Saccadic trajectory in Huntington's disease.

Trajectories of saccadic eye movements can be modulated by the presence of a competing visual distractor. It is proposed that the superior colliculus (SC) controls the initial deviation through competitive lateral interactions. Given the ramifications of connections between basal ganglia (BG) thalamo-cortical circuitry and the SC, it was anticipated that this modulation would be differentially effected in those with Huntington's disease, which in its early stages is primarily a disorder of the BG. Horizontal deviation was determined for exogenously driven and endogenously driven vertical saccades in the presence of peripheral distractors. For neurologically healthy participants, the initial trajectories of both saccade types curved away from distractor locations, as predicted. However, for HD participants exogenous saccades consistently deviated leftwards, irrespective of distractor location. Endogenous saccades also revealed anomalous horizontal deviation, with significant leftward deviation evident for saccades directed upward and significant rightward deviation for saccades directed downward. Further, both groups generated a comparable proportion of erroneous responses to distractor stimuli, but only neurologically healthy participants demonstrated a response time advantage for compatible target/distractor presentation. These results suggest anomalous regulation of distractor-related activity in HD.     

Abnormal synchrony of resting state networks in premanifest and symptomatic Huntington disease: the IMAGE-HD study

Background

Functional neural impairments have been documented in people with symptomatic Huntington disease (symp-HD) and in premanifest gene carriers (pre-HD). This study aimed to characterize synchrony in resting state cerebral networks in both pre-HD and symp-HD populations and to determine its association with disease burden and neurocognitive functions.

Methods

We acquired functional magnetic resonance imaging (fMRI) data from pre-HD, symp-HD and healthy control participants. The fMRI data were analyzed using multisubject independent component analysis and dual regression. We compared networks of interest among the groups using a nonparametric permutation method and correcting for multiple comparisons.

Results

Our study included 25 people in the pre-HD, 23 in the symp-HD and 18 in the healthy control groups. Compared with the control group, the pre-HD group showed decreased synchrony in the sensorimotor and dorsal attention networks; decreased level of synchrony in the sensorimotor network was associated with poorer motor performance. Compared with the control group, the symp-HD group showed widespread reduction in synchrony in the dorsal attention network, which was associated with poorer cognitive performance. The posterior putamen and superior parietal cortex were functionally disconnected from the frontal executive network in the symp-HD compared with control and pre-HD groups. Furthermore, the left frontoparietal network showed areas of increased synchrony in the symp-HD compared with the pre-HD group.

Limitations

We could not directly correct for influence of autonomic changes (e.g., heart rate) and respiration on resting state synchronization.

Conclusion

Our findings suggest that aberrant synchrony in the sensorimotor and dorsal attention networks may serve as an early signature of neural change in pre-HD individuals. The altered synchrony in dorsal attention, frontoparietal and corticostriatal networks may contribute to the development of clinical symptoms in people with Huntington disease.