“Temporal Patterns of Deep Brain Stimulation: From Mechanisms to Therapeutic Innovation”

Deep brain stimulation (DBS) has developed from an experimental technique to an established therapy for the treatment of movement disorders including dystonia, essential tremor, and Parkinson’s disease. High-frequency stimulation results in outcomes similar to those resulting from ablative surgical lesions of target structures in the thalamus or basal ganglia, but debate remains over the effects of high frequency stimulation on neuronal and network activity.

I will present both computational and experimental studies that illuminate the cellular and network mechanisms of DBS. I first will review the effects of extracellular stimulation on the activity in CNS neurons and use these results to motivate of a hypothesis that DBS masks pathological oscillatory activity by regularizing the activity in neurons in the stimulated nucleus. Next, I will present experimental data from preclinical experiments in an animal model of Parkinson’s disease demonstrating that effective DBS suppresses abnormal oscillatory activity and that suppression of these oscillations is responsible for the observed behavioral effects. Third, I will present data from experiments in persons with Parkinson’s disease that demonstrate the importance of the regularization of neuronal activity in the efficacy of DBS. This new understanding has important implications for novel methods of stimulation, and I will conclude with the model-based design and clinical evaluation of novel temporal patterns of stimulation. The results demonstrate the utility of an entirely new dimension of neural stimulation parameters – the timing between stimulation pulses – to increase the efficacy and efficiency of stimulation.

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