Neural basis of speech and grammar symptoms in non-fluent variant primary progressive aphasia spectrum.

The non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) is a neurodegenerative syndrome primarily defined by the presence of apraxia of speech (AoS) and/or expressive agrammatism. In addition, many patients exhibit dysarthria and/or receptive agrammatism. This leads to substantial phenotypic variation within the speech-language domain across individuals and time, in terms of both the specific combination of symptoms as well as their severity. How to resolve such phenotypic heterogeneity in nfvPPA is a matter of debate. 'Splitting' views propose separate clinical entities: 'primary progressive apraxia of speech' when AoS occurs in the absence of expressive agrammatism, 'progressive agrammatic aphasia' (PAA) in the opposite case, and 'AOS + PAA' when mixed motor speech and language symptoms are clearly present. While therapeutic interventions typically vary depending on the predominant symptom (e.g. AoS versus expressive agrammatism), the existence of behavioural, anatomical and pathological overlap across these phenotypes argues against drawing such clear-cut boundaries. In the current study, we contribute to this debate by mapping behaviour to brain in a large, prospective cohort of well characterized patients with nfvPPA (n = 104). We sought to advance scientific understanding of nfvPPA and the neural basis of speech-language by uncovering where in the brain the degree of MRI-based atrophy is associated with inter-patient variability in the presence and severity of AoS, dysarthria, expressive agrammatism or receptive agrammatism. Our cross-sectional examination of brain-behaviour relationships revealed three main observations. First, we found that the neural correlates of AoS and expressive agrammatism in nfvPPA lie side by side in the left posterior inferior frontal lobe, explaining their behavioural dissociation/association in previous reports. Second, we identified a 'left-right' and 'ventral-dorsal' neuroanatomical distinction between AoS versus dysarthria, highlighting (i) that dysarthria, but not AoS, is significantly influenced by tissue loss in right-hemisphere motor-speech regions; and (ii) that, within the left hemisphere, dysarthria and AoS map onto dorsally versus ventrally located motor-speech regions, respectively. Third, we confirmed that, within the large-scale grammar network, left frontal tissue loss is preferentially involved in expressive agrammatism and left temporal tissue loss in receptive agrammatism. Our findings thus contribute to define the function and location of the epicentres within the large-scale neural networks vulnerable to neurodegenerative changes in nfvPPA. We propose that nfvPPA be redefined as an umbrella term subsuming a spectrum of speech and/or language phenotypes that are closely linked by the underlying neuroanatomy and neuropathology.

Clinical dimensions along the non-fluent variant primary progressive aphasia spectrum.

It is debated whether primary progressive apraxia of speech (PPAOS) and progressive agrammatic aphasia (PAA) belong to the same clinical spectrum, traditionally termed non-fluent/agrammatic variant primary progressive aphasia (nfvPPA), or exist as two completely distinct syndromic entities with specific pathologic/prognostic correlates. We analysed speech, language and disease severity features in a comprehensive cohort of patients with progressive motor speech impairment and/or agrammatism to ascertain evidence of naturally occurring, clinically meaningful non-overlapping syndromic entities (e.g. PPAOS and PAA) in our data. We also assessed if data-driven latent clinical dimensions with aetiologic/prognostic value could be identified. We included 98 participants, 43 of whom had an autopsy-confirmed neuropathological diagnosis. Speech pathologists assessed motor speech features indicative of dysarthria and apraxia of speech (AOS). Quantitative expressive/receptive agrammatism measures were obtained and compared with healthy controls. Baseline and longitudinal disease severity was evaluated using the Clinical Dementia Rating Sum of Boxes (CDR-SB). We investigated the data's clustering tendency and cluster stability to form robust symptom clusters and employed principal component analysis to extract data-driven latent clinical dimensions (LCD). The longitudinal CDR-SB change was estimated using linear mixed-effects models. Of the participants included in this study, 93 conformed to previously reported clinical profiles (75 with AOS and agrammatism, 12 PPAOS and six PAA). The remaining five participants were characterized by non-fluent speech, executive dysfunction and dysarthria without apraxia of speech or frank agrammatism. No baseline clinical features differentiated between frontotemporal lobar degeneration neuropathological subgroups. The Hopkins statistic demonstrated a low cluster tendency in the entire sample (0.45 with values near 0.5 indicating random data). Cluster stability analyses showed that only two robust subgroups (differing in agrammatism, executive dysfunction and overall disease severity) could be identified. Three data-driven components accounted for 71% of the variance [(i) severity-agrammatism; (ii) prominent AOS; and (iii) prominent dysarthria]. None of these data-driven LCDs allowed an accurate prediction of neuropathology. The severity-agrammatism component was an independent predictor of a faster CDR-SB increase in all the participants. Higher dysarthria severity, reduced words per minute and expressive and receptive agrammatism severity at baseline independently predicted accelerated disease progression. Our findings indicate that PPAOS and PAA, rather than exist as completely distinct syndromic entities, constitute a clinical continuum. In our cohort, splitting the nfvPPA spectrum into separate clinical phenotypes did not improve clinical-pathological correlations, stressing the need for new biological markers and consensus regarding updated terminology and clinical classification.

