ABNORMAL FUNCTIONAL CONNECTIVITY IN HUNTINGTON'S DISEASE DURING A SEQUENTIAL MOTOR TASK

Introduction Huntington’s disease (HD) is a neurodegenerative disorder that induces striatal and cortical neuronal dysfunction and loss which main symptom is motor impairment. Goals to study whether this motor impairment is accompanied by changes in brain activity and functional connectivity. Methods Fifteen early stage HD patients with a UHDRS motor score > 5 (9 men, mean age = 48 ± 8.9, mean TFC = 11.7 ± 1.17) and 15 controls (9 men, mean age = 46.6 ± 8.1) matched in age, gender and educational background underwent 3T structural and functional MRI scanning while they performed a sequential tapping task with their right or left hand in alternated blocks. Results Compared to rest blocks, active tapping activated the contralateral primary motor, premotor and supplementary motor areas, thalamus and cerebellum in both patients and controls. However, in the right hand condition, patients deactivated the right putamen to a greater extent than controls, which suggests that patients need a greater inhibition of the ipsilateral putamen in order to suppress the movement of the opposite hand. Furthermore, HD patients showed less activation in the right putamen during the left hand condition compared to controls. These effects could be ascribed to the general imbalance in the Go and No-Go cortico-striatal pathways that is believed to occur in HD. The left precentral gyrus, was selected as a seed region for a whole brain functional connectivity analysis. Compared with controls, right precentral gyrus, right SMA and right putamen were more connected (negatively) to the left precentral gyrus in patients. This indicates that not only the right putamen, but all the right motor circuit undergoes a greater deactivation in HD patients when they move their left hand. In addition, the negative functional connectivity between the left precentral gyrus and the right putamen showed a positive correlation with the motor-UHDRS score and the TFC score. Conclusions These results indicate that HD patients need to inhibit the contralateral motor circuit of the moving hand to compensate for the hyperactivation of the dopaminergic system that underlies their motor symptoms. This effect is specific to the right hemisphere, showing an asymmetry of the motor circuit dysfunction.