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Purpose: Adults with right hemisphere damage demonstrate differences in connected speech compared to controls, but systematic, quantitative methods to capture these differences are lacking. The current study aimed to (a) investigate if measures using the Modern Cookie Theft picture description would identify discourse differences in acute right hemisphere stroke, and (b) examine if discourse differences were associated with documented cognitive impairment. Method: Eighty-four participants completed the Modern Cookie Theft picture description within 5 days of right hemisphere stroke. Descriptions were analyzed for multiple microlinguistic characteristics. Medical charts were retrospectively reviewed for documented presence of cognitive impairment. Results: Individuals with acute right hemisphere stroke produced fewer content units, total syllables, and lower left–right content unit ratios compared to controls, indicating a paucity of informativeness. Presence of cognitive impairment was associated with fewer content units produced. Conclusions: Multiple measures of microlinguistic discourse characteristics differentiated adults with right hemisphere stroke from controls, highlighting variations in both the quantity and quality of connected speech. Findings continue to underscore the contribution and correlation between cognitive skills and discourse performance. Future work is needed to assess the relationship between particular cognitive domains and discourse production as well as to investigate longitudinal changes to discourse production during stroke recovery. Supplemental Material: https://doi.org/10.23641/asha.20778541

Stroke is a common cause of disability in aging adults. A given individual's needs after stroke vary as a function of the stroke extent and location. The purpose of this review was to discuss recent clinical investigations addressing rehabilitation of an array of overlapping functional domains.Research is ongoing in the domains of movement, cognition, attention, speech, language, swallowing, and mental health. To best assist patients' recovery, innovative research has sought to develop and evaluate behavioral approaches, identify and refine synergistic approaches that augment the response to behavioral therapy, and integrate technology where appropriate, particularly to introduce and titrate real-world complexity and improve the overall experience of therapy. Recent and ongoing trials have increasingly adopted a multidisciplinary nature - augmenting refined behavioral therapy approaches with methods for increasing their potency, such as pharmaceutical or electrical interventions. The integration of virtual reality, robotics, and other technological advancements has generated immense excitement, but has not resulted in consistent improvements over more universally accessible, lower technology therapy.

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.

Lesion-related factors are associated with severity of language impairment in persons with aphasia. The extent to which demographic and health factors predict language impairment beyond traditional cortical measures remains unknown. Identifying and understanding the contributions of factors to predictive models of severity constitutes critical knowledge for clinicians interested in charting the likely course of aphasia in their patients and designing effective treatment approaches in light of those predictions.Utilizing neuroimaging and language testing from our cohort of 224 individuals in the chronic stage of recovery from a left-hemisphere stroke in a cross-sectional study, we first conducted a lesion symptom mapping (LSM) analysis to identify regions associated with aphasia severity scores. After controlling for lesion volume and damage to pre-identified areas, three models were created to predict severity scores: 1) Demographic Model (N = 147); 2) Health Model (N = 106); and 3) Overall Model (N = 106). Finally, all identified factors were entered into a Final Model to predict raw severity scores.Two areas were associated with aphasia severity-left posterior insula and left arcuate fasciculus. The results from the Demographic Model revealed non-linguistic cognitive ability, age at stroke, and time post-stroke as significant predictors of severity (P = .005; P = .02; P = .001, respectively), and results from the Health Model suggested the extent of leukoaraiosis is associated with severity (P = .0004). The Overall Model showed a relationship between aphasia severity and cognitive ability (P = .01), time post-stroke (P = .002), and leukoaraiosis (P = .01). In the Final Model, which aimed to predict raw severity scores, demographic, health, and lesion factors explained 55% of the variance in severity, with health and demographic factors uniquely explaining nearly half of performance variance.Results from this study add to the literature suggesting patient-specific variables can shed light on individual differences in severity beyond lesion factors. Additionally, our results emphasize the importance of non-linguistic cognitive ability and brain health in aphasia recovery.

Purpose: There are few evidence-based treatments for language deficits in primary progressive aphasia (PPA). PPA treatments are often adopted from the poststroke aphasia literature. The poststroke aphasia literature has shown promising results using Verb Network Strengthening Treatment (VNeST), a behavioral therapy that focuses on improving naming by producing verbs and their arguments in phrases and sentences. Emerging research in poststroke aphasia and PPA has shown promising results pairing behavioral language therapy with transcranial direct current stimulation (tDCS). Method: This study used a double-blind, within-subjects, sham-controlled crossover design to study the effect of anodal tDCS applied to left inferior frontal gyrus (IFG) plus VNeST versus VNeST plus sham stimulation in two individuals with nonfluent variant PPA and one individual with logopenic variant PPA. Participants received two phases of treatment, each with 15 1-hr sessions of VNeST. One phase paired VNeST with tDCS stimulation, and one with sham. For each phase, language testing was conducted at baseline, and at 1 week and 8 weeks posttreatment conclusion. For each participant, treatment efficacy was evaluated for each treatment phase by comparing the mean change in accuracy between baseline and the follow-up time points for naming trained verbs (primary outcome measure), untrained verbs, and nouns on the Object and Action Naming Battery. Mean change from baseline was also directly compared between tDCS and sham phases at each time point. Results: Results revealed a different pattern of outcomes for each of the participants. A tDCS advantage was not found for trained verbs for any participant. Two participants with nonfluent variant PPA had a tDCS advantage for generalization to naming of untrained verbs, which was apparent at 1 week and 8 weeks posttreatment. One participant with nonfluent variant also showed evidence of generalization to sentence production in the tDCS phase. Conclusion: VNeST plus anodal tDCS stimulation of left IFG shows promising results for improving naming in PPA.

Background: Perfusion and structural imaging play an important role in ischemic stroke. Magnetic resonance fingerprinting (MRF) arterial spin labeling (ASL) is a novel noninvasive method of ASL perfusion that allows simultaneous estimation of cerebral blood flow (CBF), bolus arrival time (BAT), and tissue T 1 map in a single scan of Methods: A total of 34 patients were scanned on 3T magnetic resonance imaging. MRF-ASL, standard single-delay pseudo-continuous ASL, T 2 -weighted, and diffusion magnetic resonance imaging were performed. Regions of interest of lesion and contralateral normal tissues were manually delineated. CBF (with 2 different compartmental models), BAT, and tissue T 1 parameters were quantified. Cross-sectional linear regression analyses were performed to examine the relationship between MRF-ASL parameters and National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale. Receiver operating characteristic analyses were performed to determine the utility of MRF-ASL in the classification of stroke lesion voxels. Results: MRF-ASL derived parameters revealed a significant difference between stroke lesion and contralateral normal regions of interest, in that lesion regions manifested a lower CBF 1-compartment ( P 2-compartment ( P P =0.002), and longer T 1 ( P 1-compartment,diff (β=−0.11, P =0.008), CBF 2-compartment,diff (β=−0.16, P =0.003), and T 1,diff (β=0.008, P =0.001). MRF-ASL parameters were also predictive of NIHSS score and modified Rankin Scale scale measured at a later stage, although the degree of the associations was weaker. These associations tended to be even stronger when the MRF-ASL data were acquired at the acute/subacute stage. Compared with standard pseudo-continuous ASL, the multiparametric capability of MRF-ASL yielded higher area under curve values in the receiver operating characteristic analyses of stroke voxel classifications. Conclusions: MRF-ASL may provide a new approach for quantitative hemodynamic and structural imaging in ischemic stroke.

