Speech entrainment (SE), the online mimicking of an audiovisual speech model, has been shown to increase speech fluency in patients with Broca's aphasia. However, not all individuals with aphasia benefit from SE. The purpose of this study was to identify patterns of cortical damage that predict a positive response SE's fluency-inducing effects. Forty-four chronic patients with left hemisphere stroke (15 female) were included in this study. Participants completed two tasks: 1) spontaneous speech production, and 2) audiovisual SE. Number of different words per minute was calculated as a speech output measure for each task, with the difference between SE and spontaneous speech conditions yielding a measure of fluency improvement. Voxel-wise lesion-symptom mapping (VLSM) was used to relate the number of different words per minute for spontaneous speech, SE, and SE-related improvement to patterns of brain damage in order to predict lesion locations associated with the fluency-inducing response to SE. Individuals with Broca's aphasia demonstrated a significant increase in different words per minute during SE versus spontaneous speech. A similar pattern of improvement was not seen in patients with other types of aphasia. VLSM analysis revealed damage to the inferior frontal gyrus predicted this response. Results suggest that SE exerts its fluency-inducing effects by providing a surrogate target for speech production via internal monitoring processes. Clinically, these results add further support for the use of SE to improve speech production and may help select patients for SE treatment.

We investigated the brain network involved in speech sensorimotor processing by studying patients with post-stroke aphasia using an altered auditory feedback (AAF) paradigm. We combined lesion-symptom-mapping analysis and behavioral testing to examine the pervasiveness of speech sensorimotor deficits and their relationship with cortical damage. Sixteen participants with aphasia and sixteen neurologically intact individuals completed a speech task under AAF. The task involved producing speech vowel sounds under the real-time pitch-shifted auditory feedback alteration. This task provided an objective measure for each individual's ability to compensate for mismatch (error) in speech auditory feedback. Results indicated that compensatory speech responses to AAF were significantly diminished in participants with aphasia compared with control. We observed that within the aphasic group, subjects with lower scores on the speech repetition task exhibited greater degree of diminished responses. Lesion-symptom-mapping analysis revealed that the onset phase (50-150 ms) of diminished AAF responses were predicted by damage to auditory cortical regions within the superior and middle temporal gyrus, whereas the rising phase (150-250 ms) and the peak (250-350 ms) of diminished AAF responses were predicted with damage to the inferior frontal gyrus and supramarginal gyrus areas, respectively. These findings suggest that damage to the auditory, motor, and auditory-motor integration networks are associated with impaired sensorimotor function for speech error processing. We suggest that a sensorimotor integration network, as revealed by brain regions related to temporal specific components of AAF responses, is related to speech processing and specific aspects of speech impairment, notably repetition deficits, in individuals with aphasia.

We aimed to identify neural regions where ischemia acutely after stroke is associated with impairment in phoneme discrimination, and to determine whether such deficits are associated with impairment of spoken word comprehension. We evaluated 33 patients within 48 h of left hemisphere ischemic stroke onset with tests of phoneme discrimination and word-picture matching. We identified Pearson correlations between accuracy in phoneme discrimination and accuracy of word comprehension and identified areas where the percentage of infarcted tissue was associated with severity of phoneme discrimination deficit. We found that 54% had deficits in phoneme discrimination relative to healthy controls. Accuracy in phoneme discrimination correlated with accuracy on word comprehension tests. Damage to left intraparietal sulcus and hypoperfusion and/or infarct of left superior temporal gyrus were associated with phoneme discrimination deficits acutely, although patients with these lesions showed improvement or resolution of the deficit by six months.

Sensory information is critical for movement control, both for defining the targets of actions and providing feedback during planning or ongoing movements. This holds for speech motor control as well, where both auditory and somatosensory information have been shown to play a key role. Recent clinical research demonstrates that individuals with severe speech production deficits can show a dramatic improvement in fluency during online mimicking of an audiovisual speech signal suggesting the existence of a visuomotor pathway for speech motor control. Here we used fMRI in healthy individuals to identify this new visuomotor circuit for speech production. Participants were asked to perceive and covertly rehearse nonsense syllable sequences presented auditorily, visually, or audiovisually. The motor act of rehearsal, which is prima facie the same whether or not it is cued with a visible talker, produced different patterns of sensorimotor activation when cued by visual or audiovisual speech (relative to auditory speech). In particular, a network of brain regions including the left posterior middle temporal gyrus and several frontoparietal sensorimotor areas activated more strongly during rehearsal cued by a visible talker versus rehearsal cued by auditory speech alone. Some of these brain regions responded exclusively to rehearsal cued by visual or audiovisual speech. This result has significant implications for models of speech motor control, for the treatment of speech output disorders, and for models of the role of speech gesture imitation in development.

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.

Altered functional connectivity is related to severity of language impairment in poststroke aphasia. However, it is not clear whether this finding specifically reflects loss of functional coherence, or more generally, is related to decreased structural connectivity due to cortical necrosis. The aim of the current study was to investigate this issue by factoring out structural connectivity from functional connectivity measures and then relating the residual data to language performance poststroke. Ninety-seven participants with a history of stroke were assessed using language impairment measures (Auditory Verbal Comprehension and Spontaneous Speech scores from the Western Aphasia Battery-Revised) and MRI (structural, diffusion tensor imaging, and resting-state functional connectivity). We analyzed the association between functional connectivity and language and controlled for multiple potential neuroanatomical confounders, namely structural connectivity. We identified functional connections within the left hemisphere ventral stream where decreased functional connectivity, independent of structural connectivity, was associated with speech comprehension impairment. These connections exist in frontotemporal and temporoparietal regions. Our results suggest poor speech comprehension in aphasia is at least partially caused by loss of cortical synchrony in a left hemisphere ventral stream network and is not only reflective of localized necrosis or structural connectivity.

