Emotion-tremor coupling in Wilson's disease: EEG microstate C as a marker of salience network dysregulation

Emotional states are known to modulate tremor severity in Wilson's disease (WD), but the neural mechanisms underlying this emotion-tremor coupling remain poorly understood. This study aimed to investigate the neurophysiological and structural substrates of emotion-induced tremor variability in WD patients using electroencephalography (EEG) microstate analysis, kinematic tremor tracking, and structural MRI.

Forty-five tremor-dominant WD patients and 20 healthy controls underwent assessments with the Body Image Disturbance Questionnaire (BIDQ), Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS), Self-Assessment Manikin (SAM), and Facial Expression Recognition (FER) tasks. Tremor kinematics were quantified via Kinovea, and EEG microstates were analyzed during emotion induction. Structural magnetic resonance imaging (MRI) was used to evaluate brain atrophy patterns.

WD patients exhibited greater social avoidance (Z = -5.721, p < 0.05), prolonged FER reaction times (1.78 s vs. 1.05 s, p < 0.001), and more negative face selections (6 vs. 5, p = 0.036). Negative emotional states were associated with significantly larger tremor amplitude (3.79 px vs. 3.16 px, p = 0.012). EEG microstates showed increased frequency of microstate C (4.74/min vs. 3.41/min, p < 0.001) and coverage (16.62% vs. 13.22%, p < 0.001) during negative emotion, which correlated with tremor severity (ρ = 0.319, p = 0.039). Regression analysis identified lentiform nucleus damage (β = 0.361), cerebellar atrophy (β = 0.300), and frontal atrophy (β = -0.386) as predictors of emotional arousal (R² = 0.277, p = 0.042).

Emotion-tremor coupling in WD involves dysregulated salience networks and cerebellar-frontal-lentiform circuits, with EEG microstate C as a potential marker for targeted interventions.