In contrast to the traditional definition of the disorder, many individuals with aphasia exhibit non-linguistic cognitive impairments, including executive control deficits. Classic lesion studies cite frontal lobe damage in executive dysfunction, but more recent lesion symptom-mapping studies in chronic aphasia present mixed results. In this study, we compared executive control abilities of acute stroke survivors with and without aphasia and investigated lesion correlates of linguistic and non-linguistic cognitive tasks. Twenty-nine participants with acute left hemisphere stroke resulting in aphasia (n = 14) or no aphasia (n = 15) completed clinical MRI and testing, including three NIH Toolbox Cognition Batteries (Pattern Comparison Processing Speed, Flanker Inhibitory Control and Attention, and Dimensional Change Card Sort Tests) and the Boston Naming Test. We compared performance between groups using Wilcoxon rank sum tests. We used Least Absolute Shrinkage and Selection Operator Regression to identify neural markers (percent regional damage, hypoperfusion within vascular territories, and total lesion volume) of executive control deficits and anomia. Group performance was comparable on the Pattern Comparison Processing Speed Test, but people with aphasia had poorer standard scores, lower accuracy, and slower response times on the Dimensional Change Card Sort Test than people without aphasia. Damage to extrasylvian regions (dorsolateral prefrontal cortex, intraparietal sulcus) was related to executive control deficits, whereas language network damage (to inferior frontal and superior and posterior middle temporal gyri) was linked to naming impairments. These results suggest people with aphasia can exhibit comorbid executive control impairments linked to damage outside classic language network areas. Supplementary Information The online version contains supplementary material available at 10.1007/s11682-021-00580-y.

Purpose: We present a 20-item naming test, the Severity-Calibrated Aphasia Naming Test (SCANT), that can serve as a proxy measure for an aphasia severity scale that is derived from a thorough test battery of connected speech production, single-word production, speech repetition, and auditory verbal comprehension. Method: We use lasso regression and cross-validation to identify an optimal subset from a set of 174 pictures to be named for prediction of aphasia severity, based on data from 200 participants with left-hemisphere stroke who were quasirandomly selected to represent the full impairment scale. Data from 20 healthy controls (i.e., participant caretakers/spouses) were also analyzed. We examine interrater reliability, test–retest reliability, sensitivity and specificity to the presence of aphasia, sensitivity to therapy gains, and external validity (i.e., correlation with aphasia severity measures) for the SCANT. Results: The SCANT has extremely high interrater reliability, and it is sensitive and specific to the presence of aphasia. We demonstrate the superiority of predictions based on the SCANT over those based on the full set of naming items. We estimate a 15% reduction in power when using the SCANT score versus the full test battery's aphasia severity score as an outcome measure; for example, to maintain the same power to detect a significant group average change in aphasia severity, a study with 25 participants using the full test battery to measure treatment effectiveness would require 30 participants if the SCANT were to be used as the testing instrument instead. Conclusion: We provide a linear model to convert SCANT scores to aphasia severity scores, and we identify a change score cutoff of four SCANT items to obtain a high degree of confidence based on test–retest SCANT data and the modeled relation between SCANT and aphasia severity scores. Supplemental Material: https://doi.org/10.23641/asha.21476871

This chapter explores the involvement of the temporal lobes in distinct language functions. The examination of cases of localized damage to the temporal lobes and the resulting pattern of impairment across language tasks and types of errors made can reveal clear neural regions and associated networks essential for word comprehension, semantics, naming, reading, and spelling. Key regions implicated in these functions include left superior temporal gyrus posterior to the temporal pole in word comprehension, bilateral anterior temporal lobes in semantics, left posterior inferior temporal gyrus (pITG) in naming, and left pITG and fusiform cortex in reading and spelling. Results we review provide evidence that the temporal lobes have a critical role in many language tasks. Although various areas and associated white matter tracts work together in supporting language, damage to specific regions of the temporal lobes results in distinct and relatively predictable impairments of language functions.

Purpose Many factors influence poststroke language recovery, yet little is known about the influence of previous stroke(s) on language after left hemisphere stroke. In this prospective longitudinal study, we investigated the role of prior stroke on language abilities following an acute left hemisphere ischemic stroke, while controlling for demographic and stroke-related factors, and examined if earlier stroke impacted language recovery at a chronic time point. Method Participants ( n = 122) with acute left hemisphere ischemic stroke completed language evaluation and clinical neuroimaging. They were divided into two groups: single stroke (SS; n = 79) or recurrent stroke (RS; n = 43). A subset of participants ( n = 31) completed chronic-stage re-evaluation. Factors studied included age, education, diabetes and hypertension diagnoses, lesion volume and broad location, group status, aphasia prevalence, and language scores. Results Groups did not differ in language performance across time points. The only significant group differences were that participants with RS were older, had smaller acute lesions, and were less educated. Stroke group membership (SS vs. RS) was not associated with language performance at either time point. In patients with prior stroke, large acute lesion volumes were associated with acute language performance, whereas both large acute and chronic volumes influenced recovery. Conclusions History of prior stroke in itself may not significantly influence language impairment after an additional acute left hemisphere stroke, unless it contributes substantially to the total volume of infarcted brain tissue. Chronic and acute lesion volumes should be accounted for in studies investigating poststroke language performance and recovery. Supplemental Material https://doi.org/10.23641/asha.14669715

Background White matter disconnection of language-specific brain regions associates with worse aphasia recovery. Despite a loss of direct connections, many stroke survivors may maintain indirect connections between brain regions. Objective To determine (1) whether preserved direct connections between language-specific brain regions relate to better poststroke naming treatment outcomes compared to no direct connections and (2) whether for individuals with a loss of direct connections, preserved indirect connections are associated with better treatment outcomes compared to individuals with no connections. Methods We computed structural whole-brain connectomes from 69 individuals with chronic left-hemisphere stroke and aphasia who completed a 3-week-long language treatment that was supplemented by either anodal transcranial direct current stimulation (A-tDCS) or sham stimulation (S-tDCS). We determined differences in naming improvement between individuals with direct, indirect, and no connections using 1-way analyses of covariance and multivariable linear regressions. Results Independently of tDCS modality, direct or indirect connections between the inferior frontal gyrus pars opercularis and angular gyrus were both associated with a greater increase in correct naming compared to no connections ( P = .027 and P = .039, respectively). Participants with direct connections between the inferior frontal gyrus pars opercularis and middle temporal gyrus who received S-tDCS and participants with indirect connections who received A-tDCS significantly improved in naming accuracy. Conclusions Poststroke preservation of indirect white matter connections is associated with better treated naming improvement in aphasia even when direct connections are damaged. This mechanistic information can be used to stratify and predict treated naming recovery in individuals with aphasia.

