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Background and Purpose: Despite comprehensive evidence that supports the utility of aphasia therapy in persons with chronic (≥6 months) stroke-induced aphasia, the amount of therapy provided to patients in the United States is typically far less than what is likely necessary to maximize recovery. Two potential contributors to this discrepancy are limited access to rehabilitation services due to the availability of providers and logistical difficulties with transportation. One way to increase access to aphasia therapy is to rely on telerehabilitation., Methods: The TEleRehabilitation foR Aphasia (TERRA) trial is a prospective, randomized, rater-blinded, multicenter phase II non-inferiority trial to evaluate telerehabilitation for aphasia therapy in persons with chronic post-stroke aphasia. Participants are randomized (1:1) to receive either aphasia remote therapy or in-clinic therapy for 30 total days of treatment (15 days of a semantically focused approach and 15 days of a phonologically focused approach) for 45 min per day. A total of 100 adults (ages 21-80) with a history of left hemisphere ischemic or hemorrhagic stroke incurred at least 12 months prior to study enrollment will be randomized. The trial will be conducted at the clinical research facilities at two sites: the Medical University of South Carolina and the University of South Carolina., Conclusions: This paper details the design of the TERRA trial, which aims to test whether aphasia therapy delivered by a remote speech-language pathologist through videoconferencing (i.e., via telerehabilitation) is not clinically worse than in-clinic therapy for individuals with chronic post-stroke aphasia to provide an opportunity to move to a definitive phase III trial., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: Venous outflow (VO) impairment predicts unfavorable outcomes in patients with acute ischemic stroke caused by large vessel occlusion (AIS-LVO). Prolonged venous transit (PVT), a visual qualitative VO marker on CT perfusion (CTP) time to maximum (Tmax) maps, has been associated with unfavorable 90-day functional outcomes despite successful reperfusion. This study investigates the association between PVT and percent change on the National Institutes of Health Stroke Scale (NIHSS) among AIS-LVO patients who have undergone successful reperfusion., Methods: We performed a retrospective analysis of prospectively collected data from consecutive adult AIS-LVO patients with successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b/2c/3). PVT+ was defined as Tmax ≥10 s in the superior sagittal sinus, torcula, or both. The primary outcome was continuous NIHSS percent change and dichotomous NIHSS percent change ≥70%. Regression analyses were performed to assess the effect of PVT on NIHSS percent change., Results: In 119 patients of median (IQR) age 71 (63-81) years, the admission and discharge NIHSS scores were significantly higher in PVT+ patients compared to PVT- patients (17 [14-23.5] vs. 13 [9.5-19], p = 0.011, and 7.5 [4-12] vs. 3 [1-7], p < 0.001, respectively). After adjusting for age, sex, hypertension, diabetes, atrial fibrillation, administration of intravenous thrombolysis (IVT), Alberta Stroke Program Early CT Scores (ASPECTS), mTICI 2c and/or 3, Tmax >6 s volume, and hemorrhagic transformation, PVT+ was significantly associated with lower NIHSS percent change (B = -0.163, 95%CI -0.326 to -0.001, p = 0.049) and was less likely to achieve higher than 70% NIHSS improvement (OR = 0.331, 95% CI 0.127-0.863, p = 0.024)., Interpretation: PVT+ was significantly associated with reduced neurological improvement despite successful reperfusion in AIS-LVO patients, highlighting the critical role of VO impairment in short-term functional outcomes. These findings further validate PVT as a valuable adjunct imaging biomarker derived from CTP for assessing VO profiles in AIS-LVO., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background and Purpose: Acute ischemic stroke due to anterior circulation large-vessel occlusion (AIS-LVO) remains a leading cause of disability despite successful reperfusion therapies. Prolonged venous transit (PVT) has emerged as a potential prognostic imaging biomarker in AIS-LVO. We aimed to investigate whether PVT is associated with a decreased likelihood of excellent functional outcome (modified Rankin Scale [mRS] score of 0-1 at 90 days) after successful reperfusion., Methods: In our prospectively collected, retrospectively reviewed database, we analyzed data from 104 patients with AIS-LVO who achieved successful reperfusion (modified Thrombolysis in Cerebral Infarction score of 2b/2c/3) between September 2017 and September 2022. PVT was defined as a time to maximum (Tmax) of ≥10 s in the superior sagittal sinus and/or torcula on computed tomography perfusion (CTP) imaging. Patients were categorized into PVT-positive (PVT+) and PVT-negative (PVT-) groups. The primary outcome was excellent functional recovery at 90 days., Results: Of the 104 patients, 30 (29%) were PVT+. Excellent functional outcome was achieved in 38 patients (37%). PVT+ patients had a significantly lower rate of excellent recovery compared to PVT- patients (11% vs. 39%; p < 0.001). After adjusting for possible confounders, PVT positivity was independently associated with lower odds of excellent recovery (adjusted odds ratio 0.11, 95% confidence interval 0.02 to 0.48; p = 0.006)., Conclusions: Among patients with AIS-LVO who achieved successful reperfusion, PVT positivity was independently associated with a decreased likelihood of excellent functional outcome at 90 days. Assessment of PVT on CTP may provide valuable prognostic information and aid in clinical decision making for patients with AIS-LVO., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Sharing neuroimaging datasets enables reproducibility, education, tool development, and new discoveries. Neuroimaging from many studies are publicly available, providing a glimpse into progressive disorders and human development. In contrast, few stroke studies are shared, and these datasets lack longitudinal sampling of functional imaging, diffusion imaging, as well as the behavioral and demographic data that encourage novel applications. This is surprising, as stroke is a leading cause of disability, and acquiring brain imaging is considered standard of care. The first release of the Aphasia Recovery Cohort includes imaging data, demographics and behavioral measures from 230 chronic stroke survivors who experienced aphasia. We also share scripts to illustrate how the imaging data can predict impairment. In conclusion, recent advances in machine learning thrive on large, diverse datasets. Clinical data sharing can contribute to improvements in automated detection of brain injury, identification of white matter hyperintensities, measures of brain health, and prognostic abilities to guide care., (© 2024. The Author(s).)

