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.

Verbal short term memory contribution to sentence comprehension decreases with increasing syntactic complexity in people with aphasia.

Sentence comprehension requires the integration of linguistic units presented in a temporal sequence based on a non-linear underlying syntactic structure. While it is uncontroversial that storage is mandatory for this process, there are opposing views regarding the relevance of general short-term-/working-memory capacities (STM/WM) versus language specific resources. Here we report results from 43 participants with an acquired brain lesion in the extended left hemispheric language network and resulting language deficits, who performed a sentence-to-picture matching task and an experimental task assessing phonological short-term memory. The sentence task systematically varied syntactic complexity (embedding depth and argument order) while lengths, number of propositions and plausibility were kept constant. Clinical data including digit-/ block-spans and lesion size and site were additionally used in the analyses. Correlational analyses confirm that performance on STM/WM-tasks (experimental task and digit-span) are the only two relevant predictors for correct sentence-picture-matching, while reaction times only depended on age and lesion size. Notably increasing syntactic complexity reduced the correlational strength speaking for the additional recruitment of language specific resources independent of more general verbal STM/WM capacities, when resolving complex syntactic structure. The complementary lesion-behaviour analysis yielded different lesion volumes correlating with either the sentence-task or the STM-task. Factoring out STM measures lesions in the anterior temporal lobe correlated with a larger decrease in accuracy with increasing syntactic complexity. We conclude that overall sentence comprehension depends on STM/WM capacity, while increases in syntactic complexity tax another independent cognitive resource.

Clinical characteristics of post-stroke basal ganglia aphasia and the study of language-related white matter tracts based on diffusion spectrum imaging.

BACKGROUND: Stroke often damages the basal ganglia, leading to atypical and transient aphasia, indicating that post-stroke basal ganglia aphasia (PSBGA) may be related to different anatomical structural damage and functional remodeling rehabilitation mechanisms. The basal ganglia contain dense white matter tracts (WMTs). Hence, damage to the functional tract may be an essential anatomical structural basis for the development of PSBGA. METHODS: We first analyzed the clinical characteristics of PSBGA in 28 patients and 15 healthy controls (HCs) using the Western Aphasia Battery and neuropsychological test batteries. Moreover, we investigated white matter injury during the acute stage using diffusion magnetic resonance imaging scans for differential tractography. Finally, we used multiple regression models in correlation tractography to analyze the relationship between various language functions and quantitative anisotropy (QA) of WMTs. RESULTS: Compared with HCs, patients with PSBGA showed lower scores for fluency, comprehension (auditory word recognition and sequential commands), naming (object naming and word fluency), reading comprehension of sentences, Mini-Mental State Examination, and Montreal Cognitive Assessment, along with increased scores in Hamilton Anxiety Scale-17 and Hamilton Depression Scale-17 within 7 days after stroke onset (P < 0.05). Differential tractography revealed that patients with PSBGA had damaged fibers, including in the body fibers of the corpus callosum, left cingulum bundles, left parietal aslant tracts, bilateral superior longitudinal fasciculus II, bilateral thalamic radiation tracts, left fornix, corpus callosum tapetum, and forceps major, compared with HCs (FDR < 0.02). Correlation tractography highlighted that better comprehension was correlated with a higher QA of the left inferior fronto-occipital fasciculus (IFOF), corpus callosum forceps minor, and left extreme capsule (FDR < 0.0083). Naming was positively associated with the QA of the left IFOF, forceps minor, left arcuate fasciculus, and uncinate fasciculus (UF) (FDR < 0.0083). Word fluency of naming was also positively associated with the QA of the forceps minor, left IFOF, and thalamic radiation tracts (FDR < 0.0083). Furthermore, reading was positively correlated with the QA of the forceps minor, left IFOF, and UF (FDR < 0.0083). CONCLUSION: PSBGA is primarily characterized by significantly impaired word fluency of naming and preserved repetition abilities, as well as emotional and cognitive dysfunction. Damaged limbic pathways, dorsally located tracts in the left hemisphere, and left basal ganglia pathways are involved in PSBGA pathogenesis. The results of connectometry analysis further refine the current functional localization model of higher-order neural networks associated with language functions.

Change of function and brain activity in patients of right spastic arm paralysis combined with aphasia after contralateral cervical seventh nerve transfer surgery.