Purpose: We aimed to investigate: (1) the clinical, diagnostic value of a written discourse task, and (2) the relationship between executive functions and written discourse within the spectrum of individuals with mild cognitive impairment (MCI). Method: To determine whether written discourse performance predicts clinical course among individuals with MCI, we retrospectively classified individuals with MCI as converters (N = 26) who were later diagnosed with dementia or as a stable MCI group (N = 45). We quantified core word measures from written discourse samples obtained from the Cookie Theft picture description task. Result: Written discourse measures differentiated converters from the stable MCI group. Converters produced a fewer number of core words than the stable MCI group. A measure of executive function significantly predicted performance on the production of core words in written discourse for the converters. In a multivariable regression, production of core words remained the only explanatory variable closely associated with the progression to dementia in MCI. Conclusion: Written discourse tasks can predict the likelihood of MCI progressing to dementia, independently of recall and an executive function measure. Correlational results suggest that written discourse performance was associated with executive function as measured by the Trail Making Test. Our findings emphasize the usefulness of including written discourse tasks in language assessment batteries targeting preclinical dementia populations.

People with aphasia demonstrate impaired production of bound inflectional morphemes, such as noun plurals (-s) and noun possession (‘s). They often show greater difficulty in marking possession versus plurality. Using a new tool for eliciting nouns, modifiers, and inflectional morphemes in aphasia, the Morphosyntactic Generation test, we assessed people with primary progressive aphasia and those in the acute and chronic phase following left hemisphere stroke. Clinical profiles were associated with different strengths and weaknesses in language production when controlling for age and education. Overall, performance of the plural -s was stronger than possessive ‘s in group analyses. However, some individuals demonstrated the inverse pattern of performance with an advantage for possessives. These participants provide counterevidence to the theory that difficulty with marking possessives is purely the result of their greater cognitive-linguistic complexity, suggesting that there is a functional double dissociation between the marking of possessives and plurals. The deficits we observed resulted from morphosyntactic impairments, at least in those patients who showed clear dissociations. Future work is needed to understand why plural and possessive markers were differently sensitive to neurological disorders of language.

INTRODUCTION: Previous studies reveal that a newly described white matter pathway, the frontal aslant tract (FAT), connecting inferior and superior frontal gyri has a role in speech and language functions. We explored the role of this tract in a phonemic and semantic fluency tasks in a cohort of multiple sclerosis patients diagnosed with cognitive impairment. METHODS: Thirty-five right-handed English-speaking MS patients with varying degrees of cognitive impairment underwent diffusion tensor imaging (DTI) and the Controlled Associated Word Test (COWAT). Fractional anisotropy (FA) of FAT and arcuate fasciculus (AF) were obtained through a supervised, atlas-based tissue segmentation and parcellation method. Phonemic and semantic fluency scores were obtained from COWAT. We ran a multivariate regression model, and partial correlation analyses adjusted for age, education, and lesion load, and corrected for multiple comparisons. False discovery rate (FDR) was used for the correction of multiple comparisons. RESULTS: Bilateral FAT FA showed significant association with phonemic verbal fluency task (Left; r=0.46, p=0.0058 and right; r=0.46, p=0.0059) but not semantic fluency task and this relation remained significant after FDR correction (p=0.02 bilaterally). Although left AF showed some significant association with phonemic fluency task (r=0.38, p=0.02), this relation was insignificant after FDR correction (p=0.07). CONCLUSION: We show that bilateral FAT are correlates of phonemic verbal fluency task but not semantic in an MS cohort with cognitive impairment. This finding suggests that FAT is more specialized in lexical retrieval function as semantic fluency test encompasses all the functions except the lexical retrieval.

The communication and behavioral manifestations of primary progressive aphasia (PPA) present ethical and practical challenges for individuals with this clinical syndrome as well as for individuals who are involved closely in their care. In this article, cases representing all three PPA variants (logopenic variant, nonfluent agrammatic, semantic variant) are presented to illustrate commonly encountered situations in which self-determination is at risk in decisions about housing, driving, social interactions, finances, and treatment interventions. Potential approaches, including patient/family education, implementation of safeguards, redirection to meaningful activities, and protections against vulnerability in treatment decisions, are described to preserve autonomy in patients with this neurodegenerative clinical syndrome.

INTRODUCTION: Stroke is among the most common causes of disability worldwide. Nonmotor symptoms of stroke are common and disabling. Many are treatable, and intervention improves the quality of life for stroke survivors. AREAS COVERED: Here the author summarizes evidence-based treatment of depression and other mood disorders, aphasia, hemispatial neglect, impairments of emotional communication and empathy, deficits in memory and other cognitive functions, sleep disorders, pain, fatigue, (1)and seizures resulting from stroke. The author focuses on treatments supported by randomized controlled trials (RCTs), from literature cited in Google Scholar, Embase, and Pubmed. EXPERT OPINION: While behavioral rehabilitation is the most common intervention for many of the sequelae of stroke, relatively small RCTs support the use of noninvasive brain stimulation (transcranial direct current stimulation and transcranial direct current stimulation) and medications that facilitate neural plasticity and recovery. These noninvasive brain stimulation methods remain investigational for post-stroke symptoms. The strongest evidence for pharmacological intervention is in the domains of post-stroke mood disorders and epilepsy, but additional RCTs are needed to confirm the efficacy of selective serotonin reuptake inhibitors and other medications for improving recovery of cognition, language, and energy after stroke.

PurposeThe purpose of this study was to describe the development and implementation of a fidelity program for an ongoing, multifacility, aphasia intervention study and to explain how initial fidelity measures are being used to improve study integrity.MethodA Clinical Core team developed and incorporated a fidelity plan in this study. The aims of the Clinical Core team were to (a) supervise data collection and data management at each clinical site, (b) optimize and monitor assessment fidelity, and (c) optimize and monitor treatment fidelity. Preliminary data are being used to guide ongoing efforts to preserve and improve the fidelity of this intervention study.ResultsPreliminary results show that specific recruitment strategies help to improve appropriate referrals and that accommodations to participants and their families help to maintain excellent retention. A streamlined and centralized training program assures the reliability of assessors and raters for the study's assessment and treatment protocols. Ongoing monitoring of both assessment and treatment tasks helps to maintain study integrity. Less-than-optimal interrater reliability data for the raters of some of the discourse measures guided the Clinical Core team to address the training and coding inconsistencies in a timely manner.ConclusionsThe creation of a Clinical Core team is instrumental in developing and implementing a fidelity plan for improved assessment and treatment fidelity. Intentional planning and assignment of study staff to implement and monitor ongoing fidelity measures assures that clinical data are reliable and valid. Ongoing review of the plan shows areas of strengths and weaknesses for continuing adjustments and improvement of study fidelity.