In this randomized, double-blind, sham-controlled trial of Cerebellar Stimulation for Aphasia Rehabilitation (CeSAR), we will determine the effectiveness of cathodal tDCS (transcranial direct current stimulation) to the right cerebellum for the treatment of chronic aphasia (>6 months post stroke). We will test the hypothesis that cerebellar tDCS in combination with an evidenced-based anomia treatment (semantic feature analysis, SFA) will be associated with greater improvement in naming untrained pictures (as measured by the change in Philadelphia Picture Naming Test), 1-week post-treatment, compared to sham plus SFA. We will also evaluate the effects of cerebellar tDCS on naming trained items as well as the effects on functional communication, content, efficiency, and word-retrieval of picture description, and quality of life. Finally, we will identify imaging and linguistic biomarkers to determine the characteristics of stroke patients that benefit from cerebellar tDCS and SFA treatment. We expect to enroll 60 participants over five years. Participants will receive 15, 25-minute sessions of cerebellar tDCS (3-5 sessions per week) or sham tDCS combined with 1 hour of SFA treatment. Participants will be evaluated prior to the start of treatment, one-week post-treatment, 1-, 3-, and 6-months post-treatment on primary and secondary outcome variables. The long-term aim of this study is to provide the basis for a Phase III randomized controlled trial of cerebellar tDCS vs sham with concurrent language therapy for treatment of chronic aphasia. Trial registration: The trial is registered with ClinicalTrials.gov NCT05093673., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lammers et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Individuals with Mild Cognitive Impairment (MCI), a transitional stage between cognitively healthy aging and dementia, are characterized by subtle neurocognitive changes. Clinically, they can be grouped into two main variants, namely patients with amnestic MCI (aMCI) and non-amnestic MCI (naMCI). The distinction of the two variants is known to be clinically significant as they exhibit different progression rates to dementia. However, it has been particularly challenging to classify the two variants robustly. Recent research indicates that linguistic changes may manifest as one of the early indicators of pathology. Therefore, we focused on MCI's discourse-level writing samples in this study. We hypothesized that a written picture description task can provide information that can be used as an ecological, cost-effective classification system between the two variants. We included one hundred sixty-nine individuals diagnosed with either aMCI or naMCI who received neurophysiological evaluations in addition to a short, written picture description task. Natural Language Processing (NLP) and a BERT pre-trained language model were utilized to analyze the writing samples. We showed that the written picture description task provided 90% overall classification accuracy for the best classification models, which performed better than cognitive measures. Written discourses analyzed by AI models can automatically assess individuals with aMCI and naMCI and facilitate diagnosis, prognosis, therapy planning, and evaluation.

Here, we review the literature on neurotypical individuals and individuals with post-stroke aphasia showing that right-hemisphere regions homologous to language network and other regions, like the right cerebellum, are activated in language tasks and support language even in healthy people. We propose that language recovery in post-stroke aphasia occurs largely by potentiating the right hemisphere network homologous to the language network and other networks that previously supported language to a lesser degree and by modulating connection strength between nodes of the right-hemisphere language network and undamaged nodes of the left-hemisphere language network. Based on this premise (supported by evidence we review), we propose that interventions should be aimed at potentiating the right-hemisphere language network through Hebbian learning or by augmenting connections between network nodes through neuroplasticity, such as non-invasive brain stimulation and perhaps modulation of neurotransmitters involved in neuroplasticity. We review aphasia treatment studies that have taken this approach. We conclude that further aphasia rehabilitation with this aim is justified., Competing Interests: Argye Hillis receives compensation from the American Heart Association as Editor-in-Chief of Stroke and from Elsevier as Associate Editor of PracticeUpdate Neurology. All authors receive salary support from NIH (NIDCD) through grants.

Pretreatment CT Perfusion (CTP) parameter rCBV < 42% lesion volume has recently been shown to predict 90-day mRS. In this study, we aim to assess the relationship between rCBV < 42% and a radiographic follow-up infarct volume delineated on FLAIR images. In this retrospective evaluation of our prospectively collected database, we included acute stroke patients triaged by multimodal CT imaging, including CT angiography and perfusion imaging, with confirmed anterior circulation large vessel occlusion between 9 January 2017 and 10 January 2023. Follow-up FLAIR imaging was used to determine the final infarct volume. Student t, Mann-Whitney-U, and Chi-Square tests were used to assess differences. Spearman's rank correlation and linear regression analysis were used to assess associations between rCBV < 42% and follow-up infarct volume on FLAIR. In total, 158 patients (median age: 68 years, 52.5% female) met our inclusion criteria. rCBV < 42% (ρ = 0.56, p < 0.001) significantly correlated with follow-up-FLAIR infarct volume. On multivariable linear regression analysis, rCBV < 42% lesion volume (beta = 0.60, p < 0.001), ASPECTS (beta = -0.214, p < 0.01), mTICI (beta = -0.277, p < 0.001), and diabetes (beta = 0.16, p < 0.05) were independently associated with follow-up infarct volume. The rCBV < 42% lesion volume is independently associated with FLAIR follow-up infarct volume.

Background: The pretreatment CT perfusion (CTP) marker the relative cerebral blood volume (rCBV) < 42% lesion volume has recently been shown to predict 90-day functional outcomes; however, studies assessing correlations of the rCBV < 42% lesion volume with other outcomes remain sparse. Here, we aim to assess the relationship between the rCBV < 42% lesion volume and the reference standard digital subtraction angiography (DSA)-derived American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN) collateral score, hereby referred as the DSA CS. Methods: In this retrospective evaluation of our prospectively collected database, we included acute stroke patients triaged by multimodal CT imaging, including CT angiography and perfusion imaging, with confirmed anterior circulation large vessel occlusion between 1 September 2017 and 1 October 2023. Group differences were assessed using the Student's t test, Mann-Whitney U test and Chi-Square test. Spearman's rank correlation and logistic regression analyses were used to assess associations between rCBV < 42% and DSA CS. Results: In total, 222 patients (median age: 69 years, 56.3% female) met our inclusion criteria. In the multivariable logistic regression analysis, taking into account age, sex, race, hypertension, hyperlipidemia, diabetes, atrial fibrillation, prior stroke or transient ischemic attack, the admission National Institute of Health stroke scale, the premorbid modified Rankin score, the Alberta stroke program early CT score (ASPECTS), and segment occlusion, the rCBV < 42% lesion volume (adjusted OR: 0.98, p < 0.05) was independently associated with the DSA CS. Conclusion: The rCBV < 42% lesion volume is independently associated with the DSA CS.

