VOLUME 29, ISSUE 4 • DECEMBER 2025.
What is the effect of DBS on non-motor symptoms in Parkinson’s disease?
Non-motor symptoms are prevalent, disabling, and difficult to treat at all stages of Parkinson's disease (PD). DBS currently seems to benefit only a few non-motor domains, such as impulse control disorders (ICD) and sleep in a subset of patients, while non-motor symptoms remain unchanged in the majority of patients. DBS can also induce non-motor side effects like apathy and hypomania.
What is adaptive DBS?
Adaptive DBS (aDBS) leverages new-generation neurostimulator ‘sensing’ abilities to record local field potentials (LFP), harboring neurophysiological biomarkers (‘physiomarkers’) indexing symptom severity. Control policies, or ‘aDBS algorithms,’ dictate how stimulation parameters respond to neural signal dynamics, closing the loop between brain and device. In the last decade, such aDBS algorithms have demonstrated to decrease stimulation-induced motor side effects and improve suppression of motor symptoms.
How could aDBS improve non-motor symptoms?
Non-motor symptom severity varies on timescales ranging from months (cognition, mood, sleep) to within a day (fatigue, pain, OFF-state anxiety). DBS target structures are important nodes in non-motor circuits, but the non-motor effects of DBS depend on stimulation location and intensity. For instance, depressed mood seems to benefit most from stimulation of the ventral STN. However, ‘overstimulation’ of the ventral STN may increase mood excessively and induce (hypo)mania. Adaptive DBS could account for these temporal and spatial dynamics of non-motor symptoms.
Current status of non-motor physiomarkers?
In summary, no non-motor subcortical physiomarkers have been established longitudinally within patients in ecological settings with stimulation enabled — which is required for use in aDBS. Group-level analyses have shown that basal ganglia low frequency power in the theta-alpha range is implicated in many neuropsychiatric symptoms, suggesting it may be among the most promising physiomarkers for non-motor aDBS.
How could future non-motor aDBS look like?
The optimal stimulation and sensing location for motor symptoms does not colocalize with those for most non-motor symptoms. Therefore, advancing non-motor aDBS may require a significant shift away from dorsolateral motor STN and beta-based motor biomarkers. Sensing and stimulation may therefore be extended to: (i) different functional STN subdomains, (ii) structures along the course of the DBS lead, or (iii) structures at distance from the DBS lead (e.g. cortex). Additional external wearable sensors may be multiplexed with these neural signals to improve non-motor symptom decoding. Multiple independent aDBS algorithms may need to run in parallel to deliver responsive stimulation at different locations.
What are the challenges?
The development of non-motor aDBS requires technical innovations like DBS electrodes with increased granularity, and neurostimulators with sophisticated capabilities like multisite sensing, complex aDBS algorithms, and versatile stimulation output. Future research into non-motor physiomarkers should leverage advances in ecological momentary assessments and at-home monitoring to establish reliable, naturalistic, patient-specific physiomarkers. To keep non-motor aDBS manageable, automatization and ease of programming should be a central tenet of development. Non-motor aDBS entails ethical challenges concerning patient safety, privacy, autonomy, and sense of self.
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