Brain : a journal of neurology
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Disconnection of cognitively important processing regions by injury to the interconnecting white matter provides a potential mechanism for cognitive dysfunction in multiple sclerosis. The contribution of tract-specific white matter injury to dysfunction in different cognitive domains in patients with multiple sclerosis has not previously been studied. We apply tract-based spatial statistics (TBSS) to diffusion tensor imaging (DTI) in a cohort of multiple sclerosis patients to identify loci where reduced white matter tract fractional anisotropy (FA) predicts impaired performance in cognitive testing. ⋯ Cognitively relevant tract localizations only partially overlapped with areas of high FLAIR lesion probability, confirming the contribution of normal-appearing white matter abnormality to cognitive dysfunction. Of note, tract localizations showing significant associations with cognitive impairment were found to interconnect cortical regions thought to be involved in processing in these cognitive domains, or involve possible compensatory processing pathways. This suggests that TBSS reveals functionally relevant tract injury underlying cognitive dysfunction in patients with multiple sclerosis.