Abstract
Background: Aberrant basal ganglia activity is a key feature of the pathophysiology of dystonia, but evidence is predominantly based on adult cohorts. Neurophysiological signatures during development remain poorly characterised. Local field potentials (LFPs) recorded by bidirectional neurostimulators provide a direct measure of globus pallidus internus (GPi) activity. In a cross-sectional paediatric cohort, we investigated whether pallidal oscillatory, aperiodic and connectivity characteristics are associated with dystonia severity and whether these differ between genetic and acquired dystonias.
Methods: We recruited 30 children and young adults (5-20 years) with medically refractory dystonia (genetic n = 10; acquired n = 20) who underwent bilateral GPi Deep Brain Stimulation (DBS) implantation. Ten minutes of pallidal LFPs were recorded using Medtronic Percept RC neurostimulators with stimulation off, before DBS activation and, where available, at 12 months. Spectral power, aperiodic exponent and interhemispheric pallidopallidal coherence were quantified across delta (1-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), beta (13-30 Hz), and low-gamma (30-45 Hz) frequency bands. Linear mixed-effects models were implemented to establish whether LFP markers were predictive of dystonia severity, as measured by the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS-Movement). Firths Bias-Reduced Logistic Regression assessed whether LFP markers were predictive of dystonia aetiology.
Results: Spectral peaks were most consistently detected in the delta, beta, and low-gamma bands. Delta and low-gamma peak power significantly predicted dystonia severity. This association was independent of medication burden, structural GPi involvement, and dystonia aetiology. Theta and alpha peaks were detected less consistently, and their power was not associated with dystonia severity. Pallidopallidal coherence significantly predicted dystonia severity in interaction with medication load in all frequency bands. Low-gamma peak power was significantly lower in acquired than genetic dystonia, but the potentially confounding influence of dystonia severity could not be excluded. The aperiodic exponent was not associated with severity or aetiology.
Conclusion: Pallidal LFP markers are associated with dystonia severity in children, with delta peak power, low-gamma peak power and pallidopallidal coherence reflecting clinically relevant features of disease expression. These findings highlight the potential of pallidal LFPs to characterise dystonia across the lifespan and motivate longitudinal studies of their developmental and clinical trajectories.