Patterns of neural activity and clinical outcomes in a juvenile Huntington's Disease patient undergoing Deep Brain Stimulation of the subthalamic nucleus

Background: Huntington's disease (HD) is a hereditary neurodegenerative disease leading to cognitive and motor impairment. HD depends on basal ganglia dysfunctions, but the role of subthalamic nucleus (STN) neurons is not completely known. Drug-resistant motor symptoms of HD can be alleviated by neuromodulation of the basal ganglia through Deep Brain Stimulation (DBS) of STN. DBS target selection is supported by intra-operative microelectrode recordings (MER). MER have been previously used to characterize neural dynamics of STN in several movement disorders and can provide information on firing patterns underlying HD. Methods: We analyzed MER data acquired during bilateral DBS of STN in a juvenile HD female patient with hypokinetic motor symptoms (generalized dystonia, stiffness, and severe gait impairment). Firing patterns of STN in HD were characterized by isolating single neuron activities (n=23) and measuring their regularity, bursting, and oscillatory behavior. Multi-unit activity recordings spectrum was used to estimate the presence of network oscillations. Results: STN neurons displayed irregular dynamics and intense and sparse bursting. Only 3/23 neurons presented oscillatory activity. However, network oscillations were detected, in particular in the beta (12-30 Hz) band. After bilateral STN-DBS surgery, the Unified Huntington's Disease Rating Scale decreased from 60 to 54. Conclusions: The most salient difference between HD and other movement disorders in STN activity is the presence of a weakly synchronized oscillatory mode, in which oscillations are evident at the network level but not at the single neuron level.