Adaptive Deep Brain Stimulation for Movement Disorders: The Long Road to Clinical Therapy

Abstract

Continuous high-frequency DBS is an established treatment for essential tremor and Parkinson's disease. Current developments focus on trying to widen the therapeutic window of DBS. Adaptive DBS (aDBS), where stimulation is dynamically controlled by feedback from biomarkers of pathological brain circuit activity, is one such development. Relevant biomarkers may be central, such as local field potential activity, or peripheral, such as inertial tremor data. Moreover, stimulation may be directed by the amplitude or the phase (timing) of the biomarker signal. In this review, we evaluate existing aDBS studies as proof-of-principle, discuss their limitations, most of which stem from their acute nature, and propose what is needed to take aDBS into a chronic setting. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Keywords: Parkinson's disease; brain-computer interface; closed-loop; deep brain stimulation; essential tremor.

Figure 1

Schematic summary displaying different forms of DBS. A shows conventional DBS where pulses occur at a constant frequency. B depicts two forms of amplitude responsive DBS; upper green panel, event‐dependent control where stimulation is triggered and terminated when a signal, like beta‐amplitude, rises above and falls below a threshold, respectively and green lower panel, continuous‐time control where stimulation varies proportionately to the amplitude of the signal. C shows phase‐responsive DBS where pulses of high‐frequency stimulation are timed to a particular phase by either event‐dependent (upper orange panel) or continuous time control (lower orange panel). [Color figure can be viewed at wileyonlinelibrary.com]

Figure 2

Improvements in motor scores assessed blinded in the studies of Little et al. 2013 and Little et al 2015. Data are presented as the mean ± standard error of the mean percentage change in UPDRS scores.

Figure 3

Potential Combined Beta‐Tremor Control loops. DBS stimulation is triggered whenever one or other or both signals cross independent thresholds and is terminated whenever both signals have fallen below their thresholds. [Color figure can be viewed at wileyonlinelibrary.com]