Fronto-thalamic networks and the left ventral thalamic nuclei play a key role in aphasia after thalamic stroke.

Thalamic aphasia results from focal thalamic lesions that cause dysfunction of remote but functionally connected cortical areas due to language network perturbation. However, specific local and network-level neural substrates of thalamic aphasia remain incompletely understood. Using lesion symptom mapping, we demonstrate that lesions in the left ventrolateral and ventral anterior thalamic nucleus are most strongly associated with aphasia in general and with impaired semantic and phonemic fluency and complex comprehension in particular. Lesion network mapping (using a normative connectome based on fMRI data from 1000 healthy individuals) reveals a Thalamic aphasia network encompassing widespread left-hemispheric cerebral connections, with Broca's area showing the strongest associations, followed by the superior and middle frontal gyri, precentral and paracingulate gyri, and globus pallidus. Our results imply the critical involvement of the left ventrolateral and left ventral anterior thalamic nuclei in engaging left frontal cortical areas, especially Broca's area, during language processing.

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.

Functional neuroimaging and behavioral correlates of multisite tDCS as an add-on to language training in a person with post-stroke non-fluent aphasia: a year-long case study.

Mary, who experienced non-fluent aphasia as a result of an ischemic stroke, received 10 years of personalized language training (LT), resulting in transient enhancements in speech and comprehension. To enhance these effects, multisite transcranial Direct Current Stimulation (tDCS) was added to her LT regimen for 15 sessions. Assessment using the Reliable Change Index showed that this combination improved her left inferior frontal connectivity and speech production for two months and significantly improved comprehension after one month. The results indicate that using multisite transcranial direct current stimulation (tDCS) can improve the effectiveness of language therapy (LT) for individuals with non-fluent aphasia.

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.

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.

Clinico-radiological factors associated with aphasia outcome in post stroke patients: A prospective follow up study from eastern part of India.

BACKGROUND: Aphasia is a language disorder acquired secondary to brain damage. This study aims to evaluate clinical and radiological profile of patients with post stroke aphasia and factors affecting its recovery. METHODS: We conducted a prospective study of patients with first left Middle or Anterior Cerebral Artery infarct or Intracerebral Hemorrhage (ICH) with aphasia admitted within 14 days of stroke onset. Aphasia Quotient (AQ) was assessed at 2 weeks (AQ1) and 3 months (AQ2) using Western Aphasia Battery-Hindi version. Magnetic Resonance Imaging of brain with Diffusion Tensor Imaging (DTI) of bilateral Arcuate Fasciculus (AF) and Corticospinal Tract was done at admission, and stroke volume, Laterality Indices of Fractional Anisotropy (LI-FA), Mean Diffusivity (LI-MD), Radial Diffusivity (LI-RD), Axial Diffusivity (LI-AD) and Apparent Diffusion Coefficient (LI-ADC) were obtained. RESULTS: 36 patients [8 ICH and 28 Acute Ischemic Stroke (AIS)] were included. AQ1 and AQ2 were significantly higher in subcortical stroke than cortical. AQ2 and increase in AQ scores (including its subscores) were significantly higher in ICH than AIS. National Institutes of Health Stroke Scale score at admission and volume of stroke had significant negative correlation with AQ1 and AQ2. Laterality Index of Fractional Anisotropy of Arcuate Fasciculus [LI-FA (AF)] had significant positive correlation with AQ2 and naming score at 3 months. Laterality Index of Mean Diffusivity of Arcuate Fasciculus [LI-MD (AF)] had significant negative correlation with AQ1, AQ2 and all subcomponents of AQ2. Significant positive correlation was seen between improvements in Modified Rankin Scale score and AQ. CONCLUSION: The study shows that DTI can be used to predict severity of aphasia at follow up and recovery in language and motor functions occur in parallel.

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.

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.

Resting-state brain network connectivity is an independent predictor of responsiveness to language therapy in chronic post-stroke aphasia.

