Background: Recent technological advances in deep brain stimulation (DBS) (e.g., directional leads, multiple independent current sources) lead to increasing DBS-optimization burden. Techniques to streamline and facilitate programming could leverage these innovations. Objective: We evaluated clinical effectiveness of algorithm-guided DBS-programming based on wearable-sensor-feedback compared to standard-of-care DBS-settings in a prospective, randomized, crossover, double-blind study in two German DBS centers. Methods: For 23 Parkinson’s disease patients with clinically effective DBS, new algorithm-guided DBS-settings were determined and compared to previously established standard-of-care DBS-settings using UPDRS-III and motion-sensor-assessment. Clinical and imaging data with lead-localizations were analyzed to evaluate characteristics of algorithm-derived programming compared to standard-of-care. Six different versions of the algorithm were evaluated during the study and 10 subjects programmed with uniform algorithm-version were analyzed as a subgroup. Results: Algorithm-guided and standard-of-care DBS-settings effectively reduced motor symptoms compared to off-stimulation-state. UPDRS-III scores were reduced significantly more with standard-of-care settings as compared to algorithm-guided programming with heterogenous algorithm versions in the entire cohort. A subgroup with the latest algorithm version showed no significant differences in UPDRS-III achieved by the two programming-methods. Comparing active contacts in standard-of-care and algorithm-guided DBS-settings, contacts in the latter had larger location variability and were farther away from a literature-based optimal stimulation target. Conclusion: Algorithm-guided programming may be a reasonable approach to replace monopolar review, enable less trained health-professionals to achieve satisfactory DBS-programming results, or potentially reduce time needed for programming. Larger studies and further improvements of algorithm-guided programming are needed to confirm these results.

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ZUSAMMENFASSUNGDas Tourette-Syndrom (TS) ist eine neuropsychiatrische Erkrankung, die durch das Auftreten motorischer und vokaler Tics charakterisiert ist. Bei einem geringen Teil der Patienten sind die Symptome durch medikamentöse und behaviorale Therapie nicht ausreichend gut behandelbar. Hier kann eine Therapieeskalation erwogen werden. Die tiefe Hirnstimulation (THS) ist ein invasives Therapieverfahren, das bei bestimmten Bewegungsstörungen etabliert ist und für die Therapie des TS zunehmend an Bedeutung gewinnt. Der folgende Artikel fasst die aktuelle Evidenz zur Anwendung der THS beim TS zusammen. Die meiste Erfahrung liegt für die thalamische und pallidale Stimulation vor, wobei bisher keines der Zielgebiete deutlich überlegen war. Die Studienlage zeigt eine durchschnittliche Reduktion der Tic-Schwere unter THS von bis zu 40 % nach einem Jahr. Inwiefern die THS zu einer Besserung der oft begleitenden psychiatrischen Komorbiditäten führt, bleibt aufgrund der geringen Fallzahlen unsicher. Beim TS ist eine erhöhte Anzahl an postoperativen Infektionen aufgefallen, deren Ursache nicht geklärt wurde. Zusammenfassend zeigen die Studien, dass eine THS beim TS eine sichere Therapieoption zur Behandlung schwerer medikamentös nicht behandelbarer Tics darstellt. Die THS sollte an Zentren durchgeführt werden, in denen Expertise sowohl in der Behandlung von Tics als auch für THS vorliegt.

Every decision that we make involves a conflict between exploiting our current knowledge of an action’s value or exploring alternative courses of action that might lead to a better, or worse outcome. The sub-cortical nuclei that make up the basal ganglia have been proposed as a neural circuit that may contribute to resolving this explore-exploit ‘dilemma’. To test this hypothesis, we examined the effects of neuromodulating the basal ganglia’s output nucleus, the globus pallidus interna, in patients who had undergone deep brain stimulation (DBS) for isolated dystonia. Neuromodulation enhanced the number of exploratory choices to the lower value option in a 2-armed bandit probabilistic reversal-learning task. Enhanced exploration was explained by a reduction in both rate of evidence accumulation (drift rate) and by the amount of evidence needed to decide (boundary separation) in a reinforcement learning drift diffusion model. We estimated the functional connectivity profile between the stimulating DBS electrode and the rest of the brain using a normative functional connectome derived from heathy controls. Variation in the extent of neuromodulation induced exploration between patients was predicted by the degree of functional connectivity between the stimulating electrode and prefrontal and sensorimotor cortices. We conclude that the basal ganglia’s output nucleus, the globus pallidus interna, can adaptively modify decision choice when faced with the dilemma to explore or exploit.