Motor Learning After Cerebellar Damage: The Role of the Primary Motor Cortex

Cerebellar damage causes the disabling movement disorder ataxia, which is characterized by impaired movement coordination affecting all body movements. In the arms, ataxia causes reaching movements with irregular, oscillating, and prolonged trajectory paths. People with cerebellar ataxia (PWCA) are also impaired in an important form of motor learning, called adaptation, which normally keeps movement well calibrated. In prior research, the principal investigator showed that PWCA can learn to correct their reaching movements if they instead employ reinforcement learning (RL). Although many PWCA learned optimally in RL conditions, this prior work found variability across individuals: some learned more than others. While adaptation critically relies on cerebellar integrity, RL depends more heavily on dopaminergic circuitry in the midbrain and excitatory plasticity in M1. Cerebellar damage has been shown to increase intracortical inhibition in M1, which may hamper the plasticity needed for RL. The repetitive TMS protocols of continuous theta burst stimulation (cTBS) and intermittent theta burst stimulation (iTBS) have further been shown to modulate intracortical inhibition: cTBS decreases it, while iTBS increases it. Here, the investigators will systematically test whether increased intracortical inhibition in M1 predicts RL capacity (Aim 1) and whether modulating inhibition in M1 can alter RL capacity in PWCA (Aim 2). 12 PWCA from a degenerative condition will complete 4 experimental sessions over a 6-month period. In session 1, TMS will be used to assess baseline recruitment curves for corticomotor excitability and short-interval intracortical inhibition, and the cortical silent period. PWCA will then complete a standardized clinical rating of their ataxia severity and an established behavioral task that requires learning a reaching skill using the RL paradigm. In sessions 2-4, PWCA will complete 3 additional sessions of the RL task. In each session, PWCA will receive cTBS, iTBS, or sham stimulation to modulate intracortical inhibition in M1 prior to performing the RL task. For Aim 1, the investigators will use multi-level regression to quantify relationships between TMS measures of M1 state and the magnitude and speed of learning in the RL task. For Aim 2, the investigators will use multi-level modeling to quantify differences in the magnitude and speed of learning across stimulation conditions. The investigators hypothesize that increased baseline inhibition in M1 will show a positive association with a lower magnitude and speed of learning in the RL task (Aim 1), and cTBS will improve the magnitude of learning, the speed of learning, or both, in the RL task relative to iTBS or sham stimulation (Aim 2).