Effects of melodic intonation therapy in patients with chronic nonfluent aphasia.

Patients with large left-hemisphere lesions and post-stroke aphasia often remain nonfluent. Melodic intonation therapy (MIT) may be an effective alternative to traditional speech therapy for facilitating recovery of fluency in those patients. In an open-label, proof-of-concept study, 14 subjects with nonfluent aphasia with large left-hemisphere lesions (171 ± 76 cc) underwent two speech/language assessments before, one at the midpoint, and two after the end of 75 sessions (1.5 h/session) of MIT. Functional MR imaging was done before and after therapy asking subjects to vocalize the same set of 10 bi-syllabic words. We found significant improvements in speech output after a period of intensive MIT (75 sessions for a total of 112.5 h) compared to two pre-therapy assessments. Therapy-induced gains were maintained 4 weeks post-treatment. Imaging changes were seen in a right-hemisphere network that included the posterior superior temporal and inferior frontal gyri, inferior pre- and postcentral gyri, pre-supplementary motor area, and supramarginal gyrus. Functional changes in the posterior right inferior frontal gyri significantly correlated with changes in a measure of fluency. Intense training of intonation-supported auditory-motor coupling and engaging feedforward/feedback control regions in the unaffected hemisphere improves speech-motor functions in subjects with nonfluent aphasia and large left-hemisphere lesions.

[Phasic disorders and aphasia in geriatrics]. / Troubles phasiques et aphasie en gériatrie.

Aphasia, resulting from a brain lesion, leads to a partial or total loss of language in the elderly. By affecting communication abilities, it has repercussions on the life of the subject and his family. There are two types of aphasia. The roles of the caregiver and the speech therapist are in all cases essential. Depending on the communication difficulties encountered by the patient, specific supports can be recommended.

[Case Report: Broca's Aphasia in a Left-Handed Patient with a Right Brain Infarction and Early Stage Aphonia].

We report a case of Broca's aphasia in a left-handed patient with a right brain infarction. The patient's speech is consistent with a particular type of aphemia, that is, without vocalization except for a few phonemes or words. The patient presented with aphonia in an early stage. The lack of speech could be due to the impairment of the phonological-speech process or speech initialization. This type of aphemia has been reported to involve the right inferior precentral gyrus or right middle and inferior frontal gyri. Our patient had both lesions. The symptom and the lesion of this type of aphemia could differ from those of another type of aphemia corresponding to apraxia of speech, and the speech of Broca's aphasia could have multiple mechanisms. Our case shows Alexander's anomalous type with atypical lateralization and distribution of the lesion. Verbal intrahemispheric dissociation apraxia was suspected in our patient. The coexistence of aphasia, anosodiaphoria of hemiplegia is a dual symptom in which bilateral hemispheric functions exist in a unilateral hemisphere. (Received 1 December, 2021; Accepted 1 February, 2022; Published 1 April, 2022).

Damage to Broca's area does not contribute to long-term speech production outcome after stroke.