Theories of language organization in the brain commonly posit that different regions underlie distinct linguistic mechanisms. However, such theories have been criticized on the grounds that many neuroimaging studies of language processing find similar effects across regions. Moreover, condition by region interaction effects, which provide the strongest evidence of functional differentiation between regions, have rarely been offered in support of these theories. Here we address this by using lesion-symptom mapping in three large, partially-overlapping groups of aphasia patients with left hemisphere brain damage due to stroke (N = 121, N = 92, N = 218). We identified multiple measure by region interaction effects, associating damage to the posterior middle temporal gyrus with syntactic comprehension deficits, damage to posterior inferior frontal gyrus with expressive agrammatism, and damage to inferior angular gyrus with semantic category word fluency deficits. Our results are inconsistent with recent hypotheses that regions of the language network are undifferentiated with respect to high-level linguistic processing.

The application of ℓ1-regularized machine learning models to high-dimensional connectomes offers a promising methodology to assess clinical-anatomical correlations in humans. Here, we integrate the connectome-based lesion-symptom mapping framework with sparse partial least squares regression (sPLS-R) to isolate elements of the connectome associated with speech repetition deficits. By mapping over 2,500 connections of the structural connectome in a cohort of 71 stroke-induced cases of aphasia presenting with varying left-hemisphere lesions and repetition impairment, sPLS-R was trained on 50 subjects to algorithmically identify connectomic features on the basis of their predictive value. The highest ranking features were subsequently used to generate a parsimonious predictive model for speech repetition whose predictions were evaluated on a held-out set of 21 subjects. A set of 10 short- and long-range parieto-temporal connections were identified, collectively delineating the broader circuitry of the dorsal white matter network of the language system. The strongest contributing feature was a short-range connection in the supramarginal gyrus, approximating the cortical localization of area Spt, with parallel long-range pathways interconnecting posterior nodes in supramarginal and superior temporal cortex with anterior nodes in both ventral and-notably-in dorsal premotor cortex, respectively. The collective disruption of these pathways indexed repetition performance in the held-out set of participants, suggesting that these impairments might be characterized as a parietotemporal disconnection syndrome impacting cortical area Spt and its associated white matter circuits of the frontal lobe as opposed to being purely a disconnection of the arcuate fasciculus.

We used left-hemisphere stroke as a model to examine how damage to sensorimotor brain networks impairs vocal auditory feedback processing and control. Individuals with post-stroke aphasia and matched neurotypical control subjects vocalized speech vowel sounds and listened to the playback of their self-produced vocalizations under normal (NAF) and pitch-shifted altered auditory feedback (AAF) while their brain activity was recorded using electroencephalography (EEG) signals. Event-related potentials (ERPs) were utilized as a neural index to probe the effect of vocal production on auditory feedback processing with high temporal resolution, while lesion data in the stroke group was used to determine how brain abnormality accounted for the impairment of such mechanisms. Results revealed that ERP activity was aberrantly modulated during vocalization vs. listening in aphasia, and this effect was accompanied by the reduced magnitude of compensatory vocal responses to pitch-shift alterations in the auditory feedback compared with control subjects. Lesion-mapping revealed that the aberrant pattern of ERP modulation in response to NAF was accounted for by damage to sensorimotor networks within the left-hemisphere inferior frontal, precentral, inferior parietal, and superior temporal cortices. For responses to AAF, neural deficits were predicted by damage to a distinguishable network within the inferior frontal and parietal cortices. These findings define the left-hemisphere sensorimotor networks implicated in auditory feedback processing, error detection, and vocal motor control. Our results provide translational synergy to inform the theoretical models of sensorimotor integration while having clinical applications for diagnosis and treatment of communication disabilities in individuals with stroke and other neurological conditions.

Deficits in lexical retrieval are commonly observed in individuals with post-stroke aphasia. Successful lexical retrieval is related to lexical diversity, lexical sophistication, and phonological word properties; however, the crucial brain regions supporting these different features are not fully understood. We performed MRI-based lesion symptom mapping in 58 individuals with a chronic left hemisphere stroke to assess how regional damage relates to spoken discourse-extracted measures of lexical diversity, lexical sophistication, and phonological word properties. For discourse transcription and word feature analysis, we used the Computerized Language Analysis (CLAN) program, Stanford Core Natural Language Processing, Irvine Phonotactic Online Dictionary, Lexical Complexity Analyzer, and Gramulator. Lesions involving the left posterior insula and supramarginal gyri and inferior fronto-occipital fasciculus were significant predictors of utterances with, on average, lower lexical diversity. Low lexical sophistication was associated with damage to the left pole of the superior temporal gyrus. Production of words with lower phonological complexity (fewer phonemes, higher phonological similarity) was associated with damage to the left supramarginal gyrus. Our findings indicate that discourse-extracted features of lexical retrieval depend on the integrity of specific brain regions involving insular and peri-Sylvian areas. The identified regions provide insight into potentially underlying mechanisms of lexically diverse, sophisticated and phonologically complex words produced during discourse.