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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.

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 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.

Introduction: As the population ages, the prevalence of cognitive impairment is expanding. Given the recent pandemic, there is a need for remote testing modalities to assess cognitive deficits in individuals with neurological disorders. Self-administered, remote, tablet-based cognitive assessments would be clinically valuable if they can detect and classify cognitive deficits as effectively as traditional in-person neuropsychological testing. Methods: We tested whether the Miro application, a tablet-based neurocognitive platform, measured the same cognitive domains as traditional pencil-and-paper neuropsychological tests. Seventy-nine patients were recruited and then randomized to either undergo pencil-and-paper or tablet testing first. Twenty-nine age-matched healthy controls completed the tablet-based assessments. We identified Pearson correlations between Miro tablet-based modules and corresponding neuropsychological tests in patients and compared scores of patients with neurological disorders with those of healthy controls using t tests. Results: Statistically significant Pearson correlations between the neuropsychological tests and their tablet equivalents were found for all domains with moderate (r > 0.3) or strong (r > 0.7) correlations in 16 of 17 tests (p < 0.05). All tablet-based subtests differentiated healthy controls from neurologically impaired patients by t tests except for the spatial span forward and finger tapping modules. Participants reported enjoyment of the tablet-based testing, denied that it provoked anxiety, and noted no preference between modalities. Conclusions: This tablet-based application was found to be widely acceptable to participants. This study supports the validity of these tablet-based assessments in the differentiation of healthy controls from patients with neurocognitive deficits in a variety of cognitive domains and across multiple neurological disease etiologies.

Background: Aphasia therapy is an effective approach to improve language function in chronic aphasia. However, it remains unclear what prognostic factors facilitate therapy response at the individual level. Here, we utilized data from the POLAR (Predicting Outcomes of Language Rehabilitation in Aphasia) trial to (a) determine therapy-induced change in confrontation naming and long-term maintenance of naming gains and (b) examine the extent to which aphasia severity, age, education, time postonset, and cognitive reserve predict naming gains at 1 week, 1 month, and 6 months posttherapy. Method: A total of 107 participants with chronic (≥ 12 months poststroke) aphasia underwent extensive case history, cognitive–linguistic testing, and a neuroimaging workup prior to receiving 6 weeks of impairment-based language therapy. Therapy-induced change in naming performance (measured as raw change on the 175-item Philadelphia Naming Test [PNT]) was assessed 1 week after therapy and at follow-up time points 1 month and 6 months after therapy completion. Change in naming performance over time was evaluated using paired t tests, and linear mixed-effects models were constructed to examine the association between prognostic factors and therapy outcomes. Results: Naming performance was improved by 5.9 PNT items (Cohen's d = 0.56, p < .001) 1 week after therapy and by 6.4 ( d = 0.66, p < .001) and 7.5 ( d = 0.65, p < .001) PNT items at 1 month and 6 months after therapy completion, respectively. Aphasia severity emerged as the strongest predictor of naming improvement recovery across time points; mild (ß = 5.85–9.02) and moderate (ß = 9.65–11.54) impairment predicted better recovery than severe (ß = 1.31–3.37) and very severe (ß = 0.20–0.32) aphasia. Age was an emergent prognostic factor for recovery 1 month (ß = −0.14) and 6 months (ß = −0.20) after therapy, and time postonset (ß = −0.05) was associated with retention of naming gains at 6 months posttherapy. Conclusions: These results suggest that therapy-induced naming improvement is predictable based on several easily measurable prognostic factors. Broadly speaking, these results suggest that prognostication procedures in aphasia therapy can be improved and indicate that personalization of therapy is a realistic goal in the near future. Supplemental Material: https://doi.org/10.23641/asha.22141829

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.

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.

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.

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.

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.

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.

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.

Most people with aphasia (PWA) improve in content of discourse over the first 6 months of stroke, but the extent to which increased content is compensatory, by learning to use more frequent or less complex words, is unknown. We hypothesized that PWA who improve in content units (CU; concepts produced by healthy speakers in describing the picture) in picture description show an increase in word frequency and decrease in articulatory complexity from acute stroke to 3 and 6 months. Methods: PWA Results: Compared to controls, PWA produced fewer CU (mean 19.4 vs 47.6; t (df81) = 7.9; p Conclusions: Improved content in discourse by aphasic individuals over the first 6 months after stroke may in part reflect compensation by selecting more frequent words or increased function words (e.g. prepositions - which are high frequency) to describe a picture. Those who improve in content show an increase in articulatory complexity of words, indicating that increased complexity reflects improvement.

