Cognitive outcome is related to functional thalamo-cortical connectivity after paediatric stroke

Abstract

The thalamus has complex connections with the cortex and is involved in various cognitive processes. Despite increasing interest in the thalamus and the underlying thalamo-cortical interaction, little is known about thalamo-cortical connections after pediatric arterial ischemic stroke. Therefore, the aim of this study was to investigate thalamo-cortical connections and their association with cognitive performance after arterial ischemic stroke. Twenty patients in the chronic phase after pediatric arterial ischemic stroke (≥ 2 years after diagnosis, diagnosed <16 years; aged 5–23 years, mean 15.1 years) and twenty healthy controls matched for age and sex were examined in a cross-sectional study design. Cognitive performance (selective attention, inhibition, working memory, and cognitive flexibility) was evaluated using standardized neuropsychological tests. Resting-state functional magnetic resonance imaging was used to examine functional thalamo-cortical connectivity. Lesion masks were integrated in the preprocessing pipeline to ensure that structurally damaged voxels did not influence functional connectivity analyses. Cognitive performance (selective attention, inhibition and working memory) was significantly reduced in patients compared to controls. Network analyses revealed significantly lower thalamo-cortical connectivity for the motor, auditory, visual, default mode network, salience, left/right executive and dorsal attention network in patients compared to controls. Interestingly, analyses revealed as well higher thalamo-cortical connectivity in some subdivisions of the thalamus for the default mode network (medial nuclei), motor (lateral nuclei), dorsal attention (anterior nuclei), and the left executive network (posterior nuclei) in patients compared to controls. Increased and decreased thalamo-cortical connectivity strength within the same networks was, however, found in different thalamic sub-divisions. Thus, alterations in thalamo-cortical connectivity strength after pediatric stroke seem to point in both directions, with stronger as well as weaker thalamo-cortical connectivity in patients compared to controls. Multivariate linear regression, with lesion size and age as covariates, revealed significant correlations between cognitive performance (selective attention, inhibition, and working memory) and the strength of thalamo-cortical connectivity in the motor, auditory, visual, default mode network, posterior default mode network, salience, left/right executive, and dorsal attention network after childhood stroke. Our data suggest that the interaction between different sub-nuclei of the thalamus and several cortical networks relates to post-stroke cognition. The variability in cognitive outcomes after pediatric stroke might partly be explained by functional thalamo-cortical connectivity strength.