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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    • "Another issue regards the focus of medial temporal lobe damage in patients. For example, the patient HM (who was studied in Bohbot and Corkin, 2007) had damage primarily to his anterior hippocampus (Annese et al., 2014). Thus, if spatial learning depends more on the posterior hippocampus, as suggested in some rat studies (Moser et al., 1993, 1995), one might not expect to see deficits in patients with primarily anterior hippocampal damage. "
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    ABSTRACT: Damage to the medial temporal lobes produces profound amnesia, greatly impairing the ability of patients to learn about new associations and events. While studies in rodents suggest a strong link between damage to the hippocampus and the ability to navigate using distal landmarks in a spatial environment, the connection between navigation and memory in humans remains less clear. Past studies on human navigation have provided mixed findings about whether patients with damage to the medial temporal lobes can successfully acquire and navigate new spatial environments, possibly due, in part, to issues related to patient demographics and characterization of medial temporal lobe damage. Here, we report findings from a young, high functioning patient who suffered severe medial temporal lobe damage. Although the patient is densely amnestic, her ability to acquire and utilize new, but coarse, spatial "maps" appears largely intact. Specifically, a novel computational analysis focused on the precision of her spatial search revealed a significant deficit in spatial precision rather than spatial search strategy. These findings argue that an intact hippocampus in humans is not necessary for representing multiple external landmarks during spatial navigation of new environments. We suggest instead that the human hippocampus may store and represent complex high-resolution bindings of features in the environment as part of a larger role in perception, memory, and navigation.
    Full-text · Article · Nov 2015 · Neuropsychologia
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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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    ABSTRACT: Much of what was assumed about the functional topography of the hippocampus was derived from a single case study over half a century ago. Given advances in the imaging sciences, a new era of discovery is underway, with potential to transform the understanding of healthy processing as well as the ability to treat disorders. Coactivation-based parcellation, a meta-analytic approach, and ultra-high field, high-resolution functional and structural neuroimaging to characterize the neurofunctional topography of the hippocampus was employed. Data revealed strong support for an evolutionarily preserved topography along the long-axis. Specifically, the left hippocampus was segmented into three distinct clusters: an emotional processing cluster supported by structural and functional connectivity to the amygdala and parahippocampal gyrus, a cognitive operations cluster, with functional connectivity to the anterior cingulate and inferior frontal gyrus, and a posterior perceptual cluster with distinct structural connectivity patterns to the occipital lobe coupled with functional connectivity to the precuneus and angular gyrus. The right hippocampal segmentation was more ambiguous, with plausible 2- and 5-cluster solutions. Segmentations shared connectivity with brain regions known to support the correlated processes. This represented the first neurofunctional topographic model of the hippocampus using a robust, bias-free, multimodal approach. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.
    Full-text · Article · Sep 2015 · Human Brain Mapping
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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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    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. © The Author 2015. Published by Oxford University Press.
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