Primary progressive aphasia (PPA) is a neurodegenerative syndrome characterized by progressive language deficits. There are three main variants of PPA – semantic (svPPA), logopenic (lvPPA), and nonfluent (nfvPPA) – that can be challenging to distinguish. Limb praxis may also be affected in PPA, but it is unclear whether different variants of PPA are associated with differences in gesture production. Prior research with neurotypical individuals indicates that the left temporal lobe is a critical locus of manipulable object and hand posture representations. Moreover, when imitating gestures, individuals whose strokes include the left temporal lobe show reduced benefit of gesture meaning and disproportionate impairment in hand posture as compared to arm kinematics. We tested the hypothesis that svPPA – who typically exhibit primarily temporal lobe atrophy – would differentially show these expected patterns of gesture imitation performance. Nineteen participants with PPA completed meaningful and meaningless gesture imitation tasks, and performance was scored for hand posture and arm kinematics accuracy. Generalized logistic mixed-effect regression models controlling for dementia severity showed overall benefits from gesture meaning, and greater impairments in hand posture than arm kinematics. We also found that svPPA participants were the most impaired in gesture imitation overall. Critically, there was also a significant three-way interaction of group, meaning, and gesture component: only svPPA participants showed relative impairments of hand posture for meaningful gestures as well as meaningless gestures. Thus, unlike lvPPA and nfvPPA, the hand postures of svPPA failed to benefit from gesture meaning. This research extends prior findings on the role of the temporal lobe in hand posture representations associated with manipulable objects, and is the first to indicate that there may be distinct gesture imitation patterns as a function of PPA variant. Characterizing componential gesture deficits in PPA may help to inform differential diagnosis, compensatory communication strategies, and cognitive praxis models of PPA.

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.

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: Progressive neurodegenerative impairment with central language features, primary progressive aphasia (PPA), can be further distinguished for many individuals into one of three variants: semantic, non-fluent/agrammatic, and logopenic variant PPA. Variants differ in their relative preservation and deficits of language skills, particularly in word finding and grammar. The majority of elicited language assessments used in this population focus on single noun and verb production, while modifiers and inflectional morphemes are far less commonly examined. AIMS: The purpose of the present study is to determine whether there was an interaction between PPA variant and production of high-frequency nouns, proper names, modifiers, and bound inflectional morphemes to better understand how the variants differ. METHODS & PROCEDURES: Forty-six people with PPA and 47 individuals with no known neurological diagnoses completed a morphosyntactic generation assessment designed to target differential production of high-frequency nouns, proper names, modifiers (number, size, color), and bound inflectional morphemes (plural -s and possessive ’s), the Morphosyntactic Generation test (MorGen). Performance is averaged for each of the seven morphosyntactic targets independently, resulting in seven separate performance scores. OUTCOMES & RESULTS: Individuals with PPA performed significantly more poorly than controls on the assessed morphemes in a repeated-measures analysis of variance, as well as on each morpheme considered independently via t-test. In a multivariable analysis of variance among PPA variants, the interaction of morpheme and PPA variant was significant, suggesting different variants produced the morphemes with a significantly different pattern of success. When morphemes were considered independently, only production of colour resulted in a significant difference between variants, driven by the performance of individuals with nfavPPA, who performed near-ceiling. When MorGen performance was used to predict PPA variant in a multinomial logistic regression the model was significant, with age, plural -s, noun, and number contributing significantly to the prediction. In a discriminate function analysis, classification of cases was best for agrammatic variant with 70% accuracy. CONCLUSIONS: Individuals with PPA, particularly semantic and logopenic variants, demonstrated difficulty on the MorGen compared to controls. The MorGen proved useful in predicting PPA variant. These findings highlight the potential benefit of examining a broader range of morphemes, particularly bound morphemes and modifiers, in addition to the more frequently investigated classes of nouns and verbs when understanding PPA.

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.

Background and AimNIHSS score is higher for left versus right hemisphere strokes of equal volumes. However, differences in each vascular territory have not been evaluated yet. We hypothesized that left versus right differences are driven by the middle cerebral artery (MCA) territory, and there is no difference between hemispheres for other vascular territories.MethodsThis study is based on data from 802 patients with evidence of acute or early subacute ischemic stroke. These patients had infarct restricted to one major arterial territory (MCA, n=437; PCA, n=209; ACA, n=21; vertebrobasilar, n=46) and received NIHSS and MRI at hospital admission. 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) and by lesion location (MCA or PCA).ResultsPatients 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). In addition, stroke volume and patient’s age significantly correlated with NIHSS.ConclusionRight MCA infarcts are larger than left MCA infarcts associated with a given NIHSS score, after accounting for other significant associations, such as patient’s age. 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.

