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

Abstract

BackgroundHuntington'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. MethodsWe 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. ResultsSTN 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. ConclusionsThe 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.