Structural Neuroplasticity Effects of Singing in Chronic Aphasia.

Singing-based treatments of aphasia can improve language outcomes, but the neural benefits of group-based singing in aphasia are unknown. Here, we set out to determine the structural neuroplasticity changes underpinning group-based singing-induced treatment effects in chronic aphasia. Twenty-eight patients with at least mild nonfluent poststroke aphasia were randomized into two groups that received a 4-month multicomponent singing intervention (singing group) or standard care (control group). High-resolution T1 images and multishell diffusion-weighted MRI data were collected in two time points (baseline/5 months). Structural gray matter (GM) and white matter (WM) neuroplasticity changes were assessed using language network region of interest-based voxel-based morphometry (VBM) and quantitative anisotropy-based connectometry, and their associations to improved language outcomes (Western Aphasia Battery Naming and Repetition) were evaluated. Connectometry analyses showed that the singing group enhanced structural WM connectivity in the left arcuate fasciculus (AF) and corpus callosum as well as in the frontal aslant tract (FAT), superior longitudinal fasciculus, and corticostriatal tract bilaterally compared with the control group. Moreover, in VBM, the singing group showed GM volume increase in the left inferior frontal cortex (Brodmann area 44) compared with the control group. The neuroplasticity effects in the left BA44, AF, and FAT correlated with improved naming abilities after the intervention. These findings suggest that in the poststroke aphasia group, singing can bring about structural neuroplasticity changes in left frontal language areas and in bilateral language pathways, which underpin treatment-induced improvement in speech production.

Predicting Language Function Post-Stroke: A Model-Based Structural Connectivity Approach.

BACKGROUND: The prediction of post-stroke language function is essential for the development of individualized treatment plans based on the personal recovery potential of aphasic stroke patients. OBJECTIVE: To establish a framework for integrating information on connectivity disruption of the language network based on routinely collected clinical magnetic resonance (MR) images into Random Forest modeling to predict post-stroke language function. METHODS: Language function was assessed in 76 stroke patients from the Non-Invasive Repeated Therapeutic Stimulation for Aphasia Recovery trial, using the Token Test (TT), Boston Naming Test (BNT), and Semantic Verbal Fluency (sVF) Test as primary outcome measures. Individual infarct masks were superimposed onto a diffusion tensor imaging tractogram reference set to calculate Change in Connectivity scores of language-relevant gray matter regions as estimates of structural connectivity disruption. Multivariable Random Forest models were derived to predict language function. RESULTS: Random Forest models explained moderate to high amount of variance at baseline and follow-up for the TT (62.7% and 76.2%), BNT (47.0% and 84.3%), and sVF (52.2% and 61.1%). Initial language function and non-verbal cognitive ability were the most important variables to predict language function. Connectivity disruption explained additional variance, resulting in a prediction error increase of up to 12.8% with variable omission. Left middle temporal gyrus (12.8%) and supramarginal gyrus (9.8%) were identified as among the most important network nodes. CONCLUSION: Connectivity disruption of the language network adds predictive value beyond lesion volume, initial language function, and non-verbal cognitive ability. Obtaining information on connectivity disruption based on routine clinical MR images constitutes a significant advancement toward practical clinical application.

Lesion-symptom Mapping of Acceptability Judgments in Chronic Poststroke Aphasia Reveals the Neurobiological Underpinnings of Receptive Syntax.

Disagreements persist regarding the neural basis of syntactic processing, which has been linked both to inferior frontal and posterior temporal regions of the brain. One focal point of the debate concerns the role of inferior frontal areas in receptive syntactic ability, which is mostly assessed using sentence comprehension involving complex syntactic structures, a task that is potentially confounded with working memory. Syntactic acceptability judgments may provide a better measure of receptive syntax by reducing the need to use high working memory load and complex sentences and by enabling assessment of various types of syntactic violations. We therefore tested the perception of grammatical violations by people with poststroke aphasia (n = 25), along with matched controls (n = 16), using English sentences involving errors in word order, agreement, or subcategorization. Lesion data were also collected. Control participants performed near ceiling in accuracy with higher discriminability of agreement and subcategorization violations than word order; aphasia participants were less able to discriminate violations, but, on average, paralleled control participants discriminability of types of violations. Lesion-symptom mapping showed a correlation between discriminability and posterior temporal regions, but not inferior frontal regions. We argue that these results diverge from models holding that frontal areas are amodal core regions in syntactic structure building and favor models that posit a core hierarchical system in posterior temporal regions.