Left hemisphere injury can cause right spastic arm paralysis and aphasia, and recovery of both motor and language functions shares similar compensatory mechanisms and processes. Contralateral cervical seventh cross transfer (CC7) surgery can provide motor recovery for spastic arm paralysis by triggering interhemispheric plasticity, and self-reports from patients indicate spontaneous improvement in language function but still need to be verified. To explore the improvements in motor and language function after CC7 surgery, we performed this prospective observational cohort study. The Upper Extremity part of Fugl-Meyer scale (UEFM) and Modified Ashworth Scale were used to evaluate motor function, and Aphasia Quotient calculated by Mandarin version of the Western Aphasia Battery (WAB-AQ, larger score indicates better language function) was assessed for language function. In 20 patients included, the average scores of UEFM increased by .40 and 3.70 points from baseline to 1-week and 6-month post-surgery, respectively. The spasticity of the elbow and fingers decreased significantly at 1-week post-surgery, although partially recurred at 6-month follow-up. The average scores of WAB-AQ were increased by 9.14 and 10.69 points at 1-week and 6-month post-surgery (P < .001 for both), respectively. Post-surgical fMRI scans revealed increased activity in the bilateral hemispheres related to language centrals, including the right precentral cortex and right gyrus rectus. These findings suggest that CC7 surgery not only enhances motor function but may also improve the aphasia quotient in patients with right arm paralysis and aphasia due to left hemisphere injuries.

Exploring neural tracking of acoustic and linguistic speech representations in individuals with post-stroke aphasia.

Aphasia is a communication disorder that affects processing of language at different levels (e.g., acoustic, phonological, semantic). Recording brain activity via Electroencephalography while people listen to a continuous story allows to analyze brain responses to acoustic and linguistic properties of speech. When the neural activity aligns with these speech properties, it is referred to as neural tracking. Even though measuring neural tracking of speech may present an interesting approach to studying aphasia in an ecologically valid way, it has not yet been investigated in individuals with stroke-induced aphasia. Here, we explored processing of acoustic and linguistic speech representations in individuals with aphasia in the chronic phase after stroke and age-matched healthy controls. We found decreased neural tracking of acoustic speech representations (envelope and envelope onsets) in individuals with aphasia. In addition, word surprisal displayed decreased amplitudes in individuals with aphasia around 195 ms over frontal electrodes, although this effect was not corrected for multiple comparisons. These results show that there is potential to capture language processing impairments in individuals with aphasia by measuring neural tracking of continuous speech. However, more research is needed to validate these results. Nonetheless, this exploratory study shows that neural tracking of naturalistic, continuous speech presents a powerful approach to studying aphasia.

Cerebellar-Induced Aphasia After Stroke: Evidence for the "Linguistic Cerebellum".

The cerebellum is traditionally known to subserve motor functions. However, for several decades, the concept of the "cerebellar cognitive affective syndrome" has evolved. Studies in healthy participants and patients have confirmed the cerebellar role in language. The exact involvement of the cerebellum regarding cerebellar aphasia remains uncertain. We included 43 cerebellar stroke patients who were tested at 3 months post-onset with the Boston Naming Test (BNT), the Token Test (TT), and the Diagnostic Instrument for Mild Aphasia (DIMA). Lesion side (left/right) and volume (cm3) were investigated. Patients significantly deviated on the following: BNT (p<0.001), TT (p<0.05), DIMA subtests: sentences repetition (p=0.001), semantic odd-picture-out (p<0.05), sentence completion (p<0.05) without an effect of lesion location (left/right) or volume (cm3) (p>0.05). Our clinical study confirms a non-lateralized cerebellar aphasia post-stroke, characterized by impairments in word retrieval, phonology, semantics, and syntax resembling cerebral-induced aphasia. The integral cerebellum appears to interact with eloquent cortico-subcortical language areas.

The role of input vs. output phonological working memory in narrative production: Evidence from case series and case study approaches.

Separable input and output phonological working memory (WM) capacities have been proposed, with the input capacity supporting speech recognition and the output capacity supporting production. We examined the role of input vs. output phonological WM in narrative production, examining speech rate and pronoun ratio - two measures with prior evidence of a relation to phonological WM. For speech rate, a case series approach with individuals with aphasia found no significant independent contribution of input or output phonological WM capacity after controlling for single-word production. For pronoun ratio, there was some suggestion of a role for input phonological WM. Thus, neither finding supported a specific role for an output phonological buffer in speech production. In contrast, two cases demonstrating dissociations between input and output phonological WM capacities provided suggestive evidence of predicted differences in narrative production, though follow-up research is needed. Implications for case series vs. case study approaches are discussed.

False Discovery Rate Control for Lesion-Symptom Mapping With Heterogeneous Data via Weighted p-Values.

