A big role for the little brain: Investigating sequence learning in the cerebellum using tDCS and fMRI - proposed research

In this project we will investigate the contribution of the cerebellum to motor sequence learning. Although sequencing has been proposed as the basic mechanism of cerebellar functioning, there is a stark discrepancy in empirical research in the domain of motor sequence learning, which generally attributes this role to the basal ganglia and association motor cortices, while the cerebellum is often overlooked. To elucidate the role of the cerebellum in motor sequence learning we will combine behavioral experiments, using the serial reaction time task (SRT task), with transcranial direct current stimulation (tDCS) and functional magnetic resonance imaging (fMRI). We will carry out multiple double-blind, sham-controlled experiments in healthy young adults. First, we will investigate the behavioral effects of repeated sessions of cerebellar tDCS on sequence learning by administering anodal (experiment 1) and cathodal (experiment 2) cerebellar tDCS (2 mA; 20 minutes each) during an SRT task, over the course of 5 daily sessions (s1-s5), in a between-subjects design (n=50 for experiment 1; n = 50 for experiment 2; participants will be randomly assigned to a real or sham cerebellar tDCS group in each experiment). We will then analyze the effect of repeated stimulation on the consolidation of sequence learning after a delay of 1 week (s6). Secondly, we will carry out two concurrent tDCS/fMRI experiments with the same task, in a within-subjects crossover design, counterbalanced across participants (n=30 per experiment). For each study, we will scan our participants four times: first (Scan 1) during their initial session of anodal (experiment 3) or cathodal (experiment 4) cerebellar tDCS, and for a second time (Scan 2), without tDCS, after one week from the last tDCS session (depending on the outcome of experiments 1 and 2, up to 4 intermediate tDCS-only sessions might be included between Scan 1 and Scan 2). After a washout period of 14 days participants will undergo the opposite stimulation condition. Dynamic causal modelling (DCM) will be used to study the interconnections between cerebellar, basal ganglia, and cerebral regions. Together, this will provide a comprehensive framework of the neural organization of sequential motor learning and clarify the potential sequence-specific role of the cerebellum.