Post-stroke aphasia recovery, especially in the chronic phase, is challenging to predict. Functional integrity of the brain and brain network topology have been suggested as biomarkers of language recovery. This study sought to investigate functional connectivity in four predefined brain networks (i.e., language, default mode, dorsal attention, and salience networks), in relation to aphasia severity and response to language therapy. Thirty patients with chronic post-stroke aphasia were recruited and received a treatment targeting word finding. Structural and functional brain scans were acquired at baseline and resting state functional connectivity for each network was calculated. Additionally, graph measures quantifying network properties were calculated for each network. These included global efficiency for all networks and average strength and clustering coefficient for the language network. Linear mixed effects models showed that mean functional connectivity in the default mode, dorsal attention, and salience networks as well as graph measures of all four networks are independent predictors of response to therapy. While greater mean functional connectivity and global efficiency of the dorsal attention and salience networks predicted greater treatment response, greater mean functional connectivity and global efficiency in the default mode network predicted poorer treatment response. Results for the language network were more nuanced with more efficient network configurations (as reflected in graph measures), but not mean functional connectivity, predicting greater treatment response. These findings highlight the prognostic value of resting-state functional connectivity in chronic treatment-induced aphasia recovery.

Disentangling neuroplasticity mechanisms in post-stroke language recovery.

A major objective in post-stroke aphasia research is to gain a deeper understanding of neuroplastic mechanisms that drive language recovery, with the ultimate goal of enhancing treatment outcomes. Subsequent to recent advances in neuroimaging techniques, we now have the ability to examine more closely how neural activity patterns change after a stroke. However, the way these neural activity changes relate to language impairments and language recovery is still debated. The aim of this review is to provide a theoretical framework to better investigate and interpret neuroplasticity mechanisms underlying language recovery in post-stroke aphasia. We detail two sets of neuroplasticity mechanisms observed at the synaptic level that may explain functional neuroimaging findings in post-stroke aphasia recovery at the network level: feedback-based homeostatic plasticity and associative Hebbian plasticity. In conjunction with these plasticity mechanisms, higher-order cognitive control processes dynamically modulate neural activity in other regions to meet communication demands, despite reduced neural resources. This work provides a network-level neurobiological framework for understanding neural changes observed in post-stroke aphasia and can be used to define guidelines for personalized treatment development.

The volume and the distribution of premorbid white matter hyperintensities: Impact on post-stroke aphasia.

White matter hyperintensities (WMH) are a radiological manifestation of progressive white matter integrity loss. The total volume and distribution of WMH within the corpus callosum have been associated with pathological cognitive ageing processes but have not been considered in relation to post-stroke aphasia outcomes. We investigated the contribution of both the total volume of WMH, and the extent of WMH lesion load in the corpus callosum to the recovery of language after first-ever stroke. Behavioural and neuroimaging data from individuals (N = 37) with a left-hemisphere stroke were included at the early subacute stage of recovery. Spoken language comprehension and production abilities were assessed using word and sentence-level tasks. Neuroimaging data was used to derive stroke lesion variables (volume and lesion load to language critical regions) and WMH variables (WMH volume and lesion load to three callosal segments). WMH volume did not predict variance in language measures, when considered together with stroke lesion and demographic variables. However, WMH lesion load in the forceps minor segment of the corpus callosum explained variance in early subacute comprehension abilities (t = -2.59, p = .01) together with corrected stroke lesion volume and socio-demographic variables. Premorbid WMH lesions in the forceps minor were negatively associated with early subacute language comprehension after aphasic stroke. This negative impact of callosal WMH on language is consistent with converging evidence from pathological ageing suggesting that callosal WMH disrupt the neural networks supporting a range of cognitive functions.

A right convergence area of the prefrontal lobe is involved in the improvement of semantic fluency in patients with post-stroke aphasia.

