Browsing by Author "Weinstock, Zachary"

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    Characterization of Parkinsonian Neuropathophysiology and its Modulation by Deep Brain Stimulation in the Behaving, Nonhuman Primate Model
    (2016) Weinstock, Zachary;
    Parkinson’s disease (PD) is a neurodegenerative disorder characterized by debilitating motor disturbances. It is believed that the signs and symptoms of PD are caused by idiopathic cell death in the basal ganglia (BG), a network of subcortical nuclei with a well-established connection to motor control. Although there is no cure for PD, deep brain stimulation (DBS) of the internal Globus pallidus, a constituent nucleus of the BG, offers hope for patients who don’t respond well to conventional medications. However, the mechanisms underlying the therapeutic effects of DBS remains unclear, a fact largely attributed to a poorly characterized pathophysiology. Here we identify characteristic, electrophysiolgical biomarkers of PD that preempt the emergence of its behavioral signs and show that DBS works to shift cortical activity back towards a more “normal” state. Using a behaving non-human primate model of PD, we observed a disruption in the normal firing patterns and frequencies of both single motor units and neuronal populations in the primary motor cortex (M1) and supplementary motor areas (SMA) following the induction of parkinsonism. During DBS, we observed an increase in task-related neuromodulation. Taken together, our results hint at a therapeutic mechanism for DBS whereby signaling in M1 and SMA is made more salient and shifted towards “normal” activity. We anticipate that our findings will serve to guide future research and instruct the development of more effective, adaptive DBS technologies.