ESSENTIAL TREMOR BEYOND OSCILLATIONS: THALAMIC SIGNATURES OF PREDICTIVE AND PRECISION PROCESSING AS CIRCUIT-SPECIFIC BIOMARKERS OF MOTOR CONTROL

Essential tremor (ET) is classically characterized as a movement disorder of oscillatory instability, although its underlying computational pathology remains poorly specified. Here, we hypothesized that ET reflects a disruption in predictive versus precision processing within motor control circuits, arising from altered estimation and updating of sensorimotor predictions and their associated precision. We sought to identify subcortical neural signatures that differentiate cerebellar recipient (VIM) and basal ganglia recipient (VO) thalamic pathways and to determine whether these nuclei exhibit distinct spectral biomarkers during planning and execution of goal-directed behavior. We recorded local field potentials (LFPs) from chronically implanted deep-brain stimulation (DBS) leads in ET patients performing a continuous force cursor task designed to engage predictive processing during a planning phase and feedback processing during an execution phase while permitting tremor expression under controlled conditions. With DBS OFF, LFPs were analyzed using time-frequency spectrograms and band-limited, time-resolved power to characterize frequency-specific and task-locked oscillatory dynamics, while power spectral density summarized interval-averaged frequency composition during cue-to-go and sensory feedback epochs. Predictive control was systematically perturbed by manipulating sensory predictability, motor precision, and task demands, enabling assessment of how each thalamic nucleus responds to changes in uncertainty and control requirements. Across these manipulations, VIM and VO exhibited distinct, nucleus-specific spectral signatures spanning broadband, tremor-related, and non-tremor frequencies, revealing persistent circuit-level biomarkers that dissociate cerebellar and basal ganglia contributions to predictive motor control in ET. Together, these findings establish the groundwork for biomarker-driven interventions that enable precise diagnosis, monitoring, and treatment of ET beyond oscillation-focused pathology.