Cerebellar tDCS modulates cortico-cortical functional networks in a regionally specific manner

Document Type

Journal Article

Publication Date

10-23-2025

Journal

The Journal of neuroscience : the official journal of the Society for Neuroscience

DOI

10.1523/JNEUROSCI.0499-25.2025

Abstract

With extensive anatomical interconnections with the cerebral cortex, the cerebellum is well-positioned to coordinate communication between cortical regions. Because different cerebellar subregions interconnect with distinct cortical networks, the impact of regional cerebellar activity should be network-specific. However, it is unclear whether or how cerebellar modulation impacts the functional connectivity of human cerebral cortical networks. To test this, young adults (n=33, 21.2±3.1 years, 22M/11F) were randomly assigned to receive 20min of 1.5mA transcranial direct current stimulation (tDCS) targeting either the posterior midline (n=17) or right posterolateral cerebellum (n=16). Each participant received anodal (excitatory), cathodal (inhibitory) or sham tDCS during separate MRI sessions. We analyzed post-tDCS resting-state fMRI data to determine whether modulating different cerebellar subregions impacted resting-state functional connectivity (FC) of distinct cortical networks. Multivariate Pattern Analyses revealed that posterior midline tDCS primarily modulated FC in the default mode network (DMN), while posterolateral cerebellar tDCS altered FC in the frontoparietal network (FPN). Seed-based connectivity analyses confirmed that posterior midline modulation increased within-network DMN FC while decreasing FC between DMN, visual, and somatomotor networks. In contrast, posterolateral cerebellar tDCS strengthened frontoparietal and attentional network FC while decoupling FPN-DMN and FPN-visual networks. These results support the hypothesis that the cerebellum modulates cortico-cortical connectivity and further suggest that the posterior midline modulates the DMN while the posterolateral cerebellum shifts the brain toward a task-ready cognitive state. These findings provide insight into how the cerebellum influences the cerebral cortex and have clinical implications for targeted interventions for a range of neurological and psychiatric conditions. The cerebellum is extensively interconnected with the cerebral cortex, and it has been proposed that the cerebellum modulates cortico-cortical functional interactions. Confirming this, transcranial direct current stimulation (tDCS) targeting two cerebellar subregions modulated functional connectivity in different cortico-cortical networks. TDCS targeting the posterior cerebellar midline altered functional connectivity in regions of the default mode network. Right posterolateral cerebellar tDCS primarily impacted the functional connectivity of the fronto-parietal network. These data confirm that the cerebellum modulates interactions between cortical networks in a topographically-specific manner and could inform therapeutic interventions using cerebellar neuromodulation for a range of neurological and psychiatric conditions.

Department

Neurology

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