OBJECTIVES: This study aimed to longitudinally observe the improvement mechanism of semantic fluency in subacute post-stroke aphasia (PSA) patients using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Twelve PSA patients, about one month after onset, were enrolled in this study and received speech-language therapy (SLT) for one month. Auditory comprehension and semantic fluency were evaluated using the Western Aphasia Battery (WAB) and the Animal Fluency Test. Before and after treatment, rs-fMRI data were collected, and the dice similarity coefficient was used to measure the spatial similarity between each patient's lesion and a reference lesion. The left posterior inferior temporal gyrus (pITG) was used as a seed to calculate the normalized functional connectivity in whole-brain voxel analysis using DPABI software for statistical analysis. RESULTS: The dice similarity coefficient between each patient's lesion and the reference lesion showed moderate to high intensity (0.57 ± 0.14) in the Montreal Neurological Institute space. After treatment, we found a significant increase in functional connectivity between the left pITG and the right prefrontal lobe convergence area (peak t = 8.219, Gaussian random field multiple comparison correction, voxel p < 0.001, cluster p < 0.05). The increase in functional connectivity was negatively correlated with the improvement in auditory comprehension (r =-0.707, p = 0.033) and positively correlated with the improvement in semantic fluency (r = 0.79, p = 0.02). CONCLUSION: The improvement of semantic fluency in subacute PSA patients may require the participation of the right convergence area of the prefrontal lobe.

Altered functional connectivity in language and non-language brain networks in patients diagnosed with acute post-stroke aphasia.

OBJECTIVE: A resting-state functional magnetic resonance imaging (rs-fMRI) approach was used to explore functional connectivity (FC) in language and non-language brain networks in acute post-stroke aphasia (PSA) patients, with a specific focus on the relationship between these fMRI results and patient clinical presentation. METHODS: In total, 20 acute PSA patients and 30 age-, sex-, and education level-matched healthy control (HC) participants were recruited and subjected to rs-fMRI imaging. In addition, western aphasia battery analyses（WAB） were used to compute aphasia quotient (AQ) values for PSA patients. Granger causality was employed to examine connections among cognition-associated resting-state brain networks, and the right middle frontal gyrus (RMFG),the mirror brain regions of Broca's area and the Wernicke's area, the right superior temporal gyrus were selected as regions of interest (ROIs). The REST plus software was then used to perform FC analyses of these regions to analyze changes in FC related to PSA pathogenesis. RESULTS: Relative to HC individuals, PSA patients exhibited significantly higher levels of intra-network FC between the right middle frontal gyrus (RMFG) and the left middle occipital gyrus (LMOG), with such FC being positively correlated with the AQ scores (P = 0.018). Moreover, reduced FC was detected between the Broca's area homolog and the left middle frontal gyrus (LMFG), while FC was enhanced between the Wernicke's area homolog and cerebellar vermis, and this FC was similarly positively correlated with patient AQ scores (P = 0.0297). CONCLUSION: These results suggest that FC between the bilateral hemispheres of the brain is significantly disrupted in acute PSA patients, interfering with the normal non-specific language network. Aphasia severity was further found to correlate with FC among many of the analyzed regions of the brain.

Functional Magnetic Resonance Imaging Activation During Unscripted Discourse in People With Poststroke Aphasia.

PURPOSE: The purpose of this project was to determine the feasibility of employing a functional magnetic resonance imaging (fMRI) task that captured activation associated with overt, unscripted (or free) discourse of people with aphasia (PWA), using a continuous scan paradigm. METHOD: Seven participants (six females, ages 48-70 years) with chronic poststroke aphasia underwent two fMRI scanning sessions that included a discourse fMRI paradigm that consisted of five 1-min picture description tasks, using personally relevant photographs, interspersed with two 30-s control periods where participants looked at a fixation cross. Audio during the continuous fMRI scan was collected and marked with speaking times and coded for correct information units. Activation maps from the fMRI data were generated for the contrast between speaking and control conditions. In order to show the effects of the multi-echo data analysis, we compared it to a single-echo analysis by using only the middle echo (echo time of 30 ms). RESULTS: Through the implementation of the free discourse fMRI task, we were able to elicit activation that included bilateral regions in the planum polare, central opercular cortex, precentral gyrus, superior temporal gyrus, middle temporal gyrus, superior temporal gyrus, Crus I of the cerebellum, as well as bilateral occipital regions. CONCLUSIONS: We describe a new tool for assessing discourse recovery in PWA. By demonstrating the feasibility of a natural language paradigm in patients with chronic, poststroke aphasia, we open a new area for future research.

Electrophysiological correlates of basic semantic composition in people with aphasia.

