Using brain imaging to re-evaluate psychology’s three most famous cases

It's 50 years since the American neurologist Norman Geschwind published his hugely influential Disconnexion Syndromes in Animals and Man, in which he argued that many brain disorders and injuries could best be understood in terms of the damage incurred to the white-matter pathways connecting different areas of the brain.

To mark this anniversary, an international team of researchers has used modern brain imaging techniques to reveal, in an open-access article for Cerebral Cortex, the likely damage to brain connectivity suffered by three of psychology's most famous cases: the 19th-century rail worker Phineas Gage, who survived an iron rod passing through his brain; Louis Victor Leborgne, the 19th-century aphasic patient studied by Paul Broca who played a key role in our understanding of language function in the brain; and the most studied amnesiac in history, Henry Molaison (known as H.M. in the literature), who died in 2008.

Michel Thiebaut de Schotten and his colleagues first obtained existing information about the brains of these three cases. For Gage, they used a CT scan taken of his skull by researchers in 2004 and mapped the signs of injury onto a simulation of his brain. Leborgne's brain is in preservation at the Dupuytren Museum in Paris and they used an MRI scan of it taken in 2007. For Molaison's brain, they used an MRI scan taken while he was still alive in 1993.

Next, the researchers created an intricately detailed map of the human brain's connective pathways. They used an advanced version of a technique known as diffusion tensor imaging to plot the connective tissues in the brains of 129 healthy volunteers (aged 18-79; 59 men). They combined the data from all these healthy people's brains to create an average road map of the human brain's connective tracts.

The final step involved applying the information on the brain damage incurred by the three famous cases onto this road map of the human brain's connective pathways, to see which important tracts had probably been affected.

In the case of Gage, the researchers estimate that he suffered widespread damage to several connective pathways in his frontal lobes, beyond the specific damage thought to have been inflicted by the passage of the iron bar. These pathways include the uncinate fasciculus, the frontal intralobar networks, and the fronto-striatal-thalamal-frontal network, with likely implications for his decision-making and emotional functioning.

Mapping Leborgne's brain lesions onto the connectivity roadmap, the researchers estimate that he suffered extensive damage to many tracts, including almost all the dorsolateral tracts of the left hemisphere which would have had profound implications for his language function (on top of the effects caused by localised damage to what is now known as Broca's area in the left frontal lobe). The researchers think Leborgne also likely suffered damage to pathways not involved in language, such as the left cortico-spinal tract (which could explain the documented paralysis of his right arm and leg).

Finally, turning to Molaison, the researchers again estimate widespread damage to connective tissues beyond the main brain regions, including the hippocampus, that were directly removed by surgery (Molaison became amnesic after radical neurosurgery to treat his epilepsy). This includes the fornix, the ventral cingulum, the uncinate fasciculus and the anterior commissure. Damage to that last tract, which is involved in processing smell, might explain lab reports that Molaison had problems with his odour discrimination.

What to make of these new insights? The researchers said they have "demonstrated the validity of applying an atlas-based approach to reappraise the effects of disconnection in 3 historic patients". Their research is certainly a fitting tribute to the legacy of Geschwind, showing how "social behaviour, language, and memory depend on the coordinated activity of different regions rather than single areas in the frontal or temporal lobes." However, the researchers also admitted that much caution is needed: their research involved many ambitious leaps and generalisations. What is for sure is that these new insights will further fuel the mythical status of these three patients. Gage, Leborgne and Molaison are the psychological case studies that just keep giving.

Further reading

Thiebaut de Schotten M, Dell'Acqua F, Ratiu P, Leslie A, Howells H, Cabanis E, Iba-Zizen MT, Plaisant O, Simmons A, Dronkers NF, Corkin S, & Catani M (2015). From Phineas Gage and Monsieur Leborgne to H.M.: Revisiting Disconnection Syndromes. Cerebral cortex (New York, N.Y. : 1991) PMID: 26271113