Introduction: Despite a growing emphasis on discourse processing in clinical neuroscience, relatively little is known about the neurobiology of discourse production impairments. Individuals with a history of left or right hemisphere stroke can exhibit difficulty with communicating meaningful discourse content, which implies both cerebral hemispheres play a role in this skill. However, the extent to which successful production of discourse content relies on network connections within domain-specific vs. domain-general networks in either hemisphere is unknown., Methods: In this study, 45 individuals with a history of either left or right hemisphere stroke completed resting state fMRI and the Cookie Theft picture description task., Results: Participants did not differ in the total number of content units or the percentage of interpretative content units they produced. Stroke survivors with left hemisphere damage produced significantly fewer content units per second than individuals with right hemisphere stroke. Intrinsic connectivity of the left language network was significantly weaker in the left compared to the right hemisphere stroke group for specific connections. Greater efficiency of communication of picture scene content was associated with stronger left but weaker right frontotemporal connectivity of the language network in patients with a history of left hemisphere (but not right hemisphere) stroke. No significant relationships were found between picture description measures and connectivity of the dorsal attention, default mode, or salience networks or with connections between language and other network regions., Discussion: These findings add to prior behavioral studies of picture description skills in stroke survivors and provide insight into the role of the language network vs. other intrinsic networks during discourse production., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Meier, Sheppard, Sebastian, Berube, Goldberg, Shea, Stein and Hillis.)

STAIR XII (12th Stroke Treatment Academy Industry Roundtable) included a workshop to discuss the priorities for advancements in neuroimaging in the diagnostic workup of acute ischemic stroke. The workshop brought together representatives from academia, industry, and government. The participants identified 10 critical areas of priority for the advancement of acute stroke imaging. These include enhancing imaging capabilities at primary and comprehensive stroke centers, refining the analysis and characterization of clots, establishing imaging criteria that can predict the response to reperfusion, optimizing the Thrombolysis in Cerebral Infarction scale, predicting first-pass reperfusion outcomes, improving imaging techniques post-reperfusion therapy, detecting early ischemia on noncontrast computed tomography, enhancing cone beam computed tomography, advancing mobile stroke units, and leveraging high-resolution vessel wall imaging to gain deeper insights into pathology. Imaging in acute ischemic stroke treatment has advanced significantly, but important challenges remain that need to be addressed. A combined effort from academic investigators, industry, and regulators is needed to improve imaging technologies and, ultimately, patient outcomes., Competing Interests: Disclosures Dr Samaniego reports compensation from Rapid Medical for consultant services; compensation from Medtronic for consultant services; compensation from iSchemaView for consultant services; compensation from MicroVention, Inc, for consultant services; and compensation from Cerenovus for consultant services. Dr Boltze reports compensation from Targed Biopharmaceuticals B.V. for consultant services; employment by the University of Warwick; and compensation from Astrocyte Pharmaceuticals for consultant services. Dr Lyden reports compensation from the NIH Clinical Center for other services; compensation from Apex Innovations for consultant services; and employment by the University of Southern California. Dr Hill reports grants from Medtronic; compensation from Brainsgate, Ltd, for consultant services; grants from Boehringer Ingelheim; grants from Medtronic; grants from NoNO, Inc; a patent issued for Systems and Methods for Assisting in Decision-Making and Triaging for Acute Stroke Patients licensed to Circle NVI; grants from Medtronic; grants from the Canadian Institutes of Health Research; grants from MicroVention, Inc; and employment by the University of Calgary. Dr Campbell reports employment by the University of Melbourne. Dr Nguyen reports compensation from Brainomix for consultant services and compensation from Idorsia for other services. Dr Silva reports compensation from Boehringer Ingelheim for consultant services; employment by UNIFESP; compensation from Bayer for consultant services; compensation from iSchemaView for consultant services; employment by Sociedade Beneficente Israelita Brasileira Albert Einstein; and compensation from Pfizer for other services. Dr Sheth reports stock holdings in Verve Therapeutics; compensation from Rhaeos for consultant services; compensation from Sense for data and safety monitoring services; compensation from Astrocyte for consultant services; compensation from Cerevasc for consultant services; grants from Hyperfine; employment by Yale School of Medicine; a patent pending for Stroke wearables licensed to Alva Health; stock holdings in AbbVie; grants from Biogen; compensation from CSL Behring for consultant services; and compensation from ZOLL Medical Corporation for data and safety monitoring services. Dr Fisher reports compensation from Simcere USA for consultant services; employment by Beth Israel Deaconess Medical Center; compensation from Lumosa for consultant services; and employment by Beth Israel Deaconess Medical Center. Dr Hillis reports employment by the Johns Hopkins University School of Medicine; compensation from Elsevier Publishing for other services; compensation from the National Institute on Deafness and Other Communication Disorders for other services; and compensation from the American Heart Association for other services. Dr Carone reports stock options in Brainomix, Ltd, and employment by Brainomix, Ltd. Dr Deljkich reports employment by Imperative Care, Inc. Dr Albers reports compensation from Genentech for consultant services; stock holdings in iSchemaView; and compensation from iSchemaView for consultant services. Dr Heit reports compensation from Medtronic for consultant services; compensation from iSchemaView for consultant services; and compensation from MicroVention, Inc, for consultant services. The other authors report no conflicts.

Objective: To examine changes to connectivity after aphasia treatment in the first 3 months after stroke., Methods: Twenty people experiencing aphasia within the first 3 months of stroke completed MRI before and immediately following 15 hours of language treatment. They were classified based on their response to treatment on a naming test of nouns as either high responders (10% improvement or more), or low responders (<10% improvement). Groups were similar in age, gender distribution, education, days since stroke, stroke volume, and baseline severity. Resting-state functional connectivity analysis was limited to the connectivity of the left fusiform gyrus with the bilateral inferior frontal gyrus, supramarginal gyrus, angular gyrus, and superior, middle, and inferior temporal gyrus, based on previous studies showing the importance of left fusiform gyrus in naming performance., Results: Baseline ipsilateral connectivity between the left fusiform gyrus and the language network was similar between high and low responders to therapy when controlling for stroke volume. Following therapy, change in connectivity was significantly greater among high responders between the left fusiform gyrus and the ipsilateral and contralateral pars triangularis, ipsilateral pars opercularis and superior temporal gyrus, and contralateral angular gyrus when compared with low responders., Interpretation: An account of these findings incorporates primarily proximal connectivity restoration, but also potentially reflects select contralateral compensatory reorganization. The latter is often associated with chronic recovery, reflecting the transitional nature of the subacute period., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

To extract meaningful and reproducible models of brain function from stroke images, for both clinical and research proposes, is a daunting task severely hindered by the great variability of lesion frequency and patterns. Large datasets are therefore imperative, as well as fully automated image post-processing tools to analyze them. The development of such tools, particularly with artificial intelligence, is highly dependent on the availability of large datasets to model training and testing. We present a public dataset of 2,888 multimodal clinical MRIs of patients with acute and early subacute stroke, with manual lesion segmentation, and metadata. The dataset provides high quality, large scale, human-supervised knowledge to feed artificial intelligence models and enable further development of tools to automate several tasks that currently rely on human labor, such as lesion segmentation, labeling, calculation of disease-relevant scores, and lesion-based studies relating function to frequency lesion maps., (© 2023. Springer Nature Limited.)