The neuroanatomical correlates of basic semantic composition have been investigated in previous neuroimaging and lesion studies, but research on the electrophysiology of the involved processes is scarce. A large literature on sentence-level event-related potentials (ERPs) during semantic processing has identified at least two relevant components - the N400 and the P600. Other studies demonstrated that these components are reduced and/or delayed in people with aphasia (PWA). However, it remains to be shown if these findings generalize beyond the sentence level. Specifically, it is an open question if an alteration in ERP responses in PWA can also be observed during basic semantic composition, providing a potential future diagnostic tool. The present study aimed to elucidate the electrophysiological dynamics of basic semantic composition in a group of post-stroke PWA. We included 20 PWA and 20 age-matched controls (mean age 58 years) and measured ERP responses while they performed a plausibility judgment task on two-word phrases that were either meaningful ("anxious horse"), anomalous ("anxious wood") or had the noun replaced by a pseudoword ("anxious gufel"). The N400 effect for anomalous versus meaningful phrases was similar in both groups. In contrast, unlike the control group, PWA did not show an N400 effect between pseudoword and meaningful phrases. Moreover, both groups exhibited a parietal P600 effect towards pseudoword phrases, while PWA showed an additional P600 over frontal electrodes. Finally, PWA showed an inverse correlation between the magnitude of the N400 and P600 effects: PWA exhibiting no or even reversed N400 effects towards anomalous and pseudoword phrases showed a stronger P600 effect. These results may reflect a compensatory mechanism which allows PWA to arrive at the correct interpretation of the phrase. When compositional processing capacities are impaired in the early N400 time-window, PWA may make use of a more elaborate re-analysis process reflected in the P600.

Diffusion tensor imaging magnetic resonance imaging (DTI-MRI) helps to tailor speech therapy: A case report with a short narrative review.

BACKGROUND: Stroke has functional sequelae, including motor weakness, spasticity, dysphagia, and neurogenic bladder deteriorating activities of daily living. Speech therapy is more often an essential part of the rehabilitation program. Studies in aphasia have primarily focused on two major pathways: the arcuate fasciculus and the superior longitudinal fasciculus. The arcuate fasciculus is a major fiber bundle connecting Broca's area (associated with language production) and Wernicke's area (associated with language comprehension). Damage to this pathway can result in different types of aphasia, depending on the location and extent of the injury. CASE DESCRIPTION: Tractography is a neuroimaging technique used to map the white matter tracts in the brain. Our patient had an occlusion of the external carotid and left carotid siphon. The patient exhibited early complex language deficits involving both motor expressive and comprehensive abilities. After three months the patient presented conduction aphasia caused by damage to the inferior parietal lobule, which extends into the subcortical white matter and damages the arcuate fascicle. This patient was re-assessed for spasticity and language treatments needs, few months after the stroke. Considering first two months language improvement followed by any further language expressive improvement from 3rd to 6th month, a diffusion tensor imaging (DTI) tractography was requested to study interconnections between cortical and subcortical matter. The brain magnetic resonance imaging (MRI) performed in our hospital showed an extensive malacic gliotic area in the left temporal-frontal parietal site. CONCLUSION: Brain MRI is confirmed as a multimodal tool evaluating the damage, both from the point of structural and functional view. Tractography in aphasia allows focusing on major pathways. The involvement of the arcuate fascicle, whose lesion disconnects Broca's and Wernicke's areas, is related to clinical improvement, and represents a neural correlate of the brain injury recovery process that physicians and speech therapists might be aware of it, tailoring the plane of care of each patient.

Treatment-induced neuroplasticity after anomia therapy in post-stroke aphasia: A systematic review of neuroimaging studies.