Modality Synchronization When People With Aphasia Read With Text-to-Speech Support.

PURPOSE: Text-to-speech (TTS) technology potentially benefits people with aphasia by presenting content through two modalities simultaneously; however, for this to help, eye fixations must synchronize with the auditory rendition of words. Researchers have yet to explore how often and to what extent people with aphasia achieve modality synchronization. This retrospective analysis examined the percent of words people with aphasia see and hear concurrently when reading passages presented via TTS technology. Text-to-speech (TTS) technology potentially benefits people with aphasia by presenting content through two modalities simultaneously; however, for this to help, eye fixations must synchronize with the auditory rendition of words. Researchers have yet to explore how often and to what extent people with aphasia achieve modality synchronization. This retrospective analysis examined the percent of words people with aphasia see and hear concurrently when reading passages presented via TTS technology. METHOD: Nine adults with aphasia had their eye movements tracked while processing TTS passages at a preselected default rate of 150 words per minute. Modality synchronization occurred whenever fixation on a written word occurred during the time span beginning 300 ms before auditory presentation and ending at the next word's initiation. Correlations between standardized test scores, unsupported reading rate, and modality synchronization percentages were informative about the association of aphasia and reading impairment severity with achievement of synchronicity. RESULTS: Three participants demonstrated consistent modality synchronization; average synchronicity ranged from 67% to 76% of passage words. One participant displayed inconsistent synchronization within passages and achieved an average of 58%. The remaining five participants rarely achieved synchronization, with fixations typically lagging substantially behind the auditory presentation. A significant positive correlation occurred between paragraph reading comprehension test scores and modality synchronization percentages. CONCLUSIONS: A default TTS presentation rate does not result in dual modality synchronization for most people with aphasia. This lack of synchronization may contribute to inconsistencies in the benefit people with aphasia experience when provided with TTS support.

Evolución de la afasia en adolescentes con secuela de ACV: serie de casos / Post-stroke aphasia in adolescents' progress: case series

La afasia como secuela de un accidente cerebrovascular es un trastorno del lenguaje poco estudiado en adolescentes, tanto en Latinoamérica como a nivel mundial. Independientemente del hecho de que un número significativo de afasias mejora espontáneamente, la necesidad del inicio oportuno del tratamiento es imprescindible. En esta serie de casos se describe la presentación clínica y evolución de la afasia en 3 adolescentes con secuelas de accidente cerebrovascular que ingresaron a un instituto de neurorehabilitación. Fueron dos mujeres y un varón, de entre 15 y 17 años, que recibieron rehabilitación integral intensiva desde las áreas de fisioterapia, terapia ocupacional, neuropsicología, psicopedagogía, musicoterapia y fonoaudiología. Fueron evaluados con la versión chilena de la herramienta Western Aphasia Battery (WAB). A los 3 meses todos mejoraron y evolucionaron a un tipo de afasia más leve. Este estudio expone la importancia del tratamiento precoz e intensivo en esta población de adolescentes en plena etapa de construcción social como personas, en donde la alteración del lenguaje impacta en sus vínculos, grupo de pertenencia, estado anímico y a nivel académico. Se considera fundamental la evaluación y seguimiento sistemático con el objetivo de identificar los cambios y avances alcanzados durante la rehabilitación.

Aphasia as a sequela of stroke is an understudied language disorder in adolescents, both in Latin America and worldwide. Although a significant number of aphasia cases improve spontaneously, it is necessary to initiate treatment as soon as possible. This cases series describes the clinical presentation and evolution of aphasia in 3 adolescents with stroke sequelae who were admitted to a neurorehabilitation facility. Two females and one male, aged between 15 and 17 years, received intensive comprehensive rehabilitation from the areas of physiotherapy, occupational therapy, neuropsychology, psychopedagogy, music therapy and speech therapy. They were evaluated with the Chilean version of the Western Aphasia Battery (WAB). After 3 months, all of them improved and evolved to a milder type of aphasia. This study shows the importance of early, intensive treatment in adolescents who are in the height of their social development, where language alteration impacts on their bonds, their groups of belonging, their mood and their academic process. Systematicassessment and follow-up are considered essential to identify the changes and progress achieved during rehabilitation.

Neural correlates of impaired vocal feedback control in post-stroke aphasia.

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.

Cerebral perfusion mediated by thalamo-cortical functional connectivity in non-dominant thalamus affects naming ability in aphasia.