Lesion-symptom mapping studies provide insight into what areas of the brain are involved in different aspects of cognition. This is commonly done via behavioral testing in patients with a naturally occurring brain injury or lesions (e.g., strokes or brain tumors). This results in high-dimensional observational data where lesion status (present/absent) is nonuniformly distributed, with some voxels having lesions in very few (or no) subjects. In this situation, mass univariate hypothesis tests have severe power heterogeneity where many tests are known a priori to have little to no power. Recent advancements in multiple testing methodologies allow researchers to weigh hypotheses according to side information (e.g., information on power heterogeneity). In this paper, we propose the use of p-value weighting for voxel-based lesion-symptom mapping studies. The weights are created using the distribution of lesion status and spatial information to estimate different non-null prior probabilities for each hypothesis test through some common approaches. We provide a monotone minimum weight criterion, which requires minimum a priori power information. Our methods are demonstrated on dependent simulated data and an aphasia study investigating which regions of the brain are associated with the severity of language impairment among stroke survivors. The results demonstrate that the proposed methods have robust error control and can increase power. Further, we showcase how weights can be used to identify regions that are inconclusive due to lack of power.

Phantasia, aphantasia, and hyperphantasia: Empirical data and conceptual considerations.

Within the past decade, the term "phantasia" has been increasingly used to describe the human capacity, faculty, or power of visual mental imagery, with extremes of imagery vividness characterised as "aphantasia" and "hyperphantasia". A substantial volume of empirical research addressing these constructs has now been published, including attempts to find inductive correlates of behaviourally defined aphantasia, for example using research questionnaires and functional magnetic resonance imaging. Mental imagery has long been noted as a source of conceptual confusions but no specific conceptual analysis of the new formulation of phantasia, aphantasia, and hyperphantasia has been undertaken hitherto. We offer some conceptual considerations on phantasia, noting the ongoing confusion of perceptual with mental images, and the ubiquitous use of unvalidated subjective assessment instruments such as the Vividness of Visual Imagery Questionnaire (VVIQ) in diagnosis and assessment, development of which was predicated on these conceptual confusions. We offer some suggestions for a conceptual framework for future empirical studies in this field, circumventing these conceptual confusions.

Clinical efficacy of pre-trained large language models through the lens of aphasia.

The rapid development of large language models (LLMs) motivates us to explore how such state-of-the-art natural language processing systems can inform aphasia research. What kind of language indices can we derive from a pre-trained LLM? How do they differ from or relate to the existing language features in aphasia? To what extent can LLMs serve as an interpretable and effective diagnostic and measurement tool in a clinical context? To investigate these questions, we constructed predictive and correlational models, which utilize mean surprisals from LLMs as predictor variables. Using AphasiaBank archived data, we validated our models' efficacy in aphasia diagnosis, measurement, and prediction. Our finding is that LLMs-surprisals can effectively detect the presence of aphasia and different natures of the disorder, LLMs in conjunction with the existing language indices improve models' efficacy in subtyping aphasia, and LLMs-surprisals can capture common agrammatic deficits at both word and sentence level. Overall, LLMs have potential to advance automatic and precise aphasia prediction. A natural language processing pipeline can be greatly benefitted from integrating LLMs, enabling us to refine models of existing language disorders, such as aphasia.

The value of action observation in speech and language rehabilitation: A systematic review and meta-analysis.

In this systematic review and meta-analysis, our aim was to identify and quantify evidence of action observation therapy (AOT) efficacy in managing language deficits in patients with aphasia. This study conducts two quantitative investigations: firstly, comparing the effects of AOT and conventional control therapy in different groups, and secondly, analyzing within AOT group to explore potential moderators of AOT effectiveness. Four databases were searched up until August 2023 to find studies utilizing AOT for aphasia management. Seven eligible studies were included. The main analyses revealed moderate evidence of improvement in naming tasks, with a large effect size (Hedge's g = 1.27, 95 %CI [0.44; 2.09], p = 0.003, I2 < 25) following AOT compared to control interventions. Furthermore, to be efficient, AOT should focus on human actions (e.g., running, jumping) rather than non-human actions (e.g., meowing or barking). These findings indicate that AOT is a promising alternative complementary approach for patients with aphasia. Future research should confirm the potential benefits of AOT with more randomized controlled studies and aim to clarify the minimal dose necessary and the possibility of transfer to various language tasks.

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.

Rational adaptation in word production: Strong conceptual ability reduces the effect of lexical impairments on verb retrieval in aphasia.