BACKGROUND: Left-hemisphere brain damage commonly affects patients’ abilities to produce and comprehend syntactic structures, a condition typically referred to as “agrammatism”. The neural correlates of agrammatism remain disputed in the literature, and distributed areas have been implicated as important predictors of performance, e.g. Broca’s area, anterior temporal areas and temporo-parietal areas. OBJECTIVE AND HYPOTHESIS: We examined the association between damage to specific language-related regions of interest and impaired syntactic processing in acute aphasia. We hypothesized that damage to the posterior middle temporal gyrus, and not Broca’s area, would predict syntactic processing abilities. METHOD: 104 individuals with acute aphasia (

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 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. Compared to subcortical stroke patients without aphasia, patients with aphasia had greater acute and total lesion volume, were older, and had significantly greater damage to the internal capsule (which did not survive controlling for total lesion volume). Patients with aphasia did not differ from non-aphasic patients by other demographic or stroke variables. Age was the only significant predictor of aphasia status in a logistic regression model. 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.

In this forthcoming multicenter, prospective, randomized, double-blind placebo-controlled trial, we will investigate the augmentative effects of a selective serotonin reuptake inhibitor, escitalopram, on language therapy in individuals with post-stroke aphasia. We hypothesize that, when combined with language therapy, daily escitalopram will result in greater improvement than placebo in an untrained picture naming task (Philadelphia Naming Test short form) administered one week after the end of language therapy. We also will examine whether escitalopram’s effect on language is independent of its effect on depression, varies with lesion location, or is associated with increased functional connectivity within the left hemisphere. Finally, we will examine whether individuals with BDNF met alleles show reduced response to treatment and reduced changes in connectivity. We expect to enroll 88 participants over four years. Participants are given escitalopram or placebo within one week of their stroke for 90 days and receive fifteen 45-minute computer-delivered sessions of language treatment beginning 60 days from the start of drug therapy. Patients then complete a comprehensive assessment of language at one, five, and twenty weeks after the last language therapy session. ELISA is the first randomized, controlled trial evaluating the effect of a selective serotonin reuptake inhibitor on the improvement of language in people with aphasia undergoing language treatment during the acute to subacute post-stroke period. Trial registration: The trial is registered with ClinicalTrials.gov NCT03843463.

In acute ischemic stroke, reported relationships between lesion metrics and behavior have largely focused on lesion volume and location. However, hypoperfusion has been shown to correlate with deficits in the acute stage. Hypoperfusion is typically identified using perfusion imaging in clinical settings, which requires contrast. Unfortunately, contrast is contraindicated for some individuals. An alternative method has been proposed to identify hypoperfusion using hyperintense vessels on fluid-attenuated inversion recovery (FLAIR) imaging. This study aimed to validate the clinical importance of considering hypoperfusion when accounting for behavior in acute stroke and demonstrate the clinical utility of scoring the presence of hyperintense vessels to quantify it. One hundred and fifty-three participants with acute ischemic stroke completed a battery of commonly-used neurological and behavioral measures. Clinical MRIs were used to determine lesion volume and to score the presence of hyperintense vessels seen on FLAIR images to estimate severity of hypoperfusion in six different vascular regions. National Institutes of Health Stroke Scale (NIHSS) scores, naming accuracy (left hemisphere strokes), and language content produced during picture description were examined in relation to lesion volume, hypoperfusion, and demographic variables using correlational analyses and multivariable linear regression. Results showed that lesion volume and hypoperfusion, in addition to demographic variables, were independently associated with performance on NIHSS, naming, and content production. Specifically, hypoperfusion in the frontal lobe independently correlated with NIHSS scores, while hypoperfusion in parietal areas independently correlated with naming accuracy and content production. These results correspond to previous reports associating hypoperfusion with function, confirming that hypoperfusion is an important consideration-beyond lesion volume-when accounting for behavior in acute ischemic stroke. Quantifying hypoperfusion using FLAIR hyperintense vessels can be an essential clinical tool when other methods of identifying hypoperfusion are unavailable or time prohibitive.

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.

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.

Primary progressive aphasia can be distinguished into one of three variants: semantic, non-fluent/agrammatic, and logopenic. While a considerable body of work exists characterizing each variant, few prior studies have addressed the problem of optimizing behavioral assessment in a typical outpatient evaluation setting. Our aim is to examine the sensitivity and specificity of a battery of cognitive and linguistic assessments and determine optimal scores for distinguishing patients' subtype based on these instruments. This was a retrospective analysis of outpatient clinical testing of individuals with known or suspected primary progressive aphasia. Evaluations included the National Alzheimer's Coordinating Center frontotemporal lobar degeneration module and additional measures of naming, semantic association, word verification, and picture description. Receiver operating characteristic analysis was used to examine the utility of each task in distinguishing each variant from the others. Logistic regressions were used to examine the combined utility of tasks for distinguishing a given subtype. We examined 435 evaluations of 222 patients retrospectively. The battery was most consistent in distinguishing semantic variant by low scores and non-fluent/agrammatic variant by high scores on a similar subset of tasks. Tasks best distinguishing semantic variant produced a model that correctly classified 86% of cases. Tasks best distinguishing non-fluent/agrammatic variant correctly classified 77% of cases. The battery of tasks was weakest in identifying logopenic variant; only the ratio of sentence reading to sentence repetition performance was identified as a reasonable predictor, and it had predictive accuracy of 67%. Naming assessments were the strongest basis for distinguishing all variants, particularly semantic variant from non-fluent/agrammatic variant. These data illustrate that a number of commonly used assessments perform at chance in distinguishing variant and preliminarily support an abbreviated battery that marginally favors tools not currently included in the frontotemporal lobar degeneration module.

The ability to string together words into a structured arrangement capable of conveying nuanced information is key to speech production. The assessment of the neural bases for structuring sentences has been challenged by the need of experts to delineate the aberrant morphosyntactic structures in aphasic speech. Most studies have relied on focused tasks with limited ecological validity. We characterized syntactic complexity during connected speech produced by patients with chronic post-stroke aphasia. We automated this process by employing Natural Language Processing (NLP). We conducted voxel-based and connectome-based lesion-symptom mapping to identify brain regions crucially associated with sentence production and syntactic complexity. Posterior-inferior aspects of left frontal and parietal lobes, as well as white matter tracts connecting these areas, were essential for syntactic complexity, particularly the posterior inferior frontal gyrus. These findings suggest that sentence structuring during word production depends on the integrity of Broca’s area and the dorsal stream of language processing.

A growing body of evidence indicates many, but not all, individuals with post-stroke aphasia experience executive dysfunction. Relationships between language and executive function skills are often reported in the literature, but the degree of interdependence between these abilities remains largely unanswered. Therefore, in this study, we investigated the extent to which language and executive control deficits dissociated in 1) acute stroke and 2) longitudinal aphasia recovery. Twenty-three individuals admitted to Johns Hopkins Hospital with a new left hemisphere stroke completed the Western Aphasia Battery-Revised (WAB-R), several additional language measures (of naming, semantics, spontaneous speech, and oral reading), and three non-linguistic cognitive tasks from the NIH Toolbox (i.e., Pattern Comparison Processing Speed Test, Flanker Inhibitory Control and Attention Test, and Dimensional Change Card Sort Test). Two participants with aphasia (PWA) with temporoparietal lesions, one of whom (PWA1) had greater temporal but less frontal and superior parietal damage than the other (PWA2), also completed testing at subacute (three months post-onset) and early chronic (six months post-onset) time points. In aim 1, principal component analysis on the acute test data (excluding the WAB-R) revealed language and non-linguistic executive control tasks largely loaded onto separate components. Both components were significant predictors of acute aphasia severity per the WAB-R Aphasia Quotient (AQ). Crucially, executive dysfunction explained an additional 17% of the variance in AQ beyond the explanatory power of language impairments alone. In aim 2, both case patients exhibited language and executive control deficits at the acute post-stroke stage. A dissociation was observed in longitudinal recovery of these patients. By the early chronic time point, PWA1 exhibited improved (but persistent) deficits in several language domains and recovered executive control. In contrast, PWA2 demonstrated mostly recovered language but persistent executive dysfunction. Greater damage to language and attention networks in these respective patients may explain the observed behavioral patterns. These results demonstrate that language and executive control can dissociate (at least to a degree), but both contribute to early post-stroke presentation of aphasia and likely influence longitudinal aphasia recovery.