Broca's area in the posterior half of the left inferior frontal gyrus has long been thought to be critical for speech production. The current view is that long-term speech production outcome in patients with Broca's area damage is best explained by the combination of damage to Broca's area and neighbouring regions including the underlying white matter, which was also damaged in Paul Broca's two historic cases. Here, we dissociate the effect of damage to Broca's area from the effect of damage to surrounding areas by studying long-term speech production outcome in 134 stroke survivors with relatively circumscribed left frontal lobe lesions that spared posterior speech production areas in lateral inferior parietal and superior temporal association cortices. Collectively, these patients had varying degrees of damage to one or more of nine atlas-based grey or white matter regions: Brodmann areas 44 and 45 (together known as Broca's area), ventral premotor cortex, primary motor cortex, insula, putamen, the anterior segment of the arcuate fasciculus, uncinate fasciculus and frontal aslant tract. Spoken picture description scores from the Comprehensive Aphasia Test were used as the outcome measure. Multiple regression analyses allowed us to tease apart the contribution of other variables influencing speech production abilities such as total lesion volume and time post-stroke. We found that, in our sample of patients with left frontal damage, long-term speech production impairments (lasting beyond 3 months post-stroke) were solely predicted by the degree of damage to white matter, directly above the insula, in the vicinity of the anterior part of the arcuate fasciculus, with no contribution from the degree of damage to Broca's area (as confirmed with Bayesian statistics). The effect of white matter damage cannot be explained by a disconnection of Broca's area, because speech production scores were worse after damage to the anterior arcuate fasciculus with relative sparing of Broca's area than after damage to Broca's area with relative sparing of the anterior arcuate fasciculus. Our findings provide evidence for three novel conclusions: (i) Broca's area damage does not contribute to long-term speech production outcome after left frontal lobe strokes; (ii) persistent speech production impairments after damage to the anterior arcuate fasciculus cannot be explained by a disconnection of Broca's area; and (iii) the prior association between persistent speech production impairments and Broca's area damage can be explained by co-occurring white matter damage, above the insula, in the vicinity of the anterior part of the arcuate fasciculus.

Analysis of an Unusual Case of Nonfluent Aphasia With Predominantly Posterior Perisylvian Lesion: An Apparent Paradox.

Lesion site-aphasia type discordance has garnered increasing interest in cognitive neuroscience over the last century. Diaschisis, the network concept of cognitive functions, and interindividual variability are among the plausible explanations cited in the literature for such unusual clinical cases. We describe here the case of a nonfluent type of aphasia following an ischemic stroke predominantly affecting the left posterior perisylvian cortex in a right-handed Bengali-speaking woman. The patient's comprehension was well preserved; however, she presented with a severe motor speech defect. MRI revealed an ischemic lesion in the left parietotemporal area, with slight involvement of the postero-inferior frontal cortex. We suggest two plausible explanations for this lesion-aphasia discordance: Our patient had bilateral representation of language receptive functions in her brain, and additional areas neighboring the classical Broca area may support some critical mechanisms of speech production. Taken together, these explanations may clarify why our patient was able to maintain the ability to decode language even though her language production was significantly affected.

Speech and Language Presentations of FTLD-TDP Type B Neuropathology.

Four right-handed patients who presented with an isolated impairment of speech or language had transactive response DNA-binding protein of 43 kDa (TDP-43) type B pathology. Comportment and pyramidal motor function were preserved at presentation. Three of the cases developed axial rigidity and oculomotor findings late in their course with no additional pyramidal or lower motor neuron impairments. However, in all 4 cases, postmortem examination disclosed some degree of upper and lower motor neuron disease (MND) pathology in motor cortex, brainstem, and spinal cord. Although TDP-43 type B pathology is commonly associated with MND and behavioral variant frontotemporal dementia, it is less recognized as a pathologic correlate of primary progressive aphasia and/or apraxia of speech as the presenting syndrome. These cases, taken together, contribute to the growing heterogeneity in clinical presentations associated with TDP pathology. Additionally, 2 cases demonstrated left anterior temporal lobe atrophy but without word comprehension impairments, shedding light on the relevance of the left temporal tip for single-word comprehension.

Differences in neuroimaging features of early- versus late-onset nonfluent/agrammatic primary progressive aphasia.

