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

Area of Science:

• Neuroscience
• Neuroanatomy
• Cognitive Psychology

Background:

• Patient Henry G. Molaison (H.M.) is central to understanding human memory, following surgery for epilepsy that caused severe amnesia.
• The precise extent of his medial temporal lobe resection, including the hippocampus, remained unknown during his lifetime.
• This lack of detailed anatomical knowledge limited understanding of the relationship between surgical damage and memory deficits.

Purpose of the Study:

• To reconstruct a high-resolution, 3D anatomical model of H.M.'s entire brain.
• To precisely measure the medial temporal lobe structures affected by the surgery.
• To identify residual brain tissue and any additional pathologies contributing to H.M.'s condition.

Main Methods:

• Developed a procedure for microscopic anatomical reconstruction of the whole brain.
• Utilized cellular-level imaging of stained histological slices for detailed analysis.
• Conducted precise 3D measurements of the medial temporal lobe region.

Main Results:

• Demonstrated significant residual hippocampal tissue with distinct cytoarchitecture, contrary to previous assumptions.
• Identified diffuse pathology in the deep white matter throughout the brain.
• Discovered a small, circumscribed lesion in the left orbitofrontal cortex.

Conclusions:

• The study provides unprecedented anatomical detail of H.M.'s brain, revealing more residual hippocampus than previously thought.
• New findings suggest that diffuse white matter pathology and orbitofrontal lesions may have contributed to H.M.'s cognitive deficits.
• These results offer crucial new evidence for understanding the complex relationship between brain pathology, memory function, and the consequences of surgical intervention.