Murter, Jamie L.

Introduction Cerebellar transcranial direct current stimulation (tDCS) combined with language therapy can aid in chronic aphasia recovery, but the neural mechanisms and biomarkers of treatment efficacy remain uncertain. Methods In this secondary analysis of data from a previously conducted clinical trial, we used a randomized, double-blind, sham-controlled, within-subject crossover design with a study sample of 19 participants with post-stroke aphasia. We assessed the degree to which baseline properties of cerebro-cerebellar white matter tracts can predict or moderate longitudinal treatment effects at three time points: post-treatment, 2 weeks post-treatment, and 2 months post-treatment. Tract properties were measured by fractional anisotropy (FA) and mean diffusivity (MD) from diffusion tensor imaging (DTI). We also tested whether there are differential effects between trained and untrained language tasks and between cerebellar tDCS polarity (anodal and cathodal). Results Baseline measures of tracts connecting the left lesioned cortex to the right posterolateral cerebellum (stimulation target) influenced treatment gains for untrained tasks, relative to sham control. In contrast, for the trained task, treatment gains were influenced by baseline measures of tracts connecting the non-stimulated left cerebellum with the contralateral right cerebral cortex. Although there were no consistent effects from cerebellar tDCS polarity, a highly consistent pattern emerged across all tasks and tracts. Specifically, language improvements were predicted by a baseline tract profile (i.e., higher FA and lower MD) typically associated with higher white matter integrity, especially within the context of stroke-induced white matter decline. Discussion These findings corroborate the potential for baseline tract properties as a biomarker of treatment efficacy and support the notion that adjuvant (cerebellar tDCS + language) therapy preferentially benefits individuals with relatively preserved structural connections within functionally relevant networks. Clinical trial registration ClinicalTrials.gov , identifier (NCT02901574).

Introduction: The influence of the cerebellum in poststroke aphasia recovery is poorly understood. Despite the right cerebellum being identified as a critical region involved in both language and cognitive functions, little is known about functional connections between the cerebellum and bilateral cortical hemispheres following stroke. This study investigated the relationship between chronic poststroke naming deficits and cerebello-cerebral resting-state functional connectivity (FC). Methods: Twenty-five cognitively normal participants and 42 participants with chronic poststroke aphasia underwent resting-state functional magnetic resonance imaging. Participants with aphasia also underwent language assessment. We conducted regions of interest (ROI)-to-ROI analyses to investigate the FC between the right cerebellar Crus I/II (seed ROI; Cereb1r/Cereb2r) and bilateral cortical language regions and compared these results to cognitively normal controls. Single-subject connectivity parameters were extracted and used as independent variables in a stepwise multiple linear regression model associating Boston Naming Test (BNT) score with FC measures. Results: FC analyses demonstrated correlations between the right cerebellar Crus I/II and both left and right cortical regions for both cognitively normal controls and stroke participants. Additionally, aphasia severity and lesion load had an effect on the cerebello-cerebral network connectivity in participants with aphasia. In a stepwise multiple linear regression, controlling for aphasia severity, time poststroke and lesion load, FC between the right Cereb2–left Cereb1 (standardized beta [std B]= −0.255, p < 0.004), right Cereb2–right anterior MTG (std B = 0.259, p < 0.004), and the right Cereb2–left anterior STG (std B = −0.208, p < 0.018) were significant predictors of BNT score. The overall model fit was R 2 = 0.786 ( p = 0.001). Conclusion: Functional connections between the right cerebellum and residual bilateral cerebral hemisphere regions may play a role in predicting naming ability in poststroke aphasia.