We systematically reviewed the literature on neural changes following anomia treatment post-stroke. We conducted electronic searches of CINAHL, Cochrane Trials, Embase, Ovid MEDLINE, MEDLINE-in-Process and PsycINFO databases; two independent raters assessed all abstracts and full texts. Accepted studies reported original data on adults with post-stroke aphasia, who received behavioural treatment for anomia, and magnetic resonance brain imaging (MRI) pre- and post-treatment. Search results yielded 2481 citations; 33 studies were accepted. Most studies employed functional MRI and the quality of reporting neuroimaging methodology was variable, particularly for pre-processing steps and statistical analyses. The most methodologically robust data were synthesized, focusing on pre- versus post-treatment contrasts. Studies more commonly reported increases (versus decreases) in activation following naming therapy, primarily in the left supramarginal gyrus, and left/bilateral precunei. Our findings highlight the methodological heterogeneity across MRI studies, and the paucity of robust evidence demonstrating direct links between brain and behaviour in anomia rehabilitation.

The language network is not engaged in object categorization.

The relationship between language and thought is the subject of long-standing debate. One claim states that language facilitates categorization of objects based on a certain feature (e.g. color) through the use of category labels that reduce interference from other, irrelevant features. Therefore, language impairment is expected to affect categorization of items grouped by a single feature (low-dimensional categories, e.g. "Yellow Things") more than categorization of items that share many features (high-dimensional categories, e.g. "Animals"). To test this account, we conducted two behavioral studies with individuals with aphasia and an fMRI experiment with healthy adults. The aphasia studies showed that selective low-dimensional categorization impairment was present in some, but not all, individuals with severe anomia and was not characteristic of aphasia in general. fMRI results revealed little activity in language-responsive brain regions during both low- and high-dimensional categorization; instead, categorization recruited the domain-general multiple-demand network (involved in wide-ranging cognitive tasks). Combined, results demonstrate that the language system is not implicated in object categorization. Instead, selective low-dimensional categorization impairment might be caused by damage to brain regions responsible for cognitive control. Our work adds to the growing evidence of the dissociation between the language system and many cognitive tasks in adults.

Methodologies for task-fMRI based prognostic biomarkers in response to aphasia treatment.

With the diversity in aphasia coupled with diminished gains at the chronic phase, it is imperative to deliver effective rehabilitation plans. Treatment outcomes have therefore been predicted using lesion-to-symptom mapping, but this method lacks holistic functional information about the language-network. This study, therefore, aims to develop whole-brain task-fMRI multivariate analysis to neurobiologically inspect lesion impacts on the language-network and predict behavioral outcomes in persons with aphasia (PWA) undergoing language therapy. In 14 chronic PWA, semantic fluency task-fMRI and behavioral measures were collected to develop prediction methodologies for post-treatment outcomes. Then, a recently developed imaging-based multivariate method to predict behavior (i.e., LESYMAP) was optimized to intake whole-brain task-fMRI data, and systematically tested for reliability with mass univariate methods. We also accounted for lesion size in both methods. Results showed that both mass univariate and multivariate methods identified unique biomarkers for semantic fluency improvements from baseline to 2-weeks post-treatment. Additionally, both methods demonstrated reliable spatial overlap in task-specific areas including the right middle frontal gyrus when identifying biomarkers of language discourse. Thus whole-brain task-fMRI multivariate analysis has the potential to identify functionally meaningful prognostic biomarkers even for relatively small sample sizes. In sum, our task-fMRI based multivariate approach holistically estimates post-treatment response for both word and sentence production and may serve as a complementary tool to mass univariate analysis in developing brain-behavior relationships for improved personalization of aphasia rehabilitation regimens.

Expressive recall and recognition as complementary measures to assess novel word learning ability in aphasia.

Novel word learning ability has been associated with language treatment outcomes in people with aphasia (PWA), and its assessment could inform prognosis and rehabilitation. We used a brief experimental task to examine novel word learning in PWA, determine the value of phonological cueing in assessing learning outcomes, and identify factors that modulate learning ability. Twelve PWA and nineteen healthy controls completed the task, and recall and recognition tests of learning ability. Most PWA showed comparable learning outcomes to those of the healthy controls. Learning assessed via expressive recall was more clearly evidenced with phonological cues. Better single word processing abilities and phonological short-term memory and higher integrity of the left inferior frontal gyrus were related to better learning performance. Brief learning tasks like this one are clinically feasible and hold promise as screening tools of verbal learning in PWA once validated and evaluated for their capacity to predict treatment outcomes.