Language users rely on both linguistic and conceptual processing abilities to efficiently comprehend or produce language. According to the principle of rational adaptation, the degree to which a cognitive system relies on one process vs. another can change under different conditions or disease states with the goal of optimizing behavior. In this study, we investigated rational adaptation in reliance on linguistic versus conceptual processing in aphasia, an acquired disorder of language. In individuals living with aphasia, verb-retrieval impairments are a pervasive deficit that negatively impacts communicative function. As such, we examined evidence of adaptation in verb production, using parallel measures to index impairment in two of verb naming's critical subcomponents: conceptual and linguistic processing. These component processes were evaluated using a standardized assessment battery designed to contrast non-linguistic (picture input) and linguistic (word input) tasks of conceptual action knowledge. The results indicate that non-linguistic conceptual action processing can be impaired in people with aphasia and contributes to verb-retrieval impairments. Furthermore, relatively unimpaired conceptual action processing can ameliorate the influence of linguistic processing deficits on verb-retrieval impairments. These findings are consistent with rational adaptation accounts, indicating that conceptual processing plays a key role in language function and can be leveraged in rehabilitation to improve verb retrieval in adults with chronic aphasia.

Validation of a Cantonese Version of the Amsterdam-Nijmegen Everyday Language Test (CANELT): A functional approach.

BACKGROUND: The current study aimed to validate the Cantonese version of the Amsterdam-Nijmegen Everyday Language Test (CANELT), a functional communication assessment tool for Cantonese speakers with aphasia. A quantitative scoring method was adopted to examine the pragmatics and informativeness of the production of people with aphasia (PWA). METHOD: CANELT was translated from its English version with cultural adaptations. The performance on the 20-item CANELT collected from 56 PWA and 100 neurologically healthy Cantonese-speaking controls aged 30 to 79 years was orthographically transcribed. Scoring was based on the completeness of the main concepts produced in the preamble and subsequent elaborations, defined as Opening (O) and New Information (NI). Measures examining the validity and reliability were conducted. RESULTS: An age effect was found in neurologically healthy controls, and therefore z scores were used for subsequent comparisons between neurologically healthy controls and PWA. The test showed strong evidence for known-group validity in both O [χ2 (2) = 95.2, p < .001] and NI [χ2 (2) = 100.4, p < .001]. A moderate to strong correlation was found between CANELT and standardized aphasia assessment tools, suggesting satisfactory concurrent validity. Reliability measures were excellent in terms of internal consistency (Cronbach's α of .95 for both 'O' and 'NI'), test-retest reliability (ICC = .96; p < .001), intra-rater reliability (ICC = 1.00; p < .001), and inter-rater reliability for O (ICC = .99; p < .001) and NI (ICC = .99; p < .001). Sensitivity and specificity for O are 97% and 76.8%, respectively, while for NI, a sensitivity of 95% and specificity of 91.1% were obtained. CONCLUSIONS: Measures on validity and reliability yielded promising results, suggesting CANELT as a useful and reliable functional communication assessment for PWA. Its application in managing PWA and potential areas for development are discussed.

The role of cognitive control and naming in aphasia.

The classical aphasia literature has placed considerable emphasis on the language-centered understanding of aphasia and failed to consider the role of executive functions (EFs) regarding different aspects of patients' performance. Many current studies suggest deficits in EFs in individuals with aphasia, however, the available data is still limited. Here, our aim was to investigate the impairment of EFs and its potential negative effects on naming (slower performance, increased reaction time and/or decreased accuracy). We sought to determine whether the poor performance observed in word fluency task correlated with similar outcomes in naming. Our study involved five Hungarian post stroke aphasic patients (2 males and 3 females) between the ages of 60 and 70, as well as a control group matched for age and gender. The participants were diagnosed with different types of aphasia (global, Wernicke's, anomic and conduction). This study employed various neuropsychological and linguistic batteries. By comparing the patients' performance to that of the control group, we aimed to investigate the impacts of stroke. Within the aphasia group, we observed difficulties in following complex commands and a connection between general slowness and reduced accuracy in naming. We concluded that impairment of executive functions may have a negative impact on naming, comprehension, and fluency. Therefore, it is important to consider functional variations in neural networks, and to base our interpretations on the available psychophysiological data in literature. Our findings provide an alternative perspective to the traditional assessment of aphasia and highlight the importance of considering the role of executive functions.

Post-traumatic Transient Neurological Dysfunction: A Proposal for Pathophysiology.

