Abstract
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is modeled to explore the mechanisms of this effective, but poorly understood, treatment for motor symptoms of drug-refractory Parkinson’s disease and dystonia. First, a neural field model of the corticothalamic-basal ganglia (CTBG) system is developed that reproduces key clinical features of Parkinson’s disease, including its characteristic 4–8 Hz and 13–30 Hz electrophysiological signatures. Deep brain stimulation of the STN is then modeled and shown to suppress the pathological 13–30 Hz (beta) activity for physiologically realistic and optimized stimulus parameters. This supports the idea that suppression of abnormally coherent activity in the CTBG system is a major factor in DBS therapy for Parkinson’s disease, by permitting normal dynamics to resume. At high stimulus intensities, nonlinear effects in the target population mediate wave-wave interactions between resonant beta activity and the stimulus pulse train, leading to complex spectral structure that shows remarkable similarity to that seen in steady-state evoked potential experiments.
Highlights
Deep brain stimulation (DBS) has become an effective treatment for a number of neurological disorders such as Parkinson’s disease (PD) and essential tremor [1, 2]
Pathological 13-30 Hz oscillations within the basal ganglia are a characteristic feature of human Parkinson’s disease which seem to correlate with symptom severity
We formulate a physiologically based population model of the corticothalamic-basal ganglia system that produces 13-30 Hz oscillations in the neural circuit formed between the globus pallidus pars externa and the subthalamic nucleus and the hyperdirect corticothalamic-basal ganglia pathway
Summary
Deep brain stimulation (DBS) has become an effective treatment for a number of neurological disorders such as Parkinson’s disease (PD) and essential tremor [1, 2]. In Parkinson’s disease DBS treatments, a macroelectrode is chronically implanted in a target nucleus, typically either the globus pallidus internus (GPi), subthalamic nucleus (STN), or the ventral intermediate nucleus of the thalamus; this electrode delivers high frequency (>100 Hz) electrical stimulation as a series of pulses. The efficacy of DBS treatments could be improved with a greater understanding of the underlying therapeutic mechanisms. It is unclear what stimulation parameters, electrode geometries, and electrode locations are most effective for the present and future uses of DBS technologies
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