ObjectiveTo determine whether right ventral stream and limbic structures (including posterior superior temporal gyrus [STG], STG, temporal pole, inferior frontal gyrus pars orbitalis, orbitofrontal cortex, amygdala, anterior cingulate, gyrus, and the sagittal stratum) are implicated in emotional prosody identification.MethodsPatients with MRI scans within 48 hours of unilateral right hemisphere ischemic stroke were enrolled. Participants were presented with 24 sentences with neutral semantic content spoken with happy, sad, angry, afraid, surprised, or bored prosody and chose which emotion the speaker was feeling based on tone of voice. Multivariable linear regression was used to identify individual predictors of emotional prosody identification accuracy from a model, including percent damage to proposed right hemisphere structures, age, education, and lesion volume across all emotions (overall emotion identification) and 6 individual emotions. Patterns of recovery were also examined at the chronic stage.ResultsThe overall emotion identification model was significant (adjusted r2 = 0.52; p = 0.043); greater damage to right posterior STG (p = 0.038) and older age (p = 0.009) were individual predictors of impairment. The model for recognition of fear was also significant (adjusted r2 = 0.77; p = 0.002), with greater damage to right amygdala (p = 0.047), older age (p < 0.001), and less education (p = 0.005) as individual predictors. Over half of patients with chronic stroke had residual impairments.ConclusionsRight posterior STG in the right hemisphere ventral stream is critical for emotion identification in speech. Patients with stroke with damage to this area should be assessed for emotion identification impairment.

BACKGROUND: Language characteristics of logopenic variant primary progressive aphasia (lvPPA) are well-defined; however, there is a paucity of research investigating behavioral characteristics specific to this subtype. OBJECTIVE: To determine the relationship between language abilities and behavior across the three variants of primary progressive aphasia (PPA). We hypothesized that, associations between language and behavior (measured by the Frontal Behavioral Inventory; FBI) would vary across subtypes due to distinct neuropathologies. More specifically, we hypothesized that the severity of language and behavioral problems would be independent in semantic (svPPA) and nonfluent (nfaPPA) PPA subtypes and related in lvPPA. METHODS: We used Spearman’s rank correlation coefficients to investigate correlations between language and behavioral scores. Total scores on the FBI-mod significantly correlated with scores on the Pyramids and Palm Trees Test (r = −0.589, p = 0.001), a Sentence Repetition test (r = −0.559, p = 0.003), and the Hopkins Assessment of Naming Actions (r = −0.550, p = 0.003) in lvPPA. CONCLUSIONS: Results were interpreted as evidence that individuals with lvPPA show a correlation between language scores and negative behavior scores because they do not develop negative behaviors until language deficits are severe, consistent with the common underlying cause of lvPPA—Alzheimer’s disease. In contrast, behavioral symptoms are early symptoms in semantic variant PPA and nonfluent agrammatic PPA. Such findings are crucial to clinical care because, after receiving a PPA diagnosis, patients, families and caregivers often seek prognoses specific to language and behavior, especially when considering the progressive nature of this disease.

Purpose To demonstrate the feasibility of mapping cerebrovascular reactivity (CVR) using resting-state functional MRI (fMRI) data without gas or other challenges in patients with cerebrovascular diseases and to show that brain regions affected by the diseases have diminished vascular reactivity. Materials and methods Two sub-studies were performed on patients with stroke and Moyamoya disease. In Study 1, 20 stroke patients (56.3 ± 9.7 years, 7 females) were enrolled and resting-state blood‑oxygenation-level-dependent (rs-BOLD) fMRI data were collected, from which CVR maps were computed. CVR values were compared across lesion, perilesional and control ROIs defined on anatomic images. Reproducibility of the CVR measurement was tested in 6 patients with follow-up scans. In Study 2, rs-BOLD fMRI and dynamic susceptibility contrast (DSC) MRI scans were collected in 5 patients with Moyamoya disease (32.4 ± 8.2 years, 4 females). Cerebral blood flow (CBF), cerebral blood volume (CBV), and time-to-peak (TTP) maps were obtained from the DSC MRI data. CVR values were compared between stenotic brain regions and control regions perfused by non-stenotic arteries. Results In stroke patients, lesion CVR (0.250 ± 0.055 relative unit (r.u.)) was lower than control CVR (0.731 ± 0.088 r.u., p = 0.0002). CVR was also lower in the perilesional regions in a graded manner (perilesion 1 CVR = 0.422 ± 0.051 r.u., perilesion 2 CVR = 0.492 ± 0.046 r.u.), relative to that in the control regions (p = 0.005 and 0.036, respectively). In the repeatability analysis, a strong correlation was observed between lesion CVR (r2 = 0.91, p = 0.006) measured at two time points, as well as between control CVR (r2 = 0.79, p = 0.036) at two time points. In Moyamoya patients, CVR in the perfusion deficit regions delineated by DSC TTP maps (0.178 ± 0.189 r.u.) was lower than that in the control regions (0.868 ± 0.214 r.u., p = 0.013). Furthermore, the extent of reduction in CVR was significantly correlated with the extent of lengthening in TTP (r2 = 0.91, p = 0.033). Conclusion Our findings suggested that rs-BOLD data can be used to reproducibly evaluate CVR in patients with cerebrovascular diseases without the use of any vasoactive challenges.

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.

This review is intended to help physicians guide patients to optimal management of post-stroke aphasia. We review literature on post-stroke aphasia treatment, focusing on: (1) when and for whom language therapy is most effective, (2) the variety of approaches that can be effective for different individuals, and (3) the extent to which behavioral therapy might be augmented by non-invasive brain stimulation and/or medications.

