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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.

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.

Background and Purpose: Left hemisphere stroke often results in a variety of language deficits due to varying patterns of damage to language networks. The Cookie Theft picture description task, a classic, quick bedside assessment, has been shown to quantify narrative speech reliably. In this study, we utilized diffusion tensor imaging (DTI) to assess language network white matter tract correlates of lexical-semantic and syntactic impairments longitudinally., Methods: Twenty-eight patients with mild to severe language impairments after left hemispheric lobar and/or subcortical ischemic stroke underwent the Cookie Theft picture description test and DTI up to three different time points: within the first three months, six months and twelve months after stroke. Dorsal and ventral stream language pathways were segmented to obtain DTI integrity metrics of both hemispheres. Multivariable regression models and partial correlation analyses adjusted for age, education, and lesion load were conducted to evaluate the temporal DTI profile of the white matter microstructural integrity of the language tracts as neural correlates of narrative speech within the first year after stroke., Results: Among all the major language white matter pathways, the integrity of the left arcuate (AF), inferior fronto-occipital, and inferior longitudinal fasciculi (ILF) were related to picture description performance. After FDR correction, left ILF fractional anisotropy correlated with syntactic cohesiveness (r=0.85,p=0.00087) within the first three months after stroke, whereas at one year post-stroke, the strongest correlations were found between lexical-semantic performance and left AF radial diffusivity (r = -0.71, p = 0.00065)., Conclusion: Our study provides a temporal profile of associations between the integrity of the main language pathways and lexical semantics and syntactic impairments in left hemispheric strokes., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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 the 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, and seizures resulting from stroke. The author focuses on treatments supported by randomized controlled trials (RCTs), from the 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.

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., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

We studied 156 individuals with acute, right hemisphere ischemic stroke on a battery of hemispatial neglect tests to distinguish between viewer-centered and stimulus-centered neglect and MRI diffusion weighted imaging. We identified the relative contributions of age, total lesion volume, and damage to subcortical and cortical grey matter regions as well as white matter tracts to both the severity and presence of significant viewer-centered and stimulus-centered neglect, using multivariable regression tests. We found that age, volume of lesion, and percent damage to the regions of interest were each independently associated with the severity of viewer-centered neglect (r 2  = .31; p < .0001). However, only age (t = 3.20; p = .002) and percent damage to the angular gyrus (t = 2.63, p = .010), a dorsal stream area, predicted severity of viewer-centered neglect independently of the other variables. The same variables predicted the presence of significant viewer-centered neglect. In contrast, these variables did not significantly predict the severity of stimulus-centered neglect. However, we found that percent damage to ventral stream regions of interest (middle temporal gyrus, inferior temporal gyrus, fusiform gyrus, inferior frontal occipital gyrus, sagittal stratum, along with total infarct volume were associated with the presence of significant stimulus-centered neglect (pseudo r 2  = .70, p < .0004). Only percent damage to right inferior temporal gyrus predicted stimulus-centered neglect independently of the other variables (p = .018)., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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., (© 2019 American Academy of Neurology.)

Background and Purpose- Stroke is the leading cause of disability in United States, and aphasia is a common sequela after a left hemisphere stroke. Functional imaging and brain stimulation studies show that right hemisphere structures are detrimental to aphasia recovery but evidence from diffusion tensor imaging is lacking. We investigated the role of homologous language pathways in naming recovery after left hemispheric stroke. Methods- Patients with aphasia after a left hemispheric stroke underwent naming assessment using the Boston Naming Test and diffusion tensor imaging at the acute and chronic time points. We analyzed diffusion tensor imaging of right arcuate fasciculus and frontal aslant tracts. We used Wilcoxon rank-sum test to evaluate structural lateralization patterns and partial Spearman correlation/multivariate generalized linear model to determine the role of right arcuate fasciculus and frontal aslant tracts in naming recovery after controlling for confounders. Results were corrected for multiple comparisons. Results- On average, the structural integrity of left language pathways deteriorated more than their right homologs, such that there was rightward lateralization in the chronic stage. Regression/correlation analyses showed that greater preservation of tract integrity of right arcuate fasciculus was associated with poorer naming recovery. Conclusions- Our study provides preliminary evidence that preservation of right homologs of language pathways is associated with poor recovery of naming after a left hemispheric stroke, consistent with previous evidence that maintaining greater reliance on left hemisphere structures is associated with better language recovery.

