weeks. He also developed a fungal infection in the exposed brain that needed to be surgically removed. His condition slowly improved after doses of calomel and beaver oil. By mid-November he was already walking around the city.

The Consequences

For three weeks after the accident, the wound was treated by doctors. During this time, he was assisted by Dr. John Harlow, who covered the head wound and then reported the case in the Boston Medical Surgery Journal. In November 1849, invited by the professor of surgery at Harvard Medical School, Henry Jacob Bigelow, Harlow took Gage to Boston and introduced him to a meeting of the Boston Society for Medical Improvement .

In his reports, Harlow described that the physical injury profoundly altered Gage's personality. Although his memory, cognition, and strength had not been altered, his once gentle personality slowly degraded. He became a man of bad and rude ways, disrespectful to colleagues, and unable to accept advice. His plans for the future were abandoned, and he acted without thinking about the consequences. And here was the main point of this curious story: Gage became irritable, irreverent, rude and profane, aspects that were not part of his way of being. His mind had changed radically. His transformation was so great that everyone said that “Gage is no longer himself.”

As a result of this personality change, he was fired and could no longer hold a steady job. He became a circus attraction and even tried life in Chile, later returning to the United States. However, there is something still little known about Gage: his personality changes lasted for about four years, slowly reverting later. As a proof of this, he worked as a long-haul driver in Chile, a job that required considerable planning and focus skills. He died on May 21, 1861, 12 years after the accident, from an epileptic seizure that was almost certainly related to his brain injury.

After his body was removed from its grave, Gage's mother donated his skull to Dr. Harlow who in turn donated it to Harvard University.

Gage's case is considered to be one of the first examples of scientific evidence indicating that damage to the frontal lobes may alter personality, emotions, and social interaction. Prior to this case, the frontal lobes were considered silent structures, without function and unrelated to human behavior. Scottish neurologist, David Ferrier, was motivated by this fact to investigate the role of frontal lobes in brain function. Ferrier removed the frontal lobes in monkeys and noted that there were no major physiological changes, but the character and behavior of the animals were altered. In other words, he confirmed the role of the frontal lobes that was suggested by Gage's accident in an experiment with a non-human animal.

Knowledge that the frontal lobe was involved with emotions continued to be studied. The surgeon Burkhardt in 1894 performed a series of surgeries in which he selectively destroyed the frontal lobes of several patients in whom he sought to control psychotic symptoms, being the modern prototype of what was later known through Antonio Egas Moniz as psychosurgery. Today, it is well understood that the prefrontal cortex of the brain controls the organization of behavior, including emotions and inhibitions.

Folkloric as it may be, but nonetheless remarkable, the contribution of Phineas Gage's case should not be overlooked, as it provided scientists the baseline for the promotion of studies in neuropsychiatry, and a source of inspiration for world medicine. In 2012, a team of neuroscientists used computer tomography of Gage's skull with typical brain MRI scans to simulate how extensive Gage's brain damage was. They confirmed that most of the damaged area was the left frontal lobe. However, surrounding areas and their neural network were also extensively severed. And it is not just the researchers who keep coming back to Gage. Medical and psychology students still learn about Gage from their history lessons. Neurosurgeons and neurologists still sometimes use Gage as a reference when evaluating certain cases. The final chapter of his life also offers us a thought-provoking discovery about cases of massive brain damage, indicating that rehabilitation may be possible.

Phineas Gage made a huge contribution to our understanding of the frontal lobe damage and its subsequent change in personality. Furthermore, his case expanded knowledge in neurology in several areas, including the study of brain topography in behavioral disorders, the development of psychosurgery, and finally the study of brain rehabilitation. Also, Gage's case had a tremendous influence on early neuropsychiatry. The specific changes observed in his behavior pointed to theories about the localization of brain function and correlated with cognitive and behavioral sequelae, thereby acquainting us with the role of the frontal cortex in higher-order actions such as reasoning, behavior and social cognition. In those years, while neuropsychiatry was in its infancy, Gage's extraordinary story served as one of the first pillars of evidence that the frontal lobe is involved in personality, which helped solidify his remarkable legacy in world medical history.

Attributions

Adapted from Phineas Gage’s Great Legacy by Vieira Teles Filho, Ricardo. Licensed CC BY 4.0 .

