Objective: To map the brain networks underlying Huntington’s Disease (HD), testing whether there are distinct networks involved in premanifest and manifest disease stages.

Background: HD is a genetic, neurodegenerative disorder that involves a myriad of cognitive, psychiatric, and motor impairments. Diagnosis of ‘manifest’ HD is determined by the presence of characteristic motor symptoms, however, gene mutation carriers prior to diagnosis (‘premanifest’ HD) also experience various nonmotor symptoms.  Whilst the etiology of HD is well established, the brain networks involved in these disease stages have not been fully elucidated.

Method: A systematic search was conducted to identify all structural and molecular neuroimaging studies reporting coordinates of significant brain abnormality in HD patients (premanifest or manifest) compared to healthy controls. These coordinates were then extracted and used in coordinate network mapping (CNM) analyses, to identify networks of brain regions that are functionally connected to all the studies’ findings. Three separate CNM analyses were conducted to delineate the networks connected to abnormalities reported in premanifest HD, manifest HD, and all HD (regardless of disease stage).

Results: 23 studies were included, examining premanifest HD (n = 9) and manifest HD (n = 14).  Brain abnormalities reported in all 23/23 studies were functionally connected to focal areas of the left caudate and putamen. CNM analyses also showed premanifest and manifest networks (areas connected to 100% of studies’ findings) localised to distinct portions of the basal ganglia and thalamus with very little overlap, suggesting different areas within these regions may be involved across disease progression. Additionally, the premanifest network encompassed the medial and middle frontal gyri, and cingulate gyrus, whilst the manifest network included the inferior frontal gyri and insula.

Conclusion: We identified brain networks involved in premanifest and manifest HD. Findings demonstrate key involvement of the striatum in HD, however, suggests different portions of these structures may be implicated throughout disease progression. Future work is needed to assess how these networks relate to the specific symptoms experienced by individuals in premanifest and manifest disease stages.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/localisation-of-distinct-brain-networks-in-premanifest-and-manifest-huntingtons-disease/