Over a century later, Phineas Gage's brain connections mapped

Ah, the curious case of Phineas Gage. In 1848, the supervisor of the Rutland and Burlington Railroad in Vermont was using a 13-pound, 3-foot-7-inch rod to pack blasting powder into a rock when he triggered an explosion that drove the rod through his left cheek and out the top of his head. The rod was later found smeared with blood and brains.

Gage lived, and he became the most famous case in the history of neuroscience (pictured). The destruction of much of his left frontal lobe left its mark on his personality and behavior: the 25-year-old went from being affable to being fitful, irreverent, and profane.

For years, scientists have argued about the exact location and degree of damage to the cerebral cortex and the impact it had on his personality.

Now, researchers from the University of California, Los Angeles used brain-imaging data to examine the damage to the pathways that connect various regions of the brain. They show how the rod damaged only a small portion of his brain, but it disrupted a much larger proportion of his white matter neural connections

White matter and its myelin sheath – the fatty coating around the nerve fibers that form the basic wiring of the brain – connect billions of neurons. It’s how we reason and remember. So this new research may help explain multiple brain disorders that are caused in part by similar damage to these connections.

A team led by Jack Van Horn of UCLA produced the image of Gage’s connectome, the trillions of microscopic links between every one of the brain's 100 billion neurons.

1. Using data from CT scans, which had been lost since 2001, they reconstructed the highest-quality resolution 3D image of Gage’s skull.
2. With some more modeling – including the degree of bone breakage, dimensions of the iron rod, and the fact that he was reportedly speaking at the moment of injury, so was likely to have had his mouth open – they determined the exact trajectory of the iron rod. ("It appeared that the rod must have kissed the edge of a tooth to knock it loose," Van Horn says.)
3. Then they took modern-day brain images of males matching Gage's age and (right) handedness and used software to position a composite of these 110 images into Gage's virtual skull. This helped them model the degree of damage.
4. They combined these data to produce a generalized map of the long-range connections in the human brain, and used computational modeling to project the passage of the rod onto it.

Watch a video of the rendering.

They found that the iron caused widespread damage to the white matter connections throughout Gage's brain, which likely was a major contributor to the behavioral changes he experienced.

• About 4% of the cerebral cortex was intersected by the rod. More than 10% of Gage’s total white matter was damaged.
• The significant loss of white matter connecting the left frontal regions and the rest of the brain may have impacted his personality and more than damage to the cortex alone.
• The regions of the brain most affected by the rod included the superior frontal sulcus, which is involved with self-awareness, and the insular cortex which controls emotion, among other things.

"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," Van Horns says in a news release. "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."

Gage eventually found a job as a stagecoach driver for several years in South America. He died in San Francisco, 12 years after the accident. The 189-year-old skull is housed at Harvard Medical School.

The work was reported in PLoS this week.

[Via UCLA news, New Scientist, Guardian]

Images: recreation by John Darrell Van Horn and the UCLA Laboratory of Neuro Imaging, 2012 / Phineas Gage with the rod from Wikimedia

This post was originally published on Smartplanet.com