Transcranial Direct-Current Stimulation in Subacute Aphasia: A Randomized Controlled Trial.

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 No patients were withdrawn due to adverse events.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

The Company Prosodic Deficits Keep Following Right Hemisphere Stroke: A Systematic Review.

OBJECTIVES: The aim of this systematic review was to identify the presence and nature of relationships between specific forms of aprosodia (i.e., expressive and receptive emotional and linguistic prosodic deficits) and other cognitive-communication deficits and disorders in individuals with right hemisphere damage (RHD) due to stroke. METHODS: One hundred and ninety articles from 1970 to February 2020 investigating receptive and expressive prosody in patients with relatively focal right hemisphere brain damage were identified via database searches. RESULTS: Fourteen articles were identified that met inclusion criteria, passed quality reviews, and included sufficient information about prosody and potential co-occurring deficits. Twelve articles investigated receptive emotional aprosodia, and two articles investigated receptive linguistic aprosodia. Across the included studies, receptive emotional prosody was not systematically associated with hemispatial neglect, but did co-occur with deficits in emotional facial recognition, interpersonal interactions, or emotional semantics. Receptive linguistic processing was reported to co-occur with amusia and hemispatial neglect. No studies were found that investigated the co-occurrence of expressive emotional or linguistic prosodic deficits with other cognitive-communication impairments. CONCLUSIONS: This systematic review revealed significant gaps in the research literature regarding the co-occurrence of common right hemisphere disorders with prosodic deficits. More rigorous empirical inquiry is required to identify specific patient profiles based on clusters of deficits associated with right hemisphere stroke. Future research may determine whether the co-occurrences identified are due to shared cognitive-linguistic processes, and may inform the development of evidence-based assessment and treatment recommendations for individuals with cognitive-communication deficits subsequent to RHD.

Aprosodia Subsequent to Right Hemisphere Brain Damage: A Systematic Review and Meta-Analysis.

OBJECTIVE: To identify which aspects of prosody are negatively affected subsequent to right hemisphere brain damage (RHD) and to evaluate the methodological quality of the constituent studies. METHOD: Twenty-one electronic databases were searched to identify articles from 1970 to February 2020 by entering keywords. Eligibility criteria for articles included a focus on adults with acquired RHD, prosody as the primary research topic, and publication in a peer-reviewed journal. A quality appraisal was conducted using a rubric adapted from Downs and Black (1998). RESULTS: Of the 113 articles appraised as eligible and appropriate for inclusion, 71 articles were selected to undergo data extraction for both meta-analyses of population effect size estimates and qualitative synthesis. Across all domains of prosody, the effect estimate was g = 2.51 [95% CI (1.94, 3.09), t = 8.66, p < 0.0001], based on 129 contrasts between RHD and non-brain-damaged healthy controls (NBD), indicating a significant random effects model. This effect size was driven by findings in emotional prosody, g = 2.48 [95% CI (1.76, 3.20), t = 6.88, p < 0.0001]. Overall, studies of higher quality (rpb = 0.18, p < 0.001) and higher sample size/contrast ratio (rpb = 0.25, p < 0.001) were more likely to report significant differences between RHD and NBD participants. CONCLUSIONS: The results confirm consistent evidence for emotional prosody deficits in the RHD population. Inconsistent evidence was observed across linguistic prosody domains and pervasive methodological issues were identified across studies, regardless of their prosody focus. These findings highlight the need for more rigorous and sufficiently high-powered designs to examine prosody subsequent to RHD, particularly within the linguistic prosody domain.

An Efficient Bedside Measure Yields Prognostic Implications for Language Recovery in Acute Stroke Patients.

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.

Distinguishing logopenic from semantic & nonfluent variant primary progressive aphasia: Patterns of linguistic and behavioral correlations.

While language characteristics of logopenic variant primary progressive aphasia (lvPPA) are well-defined, behavioral characteristics are less understood. We investigated correlations between language and behavioral scores across three variants of primary progressive aphasia (PPA) and found language performance and behavioral disturbances are correlated in lvPPA, but not other PPA subtypes. Results suggest that unlike other PPA variants, patients diagnosed with lvPPA do not develop negative behaviors until language deficits are severe. This is consistent with the underlying neuropathology of lvPPA, Alzheimer's Disease. Such findings are crucial to clinical prognosis, especially when considering the progressive nature of this disease.

