After a stroke, individuals with aphasia often recover to a certain extent over time. This recovery process may be dependent on the health of surviving brain regions. Leukoaraiosis (white matter hyperintensities on MRI reflecting cerebral small vessel disease) is one indication of compromised brain health and is associated with cognitive and motor impairment. Previous studies have suggested that leukoaraiosis may be a clinically relevant predictor of aphasia outcomes and recovery, although findings have been inconsistent. We investigated the relationship between leukoaraiosis and aphasia in the first year after stroke. We recruited 267 patients with acute left hemispheric stroke and coincident fluid attenuated inversion recovery MRI. Patients were evaluated for aphasia within 5 days of stroke, and 174 patients presented with aphasia acutely. Of these, 84 patients were evaluated at ∼3 months post-stroke or later to assess longer-term speech and language outcomes. Multivariable regression models were fit to the data to identify any relationships between leukoaraiosis and initial aphasia severity, extent of recovery, or longer-term aphasia severity. We found that leukoaraiosis was present to varying degrees in 90% of patients. However, leukoaraiosis did not predict initial aphasia severity, aphasia recovery, or longer-term aphasia severity. The lack of any relationship between leukoaraiosis severity and aphasia recovery may reflect the anatomical distribution of cerebral small vessel disease, which is largely medial to the white matter pathways that are critical for speech and language function.

Imaging studies of language processing in clinical populations can be complicated to interpret for several reasons, one being the difficulty of matching the effortfulness of processing across individuals or tasks. To better understand how effortful linguistic processing is reflected in functional activity, we investigated the neural correlates of task difficulty in linguistic and non-linguistic contexts in the auditory modality and then compared our findings to a recent analogous experiment in the visual modality in a different cohort. Nineteen neurologically normal individuals were scanned with fMRI as they performed a linguistic task (semantic matching) and a non-linguistic task (melodic matching), each with two levels of difficulty. We found that left hemisphere frontal and temporal language regions, as well as the right inferior frontal gyrus, were modulated by linguistic demand and not by non-linguistic demand. This was broadly similar to what was previously observed in the visual modality. In contrast, the multiple demand (MD) network, a set of brain regions thought to support cognitive flexibility in many contexts, was modulated neither by linguistic demand nor by non-linguistic demand in the auditory modality. This finding was in striking contradistinction to what was previously observed in the visual modality, where the MD network was robustly modulated by both linguistic and non-linguistic demand. Our findings suggest that while the language network is modulated by linguistic demand irrespective of modality, modulation of the MD network by linguistic demand is not inherent to linguistic processing, but rather depends on specific task factors.

Recovery from aphasia is thought to depend on neural plasticity, that is, the functional reorganization of surviving brain regions such that they take on new or expanded roles in language processing. We carried out a systematic review and meta-analysis of all articles published between 1995 and early 2020 that have described functional imaging studies of six or more individuals with post-stroke aphasia, and have reported analyses bearing on neuroplasticity of language processing. Each study was characterized and appraised in detail, with particular attention to three critically important methodological issues: task performance confounds, contrast validity, and correction for multiple comparisons. We identified 86 studies describing a total of 561 relevant analyses. We found that methodological limitations related to task performance confounds, contrast validity, and correction for multiple comparisons have been pervasive. Only a few claims about language processing in individuals with aphasia are strongly supported by the extant literature: First, left hemisphere language regions are less activated in individuals with aphasia than in neurologically normal controls; and second, in cohorts with aphasia, activity in left hemisphere language regions, and possibly a temporal lobe region in the right hemisphere, is positively correlated with language function. There is modest, equivocal evidence for the claim that individuals with aphasia differentially recruit right hemisphere homotopic regions, but no compelling evidence for differential recruitment of additional left hemisphere regions or domain-general networks. There is modest evidence that left hemisphere language regions return to function over time, but no compelling longitudinal evidence for dynamic reorganization of the language network.