Background: Transcranial direct current stimulation (tDCS) can be used to improve post-stroke aphasia. However, given the mixed evidence for its efficacy, individual differences may moderate the relative benefit of this strategy. In planned exploratory subgroup analyses, we examined whether age, education, sex, brain-derived neurotrophic factor status, and baseline performance individually impacted improvement in picture naming between baseline and 1 week after the end of the therapy, then whether the combination of factors that predicted recovery of naming and discourse differed for those who received concurrent tDCS., Objective: Examine whether individual differences influenced the effect of tDCS on language recovery., Methods: In this randomized, double-blind, sham-controlled, efficacy study of tDCS combined with language therapy for subacute post-stroke aphasia, patients completed an evaluation including the Philadelphia Naming Test and Cookie Theft picture description, which was analyzed for Content Units (CU) and Syllables/CU. Individual factors were examined using linear models including the interaction between treatment group and subgroup., Results: Significant interactions were observed between tDCS group and both age and education. The predictors of a positive response to tDCS differed from the predictors of a positive response to language treatment alone. While baseline performance was an important predictor of future performance regardless of treatment group, responses to treatment without tDCS were influenced by age whereas responses to treatment with tDCS were not., Conclusions: Age and education influence the efficacy of different treatment strategies. Refinement of treatment selection is important to the overall individualization and optimization of post-stroke patient care., Trial Registration: ClinicalTrials.gov NCT02674490.

Studies have shown that the integrity of white matter tracts connecting different regions in the left cerebral hemisphere is important for aphasia recovery after stroke. However, the impact of the underlying structural connection between the cortex and the cerebellum in post-stroke aphasia is poorly understood. We studied the microstructural integrity of the cerebellum and the corticocerebellar connections and their role in picture naming. Fifty-six patients with left cerebral infarcts (sparing the cerebellum) underwent diffusion tensor imaging (DTI) and Boston Naming Test. We compared the fractional anisotropy (FA) and mean diffusivity (MD) values of the right and the left cerebellum (lobular gray and white matter structures) and cerebellocortical connections. Recursive feature elimination and Spearman correlation analyses were performed to evaluate the relationship between naming performance and the corticocerebellar connections. We found that the right, relative to left, cerebellar structures and their connections with the left cerebrum showed lower FA and higher MD values, both reflecting lower microstructural integrity. This trend was not observed in the healthy controls. Higher MD values of the right major cerebellar outflow tract were associated with poorer picture naming performance. Our study provides the first DTI data demonstrating the critical importance of ascending and descending corticocerebellar connections for naming outcomes after stroke., (© 2023 Massachusetts Institute of Technology.)

Background: Although artificial intelligence systems that diagnosis among different conditions from medical images are long term aims, specific goals for automation of human-labor, time-consuming tasks are not only feasible but equally important. Acute conditions that require quantitative metrics, such as acute ischemic strokes, can greatly benefit by the consistency, objectiveness, and accessibility of automated radiological reports., Methods: We used 1,878 annotated brain MRIs to generate a fully automated system that outputs radiological reports in addition to the infarct volume, 3D digital infarct mask, and the feature vector of anatomical regions affected by the acute infarct. This system is associated to a deep-learning algorithm for segmentation of the ischemic core and to parcellation schemes defining arterial territories and classically-identified anatomical brain structures., Results: Here we show that the performance of our system to generate radiological reports was comparable to that of an expert evaluator. The weight of the components of the feature vectors that supported the prediction of the reports, as well as the prediction probabilities are outputted, making the pre-trained models behind our system interpretable. The system is publicly available, runs in real time, in local computers, with minimal computational requirements, and it is readily useful for non-expert users. It supports large-scale processing of new and legacy data, enabling clinical and translational research., Conclusion: The generation of reports indicates that our fully automated system is able to extract quantitative, objective, structured, and personalized information from stroke MRIs., (© 2023. The Author(s).)

Cerebrovascular disease is a leading cause of death globally. Prevention and early intervention are known to be the most effective forms of its management. Non-invasive imaging methods hold great promises for early stratification, but at present lack the sensitivity for personalized prognosis. Resting-state functional magnetic resonance imaging (rs-fMRI), a powerful tool previously used for mapping neural activity, is available in most hospitals. Here we show that rs-fMRI can be used to map cerebral hemodynamic function and delineate impairment. By exploiting time variations in breathing pattern during rs-fMRI, deep learning enables reproducible mapping of cerebrovascular reactivity (CVR) and bolus arrival time (BAT) of the human brain using resting-state CO 2 fluctuations as a natural "contrast media". The deep-learning network is trained with CVR and BAT maps obtained with a reference method of CO 2 -inhalation MRI, which includes data from young and older healthy subjects and patients with Moyamoya disease and brain tumors. We demonstrate the performance of deep-learning cerebrovascular mapping in the detection of vascular abnormalities, evaluation of revascularization effects, and vascular alterations in normal aging. In addition, cerebrovascular maps obtained with the proposed method exhibit excellent reproducibility in both healthy volunteers and stroke patients. Deep-learning resting-state vascular imaging has the potential to become a useful tool in clinical cerebrovascular imaging., (© 2023. The Author(s).)