How can graph theory inform the dual-stream model of speech processing? a resting-state fMRI study of post-stroke aphasia.

The dual-stream model of speech processing has been proposed to represent the cortical networks involved in speech comprehension and production. Although it is arguably the prominent neuroanatomical model of speech processing, it is not yet known if the dual-stream model represents actual intrinsic functional brain networks. Furthermore, it is unclear how disruptions after a stroke to the functional connectivity of the dual-stream model's regions are related to specific types of speech production and comprehension impairments seen in aphasia. To address these questions, in the present study, we examined two independent resting-state fMRI datasets: (1) 28 neurotypical matched controls and (2) 28 chronic left-hemisphere stroke survivors with aphasia collected at another site. Structural MRI, as well as language and cognitive behavioral assessments, were collected. Using standard functional connectivity measures, we successfully identified an intrinsic resting-state network amongst the dual-stream model's regions in the control group. We then used both standard functional connectivity analyses and graph theory approaches to determine how the functional connectivity of the dual-stream network differs in individuals with post-stroke aphasia, and how this connectivity may predict performance on clinical aphasia assessments. Our findings provide strong evidence that the dual-stream model is an intrinsic network as measured via resting-state MRI, and that weaker functional connectivity of the hub nodes of the dual-stream network defined by graph theory methods, but not overall average network connectivity, is weaker in the stroke group than in the control participants. Also, the functional connectivity of the hub nodes predicted specific types of impairments on clinical assessments. In particular, the relative strength of connectivity of the right hemisphere's homologues of the left dorsal stream hubs to the left dorsal hubs versus right ventral stream hubs is a particularly strong predictor of post-stroke aphasia severity and symptomology.

Informational Masking in Aging and Brain-lesioned Individuals.

Auditory stream segregation and informational masking were investigated in brain-lesioned individuals, age-matched controls with no neurological disease, and young college-age students. A psychophysical paradigm known as rhythmic masking release (RMR) was used to examine the ability of participants to identify a change in the rhythmic sequence of 20-ms Gaussian noise bursts presented through headphones and filtered through generalized head-related transfer functions to produce the percept of an externalized auditory image (i.e., a 3D virtual reality sound). The target rhythm was temporally interleaved with a masker sequence comprising similar noise bursts in a manner that resulted in a uniform sequence with no information remaining about the target rhythm when the target and masker were presented from the same location (an impossible task). Spatially separating the target and masker sequences allowed participants to determine if there was a change in the target rhythm midway during its presentation. RMR thresholds were defined as the minimum spatial separation between target and masker sequences that resulted in 70.7% correct-performance level in a single-interval 2-alternative forced-choice adaptive tracking procedure. The main findings were (1) significantly higher RMR thresholds for individuals with brain lesions (especially those with damage to parietal areas) and (2) a left-right spatial asymmetry in performance for lesion (but not control) participants. These findings contribute to a better understanding of spatiotemporal relations in informational masking and the neural bases of auditory scene analysis.

Application of the dual stream model to neurodegenerative disease: Evidence from a multivariate classification tool in primary progressive aphasia.

Background: A clinical diagnosis of primary progressive aphasia relies on behavioral characteristics and patterns of atrophy to determine a variant: logopenic; nonfluent/agrammatic; or semantic. The dual stream model (Hickok & Poeppel, 2000; 2004; 2007; 2015) is a contemporary paradigm that has been applied widely to understand brain-behavior relationships; however, applications to neurodegenerative diseases like primary progressive aphasia are limited. Aims: The primary aim of this study is to determine if the dual stream model can be applied to a neurodegenerative disease, such as primary progressive aphasia, using both behavioral and neuroimaging data. Methods & Procedures: We analyzed behavioral and neuroimaging data to apply a multivariate classification tool (support vector machines) to determine if the dual stream model extends to primary progressive aphasia. Sixty-four individuals with primary progressive aphasia were enrolled (26 logopenic variant, 20 nonfluent/agrammatic variant, and 18 semantic variant) and administered four behavioral tasks to assess three linguistic domains (naming, repetition, and semantic knowledge). We used regions of interest from the dual stream model and calculated the cortical volume for gray matter regions and white matter structural volumes and fractional anisotropy. We applied a multivariate classification tool (support vector machines) to distinguish variants based on behavioral performance and patterns of atrophy. Outcomes & Results: Behavioral performance discriminates logopenic from semantic variant and nonfluent/agrammatic from semantic variant. Cortical volume distinguishes all three variants. White matter structural volumes and fractional anisotropy primarily distinguish nonfluent/agrammatic from semantic variant. Regions of interest that contribute to each classification in cortical and white matter analyses demonstrate alignment of logopenic and nonfluent/agrammatic variants to the dorsal stream, while the semantic variant aligns with the ventral stream. Conclusions: A novel implementation of an automated multivariate classification suggests that the dual stream model can be extended to primary progressive aphasia. Variants are distinguished by behavioral and neuroanatomical patterns and align to the dorsal and ventral streams of the dual stream model.

