The loss and recovery of language functions are still incompletely understood. This longitudinal functional MRI study investigated the neural mechanisms underlying language recovery in patients with post-stroke aphasia putting particular emphasis on the impact of lesion site. To identify patterns of language-related activation, an auditory functional MRI sentence comprehension paradigm was administered to patients with circumscribed lesions of either left frontal (n = 17) or temporo-parietal (n = 17) cortex. Patients were examined repeatedly during the acute (≤1 week, t1), subacute (1–2 weeks, t2) and chronic phase (>6 months, t3) post-stroke; healthy age-matched control subjects (n = 17) were tested once. The separation into two patient groups with circumscribed lesions allowed for a direct comparison of the contributions of distinct lesion-dependent network components to language reorganization between both groups. We hypothesized that activation of left hemisphere spared and perilesional cortex as well as lesion-homologue cortex in the right hemisphere varies between patient groups and across time. In addition, we expected that domain-general networks serving cognitive control independently contribute to language recovery. First, we found a global network disturbance in the acute phase that is characterized by reduced functional MRI language activation including areas distant to the lesion (i.e. diaschisis) and subsequent subacute network reactivation (i.e. resolution of diaschisis). These phenomena were driven by temporo-parietal lesions. Second, we identified a lesion-independent sequential activation pattern with increased activity of perilesional cortex and bilateral domain-general networks in the subacute phase followed by reorganization of left temporal language areas in the chronic phase. Third, we observed involvement of lesion-homologue cortex only in patients with frontal but not temporo-parietal lesions. Fourth, irrespective of lesion location, language reorganization predominantly occurred in pre-existing networks showing comparable activation in healthy controls. Finally, we detected different relationships of performance and activation in language and domain-general networks demonstrating the functional relevance for language recovery. Our findings highlight that the dynamics of language reorganization clearly depend on lesion location and hence open new perspectives for neurobiologically motivated strategies of language rehabilitation, such as individually-tailored targeted application of neuro-stimulation.

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Polymorphisms in ORMDL genes are associated with asthma. Asthmatics exhibit increased ORMDL levels, suggesting that ORMDLs contribute to asthma. Formation of heterooligomers and similar interaction patterns with proteins involved in calcium homeostasis and sphingolipid metabolism could indicate shared biological roles of ORMDLs, influencing airway remodeling and hyperresponsiveness.

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