Dynamic modulation of cerebellar excitability for abrupt, but not gradual, visuomotor adaptation

Abstract

The cerebellum is critically important for error-driven adaptive motor learning, as evidenced by the fact that cerebellar patients do not adapt well to sudden predictable perturbations. However, recent work has shown that cerebellar patients adapt much better if the perturbation is gradually introduced. Here we explore physiological mechanisms that underlie this distinction between abrupt and gradual motor adaptation in humans. We used transcranial magnetic stimulation to evaluate whether neural mechanisms within the cerebellum contribute to either process during a visuomotor reach adaptation. When a visuomotor rotation was introduced abruptly, cerebellar excitability changed early in learning and approached baseline levels near the end of the adaptation block. However, we observed no modulation of cerebellar excitability when we presented the visuomotor rotation gradually during learning. Similarly, we did not observe cerebellar modulation during trial-by-trial adaptation to random visuomotor displacements or during reaches without perturbations. This suggests that the cerebellum is most active during the early phases of adaptation when large perturbations are successfully compensated.

Figure 1.

Design of behavioral task. A, Participants moved a stylus on a digitizing tablet. The stylus was secured to their index finger, and participants were asked to move their finger more than their arm. Surface EMG electrodes were placed over the FDI and used to verify activation during the behavioral task as well as measure MEPs. B, Participants performed a center-out task, moving a cursor from a central region (square) to one of eight targets (circle). C, D, Participants first received premovement TMS stimulation. Next they performed a 200 trial baseline block, followed by TMS. They then performed 192 trials with the perturbation on [shown are abrupt (C, black) and gradual (D, gray) perturbations], broken into an early and late learning blocks separated by TMS. Finally, they completed a washout block.

Figure 2.

Stimulating the cerebellum with TMS. We used two coils to measure CBI. A figure-of-eight coil was placed over the left M1 (to activate right FDI) and delivered stimuli to evoke a 1 mV MEP. A double-cone coil was placed over the right cerebellum, 3 cm inferior and lateral to the inion and used to deliver conditioning pulses. CBI is computed as the ratio between the peak-to-peak amplitude of the MEPs after the conditioned TS (bottom right) and the MEPs produced after the unconditioned TS (bottom left).

Figure 3.

Results from experiment 1. A, In the abrupt condition, participants show initially a large error that decays over time and a significant aftereffect. B, During the random condition, participants experience large errors (shown here as absolute error rather than signed error) but no aftereffects. C, The CBI ratio (conditioned MEP/unconditioned MEP) is plotted before, during, and after learning. The ratio increases (representing less inhibition from the cerebellum over M1) early in learning for the abrupt condition but not in the random perturbation condition. Asterisks indicate significance of Bonferroni's-corrected post hoc t tests, with ** indicating a significant difference in a two-tailed test and * indicating a significant difference with a one-tailed test.

Figure 4.

Results from experiment 2. A, Participants in the gradual condition do not experience large errors during learning but show an aftereffect. B, During the veridical condition, participants maintain their performance across the entire experiment. C, The CBI ratio (conditioned MEP/unconditioned MEP) is plotted before, during, and after learning. The ratio remains unchanged in the gradual as well as the veridical conditions.