Histopathological Examination of the Brain of the Amnesic Patient H.M.

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H.M. underwent an experimental operation in 1953 for the relief of medically intractable epilepsy; since that time, he has been profoundly amnesic.

Reports from the surgery indicate that the resection included the amygdala, most of the hippocampus, and surrounding parahippocampal cortex in both hemispheres. The results of experiments in which he participated revolutionized the study of learning and memory. He is indeed the yardstick against which the severity of amnesia is measured in other patients. H.M. has taught us that the critical neural substrate for long-term, declarative memory is located in the medial part of the temporal lobes. He also taught us that there are different kinds of memory with different neural substrates, such as declarative memory (including episodic and semantic memory, impaired in H.M.), skill learning (preserved in H.M.), and priming (also preserved in H.M.). Essentially, H.M.'s case first suggested that the establishment of memory has a distinct neural substrate.

The overall aim of the research project is to conduct a complete and systematic histopathological study of the brain of patient H.M. in order to reveal the precise nature of his lesion. Novel computer-assisted neuroanatomical techniques that are the expertise of our laboratory make it possible to create a digital map of the brain of patient H.M. at microscopic resolution. We will determine the locus and precise extent of the surgical resection that led to his memory impairment. We will also examine the morphological and cytological parameters of the tissue immediately surrounding the resection and in functionally connected regions in the brain. Images and quantitative anatomical information on the brain of H.M. will be made publicly available via the web to the neuroscience community.

Funded by National Science Foundation and The Dana Foundation.