Baseline Cerebro-Cerebellar Functional Connectivity in Afferent and Efferent Pathways Reveal Dissociable Improvements in Visuomotor Learning

Abstract

Visuomotor coordination is a complex process involving several brain regions, primarily the cerebellum and motor cortex. Studies have shown inconsistent resting-state functional magnetic resonance imaging (rsfMRI) results in the cerebellar cortex and dentate nucleus of the cerebro-cerebellar connections. Echoing anatomical pathways, these two different cerebellar regions are differentially responsible for afferent and efferent cerebro-cerebellar functional connections. The aim of this study was to measure the baseline resting-state functional connectivity of different cerebellar afferent and efferent pathways and to investigate their relationship to visuomotor learning abilities. We used different cerebellar repetitive transcranial magnetic stimulation (rTMS) frequencies before a pursuit rotor task to influence visuomotor performance. Thirty-eight right-handed participants were included and randomly assigned to three different rTMS frequency groups (1 Hz, 10 Hz and sham) and underwent baseline rsfMRI and pursuit rotor task assessments. We report that greater baseline functional connectivity in the afferent cerebro-cerebellar pathways was associated with greater accuracy improvements. Interestingly, lower baseline functional connectivity in the efferent dentato-thalamo-cortical pathways was associated with greater stability in visuomotor performance, possibly associated with the inhibitory role of the dentate nucleus and caused a reduction in the efferent functional connectivity. The functional dissociation of the cerebellar cortex and dentate nucleus and their connections, suggests that distinct mechanisms in the cerebellum regarding visuomotor learning, which should be investigated in future research.

Keywords: cerebellum; cerebro-cerebellar connections; dentate nucleus; dentato-thalamo-cortical pathways; functional connectivity; rTMS; visuomotor coordination.

FIGURE 1

The baseline functional connectivity of M1-cerebellum positively correlated with the improvement in distance from target. (A) The correlation between different functional connectivity and the improvement in accuracy visuomotor performance in all participants. Link colors indicate partial Spearman’s rank correlation coefficient (rho) and link widths indicate the significance of correlation. The color bar shows the correlation coefficient scale. A thicker link shows a significant relationship (p-value < 0.05) between the functional connectivity of two ROIs and the accuracy improvements, and a thinner line shows no significant association between the functional connectivity and behavior. (B) The correlation between M1-R CbC functional connectivity and the accuracy improvements (rho = 0.49, p = 0.035). (C) The correlation between different functional connectivity and the accuracy improvements among three different cerebellar rTMS groups. (D) The correlation between functional connectivity between L M1-R CbC (rho = 0.83, p = 0.002; top right panel), L M1-L CbC (rho = 0.86, p = 0.001; top left panel), L M1-Mid Cb (rho = 0.69, p = 0.03; bottom right panel) and Mid Cb-L CbC (rho = 0.65, p = 0.043; bottom left panel) functional connectivity and the accuracy improvements in the 10 Hz rTMS group. Each point is one participant. Each point is one participant. (L M1 = left motor cortex; R CbC = right cerebellar cortex; L CbC = left cerebellar cortex; R DCN = right deep cerebellar nucleus; L DCN = left deep cerebellar nucleus; Mid Cb = midline cerebellum).

FIGURE 2

The baseline functional connectivity of M1 to deep cerebellar nuclei was corelated with the improvement in trial-to-trial variability. (A) The correlation of different functional connectivity and the stability improvement in all participants. (B) The correlation between the functional connectivity of L M1-R DCN (rho = –0.50, p = 0.025; top panel) and L M1- L DCN (rho = –0.46, p = 0.034; bottom panel) functional connectivity and the stability improvements. Each point is one participant. (L M1 = left motor cortex; R CbC = right cerebellar cortex; L CbC = left cerebellar cortex; R DCN = right deep cerebellar nucleus; L DCN = left deep cerebellar nucleus; Mid Cb = midline cerebellum).

FIGURE 3

The baseline functional connectivity of M1 to dentate, fastigial, and interposed nucleus, corelated with the improvement of stability. (A) The correlation of different functional connectivity and the stability improvements in all participants. (B) The correlation between functional connectivity of L M1-R DN (rho = –0.49, p = 0.033; top panel) and L M1-L DN (rho = –0.47, p = 0.033; bottom panel) functional connectivity and the improvement of stability. Each point is one participant. (L M1 = left motor cortex; R DN = right dentate nucleus; L DN = left dentate nucleus; R FN = right fastigial nucleus; L FN = left fastigial nucleus; R IN = right interposed nucleus; L IN = left interposed nucleus).

FIGURE 4

The opposite effect of the baseline afferent and efferent pathways of functional connectivity of the cerebellum for visuomotor learning. The higher baseline functional connectivity of the cerebro-cerebellar pathway, the better accuracy learning performance; and the lower baseline functional connectivity of the cerebellar-cerebral pathway, the better stability learning performance in the visuomotor task. Functional connectivity in the efferent dentato-cerebral pathway is related to the dentato-thalamo-cortical pathway, in which the dentate nucleus reduces inhibition signals from Purkinje cells. The disinhibition of these inhibitory projections is essential for visuomotor learning. (M1 = motor cortex; DN = dentate nucleus; CbC = cerebellar cortex).