Aprosodia Following Focal Brain Damage: What's Right and What's Left?

PURPOSE: Hemispheric specialization for the comprehension and expression of linguistic and emotional prosody is typically attributed to the right hemisphere. This study used techniques adapted from meta-analysis to critically examine the strength of existing evidence for hemispheric lateralization of prosody following brain damage. METHOD: Twenty-one databases were searched for articles published from 1970 to 2020 addressing differences in prosody performance between groups defined by right hemisphere damage and left hemisphere damage. Hedges's g effect sizes were calculated for all possible prosody comparisons. Primary analyses summarize effects for four types: linguistic production, linguistic comprehension, emotion comprehension, and emotion production. Within each primary analysis, Hedges's g values were averaged across comparisons (usually from a single article) based on the same sample of individuals. Secondary analyses explore more specific classifications of comparisons. RESULTS: Out of the 113 articles investigating comprehension and production of emotional and linguistic prosody, 62 were deemed appropriate for data extraction, but only 21 met inclusion criteria, passed quality reviews, and provided sufficient information for analysis. Evidence from this review illustrates the heterogeneity of research methods and results from studies that have investigated aprosodia. This review provides inconsistent support for selective contribution of the two cerebral hemispheres to prosody comprehension and production; however, the strongest finding suggests that right hemisphere lesions disrupt emotional prosody comprehension more than left hemisphere lesions. CONCLUSION: This review highlights the impoverished nature of the existing literature; offers suggestions for future research; and highlights relevant clinical implications for the prognostication, evaluation, and treatment of aprosodia. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.20334987.

Neural correlates of syntactic comprehension: A longitudinal study.

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.

Independent contributions of structural and functional connectivity: Evidence from a stroke model.

Altered functional connectivity is related to severity of language impairment in poststroke aphasia. However, it is not clear whether this finding specifically reflects loss of functional coherence, or more generally, is related to decreased structural connectivity due to cortical necrosis. The aim of the current study was to investigate this issue by factoring out structural connectivity from functional connectivity measures and then relating the residual data to language performance poststroke. Ninety-seven participants with a history of stroke were assessed using language impairment measures (Auditory Verbal Comprehension and Spontaneous Speech scores from the Western Aphasia Battery-Revised) and MRI (structural, diffusion tensor imaging, and resting-state functional connectivity). We analyzed the association between functional connectivity and language and controlled for multiple potential neuroanatomical confounders, namely structural connectivity. We identified functional connections within the left hemisphere ventral stream where decreased functional connectivity, independent of structural connectivity, was associated with speech comprehension impairment. These connections exist in frontotemporal and temporoparietal regions. Our results suggest poor speech comprehension in aphasia is at least partially caused by loss of cortical synchrony in a left hemisphere ventral stream network and is not only reflective of localized necrosis or structural connectivity.

Clinical Implementation of Transcranial Direct Current Stimulation in Aphasia: A Survey of Speech-Language Pathologists.