Unexplained neurological deterioration is occasionally observed in patients with traumatic brain injuries (TBIs). We aimed to describe the clinical features of post-traumatic transient neurological dysfunction and provide new insight into its pathophysiology. We retrospectively collected data from patients with focal neurological deterioration of unknown origin during hospitalization for acute TBI for 48 consecutive months. Brain imaging, including computed tomography, diffusion-weighted imaging and perfusion-weighted imaging, and electroencephalography were conducted during the episodes. Fourteen (2.0%) patients experienced unexplained focal neurological deterioration among 713 patients who were admitted for traumatic intracranial hemorrhage during the study period. Aphasia was the predominant symptom in all patients, and hemiparesis or hemianopia was accompanied in three patients. These symptoms developed within 14 days after trauma. Structural imaging did not show any significant interval change, and electroencephalography showed persistent arrhythmic slowing in the corresponding hemisphere in most patients. Perfusion imaging revealed increased cerebral blood flow in the symptomatic hemisphere. Surgical intervention and anti-seizure medications were ineffective in abolishing the symptoms. The symptoms disappeared spontaneously after 4 h to 1 month. Transient neurological dysfunction (TND) can occur during the acute phase of TBI. Although TND may last longer than a typical transient ischemic attack or seizure, it eventually resolves regardless of treatment. Based on our observation, we postulate that this is a manifestation of spreading depolarization occurring in the injured brain, which is analogous to migraine aura.

Discourse- and lesion-based aphasia quotient estimation using machine learning.

Discourse is a fundamentally important aspect of communication, and discourse production provides a wealth of information about linguistic ability. Aphasia commonly affects, in multiple ways, the ability to produce discourse. Comprehensive aphasia assessments such as the Western Aphasia Battery-Revised (WAB-R) are time- and resource-intensive. We examined whether discourse measures can be used to estimate WAB-R Aphasia Quotient (AQ), and whether this can serve as an ecologically valid, less resource-intensive measure. We used features extracted from discourse tasks using three AphasiaBank prompts involving expositional (picture description), story narrative, and procedural discourse. These features were used to train a machine learning model to predict the WAB-R AQ. We also compared and supplemented the model with lesion location information from structural neuroimaging. We found that discourse-based models could estimate AQ well, and that they outperformed models based on lesion features. Addition of lesion features to the discourse features did not improve the performance of the discourse model substantially. Inspection of the most informative discourse features revealed that different prompt types taxed different aspects of language. These findings suggest that discourse can be used to estimate aphasia severity, and provide insight into the linguistic content elicited by different types of discourse prompts.

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.

Regional brain aging: premature aging of the domain general system predicts aphasia severity.

Premature brain aging is associated with poorer cognitive reserve and lower resilience to injury. When there are focal brain lesions, brain regions may age at different rates within the same individual. Therefore, we hypothesize that reduced gray matter volume within specific brain systems commonly associated with language recovery may be important for long-term aphasia severity. Here we show that individuals with stroke aphasia have a premature brain aging in intact regions of the lesioned hemisphere. In left domain-general regions, premature brain aging, gray matter volume, lesion volume and age were all significant predictors of aphasia severity. Increased brain age following a stroke is driven by the lesioned hemisphere. The relationship between brain age in left domain-general regions and aphasia severity suggests that degradation is possible to specific brain regions and isolated aging matters for behavior.

The role of language-related functional brain regions and white matter tracts in network plasticity of post-stroke aphasia.

The neural mechanisms underlying language recovery after a stroke remain controversial. This review aimed to summarize the plasticity and reorganization mechanisms of the language network through neuroimaging studies. Initially, we discussed the involvement of right language homologues, perilesional tissue, and domain-general networks. Subsequently, we summarized the white matter functional mapping and remodeling mechanisms associated with language subskills. Finally, we explored how non-invasive brain stimulation (NIBS) promoted language recovery by inducing neural network plasticity. It was observed that the recruitment of right hemisphere language area homologues played a pivotal role in the early stages of frontal post-stroke aphasia (PSA), particularly in patients with larger lesions. Perilesional plasticity correlated with improved speech performance and prognosis. The domain-general networks could respond to increased "effort" in a task-dependent manner from the top-down when the downstream language network was impaired. Fluency, repetition, comprehension, naming, and reading skills exhibited overlapping and unique dual-pathway functional mapping models. In the acute phase, the structural remodeling of white matter tracts became challenging, with recovery predominantly dependent on cortical activation. Similar to the pattern of cortical activation, during the subacute and chronic phases, improvements in language functions depended, respectively, on the remodeling of right white matter tracts and the restoration of left-lateralized language structural network patterns. Moreover, the midline superior frontal gyrus/dorsal anterior cingulate cortex emerged as a promising target for NIBS. These findings offered theoretical insights for the early personalized treatment of aphasia after stroke.