In post-stroke aphasia, language improvements following speech therapy are variable and can only be partially explained by the lesion. Brain tissue integrity beyond the lesion (brain health) may influence language recovery and can be impacted by cardiovascular risk factors, notably diabetes. We examined the impact of diabetes on structural network integrity and language recovery. Seventy-eight participants with chronic post-stroke aphasia underwent six weeks of semantic and phonological language therapy. To quantify structural network integrity, we evaluated the ratio of long-to-short-range white matter fibers within each participant's whole brain connectome, as long-range fibers are more susceptible to vascular injury and have been linked to high level cognitive processing. We found that diabetes moderated the relationship between structural network integrity and naming improvement at 1 month post treatment. For participants without diabetes (n = 59), there was a positive relationship between structural network integrity and naming improvement (t = 2.19, p = 0.032). Among individuals with diabetes (n = 19), there were fewer treatment gains and virtually no association between structural network integrity and naming improvement. Our results indicate that structural network integrity is associated with treatment gains in aphasia for those without diabetes. These results highlight the importance of post-stroke structural white matter architectural integrity in aphasia recovery., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Velocity-selective inversion (VSI) based velocity-selective arterial spin labeling (VSASL) has been developed to measure cerebral blood flow (CBF) with low susceptibility to the prolonged arterial transit time and high sensitivity to brain perfusion signal. The purpose of this magnetic resonance imaging study is to evaluate the test-retest reliability of a VSI-prepared 3D VSASL protocol with whole-brain coverage to detect baseline CBF variations among cognitively normal participants in different brain regions. Coefficients of variation (CoV) of both absolute and relative CBF across scans or sessions, subjects, and gray matter regions were calculated, and corresponding intraclass correlation coefficients (ICC) were computed. The higher between-subject CoV of absolute CBF (13.4 ± 2.0%) over within-subject CoV (within-session: 3.8 ± 1.1%; between-session: 4.9 ± 0.9%) yielded moderate to excellent ICC (within-session: 0.88±0.08; between-session: 0.77±0.14) to detect normal variations of individual CBF. The higher between-region CoV of relative CBF (11.4 ± 3.0%) over within-region CoV (within-session: 2.3 ± 0.9%; between-session: 3.3 ± 1.0%) yielded excellent ICC (within-session: 0.92±0.06; between-session: 0.85±0.12) to detect normal variations of regional CBF. Age, blood pressure, end-tidal CO 2 , and hematocrit partially explained the variability of CBF across subjects. Together these results show excellent test-retest reliability of VSASL to detect both between-subject and between-region variations supporting its clinical utility., (Copyright © 2023. Published by Elsevier Inc.)

Background and Aim: Considering the anatomical features of Middle Cerebral Artery (MCA) bifurcation, larger emboli are more likely to enter the inferior division over the superior division. Since emboli of cardiac origin are larger on average than emboli of arterial origin, we hypothesize that the infarcts in temporal and parietal lobes are more likely associated to atrial fibrillation than those in the frontal lobes, therefore occurring more often in populations with higher incidence of atrial fibrillation, such as male (compared to women) and white (compared to black) patients., Methods: We included 197 patients with MCA "temporoparietal predominant" infarcts and 105 with "frontal predominant" infarcts. Variations between stroke location (frontal or temporoparietal), sex, and race were examined via Chi-square test., Results: Male patients were more likely than female patients to be afflicted by temporoparietal strokes versus frontal strokes, while white patients had greater likelihood than black patients to be afflicted by temporoparietal strokes versus frontal strokes. Patients with confirmed diagnosis of atrial fibrillation display more temporoparietal strokes compared to frontal strokes., Conclusion: Temporoparietal MCA ischemic strokes occur more frequently in male and white patients: populations with known increased incidence of atrial fibrillation. In addition, population-specific anatomical characteristics of the MCA bifurcation might favor the larger cardiac emboli to enter the inferior division and cause temporoparietal infarcts. This association can help guide search for the most likely etiology of infarcts., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (©2023PublishedbyElsevierLtd.)

Background: Transcranial direct-current stimulation (tDCS) is a promising adjunct to therapy for chronic aphasia., Methods: This single-center, randomized, double-blind, sham-controlled efficacy trial tested the hypothesis that anodal tDCS augments language therapy in subacute aphasia. Secondarily, we compared the effect of tDCS on discourse measures and quality of life and compared the effects on naming to previous findings in chronic stroke. Right-handed English speakers with aphasia <3 months after left hemisphere ischemic stroke were included, unless they had prior neurological or psychiatric disease or injury or were taking certain medications (34 excluded; final sample, 58). Participants were randomized 1:1, controlling for age, aphasia type, and severity, to receive 20 minutes of tDCS (1 mA) or sham-tDCS in addition to fifteen 45-minute sessions of naming treatment (plus standard care). The primary outcome variable was change in naming accuracy of untrained pictures pretreatment to 1-week posttreatment., Results: Baseline characteristics were similar between the tDCS (N=30) and sham (N=28) groups: patients were 65 years old, 53% male, and 2 months from stroke onset on average. In intent-to-treat analysis, the adjusted mean change from baseline to 1-week posttreatment in picture naming was 22.3 (95% CI, 13.5-31.2) for tDCS and 18.5 (9.6-27.4) for sham and was not significantly different. Content and efficiency of picture description improved more with tDCS than sham. Groups did not differ in quality of life improvement. No patients were withdrawn due to adverse events., Conclusions: tDCS did not improve recovery of picture naming but did improve recovery of discourse. Discourse skills are critical to participation. Future research should examine tDCS in a larger sample with richer functional outcomes., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02674490.

