Phineas Gage’s miraculous survival after an explosion drove a 13-pound, 3-foot-7-inch rod into his left cheek and out of the top of his head in 1848 made him the most famous case in the history of neuroscience based on his survival of this horrific accident, which destroyed most of his left frontal lobe, but also because of the impact his profound injury had on his personality and behavior.

According to his friends, Gage changed from being a good-natured 25-year-old to being fitful, disrespectful and profane, a person who was “no longer Gage.”

Since Gage’s accident, numerous scientists have studied and argued about the exact location and degree of damage to Gage’s cerebral cortex and the subsequent effect on his personality.

UCLA researchers have now, for the first time, been able to perform a more comprehensive examination of Gage’s brain by using brain-imaging data lost to science for a decade.

A study in PLoS One describes the damage to the white matter “pathways” that connect various regions of the brain. Jack Van Horn, an UCLA assistant professor of neurology, and his team discovered that the rod intersected about 4% of Gage’s cerebral cortex, damaging over 10% of his total white matter. The rod’s passage caused widespread damage throughout Gage’s brain, which is likely to be one of the key reasons for Gage’s changed behavior.

The myelin sheath is an insulating layer made from protein and fatty substances that forms around the brain’s nerves and allows a quick and efficient transmission of impulses along the nerve cells. If myelin is damaged, the impulses slow down and can lead to dysfunction and disease. Given that the white matter and its myelin sheath connect billions of neurons that allow reasoning and memory, examining Gage’s brain not only sheds light on the mystery surrounding him, but also will ultimately result in a better understanding of multiple brain disorders that are partially caused by similar damage to these connections.

Van Horn, a member of UCLA’s Laboratory of Neuro Imaging (LONI), an ambitious joint effort with Massachusetts General Hospital and the National Institutes of Health, declared:

“What we found was a significant loss of white matter connecting the left frontal regions and the rest of the brain. We suggest that the disruption of the brain’s ‘network’ considerably compromised it. This may have had an even greater impact on Mr. Gage than the damage to the cortex alone in terms of his purported personality change.”

LONI maps trillions of microscopic links between each of the brain’s 100 billion neurons, the so-called ‘connectome’. Mapping the brain’s physical wiring will ultimately provide answers in terms of the causes of mental conditions that may be associated with the breakdown of these connections. The researchers felt that re-investigation into the damage of Gage’s brain could be a beneficial case study for LONI, in addition to being historically interesting.

Gage’s 189-year-old skull is on display at Harvard Medical School’s Warren Anatomical Museum. However, given that the skull is now fragile and cannot be subjected to medical imaging again, the researchers managed to track down the last known imaging data from 2001 that was lost for over a decade. They recovered the computed tomographic data files and were able to reconstruct the scans in the highest-quality resolution possible to model Gage’s skull. They then used advanced computer methods to model and determine the rod’s precise path as it shot through Gage’s skull.

Given the fact that the original brain tissue was obviously long gone, the researchers used modern-day brain images of matching males in terms of Gage’s age and the fact that he was right-handed, assuming that they had a similar anatomy to Gage, before positioning a composite of these 110 images into Gage’s virtual skull using computer software.

Van Horn discovered that almost 11% of Gage’s white matter and 4% of his cortex were damaged, saying:

”Our work illustrates that while cortical damage was restricted to the left frontal lobe, the passage of the tamping iron resulted in the widespread interruption of white matter connectivity throughout his brain, so it likely was a major contributor to the behavioral changes he experienced. Connections were lost between the left frontal, left temporal and right frontal cortices and the left limbic structures of the brain, which likely had considerable impact on his executive as well as his emotional functions.”

Despite Gage’s change in personality, he was eventually able to travel and find employment as a stagecoach driver for several years in South America before he died in San Francisco 12 years after his accident.

Van Horn remarked that Gage’s predicament has a modern parallel.

He said:

”The extensive loss of white matter connectivity, affecting both hemispheres, plus the direct damage by the rod, which was limited to the left cerebral hemisphere, is not unlike modern patients who have suffered a traumatic brain injury. And it is analogous to certain forms of degenerative diseases, such as Alzheimer’s disease or frontal temporal dementia, in which neural pathways in the frontal lobes are degraded, which is known to result in profound behavioral changes.”

Van Horn stated that the quantification of the changes to Gage’s brain’s pathways could potentially provide important insights in terms of modern-day brain trauma patients’ clinical assessment and outcome monitoring.

Written By Petra Rattue