title: Visuomotor integration deficits precede clinical onset in Huntington's disease.
abstract: OBJECTIVE
  Visuomotor integration deficits have been documented in Huntington disease (HD), with disproportionately more impairment when direct visual feedback is unavailable. Visuomotor integration under direct and indirect visual feedback conditions has not been investigated in the stage before clinical onset ('premanifest'). However, given evidence of posterior cortical atrophy in premanifest HD, we predicted visuomotor integration would be adversely affected, with greater impairment under conditions of indirect visual feedback.
  
  
  METHODS
  239 subjects with the HD CAG expansion, ranging from more than a decade before predicted clinical onset until early stage disease, and 122 controls, completed a circle-tracing task, which included both direct and indirect visual feedback conditions. Measures included accuracy, speed, and speed of error detection and correction. Using brain images acquired with 3T magnetic resonance imaging (MRI), we generated grey and white matter volumes with voxel-based morphometry, and analyzed correlations with circle-tracing performance.
  
  
  RESULTS
  Compared with controls, early HD was associated with lower accuracy and slower performance in both circle-tracing conditions. Premanifest HD was associated with lower accuracy in both conditions and fewer rotations in the direct condition. Comparing performance in the indirect condition with the direct condition, HD gene expansion-carriers exhibited a disproportionate increase in errors relative to controls. Premanifest and early HD groups required longer to detect and correct errors, especially in the indirect condition. Slower performance in the indirect condition was associated with lower grey matter volumes in the left somatosensory cortex in VBM analyses.
  
  
  CONCLUSIONS
  Visuomotor integration deficits are evident many years before the clinical onset of HD, with deficits in speed, accuracy, and speed of error detection and correction. The visuomotor transformation demands of the indirect condition result in a disproportionate decrease in accuracy in the HD groups. Slower performance under indirect visual feedback was associated with atrophy of the left-hemisphere somatosensory cortex, which may reflect the proprioceptive demands of the task.
authors.affiliation: UCL Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK.
authors.forename: Miranda J
authors.initials: MJ
authors.lastname: Say
authors.forename: Rebecca
authors.initials: R
authors.lastname: Jones
authors.forename: Rachael I
authors.initials: RI
authors.lastname: Scahill
authors.forename: Eve M
authors.initials: EM
authors.lastname: Dumas
authors.forename: Allison
authors.initials: A
authors.lastname: Coleman
authors.forename: Rachelle C Dar
authors.initials: RC
authors.lastname: Santos
authors.forename: Damian
authors.initials: D
authors.lastname: Justo
authors.forename: J Colin
authors.initials: JC
authors.lastname: Campbell
authors.forename: Sarah
authors.initials: S
authors.lastname: Queller
authors.forename: E Arthur
authors.initials: EA
authors.lastname: Shores
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Tabrizi
authors.forename: Julie C
authors.initials: JC
authors.lastname: Stout
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000150:complications* / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019957:Motor Skills Disorders / Q000150:complications / Q000209:etiology* / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009483:Neuropsychological Tests; D010468:Perceptual Disorders / Q000150:complications / Q000209:etiology* / Q000473:pathology; D011237:Predictive Value of Tests; D013223:Statistics as Topic