Most naming error lesion-symptom mapping (LSM) studies have focused on semantic and/or phonological errors. Anomic individuals also produce unrelated word errors, which may be linked to semantic or modality-independent lexical deficits. To investigate the neural underpinnings of rarely-studied unrelated errors, we conducted LSM analyses in 100 individuals hospitalized with a left hemisphere stroke who completed imaging protocols and language assessments. We used least absolute shrinkage and selection operator regression to capture relationships between naming errors and dysfunctional brain tissue metrics (regional damage or hypoperfusion in vascular territories) in two groups: participants with and without impaired single-word auditory comprehension. Hypoperfusion—particularly within the parietal lobe—was an important error predictor, especially for the unimpaired group. In both groups, higher unrelated error proportions were associated with primarily ventral stream damage, the language route critical for processing meaning. Nonetheless, brain metrics implicated in unrelated errors were distinct from semantic error correlates.

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 (

Background and PurposeHydration at the time of stroke may impact functional outcomes. We sought to investigate the relationship between blood pressure, hydration status, and stroke severity in patients with acute ischemic stroke (AIS).MethodsWe evaluated hydration status, determined by blood urea nitrogen (BUN)/creatinine ratio, in consecutive patients with AIS from a single comprehensive stroke center. Baseline mean arterial pressure (MAP) was analyzed using a linear spline with a knot at 90 mmHg. Baseline stroke severity was defined based on admission NIH Stroke Scale scores (NIHSSS) and MRI diffusion-weighted imaging.ResultsAmong 108 eligible subjects, 55 (51%) presented in a volume contracted state. In adjusted models, in the total sample, for every 10 mmHg higher MAP up to 90 mmHg, NIHSSS was 2.8 points lower (p = 0.053), without further statistically significant association between MAP above 90 and NIHSSS. This relationship was entirely driven by the individuals in a volume contracted state: MAP was not associated with NIHSSS in individuals who were euvolemic. For individuals in a volume contracted state, each 10 mmHg higher MAP, up to 90 mmHg, was associated with 6.9 points lower NIHSSS (95% CI −11.1, −2.6). MAP values above 90 mmHg were not related to NIHSSS in either dehydrated or euvolemic patients.ConclusionsLower MAP contributes to more severe stroke in patients who are volume contracted, but not those who are euvolemic, suggesting that hydration status and blood pressure may jointly contribute to the outcome. Hydration status should be considered when setting blood pressure goals for patients with AIS.

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.

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.

Testing Procedures Influence Allocentric and Egocentric Neglect Associations Hemispatial visual neglect is common after right hemisphere (RH) stroke and can impact attention to the left side of view (egocentric) or the left side of objects irrespective of location (allocentric). Allocentric and egocentric neglect correlations have been reported as high as 0.80; however, others report low correlations and dissociations between them using the same task but with different administration procedures. To determine if divergent results are due to distinct procedures, we compared allocentric and egocentric neglect presence and severity between the two. Thirty-eight adults (21 female, age 65±15 years, 14±2 years education, 21 black/16 white) completed neglect testing within 10 days of RH stroke. Neglect testing comprised circling 10 complete circles (egocentric task) and crossing out 20 circles with gaps (10 left gaps, 10 right gaps; allocentric task). All participants completed testing once with allocentric and egocentric tasks on separate pages and once with both tasks on the same page. We used paired t -tests, Pearson correlations, and Fisher’s Exact test for analyses. Neglect severity did not differ across single- and separate-page conditions ( allocentric : t (32)=0.68, p =0.50; egocentric : t (36)=-1.27, p =0.21). Single- and separate-page severity scores were strongly associated ( allocentric : r =0.65, p egocentric : r =0.52, p =0.004). Allocentric and egocentric neglect severity were moderately associated for single-page ( r =0.45, p =0.008) but not separate-page ( r =0.10, p =0.60) conditions. Diagnosis of allocentric ( single-page : 6%, separate-page : 3%), egocentric ( single-page : 12%, separate-page : 9%), or allocentric and egocentric ( single-page : 27%, separate-page : 39%) neglect was not dependent on page condition ( p =0.75). To conclude, assessment procedures influenced association of allocentric and egocentric neglect severity but not categorical diagnosis, and presence of both appeared more common than either alone. Studies that reported high correlations between the allocentric and egocentric neglect on the same task may have included participants with lesions causing both types of neglect due to their size and/or location.