Experience-dependent changes in cerebellar contributions to motor sequence learning

Abstract

Studies in experimental animals and humans have stressed the role of the cerebellum in motor skill learning. Yet, the relative importance of the cerebellar cortex and deep nuclei, as well as the nature of the dynamic functional changes occurring between these and other motor-related structures during learning, remains in dispute. Using functional magnetic resonance imaging and a motor sequence learning paradigm in humans, we found evidence of an experience-dependent shift of activation from the cerebellar cortex to the dentate nucleus during early learning, and from a cerebellar-cortical to a striatal-cortical network with extended practice. The results indicate that intrinsic modulation within the cerebellum, in concert with activation of motor-related cortical regions, serves to set up a procedurally acquired sequence of movements that is then maintained elsewhere in the brain.

Figure 1

(a) Materials and stimuli used in the motor sequence learning task (7, 8). The stimuli consisted of four blue boxes that were aligned in a horizontal row and a red circle that appeared above one of the boxes on each trial. These stimuli were projected on a screen located in front of the subject, and were reflected through a mirror embedded within the head coil. (b) Subjects' mean reaction time in both Random (R) and Learning (L) conditions across the three scanning sessions.

Figure 2

Merged fMRI–MRI horizontal sections through the cerebellum (z = −33) illustrating the results of the multiple regression analysis for the L–R regressor averaged over the nine subjects. The results are shown as z score maps and reveal both increases (orange) and decreases (blue) in BOLD signal over the three scanning sessions, and are displayed overlaid on a coplanar, high-resolution MRI scan of a single subject. In the horizontal sections, the z coordinate represents the position of the section relative to the anterior–posterior commissure line. The subject's right cerebellar hemisphere is on the left. (a) Significant increases and decreases of activation (z score > 3.09, P < 0.001) in both the cerebellar cortex (lobule V and crus 1) and deep nuclei across sessions. (b) Results of the subtraction analysis comparing the z score maps obtained in session 2 vs. session 1, and in session 3 vs. session 2.

Figure 3

Mean z scores of the subjects across the three sessions derived from functionally defined, activated ROIs within the cerebellar cortex and deep nuclei.

Figure 4

Merged fMRI–MRI horizontal sections illustrating the results of the subtraction of z score maps at the level of the cortex and striatum. (a) Session 2 − session 1, the results yielded an increase (z score > 1.64, P < 0.05) in BOLD signal from session 1 to session 2 in the right anterior cingulate (x = 3; y = 2, z = 45) and dorsal premotor region (x = 38; y = 3, z = 45). Both an increase and a decrease (z score < −1.64, P < 0.05) in activation was also seen in the right inferior parietal cortex (x = 40; y = −53, z = 45). Session 3 − session 2, by contrast, activations within both the right anterior cingulate and premotor regions subsequently declined (blue) in session 3, whereas a further increase in activation was observed in the right inferior parietal region (x = 56; y = −5, z = 45); this activation was located in a slightly more superior region. (b) Horizontal sections illustrate the significant increase in BOLD signal in the striatum (x = 23; y = 0, z = 0), supplementary motor area (SMA; x = 9; y = −2, z = 57), precuneus (x = 9; y = −68, z = 51), inferior parietal cortex (x = 50; y = −45, z = 51), and ventrolateral prefrontal cortex (x = 45; y = 36, z = 3).