Toward Electrophysiology-Based Intelligent Adaptive Deep Brain Stimulation for Movement Disorders

Abstract

Deep brain stimulation (DBS) represents one of the major clinical breakthroughs in the age of translational neuroscience. In 1987, Benabid and colleagues demonstrated that high-frequency stimulation can mimic the effects of ablative neurosurgery in Parkinson's disease (PD), while offering two key advantages to previous procedures: adjustability and reversibility. Deep brain stimulation is now an established therapeutic approach that robustly alleviates symptoms in patients with movement disorders, such as Parkinson's disease, essential tremor, and dystonia, who present with inadequate or adverse responses to medication. Currently, stimulation electrodes are implanted in specific target regions of the basal ganglia-thalamic circuit and stimulation pulses are delivered chronically. To achieve optimal therapeutic effect, stimulation frequency, amplitude, and pulse width must be adjusted on a patient-specific basis by a movement disorders specialist. The finding that pathological neural activity can be sampled directly from the target region using the DBS electrode has inspired a novel DBS paradigm: closed-loop adaptive DBS (aDBS). The goal of this strategy is to identify pathological and physiologically normal patterns of neuronal activity that can be used to adapt stimulation parameters to the concurrent therapeutic demand. This review will give detailed insight into potential biomarkers and discuss next-generation strategies, implementing advances in artificial intelligence, to further elevate the therapeutic potential of DBS by capitalizing on its modifiable nature. Development of intelligent aDBS, with an ability to deliver highly personalized treatment regimens and to create symptom-specific therapeutic strategies in real-time, could allow for significant further improvements in the quality of life for movement disorders patients with DBS that ultimately could outperform traditional drug treatment.

Keywords: Basal ganglia; Closed-loop DBS; Deep brain stimulation; Dystonia; Parkinson’s disease; Tourette syndrome.

Fig. 1

Exemplar DBS electrode location (a) in the subthalamic nucleus with local anatomy pictured in 3D. Local field potentials (b) can be recorded directly from DBS electrodes for the characterization of pathological and physiological oscillations in DBS patients

Fig. 2

Overview of oscillatory features related to pathological and physiological states in DBS patients

Fig. 3

Simplified schematic of a proposed deep learning network based on oscillatory features. A modular approach could benefit from multiple inputs to decode pathological and physiological states to optimize DBS parameters adaptively