In stroke aphasia, lesion volume is typically associated with aphasia severity. Although this relationship is likely present throughout recovery, different factors may affect lesion volume and behaviour early into recovery (acute) and in the later stages of recovery (chronic). Therefore, studies typically separate patients into two groups (acute/chronic), and this is often accompanied with arguments for and against using data from acute stroke patients over chronic. However, no comprehensive studies have provided strong evidence of whether the lesion-behaviour relationship early in recovery is comparable to later in the recovery trajectory. To that end, we investigated two aims: (i) whether lesion data from acute and chronic patients yield similar results in region-based lesion-symptom mapping analyses and (ii) if models based on one timepoint accurately predict the other. Lesions and aphasia severity scores from acute ( N = 63) and chronic ( N = 109) stroke survivors with aphasia were entered into separate univariate region-based lesion-symptom mapping analyses. A support vector regression model was trained on lesion data from either the acute or chronic data set to give an estimate of aphasia severity. Four model-based analyses were conducted: trained on acute/chronic using leave-one-out, tested on left-out behaviour or trained on acute/chronic to predict the other timepoint. Region-based lesion-symptom mapping analyses identified similar but not identical regions in both timepoints. All four models revealed positive correlations between actual and predicted Western Aphasia Battery-Revised aphasia-quotient scores. Lesion-to-behaviour predictions were almost equivalent when comparing within versus across stroke stage, despite differing lesion size/locations and distributions of aphasia severity between stroke timepoints. This suggests that research investigating the brain-behaviour relationship including subsets of patients from only one timepoint may also be applicable at other timepoints, although it is important to note that these comparable findings may only be seen using broad measures such as aphasia severity, rather than those aimed at identifying more specific deficits. Subtle differences found between timepoints may also be useful in understanding the nature of lesion volume and aphasia severity over time. Stronger correlations found when predicting acute behaviour (e.g. predicting acute: r = 0.6888, P < 0.001, predicting chronic r = 0.5014, P < 0.001) suggest that the acute lesion/perfusion patterns more accurately capture the critical changes in underlying vascular territories. Differences in critical brain regions between timepoints may shed light on recovery patterns. Future studies could focus on a longitudinal design to compare acute and chronic patients in a more controlled manner., Competing Interests: The authors report no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

The Alberta Stroke Program Early CT Score (ASPECTS) is a simple visual system to assess the extent and location of ischemic stroke core. The capability of ASPECTS for selecting patients' treatment, however, is affected by the variability in human evaluation. In this study, we developed a fully automatic system to calculate ASPECTS comparable with consensus expert readings. Our system was trained in 400 clinical diffusion weighted images of patients with acute infarcts and evaluated with an external testing set of 100 cases. The models are interpretable, and the results are comprehensive, evidencing the features that lead to the classification. This system adds to our automated pipeline for acute stroke detection, segmentation, and quantification in MRIs (ADS), which outputs digital infarct masks and the proportion of diverse brain regions injured, in addition to the predicted ASPECTS, the prediction probability and the explanatory features. ADS is public, free, accessible to non-experts, has very few computational requirements, and run in real time in local CPUs with a single command line, fulfilling the conditions to perform large-scale, reproducible clinical and translational research., (© 2023. The Author(s).)

Perfusion imaging is preferred for identifying hypoperfusion in the management of acute ischemic stroke, but it is not always feasible/available. An alternative method for quantifying hypoperfusion, using FLAIR-hyperintense vessels (FHVs) in various vascular regions, has been proposed, with evidence of a statistical relationship with perfusion-weighted imaging (PWI) deficits and behavior. However, additional validation is needed to confirm that areas of suspected hypoperfusion (per the location of FHVs) correspond to the location of perfusion deficits in PWI. We examined the association between the location of FHVs and perfusion deficits in PWI in 101 individuals with acute ischemic stroke, prior to the receipt of reperfusion therapies. FHVs and PWI lesions were scored as present/absent in six vascular regions (i.e., the ACA, PCA, and (four sub-regions of) the MCA territories). Chi-square analyses showed a significant relationship between the two imaging techniques for five vascular regions (the relationship in the ACA territory was underpowered). These results suggest that for most areas of the brain, the general location of FHVs corresponds to hypoperfusion in those same vascular territories in PWI. In conjunction with prior work, results support the use of estimating the amount and location of hypoperfusion using FLAIR imaging when perfusion imaging is not available.

The locus and extent of brain damage in the event of vascular insult can be quantitatively established quickly and easily with vascular atlases. Although highly anticipated by clinicians and clinical researchers, no digital MRI arterial atlas is readily available for automated data analyses. We created a digital arterial territory atlas based on lesion distributions in 1,298 patients with acute stroke. The lesions were manually traced in the diffusion-weighted MRIs, binary stroke masks were mapped to a common space, probability maps of lesions were generated and the boundaries for each arterial territory was defined based on the ratio between probabilistic maps. The atlas contains the definition of four major supra- and infra-tentorial arterial territories: Anterior, Middle, Posterior Cerebral Arteries and Vertebro-Basilar, and sub-territories (thalamoperforating, lenticulostriate, basilar and cerebellar arterial territories), in two hierarchical levels. This study provides the first publicly-available, digital, 3D deformable atlas of arterial brain territories, which may serve as a valuable resource for large-scale, reproducible processing and analysis of brain MRIs of patients with stroke and other conditions., (© 2023. The Author(s).)

For the past decade, brain health has been an emerging line of scientific inquiry assessing the impact of age-related neurostructural changes on cognitive decline and recovery from brain injury. Typically, compromised brain health is attributed to the presence of small vessel disease (SVD) and brain tissue atrophy, which are represented by various neuroimaging features. However, to date, the relationship between brain health markers and chronic aphasia severity remains unclear. Thus, the goal of this scoping review was to assess the current body of evidence regarding the relationship between SVD-related brain health biomarkers and post-stroke aphasia and cognition. In all, 187 articles were identified from 3 databases, of which 16 articles met the criteria for inclusion. Among these studies, 11 focused on cognition rather than aphasia, while 2 investigated both. Of the 10 studies that used white matter hyperintensities (WMHs) as an indicator of SVD severity, 8 studies (80%) demonstrated a relationship between WMH load and worse cognition in stroke patients. Interestingly, among the studies that specifically investigated aphasia, all 5 studies (100%) demonstrated a relationship between SVD and worse language performance. They also indicated that factors other than brain health (e.g., lesion, age, time post onset) played an important role in determining aphasia severity at a single timepoint. These findings suggest that brain health is likely a crucial factor in the context of aphasia recovery, possibly indicating the necessity of cognitive reserve thresholds for the multimodal cognitive demands associated with language recovery. While SVD and structural brain health are not commonly considered as predictors of aphasia severity, more comprehensive models incorporating brain health have the potential to improve prognosis of post-stroke cognitive and language deficits. Given the variability in the existing literature, a uniform grading system for overall SVD would be beneficial for future research on the mechanisms related to brain networks and neuroplasticity, and their translational impact., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Unilateral spatial neglect (USN) is a common and disabling cognitive consequence of stroke wherein individuals demonstrate decreased response to contralesional information. Here, we provide an updated narrative review of studies that shed light on the neural mechanisms and predictors of recovery of USN. Additionally, we report a rapid review of randomized controlled trials focusing on USN intervention, both nonpharmacological and pharmacological, published in the last 5 years. Randomized controlled trials are reviewed within the context of systematic reviews and meta-analyses of USN interventions published within the same time frame. The quality of randomized controlled trials of treatment is higher compared to quality reported in previous reviews and meta-analyses. However, remaining weaknesses in participant demographic reporting, as well as small, heterogenous samples, render generalizability and cross-study interpretation a challenge. Nevertheless, evidence regarding neural mechanisms underlying USN recovery and regarding the effectiveness of targeted USN interventions is accumulating and strengthening, setting the foundation for future investigations into patient-specific factors that may influence treatment response. We identify gaps and provide suggestions for future USN intervention research.

