| Summary: | Deep brain stimulation (DBS) is an approved therapy for the treatment of medicallyrefractory and severe movement disorders. However, most existing neurostimulators can only
apply continuous stimulation (open-loop DBS, OL-DBS), ignoring patient behavior and
environmental factors, which consequently leads to an inefficient therapy, thus limiting the
therapeutic window. Here, we established the feasibility of a self-adjusting therapeutic DBS
(closed-loop DBS, CL-DBS), fully embedded in a chronic investigational neurostimulator
(Activa PC+S), for 3 patients affected by essential tremor (ET) enrolled in a longitudinal (6
months) within-subject crossover protocol (DBS OFF, OL-DBS, CL-DBS). Most patients with
ET experience involuntary limb tremor during goal-directed movements, but not during rest.
Hence, the proposed CL-DBS paradigm explored the efficacy of modulating the stimulationamplitude based on patient-specific motor behavior, suppressing the pathological tremor ondemand based on a cortical electrode detecting upper-limb motor activity. Herein, we
demonstrated how the proposed stimulation paradigm was able to achieve clinical efficacy and
tremor suppression comparable with OL-DBS in a range of movements (cup reaching, proximal
and distal posture, water pouring, writing), while having a consistent reduction in energy
delivery. The proposed paradigm is an important step towards a behaviorally modulated fully
embedded DBS system, capable of delivering stimulation only when needed, and potentially
mitigating pitfalls of OL-DBS, such as DBS-induced side effects and premature device
replacement.
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