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What Happened to Phineas Gage?
The case of Phineas Gage has been of huge interest in the field of psychology and is a largely speculated phenomenon. Gage suffered a severe brain injury from an iron rod penetrating his skull, which he miraculously survived. After the accident, Gage's personality was said to have changed as a result of the damage to the frontal lobe of his brain.
Phineas Gage: Biography, Brain Injury, and Influence
Kendra Cherry, MS, is a psychosocial rehabilitation specialist, psychology educator, and author of the "Everything Psychology Book." Phineas Gage suffered a terrible accident that made him one of the most famous cases of traumatic brain injury. Learn Gage's story and its impact on psychology.
Lessons of the brain: The Phineas Gage story
Imagine the modern-day reaction to a news story about a man surviving a three-foot, 7-inch, 13½-pound iron bar being blown through his skull — taking a chunk of his brain with it. Then imagine that this happened in 1848, long before modern medicine and neuroscience. That was the case of Phineas Gage. Whether the Vermont construction foreman ...
Phineas Gage's great legacy
The case of Phineas Gage is an integral part of medical folklore. His accident still causes astonishment and curiosity and can be considered as the case that most influenced and contributed to the nineteenth century's neuropsychiatric discussion on the mind-brain relationship and brain topography. It was perhaps the first case to suggest the ...
Uncovering the Impact of Phineas Gage's Accident on Psychology
Phineas Gage's case profoundly impacted the field of psychology, as it was one of the first documented cases of the link between brain damage and behavior. It helped researchers understand the role of the frontal lobe in decision-making, planning, and personality. ... Gage's injury provided a unique opportunity to study the relationship ...
1.3: The Case of Phineas Gage- Connecting Brain to Behavior
The case of Phineas Gage is worthy of expanded coverage as his tragic accident establishes a clear connection between the brain and who we are. Gage, a 25-year-old man, was employed in railroad construction at the time of the accident. As the company's most capable employee, with a well-balanced mind and a sense of leadership, he was directing ...
Phineas Gage
Phineas Gage (born July 1823, New Hampshire, U.S.—died May 1860, California) American railroad foreman known for having survived a traumatic brain injury caused by an iron rod that shot through his skull and obliterated the greater part of the left frontal lobe of his brain.. Little is known about Gage's early life other than that he was born into a family of farmers and was raised on a ...
Phineas Gage's story : The University of Akron, Ohio
This is the bar that was shot through the head of Mr. Phinehas P. Gage at Cavendish, Vermont, Sept. 14, 1848. He fully recovered from the injury & deposited this bar in the Museum of the Medical College of Harvard University. Phinehas P. Gage Lebanon Grafton Cy N-H Jan 6 1850. Warren Anatomical Museum records discovered by Dominic Hall of the ...
Phineas Gage: Neuroscience's Most Famous Patient
In time, Gage became the most famous patient in the annals of neuroscience, because his case was the first to suggest a link between brain trauma and personality change. In his book An Odd Kind of ...
Phineas Gage: The man with a hole in his head
The story of Phineas Gage, a man who changed the study of neuroscience forever after a metre-long rod fired through his skull. ... different brain specialists used evidence from Phineas' case as ...
Phineas Gage
At 25 years of age Phineas Gage was the foreman of a railway construction gang building the bed for the Rutland and Burlington Railroad in central Vermont in the USA. He and his gang were blasting a cutting through a large rocky outcrop about three quarters of a mile south of the town of Cavendish. It was Gage who decided where holes would be ...
Phineas Gage: History, Facts, & Importance in Psychology
Phineas Gage's case is a fascinating and historically significant one in the fields of psychology and neuroscience. As mentioned previously, few records exist that provide details about his life. ... Here is a summary of a few key facts about Phineas Gage: ... making him a legend in the study of brain structure and function. To learn more about ...
The Curious Case of Phineas Gage's Brain : Shots
Cabinet-card portrait of brain-injury survivor Phineas Gage (1823-1860), shown holding the tamping iron that injured him. Wikimedia. It took an explosion and 13 pounds of iron to usher in the ...
Phineas Gage
Strengths of the study. Weaknesses of the study. You may have already heard of Phineas Gage, such is his infamous history with psychology. He was working on a railway line in the USA when there was an explosion, which resulted in an iron rod being fired through his head. He survived the accident even though there were serious injuries to his ...
Phineas Gage: A Neuropsychological Perspective of a Historical Case Study
Gage's case is a story of the right projectile, at the right speed and the right distance, passing through the right area of the brain, of the right patient, who was treated by the right doctor, at the right time in history (Lewandowski, 2003). The result is that his injury, treatment, and long-term recovery continue to lend interest and ...
E.L., a modern-day Phineas Gage: Revisiting frontal lobe injury
Evidence before this study. The historical case of Phineas Gage (1848) is an integral part of medical folklore, illustrating the resilience of the human brain and the involvement of the frontal lobes in problem solving, spontaneity, memory, initiation, judgement, impulse control, and social and sexual behavior.
Phineas Gage Summary
Plot Summary. Phineas Gage: A Gruesome but True Story About Brain Science is a children's nonfiction book by John Fleischman. First published in 2004 by HMH Books for Young Readers, the book tells the story of the infamous railroad construction worker who survived a hole in the head and became the subject of intense brain study.
The Case of Phineas Gage (1823
The article provides a summary of the Phineas Gage case with the inclusion of notes he made throughout the recovery. Bigelow notes this could be a "remarkable" case for brain injuries. An entry for the Iron Bar of Phineas Gage in the Warren Anatomical Museum Index, 1850-1868 ... An alternative is to continue to study from Lenn for medical research.
Phineas Gage: The brain and the behavior
Phineas Gage has long occupied a privileged position in the history of science. Few isolated cases have been as influential, in the neurological and neuroscientific thinking, and yet the documentation on which conclusions and interpretations rest are remarkably incomplete [1], [2].We do have a number of sure facts:
BBC
21 May 2008. Phineas Gage was a railway worker in 19 th century Vermont who survived a bizarre accident: A metre-long iron rod shot through his head, changing him and the study of neuroscience ...
E.L., a modern-day Phineas Gage: Revisiting frontal lobe injury
History repeated itself in August of 2012 (Gage vs E.L., Supplementary Clinical Case History). In 1848, Phineas Gage, a 25-year-old American construction foreman, sustained extensive frontal lobe damage after an iron bar - 31 mm in diameter, 1.06 meters long and weighing 6.1 kg - was propelled through the front part of his head.
Phineas Gage: A case for all reasons.
[re-examine the case of 25-yr-old Phineas P. Gage,] a medical curiosity and a famous victim of brain injury, possibly the most famous / present as full an account of his case as possible and outline the main uses to which it has been put before concluding that it supports very few neuropsychological generalizations Gage's [work] accident / Gage pre-accident / Gage in the immediate post ...
1.3: Connecting Biology to Behavior
The Tale of Phineas Gage Figure $\PageIndex{1}$: Phineas Gage Portrait After His Accident. (Public Domain; via Wikipedia Common) The case of Phineas Gage is worthy of expanded coverage as his tragic accident establishes a clear connection between the brain and who we are. Gage, a 25-year-old man, was employed in railroad construction at the ...

