Postmortem examination of patient H.M.’s brain based on histological sectioning and digital 3D reconstruction

Nature Communications (Impact Factor: 11.47). 01/2014; 5:3122. DOI: 10.1038/ncomms4122
Source: PubMed


Modern scientific knowledge of how memory functions are organized in the human brain originated from the case of Henry G. Molaison (H.M.), an epileptic patient whose amnesia ensued unexpectedly following a bilateral surgical ablation of medial temporal lobe structures, including the hippocampus. The neuroanatomical extent of the 1953 operation could not be assessed definitively during H.M.'s life. Here we describe the results of a procedure designed to reconstruct a microscopic anatomical model of the whole brain and conduct detailed 3D measurements in the medial temporal lobe region. This approach, combined with cellular-level imaging of stained histological slices, demonstrates a significant amount of residual hippocampal tissue with distinctive cytoarchitecture. Our study also reveals diffuse pathology in the deep white matter and a small, circumscribed lesion in the left orbitofrontal cortex. The findings constitute new evidence that may help elucidate the consequences of H.M.'s operation in the context of the brain's overall pathology.

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Available from: Natalie Schenker, Mar 12, 2014
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    • "Further complicating this field of research is the notion that much of what we assume about human memory and hippocampal functioning has been derived from a case study over half a century ago, when patient H.M. underwent a bilateral hippocampal resection (Scoville and Milner, 1957). It was not until the early 1990's that H.M. received a magnetic resonance imaging scan that revealed potential discrepancies in the neurosurgical account of his lesions, which were confirmed following his death when more sophisticated imaging procedures could be carried out (Annese et al., 2014; Augustinack et al., 2014). Additionally, most, if not all, studies of hippocampal subspecialization limit their investigations to a single behavioral domain (e.g., cognition) or a single paradigm that compares specific neurocognitive processes (i.e., encoding versus retrieval) (Duarte et al., 2014; Duncan et al., 2014; Prince et al., 2005). "
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    • "In particular, it is highly probable that damage included the perforant fibers between the hippocampus and the entorhinal cortex, which are important in memory processes (Witter et al. 2000), or the fibers of the stria terminalis linking amygdala to the hypothalamus and involved in the regulation of adrenergic response to acute stress. In addition, the mammillary nuclei, which receive projections from the hippocampi through the fornix, were recently reported as shrunken in a postmortem study of Molaison's brain (Annese et al. 2014). "
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