Purpose The objectives of this study are to (a) identify speech-language pathologists' (SLPs') familiarity with transcranial direct current stimulation (tDCS), (b) quantify what SLPs consider necessary tDCS-related improvement in aphasia severity (i.e., tDCS enhancement; desired improvement above and beyond traditional behavioral therapy) to implement this adjuvant therapy for the clinical management of aphasia, and (c) identify concerns that could potentially hinder the clinical adoption of tDCS. Method A brief (14-question) survey was disseminated via e-mail and social media outlets targeting SLPs working with individuals with aphasia. Results Two hundred twenty-one individuals responded, and 155 valid surveys were analyzed. Seventy-one percent of participants reported familiarity with tDCS prior to taking the survey. Clinicians reported a desired mean enhancement of 22.9% additional points on the Western Aphasia Battery-Revised Aphasia Quotient. Importantly, 94.2% of SLPs reported concerns regarding the implementation of tDCS in clinical settings (i.e., safety, cost, administrative approval, reimbursement and training). Conclusions This is the first study to identify SLPs' perspectives regarding the clinical adoption of tDCS. Results suggest the majority of queried SLPs were familiar with tDCS prior to taking the survey. Although SLPs report a desired improvement of approximately 23% additional points on the Western Aphasia Battery-Revised Aphasia Quotient to consider adopting tDCS into practice, many SLPs reported concerns regarding clinical adoption. Responses from the current survey offer important preliminary evidence to begin bridging the research-to-practice gap as it relates to the clinical implementation of tDCS. Relatedly, these results will inform future clinical trials.

Leukoaraiosis Severity Predicts Rate of Decline in Primary Progressive Aphasia.

BACKGROUND: The rate of decline in language in Primary Progressive Aphasia (PPA) is highly variable and difficult to predict at baseline. The severity of diffuse white matter disease (leukoaraiosis), a marker of overall brain health, may substantially influence the rate of decline. AIMS: To test the hypothesis that leukoaraiosis is associated with a steeper decline in naming in PPA. METHODS AND PROCEDURES: In this longitudinal, observational study, 29 individuals with PPA (all variants) were administered the Boston Naming Test (BNT) at baseline and 1 year later. Two raters evaluated leukoaraiosis on baseline MRI, using the Cardiovascular Health Study scale. We evaluated the effects of leukoaraiosis severity, age, education, and baseline BNT on decline measured by change in BNT accuracy with multivariable linear regression. We also evaluated the effects of these variables on the dichotomized outcome of faster decline in BNT (worst 50%) versus slower decline (best 50%) using logistic regression. RESULTS: Together, leukoaraiosis, age, education, and baseline BNT score predicted change in BNT score (F(3, 25) = 8.12; p=0.0006). Change in BNT score was predicted by severity of leukoaraiosis (t =-3.81; p=0.001) and education (t= -2.45; p=0.022), independently of the other variables. When we dichotomized outcome into upper 50th percentile versus lower 50th percentile (faster decline), faster decline was predicted by all variables together (chi squared = 13.91; p = 0.008). However, only leukoaraiosis independently predicted outcome (OR=2.80; 95%CI: 1.11 to 7.03). For every 1 point increase on the CHS rating scale, there was 2.8 times higher chance of showing faster decline in naming. CONCLUSION: Severity of leukoaraiosis is associated with steeper decline in naming in PPA. This imaging marker can aide in prognosis and planning by caregivers and stratification of participants in clinical trials.

Right hemisphere ventral stream for emotional prosody identification: Evidence from acute stroke.

OBJECTIVE: To 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. METHODS: Patients 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. RESULTS: The overall emotion identification model was significant (adjusted r 2 = 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 r 2 = 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. CONCLUSIONS: Right 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.

Neural processing critical for distinguishing between speech sounds.

We aimed to identify neural regions where ischemia acutely after stroke is associated with impairment in phoneme discrimination, and to determine whether such deficits are associated with impairment of spoken word comprehension. We evaluated 33 patients within 48 h of left hemisphere ischemic stroke onset with tests of phoneme discrimination and word-picture matching. We identified Pearson correlations between accuracy in phoneme discrimination and accuracy of word comprehension and identified areas where the percentage of infarcted tissue was associated with severity of phoneme discrimination deficit. We found that 54% had deficits in phoneme discrimination relative to healthy controls. Accuracy in phoneme discrimination correlated with accuracy on word comprehension tests. Damage to left intraparietal sulcus and hypoperfusion and/or infarct of left superior temporal gyrus were associated with phoneme discrimination deficits acutely, although patients with these lesions showed improvement or resolution of the deficit by six months.