Beneficial effects of cerebellar tDCS on motor learning are associated with altered putamen-cerebellar connectivity: a simultaneous tDCS-fMRI study

Abstract

Non-invasive transcranial stimulation of cerebellum and primary motor cortex (M1) has been shown to enhance motor learning. However, the mechanisms by which stimulation improves learning remain largely unknown. Here, we sought to shed light on the neural correlates of transcranial direct current stimulation (tDCS) during motor learning by simultaneously recording functional magnetic resonance imaging (fMRI). We found that right cerebellar tDCS, but not left M1 tDCS, led to enhanced sequence learning in the serial reaction time task. Performance was also improved following cerebellar tDCS compared to sham in a sequence production task, reflecting superior training effects persisting into the post-training period. These behavioral effects were accompanied by increased learning-specific activity in right M1, left cerebellum lobule VI, left inferior frontal gyrus and right inferior parietal lobule during cerebellar tDCS compared to sham. Despite the lack of group-level changes comparing left M1 tDCS to sham, activity increase in right M1, supplementary motor area, and bilateral superior frontal cortex, under M1 tDCS, was associated with better sequence performance. This suggests that lack of group effects in M1 tDCS relate to inter-individual variability in learning-related activation patterns. We further investigated how tDCS modulates effective connectivity in the cortico-striato-cerebellar learning network. Using dynamic causal modelling, we found altered connectivity patterns during both M1 and cerebellar tDCS when compared to sham. Specifically, during cerebellar tDCS, negative modulation of a connection from putamen to cerebellum was decreased for sequence learning only, effectively leading to decreased inhibition of the cerebellum. These results show specific effects of cerebellar tDCS on functional activity and connectivity in the motor learning network and may facilitate the optimization of motor rehabilitation involving cerebellar non-invasive stimulation.

Motor sequence learning deficits in idiopathic Parkinson’s disease are associated with increased substantia nigra activity

“…However, subjects of both groups made significantly more errors during random (RND) compared to sequence (SEQ) blocks. This effect is consistent with our previous findings in MSL tasks in healthy young subjects, in which larger error-rates in RND compared to SEQ blocks were found (Liebrand et al, 2020; Tzvi et al, 2016, 2015). Previously, we interpreted this effect as an implicit attempt to perform the sequence or chunks of the sequence in RND trials following sequence learning, however unsuccessfully.…”

“…We expected to find evidence for abnormal striatal activity in PD reflected in connections with putamen. Using Bayesian model selection, we found that in the optimal model in both pwPD and controls connections from M1 and premotor areas to cerebellum were modulated by the motor task, replicating our previous findings (Liebrand et al, 2020; Tzvi et al, 2017, 2015, 2014). Importantly, we found no evidence for differences in modulatory parameters between PD and controls.…”

Motor Sequence Learning across Multiple Sessions Is Not Facilitated by Targeting Consolidation with Posttraining tDCS in Patients with Progressive Multiple Sclerosis

“…However, besides local plasticity, online and offline stages of motor sequence learning rely on the dynamic recruitment of nodes of a distributed motor learning network that includes M1, the premotor cortex, the supplementary motor area, the cerebellum, basal ganglia, the hippocampus, and parietal cortical areas [ 40 – 45 ]. A recent fMRI study showed that alterations of sequence-specific motor learning in young healthy subjects induced by cerebellar tDCS were related to altered activity in M1, the cerebellum, the inferior frontal gyrus, and the right parietal lobule [ 46 ] suggesting that tDCS facilitated motor sequence learning by alterations of long-range network communication. Long-range network connectivity may be compromised in pwMS by both disease-related white matter lesions and affection of grey matter [ 47 ].…”

Cerebellar rTMS and PAS effectively induce cerebellar plasticity

“…To induce plasticity, we used procedures previously described to be effective in inducing plasticity in the cerebellum. In experiment 1, 1 Hz rTMS 50 , PAS 17 , cTBS 44,51 , and anodal tDCS [64][65][66] was used. 1 Hz rTMS was administered with 90% RMT for 20 min using a Magstim Rapid magnetic stimulator (Magstim Company, Whitland, Dyfed, UK) 50 .…”