Naming is a commonly impaired language domain in various types of aphasia. Emerging evidence supports the cortico-subcortical circuitry subserving naming processing, although neurovascular regulation of the non-dominant thalamic and basal ganglia subregions underlying post-stroke naming difficulty remains unclear. Data from 25 subacute stroke patients and 26 age-, sex-, and education-matched healthy volunteers were analyzed. Region-of-interest-wise functional connectivity (FC) was calculated to measure the strength of cortico-subcortical connections. Cerebral blood flow (CBF) was determined to reflect perfusion levels. Correlation and mediation analyses were performed to identify the relationship between cortico-subcortical connectivity, regional cerebral perfusion, and naming performance. We observed increased right-hemispheric subcortical connectivity in patients. FC between the right posterior superior temporal sulcus (pSTS) and lateral/medial prefrontal thalamus (lPFtha/mPFtha) exhibited significantly negative correlations with total naming score. Trend-level increased CBF in subcortical nuclei, including that in the right lPFtha, and significant negative correlations between naming and regional perfusion of the right lPFtha were observed. The relationship between CBF in the right lPFtha and naming was fully mediated by the lPFtha-pSTS connectivity in the non-dominant hemisphere. Our findings suggest that perfusion changes in the right thalamic subregions affect naming performance through thalamo-cortical circuits in post-stroke aphasia. This study highlights the neurovascular pathophysiology of the non-dominant hemisphere and demonstrates thalamic involvement in naming after stroke.

BONEs not CATs attract DOGs: Semantic context effects for picture naming in the lesioned language network.

The breakdown of rapid and accurate retrieval of words is a hallmark of aphasic speech and a prime target of therapeutic intervention. Complementary, psycho- and neurolinguistic research have developed a spectrum of models, how and by which neuronal network uncompromised speakers can rely on remarkable lexical retrieval capacities. Motivated by both lines of research we invited 32 participants with a chronic left hemispheric brain lesion to name pictures in the presence of distractor words. This picture-word-interference (PWI) paradigm is widely used in psycho- and neurolinguistic research. We find that also after brain lesion categorically related words (CAT â†’ [dog]picture) impede naming, while associatively related words (BONE â†’ [dog]picture) ease access, when compared to unrelated distractor words. The effects largely affecting latencies in neurotypical populations, are reproduced for error rate in our participants with lesions in the language network. Unsurprisingly, overall naming abilities varied greatly across patients. Notably, however, the two effects (categorical interference / associative facilitation) differ between participants. Correlating performance with lesion patterns we find support for the notion of a divergence of brain areas affording different aspects of the task: (i) lesions in the left middle temporal gyurs (MTG) deteriorate overall naming, confirming previous work; more notably, (ii) lesions comprising the inferior frontal hub (inferior frontal gyrus, IFG) of the language-network increase the interference effect for the categorical condition; on the contrary, (iii) lesions to the mid-to-posterior temporal hub (posterior middle and superior temporal gyri, pMTG/ pSTG) increase the facilitatory effect for the associative condition on error rates. The findings can be accommodated in a neuro-linguistic framework, which localizes lexical activation but also lexical interference in posterior parts of the language network (pMTG/pITG); conversely, selection between co-activated categorically related entries is afforded by frontal language areas (IFG). While purely experimental in nature our study highlights that lesion site differentially influences specific aspects of word retrieval. Since confrontational naming is a cornerstone of aphasia rehabilitation, this may be of note when designing and evaluating novel therapeutic regimes.

Functional differentiation in the language network revealed by lesion-symptom mapping.

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 electrophysiology of aphasia: A scoping review.

OBJECTIVE: To systematically assess the body of literature using N400 and P600 as they relate to people with aphasia. The primary aim was to reveal patterns in the literature which could be used to direct future research in the development of clinically relevant Event-Related Potentials (ERPs) for language assessment, while also identifying gaps in existing knowledge and highlight areas of further inquiry. METHODS: A literature search was performed on studies published before May 2021. Relevant studies on aphasia and the two ERPs of interest were assessed for quality, and the relationship between aphasia and these ERPs was explored. RESULTS: A total of 721 articles were identified, with 30 meeting inclusion criteria. Although there is significant variation in the literature, this scoping review revealed people with aphasia show reduced amplitude, delayed latency and different distribution compared to controls, and that ERPs are modulated by severity of aphasia. CONCLUSIONS: To develop a relevant clinical tool for the management of aphasia, future research must strive to improve consistency within ERP methodology, with a greater number of diverse aphasia subtypes included in research. SIGNIFICANCE: This scoping review reveals N400 and P600 represent promising potential biomarkers for the diagnosis and ongoing management of aphasia.

