The Motor Network in Parkinson’s Disease and Dystonia: Mechanisms of Therapy

Description

In this project investigators will develop adaptive DBS algorithms based on cortical and subcortical signals using the RC+S. This bidirectional neural interface is rechargeable (for up to 9 years of use), and is capable of delivering therapeutic open-loop stimulation or closed-loop stimulation. Its sensing capability includes four simultaneous time series channels at up to 1000 Hz sampling rate. In addition the device can stream time series data, and calculate and stream spectral power within a preset bandwidth. Twenty patients with idiopathic PD and motor fluctuations, or medically intractable tremor, will be implanted with unilateral or bilateral RC+S devices, each connected to a standard quadripolar DBS lead implanted in STN or globus pallidus, and to a 4-contact paddle type electrode placed subdurally over sensorimotor cortex. The basal ganglia lead will be used for both stimulation and LFP recordings, while the cortical lead will be used only for recording ECoG potentials, not for stimulation.

Patients with motor fluctuations cycle between a hypokinetic state (too little movement) and a hyperkinetic state (excessive movement). During open-loop DBS, brain state continues to fluctuate between these states and stimulation may induce dyskinesia or inadequately relieve akinesia.

With the goal of maintaining motor function within a normal range away from these two extremes, investigators will develop and test stimulation algorithms that utilize putative markers of both kinetic states. Investigators will also study neural signals of sleep and test stimulation to support specific sleep stages. The basic strategy is to automatically adjust stimulation parameters until the physiological signature of abnormal function is minimized. First, investigators will prototype adaptive stimulation paradigms and briefly (2 hours) test them in clinic, using a “distributed” configuration (streaming to a computer). Then, investigators will embed these algorithms in RC+S to test chronic and fully closed-loop DBS in a small double-blinded clinical trial. Investigators will pay careful attention to the possibility of progressive reduction in stimulation currents over the course of the study, which could support the hypothesis that “adaptive stimulation” might make the brain progressively less dependent on the device. In quantifying DBS amplitude and comparing open loop with adaptive stimulation, an important parameter is the total electrical energy delivered (TEED). TEED is calculated by the following equation as suggested by Koss and colleagues (TEED1sec = ((voltage2 x frequency x pulsewidth)/impedance) x 1sec). This can be used as measure of the energy saved when stimulation is delivered in closed-loop mode relative to empiric open-loop stimulation.