Understanding a word requires mapping sounds to a word-form and then identifying its correct meaning, which in some cases necessitates the recruitment of cognitive control processes to direct the activation of semantic knowledge in a task appropriate manner (i.e., semantic control). Neuroimaging and neuropsychological studies identify a fronto-temporal network important for word comprehension. However, little is known about the connectional architecture subserving controlled retrieval and selection of semantic knowledge during word comprehension. We used diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rs-fMRI) in aphasic individuals with varying degrees of word comprehension deficits to examine the role of three white matter pathways within this network: the uncinate fasciculus (UF), inferior longitudinal fasciculus (ILF), and inferior fronto-occipital fasciculus (IFOF). Neuroimaging data from a group of age-matched controls were also collected in order to establish that the patient group had decreased structural and functional connectivity profiles. We obtained behavioral data from aphasic participants on two measures of single word comprehension that involve semantic control, and assessed pathway functional significance by correlating patients' performance with indices of pathway structural integrity and the functional connectivity profiles of regions they connect. Both the structural integrity of the UF and the functional connectivity strength of regions it connects predicted patients' performance. This result suggests the semantic control impairment in word comprehension resulted from poor neural communication between regions the UF connects. Inspections of other subcortical and cortical structures revealed no relationship with patients' performance. We conclude that the UF mediates semantic control during word comprehension by connecting regions specialized for cognitive control with those storing word meanings. These findings also support a relationship between structural and functional connectivity measures, as the rs-fMRI results provide converging evidence with those obtained using DTI.
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