Primary Progressive Aphasia (PPA) is a neurodegenerative disorder primarily affecting language functions. Neuromodulatory techniques (e.g., transcranial direct current stimulation, active-tDCS) and behavioral (speech-language) therapy have shown promising results in treating speech and language deficits in PPA patients. One mechanism of active-tDCS efficacy is through modulation of network functional connectivity (FC). It remains unknown how biological sex influences FC and active-tDCS or language treatment(s). In the current study, we compared sex differences, induced by active-tDCS and language therapy alone, in the default mode and language networks, acquired during resting-state fMRI in 36 PPA patients. Using a novel statistical method, the covariate-assisted-principal-regression (CAPs) technique, we found sex and age differences in FC changes following active-tDCS. In the default mode network (DMN): (1) men (in both conditions) showed greater FC in DMN than women. (2) men who received active-tDCS showed greater FC in the DMN than men who received language-treatment only. In the language network: (1) women who received active-tDCS showed significantly greater FC across the language network than women who received sham-tDCS. As age increases, regardless of sex and treatment condition, FC in language regions decreases. The current findings suggest active-tDCS treatment in PPA alters network-specific FC in a sex-dependent manner., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Wernicke's area has been assumed since the 1800s to be the primary region supporting word and sentence comprehension. However, in 2015 and 2019, Mesulam and colleagues raised what they termed the 'Wernicke conundrum', noting widespread variability in the anatomical definition of this area and presenting data from primary progressive aphasia that challenged this classical assumption. To resolve the conundrum, they posited a 'double disconnection' hypothesis: that word and sentence comprehension deficits in stroke-based aphasia result from disconnection of anterior temporal and inferior frontal regions from other parts of the brain due to white matter damage, rather than dysfunction of Wernicke's area itself. To test this hypothesis, we performed lesion-deficit correlations, including connectome-based lesion-symptom mapping, in four large, partially overlapping groups of English-speaking chronic left hemisphere stroke survivors. After removing variance due to object recognition and associative semantic processing, the same middle and posterior temporal lobe regions were implicated in both word comprehension deficits and complex non-canonical sentence comprehension deficits. Connectome lesion-symptom mapping revealed similar temporal-occipital white matter disconnections for impaired word and non-canonical sentence comprehension, including the temporal pole. We found an additional significant temporal-parietal disconnection for non-canonical sentence comprehension deficits, which may indicate a role for phonological working memory in processing complex syntax, but no significant frontal disconnections. Moreover, damage to these middle-posterior temporal lobe regions was associated with both word and non-canonical sentence comprehension deficits even when accounting for variance due to the strongest anterior temporal and inferior frontal white matter disconnections, respectively. Our results largely agree with the classical notion that Wernicke's area, defined here as middle superior temporal gyrus and middle-posterior superior temporal sulcus, supports both word and sentence comprehension, suggest a supporting role for temporal pole in both word and sentence comprehension, and speak against the hypothesis that comprehension deficits in Wernicke's aphasia result from double disconnection., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The differences in mental health outcomes of right and left hemisphere strokes are well studied; however, there is a long-standing controversy surrounding whether depression is associated with lateralization of stroke or not. In this investigation, we examined the effect of lesion location on post-stroke depression controlling for lesion size and hemiparesis in a longitudinal sample assessed at acute, subacute, and chronic timepoints. As a secondary aim, we further examined the effect of lesion location on self-reported difficulties across a wide array of domains. A series of 134 patients with left hemisphere strokes and 79 with right hemisphere strokes completed the Patient Health Questionnaire-9 and an inventory of post-stroke abilities at within acute, subacute, and chronic windows following stroke. When controlling for hemiparesis and overall lesion volume, we found no difference in depression between groups at any timepoint. Additional exploratory analyses provided a further look at differing challenges associated with depression in each group., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Stockbridge, Vitti, Faria and Hillis.)

Aphasia, the loss of language ability following damage to the brain, is among the most disabling and common consequences of stroke. Subcortical stroke, occurring in the basal ganglia, thalamus, and/or deep white matter can result in aphasia, often characterized by word fluency, motor speech output, or sentence generation impairments. The link between greater lesion volume and acute aphasia is well documented, but the independent contributions of lesion location, cortical hypoperfusion, prior stroke, and white matter degeneration (leukoaraiosis) remain unclear, particularly in subcortical aphasia. Thus, we aimed to disentangle the contributions of each factor on language impairments in left hemisphere acute subcortical stroke survivors. Eighty patients with acute ischemic left hemisphere subcortical stroke (less than 10 days post-onset) participated. We manually traced acute lesions on diffusion-weighted scans and prior lesions on T2-weighted scans. Leukoaraiosis was rated on T2-weighted scans using the Fazekas et al. (1987) scale. Fluid-attenuated inversion recovery (FLAIR) scans were evaluated for hyperintense vessels in each vascular territory, providing an indirect measure of hypoperfusion in lieu of perfusion-weighted imaging. We found that language performance was negatively correlated with acute/total lesion volumes and greater damage to substructures of the deep white matter and basal ganglia. We conducted a LASSO regression that included all variables for which we found significant univariate relationships to language performance, plus nuisance regressors. Only total lesion volume was a significant predictor of global language impairment severity. Further examination of three participants with severe language impairments suggests that their deficits result from impairment in domain-general, rather than linguistic, processes. Given the variability in language deficits and imaging markers associated with such deficits, it seems likely that subcortical aphasia is a heterogeneous clinical syndrome with distinct causes across individuals., Competing Interests: No disclosures or conflicts of interest to report.

