Optimal deep brain stimulation of the subthalamic nucleus--a computational study.

Deep brain stimulation (DBS) of the subthalamic nucleus, typically with periodic, high frequency pulse trains, has proven to be an effective treatment for the motor symptoms of Parkinson's disease (PD). Here, we use a biophysically-based model of spiking cells in the basal ganglia (Terman et al., Journal of Neuroscience, 22, 2963-2976, 2002; Rubin and Terman, Journal of Computational Neuroscience, 16, 211-235, 2004) to provide computational evidence that alternative temporal patterns of DBS inputs might be equally effective as the standard high-frequency waveforms, but require lower amplitudes. Within this model, DBS performance is assessed in two ways. First, we determine the extent to which DBS causes Gpi (globus pallidus pars interna) synaptic outputs, which are burstlike and synchronized in the unstimulated Parkinsonian state, to cease their pathological modulation of simulated thalamocortical cells. Second, we evaluate how DBS affects the GPi cells' auto- and cross-correlograms. In both cases, a nonlinear closed-loop learning algorithm identifies effective DBS inputs that are optimized to have minimal strength. The network dynamics that result differ from the regular, entrained firing which some previous studies have associated with conventional high-frequency DBS. This type of optimized solution is also found with heterogeneity in both the intrinsic network dynamics and the strength of DBS inputs received at various cells. Such alternative DBS inputs could potentially be identified, guided by the model-free learning algorithm, in experimental or eventual clinical settings.