Phineas Gage: His Accident and Impact on Psychology

Key Takeaways

What happened to Phineas Gage?

How Did Phineas Gage’s Personality Change?

Accuracy of Sources

Severity of Gage’s Brain Damage

What Happened to Phineas Gage After the Brain Damage?

How did Phineas Gage die?

Why Is Phineas Gage Important to Psychology?

Further Reading

If a person suffers from a traumatic brain injury in the prefrontal cortex, similar to that of Phineas Gage, what changes might occur?

Phineas Gage: His Accident and Impact on Psychology

What Happened to Phineas Gage After the Brain Damage?

At a Glance

Phineas Gage's Accident

The Recovery Process

Theories About Gage's Survival and Recovery

How Did Phineas Gage's Personality Change?

Severity of Gage's Brain Damage

Why Is Phineas Gage Important to Psychology?

Bottom Line

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Lessons of the brain: The Phineas Gage story

In 1848, an iron bar pierced his brain, his case providing new insights on both trauma and recovery

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Uncovering the Impact of Phineas Gage’s Accident on Psychology

The Life of Phineas Gage

Early Years

Career as a Railroad Construction Foreman

Phineas Gage: The Accident

Immediate Aftermath

Medical and Psychological Impact

Physical Consequences

Behavioral Changes

Long-Term Effects

Significance in Psychology

Insights into Brain Function

Influence on Neuropsychology

Implications for Personality Theory

Public Response and Legacy

Legacy in Science and Popular Culture

Frequently Asked Questions

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Phineas Gage: Neuroscience’s Most Famous Patient

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Why Brain Scientists Are Still Obsessed With The Curious Case Of Phineas Gage

One Account Of Gage's Personality Shift

Phineas Gage

Strengths of the study

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41 Phineas Gage: A Neuropsychological Perspective of a Historical Case Study

Introduction

The Accident Site

The Accident

Eyewitness Accounts

First Responder

The Treating Physician

Harlow’s Physical Medicine and Rehabilitation