Wednesday, 23 May 2012

Neuroscience still haunted by Phineas Gage

From Van Horn et al 2012
Seven years after his death, Phineas Gage's body was dug out of the ground and his skull passed to a doctor, John Harlow, who'd treated him in life. Although Gage's brain had long-since decayed, his skull remained intact and was of particular medical interest because in 1848, in an explosives accident, Gage had survived a three and a half foot long iron rod shooting straight into his face, through his brain, and out the top of his head. Although he died in 1860, Gage has lived on as one of psychology's foundation myths - a classic example of frontal brain damage affecting personality.

Traditional accounts have it that Gage was permanently changed by his injury, becoming a drunken, aggressive waster. But in recent years a reappraisal of Gage's activities during the remainder of his life suggests he underwent an impressive social recovery. For example, he worked as a stagecoach driver along a 100-mile route in Chile, a job that would have required significant psychosocial competence.

If we could ever find out exactly the brain damage that Gage suffered it would help inform the debates surrounding how much he did or didn't recover and provide intriguing insights about neurorehabilitation. That's what Harlow hoped to do back in the nineteenth century. From inspecting Gage's skull he concluded that the left frontal and middle lobes must have been destroyed and that the partial recovery made by Gage was likely due to compensation by the right hemisphere.

Housed in a museum together with the rod that made him famous, Gage's skull was then left untouched for nearly a hundred years. However, beginning in the 1980s, each new generation of scientists has used the technology of the day to make another attempt to recreate Gage's injury.

In 1982, using CT scans of the skull, Rick and Ken Tyler concluded that although the left side of the brain suffered the most damage, the right hemisphere was probably damaged too. In the nineties, Hanna Damasio and her colleagues performed a 3D reconstruction of Gage's injury and they too concluded the damage was bilateral (pdf). Another ten years went by and then another simulation. In the most sophisticated analysis to date, Peter Ratiu and his colleagues overlaid a 3D representation of a brain within a 3D reconstruction of Gage's skull and simulated the path of the iron rod (pdf). They concluded that the damage was only to the left, just as Harlow had said, which would make the new claims about Gage's recovery more explicable.

Now Gage's skull has been analysed yet again. A team of experts, led by John Van Horn, based at the University of California and Harvard Medical School, has used diffusion imaging data, together with anatomical MRI, to try to find out how Gage's injury affected the connective tissues of his brain. As they explain: "while many authors have focused on the gross damage done by the iron to Gage's frontal cortical grey matter, little consideration has been given to the degree of damage to and destruction of major connections between discretely affected regions and the rest of his brain."

Van Horn's team scanned the brains of 110 right-handed men (Gage was right-handed) of a similar age to Gage at the time of his injury (the range was 25 to 36; Gage was aged 25 when the rod entered his head). The scans used diffusion tensor imaging to map the connective white-matter tracts of the men's brains in intricate detail. Next, these scans were averaged and integrated with the 3D reconstruction of Gage's skull that was created by Ratiu's team back in 2004. The trajectory of the rod was simulated and an estimate was made of the damage the rod would have done to the connective tissues of Gage's brain, based on it resembling the average of the 110 healthy men's brains.

Is it reasonable to suppose that the connective networks of Gage's brain were akin to the averaged networks of 110 healthy men scanned in the twenty-first century? "Such a supposition may have its limitations and could be open to debate," the researchers conceded. "Nevertheless, ours represents the best current estimation as to the extent of brain damage likely to have occurred at the level of both cortex and white matter fiber pathways."

So what damage do they think Gage incurred? Van Horn's team think that 4 per cent of Gage's cortical grey matter was damaged in the left hemisphere and 11 per cent of his cortical white matter. Among the important connective bundles that were damaged, they said, are the uncinate fasciculus (which connects the frontal lobes with the limbic system), the cingulum bundle (connecting parts of the limbic system with each other), and the superior longitudinal fasciculus (long-distance fibres linking the front and back of the brain). Abnormalities in the uncinate fasciculus, they explained, have previously been associated with mental illness and related to cognitive deficits in traumatic brain injury. This spread of damage to Gage's white matter tracts would have affected not only the left frontal lobe, the researchers explained, but indirectly would have affected the functioning of the right hemisphere too.

The pattern of damage Gage suffered would be expected to have a profound effect, the researchers said, having "a considerable impact on executive as well as emotional functions," and "likely combined to give rise to the behavioural and cognitive symptomatology originally reported by Harlow." However, they stressed that it could have been a lot worse. A simulation of 500 random similarly-sized lesions showed the damage caused by the iron rod was below the average you'd expect by chance. Gage was lucky not to have been left blinded or dead.

The researchers concluded that "consideration of white matter damage and connectivity loss is ... an essential consideration when interpreting and discussing this famous case study and its role in the history of neuroscience." But how useful is this new analysis really? In particular, does it shed any light on the re-appraisal of the Gage myth that's emerged over the last decade or so, in which Gage is considered to have made an impressive psychosocial recovery?

This photo of Gage was discovered in 2009
The man responsible for much of this reassessment is the historian Malcolm Macmillan, the author of An Odd Kind of Fame: Stories of Phineas Gage, and several subsequent articles. He told the Digest that the results were "very interesting" and that it was "particularly gratifying" that the new analysis had confirmed the earlier conclusions of Ratiu's team that Gage's damage was left frontal. However, Macmillan has some reservations - for example he pointed out the limitations in the method of averaging from multiple brains to estimate the structure of Gage's brain.

Moreover, whilst the inferred damaged to Gage's connective pathways might explain the changes to his behaviour in the first two to three years post-accident, Macmillan and his colleague Matthew Lena, "are most interested in what happened in the last five or six years of Phineas' life. If Lena and I are right about the post-accident Phineas gradually changing from the commonly portrayed impulsive and uninhibited person into one who made a reasonable 'social recovery,'" Macmillan said, "we need to know if and how changes in the tracts contributed. As I see it, and unfortunately, it seems unlikely that we will ever be able to reconstruct those long-term changes."

But there's always room for hope. Macmillan added: "From people who use tractography to map the changes in the connections following traumatic brain injury, I understand there is evidence that damaged tracts may re-establish their original connections or build alternative pathways as the brain recovers from oedema. In the short-term, some of the original functions may thus recover. It would be truly wonderful if were we able to confirm that possibility in Phineas' case."
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ResearchBlogging.orgVan Horn, J., Irimia, A., Torgerson, C., Chambers, M., Kikinis, R., and Toga, A. (2012). Mapping Connectivity Damage in the Case of Phineas Gage. PLoS ONE, 7 (5) DOI: 10.1371/journal.pone.0037454

Post written by Christian Jarrett for the BPS Research Digest.

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