Cognitive training in Parkinson’s disease induces local, not global, changes in white matter microstructure

ABSTRACT Previous studies have shown that cognitive training can improve cognitive performance in various neurodegenerative diseases but relatively little is known about the effects of cognitive training on the brain. Here we investigated the effects of our cognitive training paradigm, COGTIPS, on regional white matter microstructure and topology of the structural network. We previously showed that COGTIPS has small, positive effects on processing speed. A subsample of 79 PD patients (N=40 cognitive training group, N=39 active control group) underwent multi-shell diffusion weighted imaging pre- and post-intervention. Our pre-registered analysis plan (osf.io/cht6g) entailed calculating white matter microstructural integrity in five tracts of interest, including the anterior thalamic radiation (ATR) and calculating the topology of the structural connectome. Training-induced changes were analyzed with linear mixed-models. Relative to the active control condition, cognitive training had no effect on network topology. Cognitive training did lead to a reduction in fractional anisotropy in the ATR (B[SE]: -0.32 [0.12], p=0.01). This reduction was associated with faster responses on the ToL task (r = 0.42, P = 0.007), but this just fell short of our statistical threshold (P<0.006). Post-hoc analyses showed that this was not due to changes in fiber density and cross-section, suggesting that that the observed effect in the ATR are due to training-induced alterations in neighboring fibers running through the same voxels, such as intra-striatal and thalamo-striatal fibers. These results indicate that eight weeks of cognitive training do not alter network topology, but can have subtle local effects on structural connectivity.