Objective: To assess the role of local field potential (LFP) as an acute biomarker of maximal tolerable stimulation (MTS) in dystonia patients.

Background: Dystonia is the third most prevalent movement disorder, characterized by involuntary muscle contractions [1]. Deep Brain Stimulation (DBS) can effectively reduce dystonia symptoms, but programming remains challenging due to individualized stimulation needs, delayed clinical responses, and variable outcomes [2-10]. While effective stimulation reduces dystonia, imbalanced stimulation titration can worsen symptoms [11-17]. LFP features have been linked with dystonia severity in acute settings [18-21], indicating potential utility for guiding DBS programming and clinical decision making.

Method: Continuous real-time globus pallidus internus (GPi) LFP recordings (BrainSense Streaming) were obtained from 3 patients with generalized dystonia (1 idiopathic; 2–3 with TOR1A:p.303delE mutation) during DBS programming. LFP power spectral density (PSD) and changes in dystonia severity (Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS) Movement subscale) were recorded during carefully titrated stimulation amplitude adjustments made under clinician guidance. MTS was empirically defined by individual tolerance to stimulation adjustments. Data was analyzed retrospectively using Matlab(2024b), after gaining informed consent.

Results: Stepwise increases in stimulation amplitude up to MTS led to increased power across multiple canonical frequency bands in all 3 cases, corresponding with clinical overstimulation measured by BFMDRS [figure1, table1]. LFP power during MTS was significantly higher compared to baseline values [figure2]. Subsequent reduction of stimulation amplitude below MTS resulted in overall decrease in LFP power. Linear mixed modelling shows that stimulation amplitude and LFP power positively correlate with dystonia severity in all 3 instances [figure3], both separately (mA:4.039, LFP power:2.912), and jointly (mA:LFP power:0.986).

Conclusion: These findings suggest that LFP features can be putative indicators of dystonia severity. Although increased LFP band power correlated with clear clinical worsening in these patients, not all dystonia patients will show immediate signs of worsening. Increased LFP band power during increasing stimulation amplitude may represent a biomarker for patients at-risk of manifesting delayed clinical worsening.

figure1

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table1

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MDS Abstracts - https://www.mdsabstracts.org/abstract/power-spectral-density-increases-covary-with-clinical-overstimulation-during-dystonia-deep-brain-stimulation-programming/