Background: Previous studies utilized lesion-centric approaches to study the role of the thalamus in language. In this study, we tested the hypotheses that non-lesioned dorsomedial and ventral anterior nuclei (DMVAC) and pulvinar lateral posterior nuclei complexes (PLC) of the thalamus and their projections to the left hemisphere show secondary effects of the strokes, and that their microstructural integrity is closely related to language-related functions. Methods: Subjects with language impairments after a left-hemispheric cortical and/or subcortical, early stroke (n = 31, ≤6 months) or late stroke (n = 30, ≥12 months) sparing thalamus underwent the Boston Naming Test (BNT) and diffusion tensor imaging (DTI). The tissue integrity of DMVAC, PLC, and their cortical projections was quantified with DTI. The right-left asymmetry profiles of these structures were evaluated in relation to the time since stroke. The association between microstructural integrity and BNT score was investigated in relation to stroke chronicity with partial correlation analyses adjusted for confounds. Results: In both early stroke and late stroke groups, left-sided tracts showed significantly higher mean diffusivities (MDs), which were likely due to Wallerian degeneration. Higher MD values of the cortical projections from the left PLC (r = −0.5, p = 0.005) and DMVAC (r = −0.53, p = 0.002) were correlated with lower BNT score in the late stroke but not early stroke group. Conclusion: Nonlesioned thalamic nuclei and thalamocortical pathways show rightward lateralization of the microstructural integrity after a left hemispheric stroke, and this pattern is associated with poorer naming. IMPACT STATEMENT: To the best of our knowledge, our study is the first diffusion tensor imaging study suggesting that the thalamic nuclei and pathways of the left hemisphere spared by direct ischemic insult undergo secondary degeneration over time that is associated with poorer picture naming. Our study may pave the way for targeted interventions such as invasive or noninvasive brain stimulation techniques that engage these spared pathways to prevent secondary degeneration and lead to better outcomes in poststroke aphasia.

Background Transcranial direct current stimulation (tDCS), in conjunction with language therapy, improves language therapy outcomes in primary progressive aphasia (PPA). However, no studies show whether white matter integrity predicts language therapy or tDCS effects in PPA. Objective We aimed to determine whether white matter integrity, measured by diffusion tensor imaging (DTI), predicts written naming/spelling language therapy effects (letter accuracy on trained and untrained words) with and without tDCS over the left inferior frontal gyrus (IFG) in PPA. Methods Thirty-nine participants with PPA were randomly assigned to tDCS or sham condition, coupled with language therapy for 15 daily sessions. White matter integrity was measured by mean diffusivity (MD) and fractional anisotropy (FA) in DTI scans before therapy. Written naming outcomes were evaluated before, immediately after, 2 weeks, and 2 months posttherapy. To assess tDCS treatment effect, we used a mixed-effects model with treatment evaluation and time interaction. We considered a forward model selection approach to identify brain regions/fasciculi of which white matter integrity can predict improvement in performance of word naming. Results Both sham and tDCS groups significantly improved in trained items immediately after and at 2 months posttherapy. Improvement in the tDCS group was greater and generalized to untrained words. White matter integrity of ventral language pathways predicted tDCS effects in trained items whereas white matter integrity of dorsal language pathways predicted tDCS effects in untrained items. Conclusions White matter integrity influences both language therapy and tDCS effects. Thus, it holds promise as a biomarker for deciding which patients will benefit from language therapy and tDCS.

Recent studies have combined multiple neuroimaging modalities to gain further understanding of the neurobiological substrates of aphasia. Following this line of work, the current study uses machine learning approaches to predict aphasia severity and specific language measures based on a multimodal neuroimaging dataset. A total of 116 individuals with chronic left‐hemisphere stroke were included in the study. Neuroimaging data included task‐based functional magnetic resonance imaging (fMRI), diffusion‐based fractional anisotropy (FA)‐values, cerebral blood flow (CBF), and lesion‐load data. The Western Aphasia Battery was used to measure aphasia severity and specific language functions. As a primary analysis, we constructed support vector regression (SVR) models predicting language measures based on (i) each neuroimaging modality separately, (ii) lesion volume alone, and (iii) a combination of all modalities. Prediction accuracy across models was subsequently statistically compared. Prediction accuracy across modalities and language measures varied substantially (predicted vs. empirical correlation range: r = .00–.67). The multimodal prediction model yielded the most accurate prediction in all cases (r = .53–.67). Statistical superiority in favor of the multimodal model was achieved in 28/30 model comparisons (p‐value range, The current study used machine learning approaches to predict aphasia severity and specific language measures based on a multimodal neuroimaging dataset. Our findings revealed a complementary advantage of integrating several neuroimaging modalities within the same model framework, as compared to any single modality prediction model.

Introduction Speakers naturally produce prosodic variations depending on their emotional state. Receptive prosody has several processing stages. We aimed to conduct lesion-symptom mapping to determine whether damage (core infarct or hypoperfusion) to specific brain areas was associated with receptive aprosodia or with impairment at different processing stages in individuals with acute right hemisphere stroke. We also aimed to determine whether different subtypes of receptive aprosodia exist that are characterized by distinctive behavioral performance patterns. Methods Twenty patients with receptive aprosodia following right hemisphere ischemic stroke were enrolled within five days of stroke; clinical imaging was acquired. Participants completed tests of receptive emotional prosody, and tests of each stage of prosodic processing (Stage 1: acoustic analysis; Stage 2: analyzing abstract representations of acoustic characteristics that convey emotion; Stage 3: semantic processing). Emotional facial recognition was also assessed. LASSO regression was used to identify predictors of performance on each behavioral task. Predictors entered into each model included 14 right hemisphere regions, hypoperfusion in four vascular territories as measured using FLAIR hyperintense vessel ratings, lesion volume, age, and education. A k-medoid cluster analysis was used to identify different subtypes of receptive aprosodia based on performance on the behavioral tasks. Results Impaired receptive emotional prosody and impaired emotional facial expression recognition were both predicted by greater percent damage to the caudate. The k-medoid cluster analysis identified three different subtypes of aprosodia. One group was primarily impaired on Stage 1 processing and primarily had frontotemporal lesions. The second group had a domain-general emotion recognition impairment and maximal lesion overlap in subcortical areas. Finally, the third group was characterized by a Stage 2 processing deficit and had lesion overlap in posterior regions. Conclusions Subcortical structures, particularly the caudate, play an important role in emotional prosody comprehension. Receptive aprosodia can result from impairments at different processing stages.

Background It is estimated that ∼30% of stroke survivors have aphasia, a language disorder resulting from damage to left-hemisphere language networks. In acute care settings, efficient identification of aphasia is critical, but there is a paucity of efficient bedside assessments. Objective To determine whether objective measures on a picture description task administered within 48 hours post stroke (a) predict language recovery, (b) estimate left-hemisphere lesion volume and location, and (c) correlate with other bedside language assessments. Method Behavioral data were scored at acute and chronic time points. Neuroimaging data were used to determine associations between the picture description task, other language assessments, and lesion volume and location. Results Acute content units, age, and total lesion volume predicted communication recovery; F3,18 = 3.98, P = 0.024; r = 0.40. Significant correlations were found between the picture description task and lesion volume and location. Picture description outcomes were also associated with other clinical language assessments. Discussion This picture description task quickly predicted the language performance (communication recovery and outcome) for patients who suffered a left-hemisphere stroke. Picture description task measures correlated with damage in the left hemisphere and with other, more time-consuming and cumbersome language assessments that are typically administered acutely at bedside. Conclusion The predictive value of this picture description task and correlations with existing language assessments substantiate the clinical importance of a reliable yet rapid bedside measure for acute stroke patients that can be administered by a variety of health care professionals.

