Monday, April 21, 2014

The Life and Brain of H.M.



Dr. Suzanne Corkin on H.M.

One of the highlights of this year's Cognitive Neuroscience Society Meeting was Dr. Corkin's keynote address about Henry Molaison the person and his lasting contribution to the neurobiology of memory. In her more timely recap of the meeting, Daisy Yuhas included this moving quote from H.M., who could not remember meeting Corkin even after decades of testing:
Corkin also discussed the man behind the initials, describing his gentle and remarkably upbeat disposition, given that he was repeatedly confronting a confusing, context-free present. Her talk included a poignant and powerful audio recording of Corkin and H.M. chatting in 1992. In the excerpt, H.M. professes to “not mind” all of the tests and studies, saying simply, “I figure what’s wrong about me helps you help others.”

Henry Molaison died on December 6, 2008. Corkin described the post-mortem handling of H.M.'s brain, which was first scanned before autopsy. Then the brain was removed and preserved in formaldehyde for 10 weeks, and later scanned in a 7T magnet (see Annese et al., 2014 for details).1


H.M.'s brain flew Jet Blue


H.M.'s brain was transported across the country, where it underwent lengthy processing prior to sectioning into 2,401 slices on a heavy duty frozen microtome (Annese et al., 2014).2 This event was webcast live at the Brain Observatory, which she said was “like watching paint dry.”  I beg to differ.  I thought the live coverage was like the Stanley Cup of Neuroscience, as mesmerizing as watching the Zamboni clean the ice at a hockey game.



At the time, I noted that “H.M.'s ventricles are quite enlarged. Then again, he was 82 when he died (so that's not unexpected).”

H.M. was, in fact, demented when he died. His cerebellum was severely atrophied after years on the anticonvulsant drug Dilantin. Cerebellar dysfunction on its own can be associated with explicit memory deficits (Baillieux et al., 2008). And finally, his amygdalae were gone bilaterally (Annese et al., 2014): 
The excision of the anterior hippocampus, together with the bulk of the amygdala, may explain H.M.’s dampened expression of emotions, poor motivation and lack of initiative19. The fact that he was impaired in reporting internal states such as pain, hunger and thirst and his apparent lack of initiative was ascribed to the almost complete removal of the amygdala...

Dr. Corkin has long said that “H.M.'s amnesia was pure.” But these additional issues, along with some reports that his language production and visual cognition were not entirely normal, raise questions about his status as the definitive hippocampal amnesic. Nonetheless, there's no denying the immense importance of what H.M. so generously taught us about memory. “It’s a funny thing,” he said, “you live and learn. I’m living and you’re learning.”


Footnotes

1 H.M's brain was...
...fixed in standard buffered formalin (4% formaldehyde; postmortem interval of ∼14 h). The brain was fixed for 10 weeks at 4 °C with three changes of fixative during that time; it was suspended upside down, hung by the basilar artery. When the tissue was firm enough, the brain was immersed in fixative laying on a cushion of hydrophilic cotton. Subsequently, multiple series of MRI scans of the fixed specimen were acquired in 3T and 7T scanners.

2 Annese et al., 2014:
The results of our examination are based on 2,401 digital anatomical images and selected corresponding histological sections that were collected at an interval of 70 μm over the course of an uninterrupted 53-hour procedure. The series of digital images of the block’s surface was obtained using a digital camera mounted directly above the microtome stage. Volumetric reconstruction from these images was the basis for subsequent visualization and 3D measurements along arbitrary planes. The dissection of the brain was video-recorded and streamed live on the web to permit scientific scrutiny and to foster public engagement in the study.


References  [added 4/27/14]

Annese, J., Schenker-Ahmed, N., Bartsch, H., Maechler, P., Sheh, C., Thomas, N., Kayano, J., Ghatan, A., Bresler, N., Frosch, M., Klaming, R., & Corkin, S. (2014). Postmortem examination of patient H.M.’s brain based on histological sectioning and digital 3D reconstruction Nature Communications, 5.  DOI: 10.1038/ncomms4122

Baillieux H, De Smet HJ, Paquier PF, De Deyn PP, Mariën P. (2008). Cerebellar neurocognition: insights into the bottom of the brain. Clin Neurol Neurosurg. 110(8):763-73.

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