Cerebellar Theta-Burst Stimulation Impairs Memory Consolidation in Eyeblink Classical Conditioning

Abstract

Associative learning of sensorimotor contingences, as it occurs in eyeblink classical conditioning (EBCC), is known to involve the cerebellum, but its mechanism remains controversial. EBCC involves a sequence of learning processes which are thought to occur in the cerebellar cortex and deep cerebellar nuclei. Recently, the extinction phase of EBCC has been shown to be modulated after one week by cerebellar continuous theta-burst stimulation (cTBS). Here, we asked whether cerebellar cTBS could affect retention and reacquisition of conditioned responses (CRs) tested immediately after conditioning. We also investigated a possible lateralized cerebellar control of EBCC by applying cTBS on both the right and left cerebellar hemispheres. Both right and left cerebellar cTBSs induced a statistically significant impairment in retention and new acquisition of conditioned responses (CRs), the disruption effect being marginally more effective when the left cerebellar hemisphere was stimulated. These data support a model in which cTBS impairs retention and reacquisition of CR in the cerebellum, possibly by interfering with the transfer of memory to the deep cerebellar nuclei.

Figure 1

EBCC learning, extinction, and consolidation in the right, left cTBS, and sham groups at T0 (a) and at T1 (b). In all groups, the number of CRs was significantly higher in blocks 2–6 than in block 1 (all p < 0.05), whereas differences in CRs in each block were not statistically significant among the three groups. After cerebellar conditioning, both the right and left cerebellar cTBSs led to a decrease in the number of CRs in blocks 1–6 compared to sham stimulation. Dotted rectangles indicate the extinction block. Error bars indicate the standard error.

Figure 2

Effects of cTBS on ∆CR, measured as the number of CRs after cTBS minus the number of CRs before cTBS. (a) Both the right and left cTBS groups induced a statistically significant decrease in the total number of ∆CRs compared to the sham group (both p < 0.001). (b) ∆CR was significantly smaller in the right and left cTBS groups compared to the sham group in blocks 1–6 (all p < 0.05). Dotted rectangles indicate the extinction block. Error bars indicate the standard error. Asterisks indicate the statistical significance.

Figure 3

Effects of cTBS on retention and extinction. (a) Effects of cTBS on retention, measured as the difference of CRs in block 1 after cTBS and CRs in block 6 before cTBS separately in each group. Both the right and left cTBS groups led to a statistically significant decrease in retention compared to the sham group (both p < 0.001). (b) Effects of cTBS on extinction, measured as the number of CRs in block 7 before (T0) and after (T1) cTBS in the three groups separately. There were no statistically significant effects of cTBS on extinction. Error bars indicate the standard error. Asterisks indicate the statistical significance.