Isolating the white matter circuitry of the dorsal language stream: Connectome-Symptom Mapping in stroke induced aphasia.

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.

Cortical microstructural changes associated with treated aphasia recovery.

OBJECTIVES: To investigate the hypothesis that language recovery in post-stroke aphasia is associated with structural brain changes. METHODS: We evaluated whether treatment-induced improvement in naming is associated with reorganization of tissue microstructure within residual cortical regions. To this end, we performed a retrospective longitudinal treatment study using comprehensive language-linguistic assessments and diffusion MRI sequences optimized for the assessment of complex microstructure (diffusional kurtosis imaging) to evaluate the relationship between language treatment response and cortical changes in 26 individuals with chronic stroke-induced aphasia. We employed elastic net statistical models controlling for baseline factors including age, sex, and time since the stroke, as well as lesion volume. RESULTS: We observed that improved naming accuracy (Philadelphia Naming Test) was statistically associated with increased post-treatment microstructural integrity in the left posterior superior temporal gyrus. Moreover, increase in microstructural integrity in the left middle temporal gyrus and left inferior temporal gyrus was specifically associated with a decrease in semantic paraphasias. This longitudinal relationship between brain tissue integrity and language improvement was not observed in other non-language related brain regions. INTERPRETATION: Our findings provide evidence that structural brain changes in the preserved left hemisphere regions are associated with treatment-induced language recovery in aphasia and are part of the mechanisms supporting language and brain injury recovery.

A case-study of language-specific executive disorder.

Executive control is recruited for language processing, particularly in complex linguistic tasks. Although the issue of the existence of an executive control specific to language is still an open issue, there is much evidence that executively-demanding language tasks rely on domain-general rather than language-specific executive resources. Here, we addressed this issue by assessing verbal and non-verbal executive capacities in LG, an aphasic patient after a stroke. First, we showed that LG's performance was spared in all non-verbal tasks regardless of the executive demands. Second, by contrasting conditions of high and low executive demand in verbal tasks, we showed that LG was only impaired in verbal task with high executive demand. The performance dissociation between low and high executive demand conditions in the verbal domain, not observed in the non-verbal domain, shows that verbal executive control partly dissociates from non-verbal executive control. This language-specific executive disorder suggests that some executive processes might be language-specific.

Association between aphasia severity and brain network alterations after stroke assessed using the electroencephalographic phase synchrony index.

Electroencephalographic synchrony can help assess brain network status; however, its usefulness has not yet been fully proven. We developed a clinically feasible method that combines the phase synchrony index (PSI) with resting-state 19-channel electroencephalography (EEG) to evaluate post-stroke motor impairment. In this study, we investigated whether our method could be applied to aphasia, a common post-stroke cognitive impairment. This study included 31 patients with subacute aphasia and 24 healthy controls. We assessed the expressive function of patients and calculated the PSIs of three motor language-related regions: frontofrontal, left frontotemporal, and right frontotemporal. Then, we evaluated post-stroke network alterations by comparing PSIs of the patients and controls and by analyzing the correlations between PSIs and aphasia scores. The frontofrontal PSI (beta band) was lower in patients than in controls and positively correlated with aphasia scores, whereas the right frontotemporal PSI (delta band) was higher in patients than in controls and negatively correlated with aphasia scores. Evaluation of artifacts suggests that this association is attributed to true synchrony rather than spurious synchrony. These findings suggest that post-stroke aphasia is associated with alternations of two different networks and point to the usefulness of EEG PSI in understanding the pathophysiology of aphasia.

Functional Magnetic Resonance Imaging of Language Following Constraint-Induced Aphasia Therapy Primed with Intermittent Theta Burst Stimulation in 13 Patients with Post-Stroke Aphasia.

