Transcranial direct current stimulation of cerebellum alters spiking precision in cerebellar cortex: A modeling study of cellular responses

Author summaryTranscranial direct current stimulation (tDCS) of the cerebellum is gaining momentum as a neuromodulation tool for the treatment of neurological diseases like movement disorders. Nonetheless, the response of cells in the cerebellum to tDCS is unclear and hardly generalizes from our understanding of tDCS of the cerebral cortex. We use computational models to investigate the response of several types of cerebellar neurons to the electric field induced by tDCS and show that, differently from the cerebral cortex, tDCS has significant acute effects on the cerebellar cortex. These effects (i) primarily alter the way Purkinje cells encode synaptic stimuli from the molecular layer and (ii) can help hyperactive cells regain postsynaptic spiking precision. Since the spatiotemporal precision of the Purkinje cell spiking is critical to learning and coordination, the study shows how tDCS can operate at the cellular level to treat movement disorders like tremor and ataxia. Transcranial direct current stimulation (tDCS) of the cerebellum has rapidly raised interest but the effects of tDCS on cerebellar neurons remain unclear. Assessing the cellular response to tDCS is challenging because of the uneven, highly stratified cytoarchitecture of the cerebellum, within which cellular morphologies, physiological properties, and function vary largely across several types of neurons. In this study, we combine MRI-based segmentation of the cerebellum and a finite element model of the tDCS-induced electric field (EF) inside the cerebellum to determine the field imposed on the cerebellar neurons throughout the region. We then pair the EF with multicompartment models of the Purkinje cell (PC), deep cerebellar neuron (DCN), and granule cell (GrC) and quantify the acute response of these neurons under various orientations, physiological conditions, and sequences of presynaptic stimuli. We show that cerebellar tDCS significantly modulates the postsynaptic spiking precision of the PC, which is expressed as a change in the spike count and timing in response to presynaptic stimuli. tDCS has modest effects, instead, on the PC tonic firing at rest and on the postsynaptic activity of DCN and GrC. In Purkinje cells, anodal tDCS shortens the repolarization phase following complex spikes (-14.7 +/- 6.5% of baseline value, mean +/- S.D.; max: -22.7%) and promotes burstiness with longer bursts compared to resting conditions. Cathodal tDCS, instead, promotes irregular spiking by enhancing somatic excitability and significantly prolongs the repolarization after complex spikes compared to baseline (+37.0 +/- 28.9%, mean +/- S.D.; max: +84.3%). tDCS-induced changes to the repolarization phase and firing pattern exceed 10% of the baseline values in Purkinje cells covering up to 20% of the cerebellar cortex, with the effects being distributed along the EF direction and concentrated in the area under the electrode over the cerebellum. Altogether, the acute effects of tDCS on cerebellum mainly focus on Purkinje cells and modulate the precision of the response to synaptic stimuli, thus having the largest impact when the cerebellar cortex is active. Since the spatiotemporal precision of the PC spiking is critical to learning and coordination, our results suggest cerebellar tDCS as a viable therapeutic option for disorders involving cerebellar hyperactivity such as ataxia.

Automated summary

This study investigates the acute effects of transcranial direct current stimulation (tDCS) on cerebellar neurons, particularly focusing on the response of Purkinje cells to the electric field induced by tDCS. The results show that tDCS significantly modulates the synaptic encoding and postsynaptic spiking precision of Purkinje cells in the cerebellar cortex, suggesting tDCS as a potential therapeutic option for movement disorders involving cerebellar hyperactivity such as ataxia.