Objective To determine the contribution of white matter hyperintensities (WMH) to language deficits while accounting for cortical atrophy in individuals with primary progressive aphasia (PPA). Method Forty-three individuals with PPA completed neuropsychological assessments of nonverbal semantics, naming, and sentence repetition plus T2-weighted and fluid-attenuated inversion recovery scans. Using three visual scales, we rated WMH and cerebral ventricle size for both scan types. We used Spearman correlations to evaluate associations between the scales and scans. To test whether visual ratings-particularly of WMH-are associated with language, we compared a base model (including gray matter component scores obtained via principal component analysis, age, and days between assessment and MRI as independent variables) with full models (ie, the base model plus visual ratings) for each language variable. Results Visual ratings were significantly associated within and between scans and were significantly correlated with age but not with other vascular risk factors. Only the T2 scan ratings were associated with language abilities. Specifically, controlling for other variables, poorer naming was significantly related to larger ventricles (P = 0.033) and greater global (P = 0.033) and periventricular (P = 0.049) WMH. High global WMH (P = 0.034) were also correlated with worse sentence repetition skills. Conclusion Visual ratings of global brain health were associated with language deficits in PPA independent of cortical atrophy and age. While WMH are not unique to PPA, measuring WMH in conjunction with cortical atrophy may elucidate more accurate brain structure-behavior relationships in PPA than cortical atrophy measures alone.

The current study aims to determine the brain areas critical for response to anodal transcranial direct current stimulation (tDCS) in PPA. Anodal tDCS and sham were administered over the left inferior frontal gyrus (IFG), combined with written naming/spelling therapy. Thirty people with PPA were included in this study, and assessed immediately, 2 weeks, and 2 months post-therapy. We identified anatomical areas whose volumes significantly predicted the additional tDCS effects. For trained words, the volumes of the left Angular Gyrus and left Posterior Cingulate Cortex predicted the additional tDCS gain. For untrained words, the volumes of the left Middle Frontal Gyrus, left Supramarginal Gyrus, and right Posterior Cingulate Cortex predicted the additional tDCS gain. These findings show that areas involved in language, attention and working memory contribute to the maintenance and generalization of stimulation effects. The findings highlight that tDCS possibly affects areas anatomically or functionally connected to stimulation targets.

Broca’s area is frequently implicated in sentence comprehension but its specific role is debated. Most lesion studies have investigated deficits at the chronic stage. We aimed (1) to use acute imaging to predict which left hemisphere stroke patients will recover sentence comprehension; and (2) to better understand the role of Broca’s area in sentence comprehension by investigating acute deficits prior to functional reorganization. We assessed comprehension of canonical and noncanonical sentences in 15 patients with left hemisphere stroke at acute and chronic stages. LASSO regression was used to conduct lesion symptom mapping analyses. Patients with more severe word-level comprehension deficits and a greater proportion of damage to supramarginal gyrus and superior longitudinal fasciculus were likely to experience acute deficits prior to functional reorganization. Broca’s area was only implicated in chronic deficits. We propose that when temporoparietal regions are damaged, intact Broca’s area can support syntactic processing after functional reorganization occurs.

This scientific commentary refers to ‘How right hemisphere damage after stroke can impair speech comprehension', by Gajardo-Vidal et al. (doi: 10.1093/brain/awy270 ).

The types of errors during speech production can vary across individuals with chronic post-stroke aphasia, possibly due to the location and extent of brain damage. In this study, we evaluated the relationship between semantic vs. phonemic errors during confrontational naming, and their relationship with the degree of damage to ventral and dorsal white matter pathways extending beyond the necrotic stroke lesion. Based on the dual stream model of language processing, we tested the hypothesis that semantic errors would be associated with ventral stream damage, whereas phonemic errors would be associated with dorsal stream damage, but not vice-versa. Multi-shell diffusion MRI was used to obtain kurtosis-based white matter tractography from 32 chronic stroke survivors. Using diffusion microstructural tissue modeling, we estimated axonal loss along the length of the inferior and superior longitudinal fasciculi (ILF and SLF), representing the main pathways in the ventral and dorsal streams, respectively. The frequency of semantic paraphasias was strongly associated with ILF axonal loss, whereas phonemic paraphasias were strongly associated with SLF axonal loss, but not vice versa. This dissociation between semantic and phonological processing is in agreement with the dual stream model of language processing and corroborates the concept that, during speech production, knowledge association (semantics) depends on the integrity of ventral, whereas form encoding (phonological encoding) is more localized to dorsal pathways. These findings also demonstrate the importance of the residual integrity of specific white matter pathways beyond regional gray matter damage for speech production.

ObjectiveTo test the hypothesis that severity of leukoaraiosis in the noninfarcted hemisphere at onset is associated with poorer language outcome after poststroke aphasia independently of volume of infarct, damage to 3 critical language areas (left inferior frontal gyrus, superior longitudinal fasciculus, and superior temporal gyrus), comorbid conditions, and time since stroke.MethodsIn this cross-sectional study, we evaluated naming outcome (>3 months after stroke) in 42 individuals who initially had aphasia after stroke. We rated leukoaraiosis in the right hemisphere 1 to 4 weeks from onset of stroke using the Cardiovascular Health Study rating scale. We evaluated associations between severity of leukoaraiosis and each measure of naming using Spearman correlations and evaluated the independent contributions of leukoaraiosis, lesion volume, months since onset, comorbid conditions, and damage to critical nodes of the language network on language outcomes using logistic regression. We also evaluated associations between dichotomously defined leukoaraiosis and language outcomes using χ2 tests.ResultsSeverity of leukoaraiosis at onset correlated with object naming (ρ = −0.56, p = 0.0008) and word fluency (ρ = −0.37, p = 0.01) outcomes. Severe leukoaraiosis was associated with failure to achieve the highest quartile of object naming and word fluency. Severity of leukoaraiosis was associated with degree of naming outcome with the use of both measures after controlling for lesion volume, months since stroke, comorbid conditions, and damage to specific locations.ConclusionNaming outcome after poststroke aphasia is influenced by the initial severity of right hemisphere leukoaraiosis independently of other variables. Degree of recovery from aphasia may depend on the integrity of the noninfarcted brain tissue.

Here we illustrate how investigation of individuals acutely after stroke, before structure/function reorganization through recovery or rehabilitation, can be helpful in answering questions about the role of specific brain regions in language functions. Although there is converging evidence from a variety of sources that the left posterior-superior temporal gyrus plays some role in spoken word comprehension, its precise role in this function has not been established. We hypothesized that this region is essential for distinguishing between semantically related words, because it is critical for linking the spoken word to the complete semantic representation. We tested this hypothesis in 127 individuals with 48 hours of acute ischemic stroke, before the opportunity for reorganization or recovery. We identified tissue dysfunction (acute infarct and/or hypoperfusion) in gray and white matter parcels of the left hemisphere, and we evaluated the association between rate of semantic errors in a word-picture verification tasks and extent of tissue dysfunction in each region. We found that after correcting for lesion volume and multiple comparisons, the rate of semantic errors correlated with the extent of tissue dysfunction in left posterior-superior temporal gyrus and retrolenticular white matter.

