Thalamic disconnection from prefrontal cognitive control networks contributes to thalamic aphasia

Abstract

Language impairments after thalamic lesions, referred to as thalamic aphasia, underscore a subcortical involvement in language processing. In this study, we investigated how the thalamus structurally connects to the cortex to support language functions. Our hypothesis posits that disconnection of white matter tracts between the left thalamus and regions of left hemisphere language and cognitive control networks, such as prefrontal, inferior frontal, and temporal cortices, are associated with thalamic aphasia. We employed a non-parametric lesion-network mapping approach in a retrospective cohort of patients with first-ever thalamic stroke. This method enables the identification of structural disconnections that disrupt signal transmission along white matter fibre pathways, subsequently impairing processing within brain networks. To investigate potential associations between disconnection patterns and thalamic aphasia, we individually mapped fibre tracts affected by the thalamic stroke lesions using diffusion-weighted normative structural connectome data. Statistical comparisons were then made between disconnection maps of patients with and without language impairments. The study encompassed 101 patients, with a mean age of 64.1 years (standard deviation, 14.6), including 57 patients with left-sided, 42 with right-sided, and 2 with bilateral thalamic lesions. We observed that language impairments were linked to disconnection of fibres in the left anterior limb of the internal capsule. These fibres constitute a pathway within the anterior thalamic radiation, connecting the mediodorsal thalamus to a region in the left dorsomedial prefrontal cortex. An additional exploratory analysis revealed functional connectivity between this cortical area and the left hemisphere’s language-related inferior frontal and lateral temporal cortices. Meanwhile, we found no evidence for direct structural disconnection between the thalamus and left inferior frontal or temporal cortices. Interrupted signalling along the left anterior thalamic radiation to the left dorsomedial prefrontal cortex is a potential mechanism underlying thalamic aphasia. Given its significance for the subcortical involvement in language processing, our findings suggest a plausible path for thalamic signals to participate in the interplay between networks for cognitive control and language processing.