Cerebellar Contributions to Whole-Brain Resting-State Networks: A Combined Tdcs-Fmri Study

Background:  Differences in cerebellar structure and function are amongst the most consistent neural findings in autism spectrum disorder (ASD). In particular, right lobule VII of the cerebellum (including Crus I/II) show grey matter reductions and differences in activation patterns in ASD individuals. This region is structurally and functionally connected to association regions of the cerebral cortex, participating in cerebro-cerebellar loops that form part of cognitive control and default mode networks. It has been proposed that the cerebellum is important in both the optimization of structure and function in the cerebral cortex during development, providing a framework for understanding a potential role for the cerebellum in ASD. However, the effects of cerebellar activity on these broader cerebro-cerebellar circuits is not yet clear, even in typically-developing (TD) adults. 

Objectives:  Here, we examined the effects of cerebellar transcranial direct current stimulation (tDCS) on resting-state functional connectivity patterns in TD young adults. We hypothesized that right cerebellar tDCS would modulate neural activation patterns throughout the brain, particularly in frontoparietal and default mode networks (DMN). 

Methods:  We combined 20min of 1.5 mA anodal or sham tDCS over the right posterolateral cerebellum with functional MRI in TD adults (n=27; µ=24.4 years old). Sixteen participants received active tDCS, and 11 participants received sham tDCS, where the current is ramped up over 15s and then ramped down before any clinically significant current is applied. The active (anodal) electrode was placed over the right posterolateral cerebellum (1cm down and 4cm over from inion; estimated to be over lobule VII) and the reference electrode was placed on the right pectoral muscle. Seven minutes of resting-state functional images were acquired both pre- and post-tDCS (47 interleaved slices, 168 volumes, TR 2500ms, TE 30ms, 3.2mm isotropic voxels, flip angle 90º, FOV 205mm). 

Results:  Relative to sham, anodal tDCS increased activation in right cerebellar Crus I/II. When functional connectivity was examined between right Crus I and the rest of the brain (seed-to-voxel analysis), we found that tDCS modulated cortical resting-state connectivity, shifting right Crus I connectivity patterns outside of canonically connected networks. Specifically, within frontoparietal networks, anodal tDCS increased functional connectivity between right Crus I of the cerebellum and the anterior cingulate cortex, regions that are typically anti-correlated in the frontoparietal network. Within the DMN, anodal tDCS increased functional connectivity between the right Crus I of the cerebellum and the bilateral precuneus (a DMN node) as well as occipital regions. 

Conclusions:  These preliminary results are consistent with the proposed role of the right posterolateral cerebellum in the modulation of broader cerebro-cerebellar networks. When anodal tDCS is applied over the right cerebellum in TD adults, the functional connectivity acquires an ASD-like pattern – increased out-of-network functional connectivity within frontoparietal cognitive control networks, and increased cerebro-cerebellar functional connectivity both within the DMN as well as outside of canonical DMN nodes. These findings are consistent with the deficits in resting-state network segregation found in ASD and provide testable hypotheses for future application of cerebellar tDCS in ASD populations.