Chronic stroke results in significant downstream changes at connected cortical sites. However, less is known about the impact of cortical stroke on cerebellar structure. Here, we examined the relationship between chronic stroke, cerebellar volume, cerebellar symmetry, language impairment, and treatment trajectories in a large cohort ( N = 249) of chronic left hemisphere (LH) stroke patients with aphasia, using a healthy aging cohort ( N = 244) as control data. Cerebellar gray matter volume was significantly reduced in chronic LH stroke relative to healthy control brains. Within the chronic LH stroke group, we observed a robust relationship between cerebellar volume, lesion size, and days post-stroke. Notably, the extent of cerebellar atrophy in chronic LH patients, particularly in the contralesional (right) cerebellar gray matter, explained significant variability in post-stroke aphasia severity, as measured by the Western Aphasia Battery—Revised, above and beyond traditional considerations such as cortical lesion size, days post-stroke, and demographic measures (age, race, sex). In a subset of participants that took part in language treatment studies, greater cerebellar gray matter volume was associated with greater treatment gains. These data support the importance of considering both cerebellar volume and symmetry in models of post-stroke aphasia severity and recovery.

Sentence structure, or syntax, is potentially a uniquely creative aspect of the human mind. Neuropsychological experiments in the 1970s suggested parallel syntactic production and comprehension deficits in agrammatic Broca’s aphasia, thought to result from damage to syntactic mechanisms in Broca’s area in the left frontal lobe. This hypothesis was sometimes termed overarching agrammatism , converging with developments in linguistic theory concerning central syntactic mechanisms supporting language production and comprehension. However, the evidence supporting an association among receptive syntactic deficits, expressive agrammatism, and damage to frontal cortex is equivocal. In addition, the relationship among a distinct grammatical production deficit in aphasia, paragrammatism, and receptive syntax has not been assessed. We used lesion-symptom mapping in three partially overlapping groups of left-hemisphere stroke patients to investigate these issues: grammatical production deficits in a primary group of 53 subjects and syntactic comprehension in larger sample sizes ( N = 130, 218) that overlapped with the primary group. Paragrammatic production deficits were significantly associated with multiple analyses of syntactic comprehension, particularly when incorporating lesion volume as a covariate, but agrammatic production deficits were not. The lesion correlates of impaired performance of syntactic comprehension were significantly associated with damage to temporal lobe regions, which were also implicated in paragrammatism, but not with the inferior and middle frontal regions implicated in expressive agrammatism. Our results provide strong evidence against the overarching agrammatism hypothesis. By contrast, our results suggest the possibility of an alternative grammatical parallelism hypothesis rooted in paragrammatism and a central syntactic system in the posterior temporal lobe.

The role of left inferior frontal cortex (LIFC) in canonical sentence comprehension is controversial. Many studies have found involvement of LIFC in sentence production or complex sentence comprehension, but negative or mixed results are often found in comprehension of simple or canonical sentences. We used voxel-, region-, and connectivity-based lesion symptom mapping (VLSM, RLSM, CLSM) in left-hemisphere chronic stroke survivors to investigate canonical sentence comprehension while controlling for lexical-semantic, executive, and phonological processes. We investigated how damage and disrupted white matter connectivity of LIFC and two other language-related regions, the left anterior temporal lobe (LATL) and posterior temporal-inferior parietal area (LpT-iP), affected sentence comprehension. VLSM and RLSM revealed that LIFC damage was not associated with canonical sentence comprehension measured by a sensibility judgment task. LIFC damage was associated instead with impairments in a lexical semantic similarity judgment task with high semantic/executive demands. Damage to the LpT-iP, specifically posterior middle temporal gyrus (pMTG), predicted worse sentence comprehension after controlling for visual lexical access, semantic knowledge, and auditory-verbal short-term memory (STM), but not auditory single-word comprehension, suggesting pMTG is vital for auditory language comprehension. CLSM revealed that disruption of left-lateralized white-matter connections from LIFC to LATL and LpT-iP was associated with worse sentence comprehension, controlling for performance in tasks related to lexical access, auditory word comprehension, and auditory-verbal STM. However, the LIFC connections were accounted for by the lexical semantic similarity judgment task, which had high semantic/executive demands. This suggests that LIFC connectivity is relevant to canonical sentence comprehension when task-related semantic/executive demands are high.

The fundamental distinction of grammatical deficits in aphasia, agrammatism and paragrammatism, was made over a century ago. However, the extent to which the agrammatism/paragrammatism distinction exists independently of differences in speech fluency has not clearly been investigated. Despite much research on agrammatism, the lesion correlates of paragrammatism are essentially unknown. Lesion-symptom mapping was used to investigate the degree to which the lesion correlates of agrammatism and paragrammatism overlap or dissociate. Four expert raters assessed videos of 53 right-handed patients with aphasia following chronic left-hemisphere stroke retelling the Cinderella story. Consensus discussion determined each subject’s classification with respect to grammatical deficits as Agrammatic, Paragrammatic, Both, or No Grammatical Deficit. Each subject’s lesion was manually drawn on a high-resolution MRI and warped to standard space for group analyses. Lesion-symptom mapping analyses were performed in NiiStat including lesion volume as a covariate. Secondary analyses included speech rate (words per minute) as an additional covariate. Region of interest analyses identified a double dissociation between these syndromes: damage to Broca’s area was significantly associated with agrammatism, p = 0.001 (but not paragrammatism, p = 0.930), while damage to the left posterior superior and middle temporal gyri was significantly associated with paragrammatism, p < 0.001 (but not agrammatism, p = 0.873). The same results obtained when regressing out the effect of speech rate, and nonoverlapping lesion distributions between the syndromes were confirmed by uncorrected whole brain analyses. Our results support a fundamental distinction between agrammatism and paragrammatism.