This study investigated distinct neuroimaging features measured by cortical thickness and subcortical structural shape abnormality in early-onset (EO, onset age <65 years) and late-onset (LO, onset age ≥65 years) nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA) patients. Cortical thickness and subcortical structural shape analyses were performed using a surface-based method from 38 patients with nfvPPA and 76 cognitively normal individuals. To minimize the effects of physiological aging, we used W-scores in comparisons between the groups. The EO-nfvPPA group exhibited more extensive cortical thickness reductions predominantly in the left perisylvian, lateral and medial prefrontal, temporal, posterior cingulate, and precuneus regions than the LO-nfvPPA group. The EO-nfvPPA group also exhibited significantly greater subcortical structural shape abnormality than the LO-nfvPPA group, mainly in the left striatum, hippocampus, and amygdala. Our findings suggested that there were differences in neuroimaging features between these groups by the age of symptom onset, which might be explained by underlying heterogeneous neuropathological differences or the age-related brain reserve hypothesis.

Progressive agrammatic aphasia without apraxia of speech as a distinct syndrome.

Agrammatic aphasia affects grammatical language production and can result from a neurodegenerative disease. Although it typically presents with concomitant apraxia of speech, this is not always the case. Little is known about the clinical course and imaging features of patients that present with agrammatism in the absence of apraxia of speech, which we will refer to as progressive agrammatic aphasia. We aimed to make a detailed description of the longitudinal clinical, linguistic, and neuroimaging features of a cohort of 11 patients with progressive agrammatic aphasia to provide a complete picture of this syndrome. All patients underwent detailed speech and language, neurological and neuropsychological assessments, 3 T structural and diffusion tensor imaging MRI, 18F-fluorodeoxyglucose and Pittsburgh compound B PET. The 11 patients were matched by age and gender to 22 patients who had mixed apraxia of speech and agrammatism. The progressive agrammatic aphasia patients performed abnormally on tests of language, general cognition, executive function, and functional ability at baseline and declined in these measures over time. Only two patients eventually developed apraxia of speech, while parkinsonism was absent-to-mild throughout all visits for all patients. When compared to the patients with mixed apraxia of speech and agrammatism, the patients with progressive agrammatic aphasia performed better on tests of motor speech and parkinsonism but more poorly, and declined faster over time, on tests of general aphasia severity, agrammatism, and naming. The patients with progressive agrammatic aphasia also showed different neuroimaging abnormalities, with greater atrophy, hypometabolism and white matter tract degeneration in the prefrontal and anterior temporal lobes compared to patients with mixed apraxia of speech and agrammatism. These differences were more pronounced as the disease progressed. These results demonstrate that progressive agrammatic aphasia has a different clinical disease course and different underlying neuroanatomical abnormalities than patients with the more common syndrome of mixed agrammatism and apraxia of speech. This supports the distinction of progressive agrammatic aphasia and has implications for the classification of patients with agrammatic aphasia.

Left Sylvian Fissure Epidermoid Cyst Presenting with Progressive Aphasia.

INTRODUCTION: Epidermoid cysts within the sylvian fissure are extremely rare. Expressive aphasia and neurocognitive dysfunction because of mass effect have never been reported previously. CASE PRESENTATION: We discuss the case of a 53-year-old male who presented with an acute episode of expressive aphasia and vision changes along with progressive headaches and cognitive slowing over the 2.5 years prior to presentation. A detailed neurologic examination revealed subtle conductive aphasia, as well as mild short-term memory dysfunction. Magnetic resonance imaging revealed a cystic mass consistent with epidermoid cyst within the left sylvian fissure. High-definition fiber tractography showed that the arcuate fasciculus was stretched by the tumor. A left frontotemporal craniotomy allowed for near-total excision of the cyst and led to rapid and complete resolution of symptoms. CONCLUSION: Although rare, epidermoid cysts of the dominant sylvian fissure can present with progressive aphasia due to mass effect on the arcuate fasciculus. Despite the long-standing symptoms, surgical resection can lead to their complete resolution.

The effects of silent visuomotor cueing on word retrieval in Broca's aphasies: A pilot study.

