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Background/aims Visuomotor integration deficits have been documented in manifest Huntington's disease, with disproportionate impairments when indirect visual cues are relied upon. Visuomotor integration in premanifest gene expansion carriers has not been studied under such conditions. Methods 239 gene expansion carriers spanning over a decade before predicted onset until early stage disease and 122 control subjects were administered a circle tracing task. Performance was guided by direct or indirect visual cues. Outcome measures targeted accuracy, speed and speed of error detection and correction. Predictor variables included disease group and disease burden (age×(CAG−35.5)). Correlations with 3T MRI voxel based morphometry of grey and white matter volume reduction were computed. Results Increased HD disease burden was associated with reduced accuracy and slowed performance in both direct and indirect circle tracing conditions. Expansion carriers who were more than a decade before predicted clinical onset showed deficits in performance compared with controls. Comparing performance in the indirect with the direct condition, expansion carriers had a disproportionate increase in errors than controls. Expansion carriers showed greater latencies in detecting an error when heading away from target, and in correcting an error when heading back to target. Slowed performance in the indirect circle tracing condition was associated with grey matter volume reduction within the left somatosensory cortex in voxel based morphometry analyses. Conclusions Visuomotor integration deficits appear in expansion carriers many years before onset with the use of indirect visual cues especially appearing to impact adversely on accuracy. Slowed performance under indirect visual cues appears to be associated with atrophy of the left hemisphere somatosensory cortex, which likely reflects the proprioceptive demands of the task. [ABSTRACT FROM PUBLISHER]

Putaminal metabolites examined using cross-sectional magnetic resonance spectroscopy (MRS) can distinguish pre-manifest and early Huntington's Disease (HD) individuals from controls. An ideal biomarker, however, will demonstrate longitudinal change over short durations. The objective here was to evaluate longitudinal in vivo brain metabolite profiles in HD over 24 months. Eighty-four participants (30 controls, 25 pre-manifest HD, 29 early HD) recruited as part of TRACK-HD were imaged at baseline, 12 months, and 24 months using 3T MRS of left putamen. Automated putaminal volume measurement was performed simultaneously. To quantify partial volume effects, spectroscopy was performed in a second, white matter voxel adjacent to putamen in six subjects. Subjects underwent TRACK-HD motor assessment. Statistical analyses included linear regression and one-way analysis of variance (ANOVA). At all time-points N-acetyl aspartate and total N-acetyl aspartate (NAA), neuronal integrity markers, were lower in early HD than in controls. Total NAA was lower in pre-manifest HD than in controls, whereas the gliosis marker myo-inositol (MI) was robustly elevated in early HD. Metabolites were stable over 24 months with no longitudinal change. Total NAA was not markedly different in adjacent white matter than putamen, arguing against partial volume confounding effects in cross-sectional group differences. Total NAA correlations with disease burden score suggest that this metabolite may be useful in identifying neurochemical responses to therapeutic agents. We demonstrate almost consistent group differences in putaminal metabolites in HD-affected individuals compared with controls over 24 months. Future work establishing spectroscopy as an HD biomarker should include multi-site assessments in large, pathologically diverse cohorts., (© 2015 International Parkinson and Movement Disorder Society.)

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., (Copyright © 2011 Movement Disorder Society.)