Polarity-dependent modulation of sensory circuits by cerebellar tDCS: local and distant effects

Abstract Cerebellar transcranial direct current stimulation (Cb-tDCS) is a promising tool for non-invasive modulation of cerebellar function and is under investigation for treating cerebellum-related disorders. However, its local and remote effects on sensory processing remain poorly understood. We investigated the immediate and long-term effects of Cb-tDCS on sensory-evoked responses in the cerebellum and primary somatosensory cortex (S1) of awake mice. Sensory-evoked potentials (SEPs) were recorded in Crus I/II and S1 during and after short (15 s) or long (20 min) sessions of anodal or cathodal Cb-tDCS. In addition, vGLUT1 and GAD65–67 immunoreactivity were quantified, and spectral changes in local field potentials were assessed. Anodal and cathodal Cb-tDCS respectively induced an immediate increase and decrease in the trigeminal component in Crus I/II but no aftereffects were observed 20 min post-stimulation. In S1, Cb-tDCS resulted in polarity and intensity-dependent modulation of the N1 component during stimulation, which was opposite to the changes induced in Crus I/II, as well as a polarity-dependent modulation after stimulation. In addition, anodal Cb-tDCS was associated with reduced GAD65–67 immunoreactivity in S1, whereas vGLUT1 remained unchanged. While power spectrum analysis revealed no changes in Crus I/II, Cb-tDCS induced polarity-dependent post-stimulation changes in S1 spectral power, with higher values after cathodal stimulation. These findings show that Cb-tDCS differentially modulates sensory processing in cerebellar and cortical circuits. While cerebellar effects are mainly transient, stimulation induces longer-lasting changes in the remote cortical area investigated, S1. This underscores the need to consider both local and distant network effects when applying Cb-tDCS in translational and clinical settings. Competing Interest Statement The authors have declared no competing interest. Footnotes Declaration of interests: The authors declare no competing financial interests. This version includes a full reanalysis of the electrophysiological, immunohistochemical, and spectral datasets using linear mixed effects models. As a result, the Statistical Analysis, Results, and several figures were updated. The revised analyses confirmed the main conclusions of the study while refining some specific interpretations, particularly for long term SEP effects and spectral power changes. The manuscript was also edited throughout to improve clarity and precision. The Abstract, Methods, Results, Discussion, and figure legends were revised, methodological details were expanded, and some interpretations were made more cautious. Individual data points were added to selected figures, and the source data underlying the main figures are now publicly available in Zenodo.