About a quarter of stroke patients worldwide suffer serious language disorders such as aphasias. Most common symptoms of Broca's aphasia are word naming disorders which highly impact verbal communication and the quality of life of aphasic patients. In order to recover disturbances in word retrieval, several cueing methods (i.e. phonemic and semantic) have been established to improve lexical access establishing effective language rehabilitation techniques. Based on recent evidence from action-perception theories, which postulate that neural circuits for speech perception and articulation are tightly coupled, in the present work, we propose and investigate an alternative type of cueing using silent articulation-related visual stimuli. We hypothesize that providing patients with primes in the form of silent videos showing lip motions representative of correct pronunciation of target words, will result in faster word retrieval than when no such cue is provided. To test our prediction, we realize a longitudinal clinical virtual reality-based trial with four post-stroke Broca's patients and compare the interaction times between the two conditions over the eight weeks of the therapy. Our results suggest that silent visuomotor cues indeed facilitate word retrieval and verbal execution, and might be beneficial in lexical relearning in chronic Broca's patients.

Treatment of dysphasia with rTMS and language therapy after childhood stroke: Multimodal imaging of plastic change.

Expressive dysphasia accompanies left inferior frontal gyrus (IFG/Broca) injury. Recovery may relate to interhemispheric balance with homologous, contralesional IFG but is unexplored in children. We evaluated effects of inhibitory rTMS to contralesional IFG combined with intensive speech therapy (SLT). A 15year-old, right-handed male incurred a left middle cerebral artery stroke. After 30months, severe non-fluent dysphasia impacted quality of life. Language networks, neuronal metabolism and white matter pathways were explored using MRI. Language function was measured longitudinally. An intensive SLT program was combined with contralesional inhibitory rTMS of right pars triangularis. Procedures were well tolerated. Language function improved persisting to four months. Post-treatment fMRI demonstrated increased left perilesional IFG activations and connectivity at rest. Bilateral changes in inositol and glutamate metabolism were observed. Contralesional, inhibitory rTMS appears safe in childhood stroke-induced dysphasia. We observed clinically significant improvements after SLT coupled with rTMS. Advanced neuroimaging can evaluate intervention-induced plasticity.

Frontal Aslant Tract Abnormality on Diffusion Tensor Imaging in an Aphasic Patient With 49, XXXXY Syndrome.

BACKGROUND: The karyotype 49, XXXXY is one of the most severe forms of chromosome aneuploidy and is characterized clinically by developmental delay and profound language impairment, particularly involving expressive language functions. We describe the neurocognitive profile and structural anatomy of language pathway in a 2-year-old boy with 49, XXXXY syndrome with expressive aphasia. METHODS: Retrospective chart review of the patient was performed. We characterized the language deficits using neuropsychologic testing. We further studied the language pathways using diffusion tensor imaging analytical technique. RESULTS: The neurocognitive profile of the patient showed relative weakness of expressive language skills compared with other domains. Diffusion tensor imaging analysis demonstrated a poorly developed frontal aslant tract, a weak indirect segment of arcuate fasciculus, and normally developed direct segment of arcuate fasciculus. The frontal aslant tract is a novel pathway that connects the Broca's area with the anterior cingulate and presupplementary motor area and plays a role in the "motor stream" of language. CONCLUSION: A poorly developed frontal aslant tract may underlie the expressive language deficits and provide some insight into the role of X chromosome in modulating the development of language tracts.

Where language meets meaningful action: a combined behavior and lesion analysis of aphasia and apraxia.

It is debated how language and praxis are co-represented in the left hemisphere (LH). As voxel-based lesion-symptom mapping in LH stroke patients with aphasia and/or apraxia may contribute to this debate, we here investigated the relationship between language and praxis deficits at the behavioral and lesion levels in 50 sub-acute stroke patients. We hypothesized that language and (meaningful) action are linked via semantic processing in Broca's region. Behaviorally, half of the patients suffered from co-morbid aphasia and apraxia. While 24% (n = 12) of all patients exhibited aphasia without apraxia, apraxia without aphasia was rare (n = 2, 4%). Left inferior frontal, insular, inferior parietal, and superior temporal lesions were specifically associated with deficits in naming, reading, writing, or auditory comprehension. In contrast, lesions affecting the left inferior frontal gyrus, premotor cortex, and the central region as well as the inferior parietal lobe were associated with apraxic deficits (i.e., pantomime, imitation of meaningful and meaningless gestures). Thus, contrary to the predictions of the embodied cognition theory, lesions to sensorimotor and premotor areas were associated with the severity of praxis but not language deficits. Lesions of Brodmann area (BA) 44 led to combined apraxic and aphasic deficits. Data suggest that BA 44 acts as an interface between language and (meaningful) action thereby supporting parcellation schemes (based on connectivity and receptor mapping) which revealed a BA 44 sub-area involved in semantic processing.

