The structural involvement of the cingulate cortex in premanifest and early Huntington's disease

Abstract

The impact of Huntington's disease neuropathology on the structure of the cingulate is uncertain, with evidence of both cortical enlargement and atrophy in this structure in early clinical disease. We sought to determine differences in cingulate volume between premanifest Huntington's disease and early Huntington's disease groups compared with controls using detailed manual measurements. Thirty controls, 30 subjects with premanifest Huntington's disease, and 30 subjects with early Huntington's disease were selected from the Vancouver site of the TRACK-HD study. Subjects underwent 3 Tesla magnetic resonance imaging and motor, cognitive, and neuropsychiatric assessment. The cingulate was manually delineated and subdivided into rostral, caudal, and posterior segments. Group differences in volume and associations with performance on 4 tasks thought to utilize cingulate function were examined, with adjustment for appropriate covariates. Cingulate volumes were, on average, 1.7 mL smaller in early Huntington's disease (P=.001) and 0.9 mL smaller in premanifest Huntington's disease (P=.1) compared with controls. Smaller volumes in subsections of the cingulate were associated with impaired recognition of negative emotions (P=.04), heightened depression (P=.009), and worse visual working memory performance (P=.01). There was no evidence of associations between volume and ability on a performance-monitoring task. This study disputes previous findings of enlargement of the cingulate cortex in Huntington's disease and instead suggests that the cingulate undergoes structural degeneration during early Huntington's disease with directionally consistent, nonsignificant differences seen in premanifest Huntington's disease. Cingulate atrophy may contribute to deficits in mood, emotional processing, and visual working memory in Huntington's disease.