253 Evidence for at Least Three Distinct Mechanisms of Frequency-Specific Task Disruption During Hand Primary Motor Cortex Stimulation

INTRODUCTION: Interest in stimulation-induced neuroplasticity (i.e., “prehabilitation”) is growing. Potential applications include remapping the brain around invasive tumors to extend resections into previously unresectable areas while protecting neurological function. To achieve this goal, focal cortical stimulation must functionally inhibit a portion of the brain so physiotherapy can encourage other parts of the network to assume its function. While clinical stimulation (i.e., 50-60 Hz) of language cortex inhibits function, stimulation of primary motor areas (M1) activates function by inducing clonus or tonus. While there are reports of motor task inhibition by stimulation of “negative” (i.e., supplemental) motor areas, inhibiting “positive” (i.e., primary) motor areas have not been convincingly demonstrated. METHODS: 10 participants performed an index finger flexion task (i.e., finger individuation) during an awake craniotomy for tumor resection with access to hand M1 A 4x1 electrode strip was then placed over hand M1 and connected to a NeuroPace Responsive Neurostimulation System (RNS). Up to six frequencies from 1-330Hz (device limits) were applied for 5sec bursts at amplitudes just below those that generated motor evoked potentials (i.e., subthreshold), and subjects were prompted to complete the task during the stimulation. Clinical electrocorticography, EMG, and hand kinematic data were recorded and synchronized. RESULTS: In 4 participants, we observed 3 different mechanisms of stimulation-induced disruption: 1) flexor inhibition (250 Hz and 330 Hz), 2) discoordination (10 Hz), and 3) after discharge-related inhibition (250 Hz). Notably, movement disruption was only achieved in cortical locations that caused finger or wrist extension during suprathreshold stimulation. CONCLUSIONS: Here we provide initial evidence for the frequency-dependent functional effects of hand M1 stimulation, and we report evidence for at least three distinct mechanisms of frequency-specific task disruption.