Compensating arithmetic ability with derived fact strategies in Broca's aphasia: a case report.

We investigated derived fact strategy use in RR, an aphasic patient with severely impaired working memory (no phonological loop), and 16 neurologically healthy matched controls. Participants were tested on derived fact strategy use in multi-digit addition, subtraction, multiplication, and division. RR's accuracy only differed from controls in multiplication. He was as quick as controls in addition and subtraction when able to use the strategies, though significantly slower in addition, division, and multiplication without strategies. Our findings suggest the phonological loop is non-essential for multi-digit arithmetic, and derived fact strategies can help speed up arithmetic in individuals with impaired working memory.

Predicting aphasia type from brain damage measured with structural MRI.

Chronic aphasia is a common consequence of a left-hemisphere stroke. Since the early insights by Broca and Wernicke, studying the relationship between the loci of cortical damage and patterns of language impairment has been one of the concerns of aphasiology. We utilized multivariate classification in a cross-validation framework to predict the type of chronic aphasia from the spatial pattern of brain damage. Our sample consisted of 98 patients with five types of aphasia (Broca's, Wernicke's, global, conduction, and anomic), classified based on scores on the Western Aphasia Battery (WAB). Binary lesion maps were obtained from structural MRI scans (obtained at least 6 months poststroke, and within 2 days of behavioural assessment); after spatial normalization, the lesions were parcellated into a disjoint set of brain areas. The proportion of damage to the brain areas was used to classify patients' aphasia type. To create this parcellation, we relied on five brain atlases; our classifier (support vector machine - SVM) could differentiate between different kinds of aphasia using any of the five parcellations. In our sample, the best classification accuracy was obtained when using a novel parcellation that combined two previously published brain atlases, with the first atlas providing the segmentation of grey matter, and the second atlas used to segment the white matter. For each aphasia type, we computed the relative importance of different brain areas for distinguishing it from other aphasia types; our findings were consistent with previously published reports of lesion locations implicated in different types of aphasia. Overall, our results revealed that automated multivariate classification could distinguish between aphasia types based on damage to atlas-defined brain areas.

A multimodal neuroimaging study of a case of crossed nonfluent/agrammatic primary progressive aphasia.

Crossed aphasia has been reported mainly as post-stroke aphasia resulting from brain damage ipsilateral to the dominant right hand. Here, we described a case of a crossed nonfluent/agrammatic primary progressive aphasia (nfvPPA), who developed a corticobasal syndrome (CBS). We collected clinical, cognitive, and neuroimaging data for four consecutive years from a 55-year-old right-handed lady (JV) presenting with speech disturbances. 18-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) and DaT-scan with (123)I-Ioflupane were obtained. Functional MRI (fMRI) during a verb naming task was acquired to characterize patterns of language lateralization. Diffusion tensor MRI was used to evaluate white matter damage within the language network. At onset, JV presented with prominent speech output impairment and right frontal atrophy. After 3 years, language deficits worsened, with the occurrence of a mild agrammatism. The patient also developed a left-sided mild extrapyramidal bradykinetic-rigid syndrome. The clinical picture was suggestive of nfvPPA with mild left-sided extrapyramidal syndrome. At this time, voxel-wise SPM analyses of (18)F-FDG PET and structural MRI showed right greater than left frontal hypometabolism and damage, which included the Broca's area. DaT-scan showed a reduced uptake in the right striatum. FMRI during naming task demonstrated bilateral language activations, and tractography showed right superior longitudinal fasciculus (SLF) involvement. Over the following year, JV became mute and developed frank left-sided motor signs and symptoms, evolving into a CBS clinical picture. Brain atrophy worsened in frontal areas bilaterally, and extended to temporo-parietal regions, still with a right-sided asymmetry. Tractography showed an extension of damage to the left SLF and right inferior longitudinal fasciculus. We report a case of crossed nfvPPA followed longitudinally and studied with advanced neuroimaging techniques. The results highlight a complex interaction between individual premorbid developmental differences and the clinical phenotype.

Speech entrainment compensates for Broca's area damage.

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.