The multidimensional nature of aphasia recovery post-stroke.

Language is not a single function, but instead results from interactions between neural representations and computations that can be damaged independently of each other. Although there is now clear evidence that the language profile in post-stroke aphasia reflects graded variations along multiple underlying dimensions ('components'), it is still entirely unknown if these distinct language components have different recovery trajectories and rely on the same, or different, neural regions during aphasia recovery. Accordingly, this study examined whether language components in the subacute stage: (i) mirror those observed in the chronic stage; (ii) recover together in a homogeneous manner; and (iii) have recovery trajectories that relate to changing activation in distinct or overlapping underlying brain regions. We analysed longitudinal data from 26 individuals with mild-moderate aphasia following left hemispheric infarct who underwent functional MRI and behavioural testing at ∼2 weeks and ∼4 months post-stroke. The language profiles in early post-stroke aphasia reflected three orthogonal principal components consisting of fluency, semantic/executive function and phonology. These components did not recover in a singular, homogeneous manner; rather, their longitudinal trajectories were uncorrelated, suggesting that aphasia recovery is heterogeneous and multidimensional. Mean regional brain activation during overt speech production in unlesioned areas was compared with patient scores on the three principal components of language at both the early and late time points. In addition, the change in brain activation over time was compared with the change on each of the principal component scores, both before and after controlling for baseline scores. We found that different language components were associated with changing activation in multiple, non-overlapping bilateral brain regions during aphasia recovery. Specifically, fluency recovery was associated with increasing activation in bilateral middle frontal gyri and right temporo-occipital middle temporal gyrus; semantic/executive recovery was associated with reducing activation in bilateral anterior temporal lobes; while phonology recovery was associated with reducing activation in bilateral precentral gyri, dorso-medial frontal poles and the precuneus. Overlapping clusters in the ventromedial prefrontal cortex were positively associated with fluency recovery but negatively associated with semantic/executive and phonology recovery. This combination of detailed behavioural and functional MRI data provides novel insights into the neural basis of aphasia recovery. Because different aspects of language seem to rely on different neural regions for recovery, treatment strategies that target the same neural region in all stroke survivors with aphasia might be entirely ineffective or even impair recovery, depending on the specific language profile of each individual patient.