The association between age and language recovery in stroke remains unclear. Here, we used neuroimaging data to estimate brain age, a measure of structural integrity, and examined the extent to which brain age at stroke onset is associated with (i) cross-sectional language performance, and (ii) longitudinal recovery of language function, beyond chronological age alone. A total of 49 participants (age: 65.2 ± 12.2 years, 25 female) underwent routine clinical neuroimaging (T1) and a bedside evaluation of language performance (Bedside Evaluation Screening Test-2) at onset of left hemisphere stroke. Brain age was estimated from enantiomorphically reconstructed brain scans using a machine learning algorithm trained on a large sample of healthy adults. A subsample of 30 participants returned for follow-up language assessments at least 2 years after stroke onset. To account for variability in age at stroke, we calculated proportional brain age difference, i.e. the proportional difference between brain age and chronological age. Multiple regression models were constructed to test the effects of proportional brain age difference on language outcomes. Lesion volume and chronological age were included as covariates in all models. Accelerated brain age compared with age was associated with worse overall aphasia severity (F(1, 48) = 5.65, P = 0.022), naming (F(1, 48) = 5.13, P = 0.028), and speech repetition (F(1, 48) = 8.49, P = 0.006) at stroke onset. Follow-up assessments were carried out ≥2 years after onset; decelerated brain age relative to age was significantly associated with reduced overall aphasia severity (F(1, 26) = 5.45, P = 0.028) and marginally failed to reach statistical significance for auditory comprehension (F(1, 26) = 2.87, P = 0.103). Proportional brain age difference was not found to be associated with changes in naming (F(1, 26) = 0.23, P = 0.880) and speech repetition (F(1, 26) = 0.00, P = 0.978). Chronological age was only associated with naming performance at stroke onset (F(1, 48) = 4.18, P = 0.047). These results indicate that brain age as estimated based on routine clinical brain scans may be a strong biomarker for language function and recovery after stroke., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Cerebrovascular Reactivity (CVR) provides an assessment of the brain's vascular reserve and has been postulated to be a sensitive marker in cerebrovascular diseases. MRI-based CVR measurement typically employs alterations in arterial carbon dioxide (CO2) level while continuously acquiring Blood-Oxygenation-Level-Dependent (BOLD) images. CO2-inhalation and resting-state methods are two commonly used approaches for CVR MRI. However, processing of CVR MRI data often requires special expertise and may become an obstacle in broad utilization of this promising technique. The aim of this work was to develop CVR-MRICloud, a cloud-based CVR processing pipeline, to enable automated processing of CVR MRI data. The CVR-MRICloud consists of several major steps including extraction of end-tidal CO2 (EtCO2) curve from raw CO2 recording, alignment of EtCO2 curve with BOLD time course, computation of CVR value on a whole-brain, regional, and voxel-wise basis. The pipeline also includes standard BOLD image processing steps such as motion correction, registration between functional and anatomic images, and transformation of the CVR images to canonical space. This paper describes these algorithms and demonstrates the performance of the CVR-MRICloud in lifespan healthy subjects and patients with clinical conditions such as stroke, brain tumor, and Moyamoya disease. CVR-MRICloud has potential to be used as a data processing tool for a variety of basic science and clinical applications., Competing Interests: The authors have declared that no competing interests exist.

Magnetic resonance imaging perfusion (MRP) techniques can improve the selection of acute ischemic stroke patients for treatment by estimating the salvageable area of decreased perfusion, that is, penumbra. Arterial spin labeling (ASL) is a noncontrast MRP technique that is used to assess cerebral blood flow without the use of intravenous gadolinium contrast. Thus, ASL is of particular interest in stroke imaging. This article will review clinical applications of ASL in stroke such as assessment of the core infarct and penumbra, localization of the vascular occlusion, and collateral status. Given the nonspecific symptoms that patients can present with, differentiating between stroke and a stroke mimic is a diagnostic dilemma. ASL not only helps in differentiating stroke from stroke mimic but also can be used to specify the exact mimic when used in conjunction with the symptomatology and structural imaging. In addition to a case-based overview of clinical applications of the ASL in stroke and stroke mimics in this article, the more commonly used ASL labeling techniques as well as emerging ASL techniques, future developments, and limitations will be reviewed.

A number of pharmaceuticals have been identified as potential adjuvants to speech language therapy following stroke, but it is also important to consider which pharmaceuticals may result in a less robust recovery. Here we examine whether post-stroke language recovery was meaningfully impeded by cholinergic, GABAergic, or dopaminergic medications patients received. Eighty participants with left hemisphere stroke were examined retrospectively to see whether the use of one of these three classes of medication prior to admission for acute stroke, during their inpatient stay, or at discharge was associated with differences in recovery on three common measures of language. While prescription of any of the candidate drugs was relatively uncommon, groups were very well matched for many common factors that impact performance. When age, education, and acute lesion volume were controlled, there were no significant differences in performance among those taking cholinergic, GABAergic, or dopaminergic medications and those who were not. Those who experienced a "good recovery" of language (≥10% improvement on any one language measure over time) had similar exposure to these drugs to those with a poor recovery. This work represents a first look at these drug classes with regard to their effects on the recovery of language after stroke and should not be interpreted as resolving all potential for concern, but these results do offer modest reassurance that these common classes of pharmacotherapy, when given for short periods in this population, do not appear to have marked deleterious effects on post-stroke recovery of language., Competing Interests: The authors have declared that no competing interests exist.

NIHSS score is higher for left vs. right hemisphere strokes of equal volumes. However, differences in each vascular territory have not been evaluated yet. We hypothesized that left vs. right differences are driven by the middle cerebral artery (MCA) territory, and there is no difference between hemispheres for other vascular territories. This study is based on data from 802 patients with evidence of acute ischemic stroke in one major arterial territory (MCA, n = 437; PCA, n = 209; ACA, n = 21; vertebrobasilar, n = 46). We examined differences in patients with left or right strokes regarding to lesion volume, NIHSS, and other covariates (age, sex, race). We used linear models to test the effects of these covariates on NIHSS. We looked at the whole sample as well as in the sample stratified by NIHSS (≤5 or >5) and by lesion location (MCA or PCA). Patients with left MCA strokes had significantly higher NIHSS than those with right strokes. Only patients with MCA strokes showed NIHSS score affected by the hemisphere when controlling for stroke volume and patient's age. This difference was driven by the more severe strokes (NIHSS>5). It is important to consider this systematic bias in the NIHSS when using the score for inclusion criteria for treatment or trials. Patients with right MCA stroke may be under-treated and left with disabling deficits that are not captured by the NIHSS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Vitti, Kim, Stockbridge, Hillis and Faria.)