Independent contributions of language activations in left and right temporal cortex to aphasia outcomes after stroke

Recovery from aphasia after stroke has been hypothesized to depend on neuroplasticity in surviving brain regions. Many studies have investigated this process, but progress has been impeded by methodological limitations relating to task performance confounds, contrast validity, and sample sizes. Furthermore, few studies have accounted for the complex relationships that exist between patterns of structural damage, distributed networks of functional activity, and behavioral outcomes. The present cross-sectional study aimed to overcome these critical methodological limitations and to disentangle the relationships between structure, function, and behavior. We recruited 70 individuals with post-stroke aphasia and 45 neurologically normal comparison participants. We used a valid and reliable language mapping fMRI paradigm that adapted dynamically to each participants task performance, and carried out whole-brain permutation analyses along with hypothesis-driven analyses of individually defined functional regions of interest (ROIs). Multivariable models were constructed that incorporated lesion load estimates derived from machine learning and language activations across multiple brain regions. We found strong evidence that left posterior temporal cortex is the most critical region for language processing in post-stroke aphasia: functional activity in this region was reduced in aphasia, predictive of aphasia outcomes in a whole-brain analysis above and beyond the contribution of lesion load, and remained predictive even above and beyond other functional predictors, with a medium effect size (f2 = 0.15). We also found that right posterior temporal cortex made an independent contribution to aphasia outcomes: functional activity was attenuated in aphasia, suggesting diaschisis, yet was predictive of aphasia outcomes above and beyond left hemisphere lesion load and functional predictors, with a small effect size (f2 = 0.08). We corroborated the importance of left frontal cortex: functional activity was attenuated in aphasia and predictive of aphasia outcomes over and beyond the contribution of lesion load; however, unlike in the bilateral temporal regions, functional activity in the left frontal lobe did not remain predictive once other functional predictors were included in the model. There was no support for other potential compensatory mechanisms such as recruitment of the right frontal lobe, the bilateral multiple demand network, or perilesional regions. Taken together, our findings demonstrate that functional imaging can provide critical insights into language processing in aphasia that cannot be obtained from structural imaging alone, with the left and right posterior temporal cortices making independent contributions to aphasia outcomes after stroke.