Improved efficacy of temporally non-regular deep brain stimulation in Parkinson's disease

Abstract

High frequency deep brain stimulation is an effective therapy for motor symptoms in Parkinson's disease. However, the relative clinical efficacy of regular versus non-regular temporal patterns of stimulation in Parkinson's disease remains unclear. To determine the temporal characteristics of non-regular temporal patterns of stimulation important for the treatment of Parkinson's disease, we compared the efficacy of temporally regular stimulation with four non-regular patterns of stimulation in subjects with Parkinson's disease using an alternating finger tapping task. The patterns of stimulation were also evaluated in a biophysical model of the parkinsonian basal ganglia that exhibited prominent oscillatory activity in the beta frequency range. The temporal patterns of stimulation differentially improved motor task performance. Three of the non-regular patterns of stimulation improved performance of the finger tapping task more than temporally regular stimulation. In the computational model all patterns of deep brain stimulation suppressed beta band oscillatory activity, and the degree of suppression was strongly correlated with the clinical efficacy across stimulation patterns. The three non-regular patterns of stimulation that improved motor performance over regular stimulation also suppressed beta band oscillatory activity in the computational model more effectively than regular stimulation. These data demonstrate that the temporal pattern of stimulation is an important consideration for the clinical efficacy of deep brain stimulation in Parkinson's disease. Furthermore, non-regular patterns of stimulation may ameliorate motor symptoms and suppress pathological rhythmic activity in the basal ganglia more effectively than regular stimulation. Therefore, non-regular patterns of deep brain stimulation may have useful clinical and experimental applications.