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. 2015 Dec;25(12):4812-27.
doi: 10.1093/cercor/bhv173. Epub 2015 Aug 12.

From Phineas Gage and Monsieur Leborgne to H.M.: Revisiting Disconnection Syndromes

M Thiebaut de Schotten  1 , F Dell'Acqua  2 , P Ratiu  3 , A Leslie  2 , H Howells  2 , E Cabanis  4 , M T Iba-Zizen  4 , O Plaisant  5 , A Simmons  6 , N F Dronkers  7 , S Corkin  8 , M Catani  2
Affiliations

From Phineas Gage and Monsieur Leborgne to H.M.: Revisiting Disconnection Syndromes

M Thiebaut de Schotten et al. Cereb Cortex. 2015 Dec.

Abstract

On the 50th anniversary of Norman Geschwind's seminal paper entitled 'Disconnexion syndrome in animal and man', we pay tribute to his ideas by applying contemporary tractography methods to understand white matter disconnection in 3 classic cases that made history in behavioral neurology. We first documented the locus and extent of the brain lesion from the computerized tomography of Phineas Gage's skull and the magnetic resonance images of Louis Victor Leborgne's brain, Broca's first patient, and Henry Gustave Molaison. We then applied the reconstructed lesions to an atlas of white matter connections obtained from diffusion tractography of 129 healthy adults. Our results showed that in all 3 patients, disruption extended to connections projecting to areas distant from the lesion. We confirmed that the damaged tracts link areas that in contemporary neuroscience are considered functionally engaged for tasks related to emotion and decision-making (Gage), language production (Leborgne), and declarative memory (Molaison). Our findings suggest that even historic cases should be reappraised within a disconnection framework whose principles were plainly established by the associationist schools in the last 2 centuries.

Keywords: behavioral neurology; brain lesion; diaschisis; disconnection syndromes; white matter.

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Figures

Figure 1.
Figure 1.
CAT scan of Gage's skull registered to MNI152 space. The trajectory of the bar through the skull is indicated in red.
Figure 2.
Figure 2.
T1-weighted MRI images of Leborgne's brain, registered to MNI152 space. The damage produced by the stroke is indicated in red.
Figure 3.
Figure 3.
T1-weighted MRI images of Molaison's brain, registered to MNI152 space. The bilateral temporal damage produced by the surgery is shown in red.
Figure 4.
Figure 4.
Summary of all the tracts included in our analysis.
Figure 5.
Figure 5.
Major tracts that were damaged in Gage (damage affected at least 30% of the tracts' volume, z-score = 1.7), in Leborgne (damage affected at least 55% of the tracts' volume, z-score = 1.29), and in Molaison (damage affected at least 5% of the tracts' volume, z-score = 1.39).
Figure 6.
Figure 6.
3D reconstruction of Gage's skull co-registered in the MNI space with a brain averaged from 152 subjects. (a) The trajectory of the bar through the brain is in red and shows damage to cortical areas and subcortical white matter. A blue-to-orange gradient indicates the probability of disconnection of areas not directly affected by the bar. (b) Meta-analysis of functional MRI studies reporting activations related to decision-making tasks (66 studies) and emotions (215 studies).
Figure 7.
Figure 7.
3D reconstruction of Leborgne's brain in MNI space. (a) The lesion (red) damaged both cortical structures (posterior inferior frontal cortex) and subcortical white matter (perisylvian pathways). (b) 3D reconstruction of the MNI152 template, with a blue-to-orange gradient indicating the probability of disconnection of those areas not directly affected by the lesion; red color indicate damage caused by the lesion. (c) Meta-analysis of functional MRI studies reporting activations related to the performance of fluency tasks (75 studies).
Figure 8.
Figure 8.
3D reconstruction of Molaison's brain registered in MNI space. (a) The damage produced by the surgery (red) affected cortical regions and subcortical white matter. A blue-to-orange gradient indicates the probability of disconnection of areas not directly affected by the excision. (b) Meta-analysis of functional MRI studies reporting activations related to encoding and retrieval of declarative memories (Spaniol et al. 2009).
See this image and copyright information in PMC

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