BACKGROUND Aphasia is a debilitating consequence of stroke. This study aimed to investigate the role of functional magnetic resonance imaging (fMRI) activation changes during overt language tasks in promoting language improvements following constraint-induced aphasia therapy (CIAT) primed with intermittent theta burst stimulation (iTBS) in 13 patients with aphasia following ischemic stroke. MATERIAL AND METHODS Participants with post-stroke aphasia participated in CIAT primed with iTBS on 10 consecutive weekdays. They also underwent language testing and fMRI while performing overt language tasks at baseline (N=13), immediately post-treatment (N=13), and after 3 months (N=12). Outcome measures were compared between time points, and relationships between changes in language ability and fMRI activation were examined. RESULTS We observed improvements in naming (p<0.001), aphasia symptoms (p=0.038), apraxia of speech symptoms (p=0.040), perception of everyday communicative ability (p=0.001), and the number of spoken words produced during fMRI (p=0.028). Pre- to post-treatment change in naming was negatively correlated with change in right postcentral gyrus activation related to noun-verb associations (rho=-0.554, p=0.0497). Change in aphasia symptoms from immediately after to 3 months post-treatment was negatively correlated with change in bilateral supplementary motor area activation related to verbal encoding (rho=-0.790, p=0.0022). CONCLUSIONS Aphasia improvements coupled with fMRI activation changes over time provide support for treatment-induced neuroplasticity with CIAT primed with iTBS. However, a larger randomized sham-controlled study is warranted to confirm our findings and further our understanding of how iTBS can potentiate beneficial effects of language therapy in post-stroke aphasia.

Domains of Health-Related Quality of Life Are Associated With Specific Deficits and Lesion Locations in Chronic Aphasia.

BACKGROUND: Health-related quality of life (HRQL) in stroke survivors is related to numerous factors, but more research is needed to delineate factors related to HRQL in people with aphasia. OBJECTIVE: To examine the relationship between HRQL and demographic factors, impairment-based measures, and lesion characteristics in chronic aphasia. METHODS: A total of 41 left-hemisphere stroke survivors with aphasia underwent cognitive testing and magnetic resonance imaging. To address relationships with demographic and impairment-based measures, test scores were entered into a principal component analysis (PCA) and multiple linear regression was performed for overall and domain (physical, communication, psychosocial) scores of the Stroke and Aphasia Quality of Life Scale (SAQOL-39g). Independent variables included factor scores from the PCA, motricity, lesion volume, depressed mood, and demographic variables. To address relationships with lesion location, multivariate support vector regression lesion-symptom mapping (SVR-LSM) was used to localize lesions associated with SAQOL-39g scores. RESULTS: The PCA yielded 3 factors, which were labeled Language Production, Nonlinguistic Cognition, and Language Comprehension. Multiple linear regression revealed that depression symptoms predicted lower SAQOL-39g average and domain scores. Lower motricity scores predicted lower SAQOL-39g average and physical scores, and lower Language Production factor scores predicted lower communication scores. SVR-LSM demonstrated that basal ganglia lesions were associated with lower physical scores, and inferior frontal lesions were associated with lower psychosocial scores. CONCLUSIONS: HRQL in chronic left-hemisphere stroke survivors with aphasia relates to lesion location, depression symptoms, and impairment-based measures. This information may help identify individuals at risk for specific aspects of low HRQL and facilitate targeted interventions to improve well-being.

Effects of Low-Frequency Repetitive Transcranial Magnetic Stimulation on Language Recovery in Poststroke Survivors With Aphasia: An Updated Meta-analysis.

The effects of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) on treating poststroke aphasia (PSA) remain inconclusive. We aimed to evaluate the efficacy and safety of LF-rTMS on language function poststroke and determine potential factors that may affect treatment effects. Electronic databases, including MEDLINE, EMBASE, and Cochrane Library were searched to identify relevant randomized controlled trials (RCTs) concerning the effects of LF-rTMS on language performance poststroke. We adopted fixed- and random-effects models to estimate intervention effects, which were represented by the Hedges' g and 95% CIs. Subgroup analyses regarding several factors potentially influencing the effects of LF-rTMS on language recovery were also conducted. A total of 14 RCTs involving 374 participants were included in the meta-analysis. The pooled analysis showed the positive and significant effects of LF-rTMS on language function, both short-term (Hedges' g = 0.65; P < .05) and long-term (Hedges' g = 0.46; P < .05). Subgroup analyses demonstrated that LF-rTMS for 20 minutes per day over 10 days yielded the largest effect size (Hedges' g = 1.02; P < .05) and that LF-rTMS significantly improved language performance in the chronic stage after stroke (Hedges' g = 0.55; P < .05). Patients with different native languages might have diverse responses to LF-rTMS treatment efficacy. Additionally, there were significant improvements in language subtests, including naming, repetition, comprehension, and writing. Overall, this updated meta-analysis demonstrated that LF-rTMS has significant positive effects on PSA, with moderate treatment effects. It provides additional evidence to support LF-rTMS as a promising complementary therapy to promote language recovery in PSA.

