Hypometric primary saccades and increased variability in visually-guided saccades in Huntington's disease.

Eye movement abnormalities can be distinctive and suggestive of a specific pathophysiology. To further investigate the deficits in the control of saccades in patients with Huntington's disease (HD), we investigated the ability of 11 HD patients and 11 matched controls to perform visually-guided saccades. We adopted reflexive saccade tasks involving predictable and unpredictable sequences, at different amplitudes of target step (10 degrees, 20 degrees, 30 degrees, 40 degrees ), as well as voluntary self-paced saccades. Prolongation of initiation was observed in the HD group as the target amplitude of predictable saccades increased. During the self-paced saccade task, the HD patients had increased intersaccadic intervals, performed fewer saccades in the allocated time and displayed an increased temporal variability in comparison to the controls. Furthermore, hypometric primary saccades, and an increased number of corrective saccades, were observed during both reflexive and voluntary saccades in the HD group. The delayed initiation of large saccades, deficits in voluntary, self-paced saccades, impaired saccadic accuracy and increased corrective saccades in HD, were interpreted in light of other ocular motor and limb studies, and appear to be due to damage to the fronto-striatal loop, including the supplementary eye fields, as well as possible brainstem and cerebellar involvement.

Genetic variations in dopamine and inhibitory control: lack of influence on action restraint.

Failures of inhibitory control can severely affect everyday life in healthy individuals and represent a common feature of many neuropsychiatric conditions, particularly disorders with dopaminergic disturbances implicated. This study's aim was to examine the interacting influences of three common and functional gene variants that influence dopaminergic pathways on an aspect of inhibitory control (action restraint). Three hundred and twenty two healthy adults were selected from an international consortium linked to Brain Research and Integrative Neuroscience (BRAINnet). DNA was extracted from cheek swab samples and participants were genotyped for the Val158Met single nucleotide polymorphism on COMT (rs 4680), C957T on DRD2 (rs 6277) and the 40bp variable number of tandem repeat on the DAT1 (SLC6A3, 10/10 vs 9+). Response inhibition was measured using a computerised Go/No-Go task. Main effects and interactions between genotypes were explored. We did not observe a genotype effect on fundamental measures of response inhibition, i.e. reaction time (RT) and commission errors. RT variability was significantly increased in DRD2 C957T heterozygotes. In conclusion, this large, non-clinical study reveals that the selected genetic polymorphisms regulating dopamine (COMT, DRD2 and DAT1) do not influence one aspect of response inhibition, action restraint, as measured by the Go/No-Go task, reinforcing the neuropharmacological dissociation between stop-signal and Go/No-Go tasks. Genetic variation in striatal dopamine may, however, contribute to intraindividual RT variability.