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Delineating the neural substrates of autobiographical memory impairment in Huntington's disease

Kristina Horne1,2, Anna Carmichael3, Emily-Clare Mercieca3

  • 1Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia.

The European Journal of Neuroscience
|October 17, 2024
PubMed

Insights

Autobiographical memory recall is impaired in Huntington's disease (HD) due to atrophy in a widespread brain network, affecting both premanifest and manifest stages of the disease.

Area of Science:

  • Neuroscience
  • Neurobiology
  • Cognitive Neurology

Background:

  • Huntington's disease (HD) is a neurodegenerative disorder known to affect cognitive functions, including memory.
  • Autobiographical memory (ABM) impairments are increasingly recognized in HD, often linked to frontostriatal dysfunction.
  • The specific neural substrates underlying ABM deficits in HD have not been fully elucidated.

Purpose of the Study:

  • To investigate the neural correlates of autobiographical memory (ABM) impairment in individuals with Huntington's disease (HD).
  • To examine ABM performance across different stages of HD (premanifest and manifest) and compare it to healthy controls.
  • To identify specific brain regions associated with ABM deficits using structural neuroimaging.

Main Methods:

  • Structural brain imaging (voxel-based morphometry) and the Autobiographical Interview were administered to 30 participants with HD and 24 healthy controls.
  • Grey matter atrophy was analyzed for associations with ABM recall performance (free and probed).
  • Statistical analyses included False Discovery Rate correction for multiple comparisons.

Main Results:

  • Participants with HD showed significantly reduced detail in ABM recall compared to controls, regardless of disease stage (premanifest/manifest).
  • No significant difference in ABM recall was observed between premanifest and manifest HD groups.
  • Poorer ABM performance correlated with grey matter atrophy in a distributed cortico-subcortical network, including occipital cortex, precuneus, parahippocampal gyrus, caudate nucleus, frontal regions, hippocampus, and cerebellum.

Conclusions:

  • Autobiographical memory deficits in HD result from progressive degeneration within a widespread network involving medial temporal, frontal, striatal, and posterior parietal areas.
  • These findings highlight the neuroanatomical basis of ABM impairment in HD, extending beyond traditional frontostriatal models.
  • Understanding these neural substrates is crucial for developing future interventions to support memory function in individuals with HD.

Keywords:
cerebellumdementiaepisodic memoryhippocampusneurodegenerationstriatumvoxel‐based morphometry

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