Delayed development of aphasia related to degeneration of the arcuate fasciculus in the dominant hemisphere nine years after the onset in a patient with intracerebral hemorrhage: a case report.

BACKGROUND: We report on a patient with an intracerebral hemorrhage (ICH), who showed delayed development of aphasia, which was demonstrated via follow up diffusion tensor tractography (DTT) to be related to neural degeneration of the arcuate fasciculus (AF). CASE PRESENTATION: A 51-year-old, right-handed male presented with right hemiparesis, which occurred at the onset of a spontaneous ICH in the left corona radiata and basal ganglia. Brain magnetic resonance images showed a hematoma in the left subcortical area at one month after onset and hemosiderin deposits in the left subcortical area at nine years after onset. At four weeks after onset, he exhibited severe aphasia, and Western Aphasia Battery (WAB) testing revealed an aphasia quotient in the 39.6 percentile (%ile). However, his aphasia improved to nearly a normal state, and at three months after onset, his aphasia quotient was in the 90.5 %ile. At approximately eight years after onset, he began to show aphasia, and his aphasia increased slowly with time resulting in a WAB aphasia quotient in the 12.5 %ile at nine years after onset. The integrity of the left AF over the hematoma was preserved on 1-month post-onset DTT. However, the middle portion of the left AF in the middle of the hemosiderin deposits showed discontinuation on 9-year post-onset DTT. The fractional anisotropy value of the left AF was higher on the 9-year post-onset DTT (0.48) than that on the 1-month post-onset DTT (0.35), whereas the mean diffusivity value was lower on the 9-year post-onset DTT (0.10) than that on the 1-month post-onset DTT (0.32). The fiber number of the left AF was decreased to 175 on the 9-year post-onset DTT from 239 on the 1-month post-onset DTT. CONCLUSIONS: We report on a patient with ICH who showed delayed development of aphasia, which appeared to be related to degeneration of the AF in the dominant hemisphere. Our results suggest that DTT would be useful in ruling out neural degeneration of the AF.

Language networks in aphasia and health: A 1000 participant activation likelihood estimation meta-analysis.

Aphasia recovery post-stroke is classically and most commonly hypothesised to rely on regions that were not involved in language premorbidly, through 'neurocomputational invasion' or engagement of 'quiescent homologues'. Contemporary accounts have suggested, instead, that recovery might be supported by under-utilised areas of the premorbid language network, which are downregulated in health to save neural resources ('variable neurodisplacement'). Despite the importance of understanding the neural bases of language recovery clinically and theoretically, there is no consensus as to which specific regions are more likely to be activated in post-stroke aphasia (PSA) than healthy individuals. Accordingly, we performed an Activation Likelihood Estimation (ALE) meta-analysis of language functional neuroimaging studies in PSA. We obtained coordinate-based functional neuroimaging data for 481 individuals with aphasia following left-hemisphere stroke and 530 linked controls from 33 studies that met predefined inclusion criteria. ALE identified regions of consistent, above-chance spatial convergence of activation, as well as regions of significantly different activation likelihood, between participant groups and language tasks. Overall, these findings dispute the prevailing theory that aphasia recovery involves recruitment of novel right hemisphere territory into the language network post-stroke. Instead, multiple regions throughout both hemispheres were consistently activated during language tasks in both PSA and controls. Regions of the right anterior insula, frontal operculum and inferior frontal gyrus (IFG) pars opercularis were more likely to be activated across all language tasks in PSA than controls. Similar regions were more likely to be activated during higher than lower demand comprehension or production tasks, consistent with them representing enhanced utilisation of spare capacity within right hemisphere executive-control related regions. This provides novel evidence that 'variable neurodisplacement' underlies language network changes that occur post-stroke. Conversely, multiple undamaged regions were less likely to be activated across all language tasks in PSA than controls, including domain-general regions of medial superior frontal and paracingulate cortex, right IFG pars triangularis and temporal pole. These changes might represent functional diaschisis, and demonstrate that there is not global, undifferentiated upregulation of all domain-general neural resources during language in PSA. Such knowledge is essential if we are to design neurobiologically-informed therapeutic interventions to facilitate language recovery.