White Matter Predictors of Cerebellar tDCS Treatment Effects in Aphasia Rehabilitation

Micah Alan Johnson¹Zafer Keser²Becky Lammers³Myra Sydnor³Jamie Murter³Patrick Sadil¹Yiyang Zhang⁴John Desmond⁵Argye Hillis^3,5,6Martin A Lindquist¹Rajani Sebastian^3*

• ¹Johns Hopkins University Bloomberg School of Public Health, Baltimore, United States
• ²Department of Neurology, Mayo Clinic, Rochester, MN, United States
• ³Johns Hopkins Medicine Department of Physical Medicine and Rehabilitation, Baltimore, United States
• ⁴University of California Los Angeles Department of Psychology, Los Angeles, United States
• ⁵Johns Hopkins Medicine Department of Neurology and Neurosurgery, Baltimore, United States
• ⁶Johns Hopkins University Department of Cognitive Science, Baltimore, United States

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. In this secondary analysis of data from a previously conducted clinical trial (ClinicalTrials.gov ID: NCT02901574) using 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, as measured by fractional anisotropy (FA) and mean diffusivity (MD) from diffusion tensor imaging (DTI), can predict or moderate longitudinal treatment effects (post-treatment, 2-weeks post-treatment, 2-months post-treatment). We also tested whether there are differential effects between trained and untrained language tasks and between cerebellar tDCS polarity (anodal and cathodal). We showed that baseline measures of tracts connecting the left lesioned cortex to the right posterolateral cerebellum (stimulation target) influenced treatment gains, relative to sham control, for untrained tasks but, 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 across all tasks and tracts was that the 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. 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.