In most cases, aphasia is caused by strokes involving the left hemisphere, with more extensive damage typically being associated with more severe aphasia. The classical model of aphasia commonly adhered to in the Western world is the Wernicke-Lichtheim model. The model has been in existence for over a century, and classification of aphasic symptomatology continues to rely on it. However, far more detailed models of speech and language localization in the brain have been formulated. In this regard, the dual stream model of cortical brain organization proposed by Hickok and Poeppel is particularly influential. Their model describes two processing routes, a dorsal stream and a ventral stream, that roughly support speech production and speech comprehension, respectively, in normal subjects. Despite the strong influence of the dual stream model in current neuropsychological research, there has been relatively limited focus on explaining aphasic symptoms in the context of this model. Given that the dual stream model represents a more nuanced picture of cortical speech and language organization, cortical damage that causes aphasic impairment should map clearly onto the dual processing streams. Here, we present a follow-up study to our previous work that used lesion data to reveal the anatomical boundaries of the dorsal and ventral streams supporting speech and language processing. Specifically, by emphasizing clinical measures, we examine the effect of cortical damage and disconnection involving the dorsal and ventral streams on aphasic impairment. The results reveal that measures of motor speech impairment mostly involve damage to the dorsal stream, whereas measures of impaired speech comprehension are more strongly associated with ventral stream involvement. Equally important, many clinical tests that target behaviours such as naming, speech repetition, or grammatical processing rely on interactions between the two streams. This latter finding explains why patients with seemingly disparate lesion locations often experience similar impairments on given subtests. Namely, these individuals' cortical damage, although dissimilar, affects a broad cortical network that plays a role in carrying out a given speech or language task. The current data suggest this is a more accurate characterization than ascribing specific lesion locations as responsible for specific language deficits.5705668782001awx363media15705668782001.

Transcranial direct current stimulation (tDCS) is an innovative technique recently shown to improve language outcomes even in neurodegenerative conditions such as primary progressive aphasia (PPA), but the underlying brain mechanisms are not known. The present study tested whether the additional language gains with repetitive tDCS (over sham) in PPA are caused by changes in functional connectivity between the stimulated area (the left inferior frontal gyrus (IFG)) and the rest of the language network.We scanned 24 PPA participants (11 female) before and after language intervention (written naming/spelling) with a resting-state fMRI sequence and compared changes before and after three weeks of tDCS or sham coupled with language therapy. We correlated changes in the language network as well as in the default mode network (DMN) with language therapy outcome measures (letter accuracy in written naming).Significant tDCS effects in functional connectivity were observed between the stimulated area and other language network areas and between the language network and the DMN. TDCS over the left IFG lowered the connectivity between the above pairs. Changes in functional connectivity correlated with improvement in language scores (letter accuracy as a proxy for written naming) evaluated before and after therapy.These results suggest that one mechanism for anodal tDCS over the left IFG in PPA is a decrease in functional connectivity (compared to sham) between the stimulated site and other posterior areas of the language network. These results are in line with similar decreases in connectivity observed after tDCS over the left IFG in aging and other neurodegenerative conditions. Keywords: Primary progressive aphasia (PPA), Transcranial direct current stimulation (tDCS), Resting-state fMRI (rsfMRI), Functional connectivity, Neurodegenerative diseases

Auditory word comprehension is a cognitive process that involves the transformation of auditory signals into abstract concepts. Traditional lesion-based studies of stroke survivors with aphasia have suggested that neocortical regions adjacent to auditory cortex are primarily responsible for word comprehension. However, recent primary progressive aphasia and normal neurophysiological studies have challenged this concept, suggesting that the left temporal pole is crucial for word comprehension. Due to its vasculature, the temporal pole is not commonly completely lesioned in stroke survivors and this heterogeneity may have prevented its identification in lesion-based studies of auditory comprehension. We aimed to resolve this controversy using a combined voxel-based—and structural connectome—lesion symptom mapping approach, since cortical dysfunction after stroke can arise from cortical damage or from white matter disconnection. Magnetic resonance imaging (T1-weighted and diffusion tensor imaging-based structural connectome), auditory word comprehension and object recognition tests were obtained from 67 chronic left hemisphere stroke survivors. We observed that damage to the inferior temporal gyrus, to the fusiform gyrus and to a white matter network including the left posterior temporal region and its connections to the middle temporal gyrus, inferior temporal gyrus, and cingulate cortex, was associated with word comprehension difficulties after factoring out object recognition. These results suggest that the posterior lateral and inferior temporal regions are crucial for word comprehension, serving as a hub to integrate auditory and conceptual processing. Early processing linking auditory words to concepts is situated in posterior lateral temporal regions, whereas additional and deeper levels of semantic processing likely require more anterior temporal regions. 10.1093/brain/awx169_video1 awx169media1 5555638084001

Imaging studies have described hemodynamic activity during fear conditioning protocols with stimulus trains in which a visual conditioned stimulus (CS+) is paired with an aversive unconditioned stimulus (US, painful laser pulse) while another visual stimulus is unpaired (CS−). We now test the hypothesis that CS Event-Related Spectral Perturbations (ERSPs) are related to ratings of CS Expectancy (likelihood of pairing with the US), Valence (unpleasantness) and Salience (ability to capture attention). ERSP windows in EEG were defined by both time after the CS and frequency, and showed increased oscillatory power (Event Related Synchronization, ERS) in the delta/theta Windows (0–8 Hz) and the gamma Window (30–55 Hz). Decreased oscillatory power (Event Related Desynchronization – ERD) was found in alpha (8–14 Hz) and beta Windows (14–30 Hz). The delta/theta ERS showed a differential effect of CS+ versus CS− at Prefrontal, Frontal and Midline Channels, while alpha and beta ERD were greater at Parietal and Occipital Channels early in the stimulus train. The gamma ERS Window increased from Habituation to Acquisition over a broad area from Frontal and occipital electrodes. The CS Valence and Salience were greater for CS+ than CS−, and were correlated with each other and with the ERD at overlapping Channels, particularly in the alpha Window. Expectancy and CS Skin Conductance Response were greater for CS+ than CS− and were correlated with ERSP at fewer Channels than Valence or Salience. These results suggest that alpha ERSP activity during fear conditioning reflects Valence and Salience of the CSs more than conditioning per se. The CS Valence and Salience were correlated with each other and with ERSP in the alpha Window more commonly than in other windows. Delta/theta ERSP differentiates between CS+ and CS− over a Midline Channel at which ERSP is correlated with Expectancy ratings. Although, both Expectancy and CS Skin Conductance Response (SCR) were correlated with ERSP this correlation occurred at fewer and different Channels than those for Valence or Salience. These results suggest that ERSP activity is related to Valence and Salience of the CSs more than to conditioning per se.

We hypothesized that distinct acute right hemisphere lesions disrupt separate components of valuation and emotional response to winning and losing money and of emotional empathy in observing a partner win or lose money. We measured skin conductance response (SCR) and ratings of emotions when acute right hemisphere stroke patients or healthy controls won or lost money in roulette, or when they watched a partner win or lose. Our results showed that percentage of damage after stroke to right anterior insula and frontal operculum negatively correlated with both SCR to winning and losing and difference between rating wins versus losses.