Predictors of treatment effects allow individual tailoring of treatment characteristics, thereby saving resources and optimizing outcomes. Electrical stimulation coupled with language intervention has shown promising results in improving language performance in individuals with Primary Progressive Aphasia (PPA). The current study aimed to identify language and cognitive variables associated with response to therapy consisting of language intervention combined with transcranial direct current stimulation (tDCS). Forty individuals with PPA received written naming/spelling intervention combined with anodal tDCS or Sham, using a between-subjects, randomized design, with intervention delivered over a period of 3 weeks. Participants were assessed using a battery of neuropsychological tests before and after each phase. We measured letter accuracy during spelling of trained and untrained words, before, immediately after, 2 weeks, and 2 months after therapy. We used step-wise regression methods to identify variables amongst the neuropsychological measures and experimental factors that were significantly associated with therapy outcomes at each time-point. For trained words, improvement was related to pre-therapy scores, in RAVLT (5 trials sum), pseudoword spelling, object naming, digit span backward, spatial span backward and years post symptom onset. Regarding generalization to untrained words, improvement in spelling was associated with pseudoword spelling, RAVLT proactive interference, RAVLT immediate recall. Generalization effects were larger under tDCS compared to Sham at the 2-month post training measurement. We conclude that, for trained words, patients who improve the most are those who retain for longer language skills such as sublexical spelling processes (phoneme-to-grapheme correspondences) and word retrieval, and other cognitive functions such as executive functions and working memory, and those who have a better learning capacity. Generalization to untrained words occurs through improvement in knowledge of phoneme-to-grapheme correspondences. Furthermore, tDCS enhances the generalizability and duration of therapy effects., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose The 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. Method A 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. Results Preliminary 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. Conclusions The 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.

Advanced imaging studies in neurodegenerative disease have yielded new insights into subtypes of disease, progression of disease in various brain regions, and changes in structural and functional connectivity between brain regions related to symptom progression. However, few studies have revealed imaging markers at baseline that correlate with rate or degree of decline in function. Here we tested the hypothesis that imaging features at baseline correlate with outcome of naming in primary progressive aphasia. We obtained longitudinal multimodal imaging in 15 individuals with primary progressive aphasia at the same time points as assessment of naming. We found that functional connectivity between particular brain regions (measured with resting state functional connectivity magnetic resonance imaging) is strongly associated with accuracy of naming 21 months later, independently of baseline severity of naming impairment. These data indicate that functional connectivity may carry information about later performance in naming, and is potentially useful for refining prognosis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Parkinson's disease is a genetically complex disorder. Multiple genes have been shown to contribute to the risk of Parkinson's disease, and currently 90 independent risk variants have been identified by genome-wide association studies. Thus far, a number of genes (including SNCA, LRRK2, and GBA) have been shown to contain variability across a spectrum of frequency and effect, from rare, highly penetrant variants to common risk alleles with small effect sizes. Variants in GBA, encoding the enzyme glucocerebrosidase, are associated with Lewy body diseases such as Parkinson's disease and Lewy body dementia. These variants, which reduce or abolish enzymatic activity, confer a spectrum of disease risk, from 1.4- to >10-fold. An outstanding question in the field is what other genetic factors that influence GBA-associated risk for disease, and whether these overlap with known Parkinson's disease risk variants. Using multiple, large case-control datasets, totalling 217 165 individuals (22 757 Parkinson's disease cases, 13 431 Parkinson's disease proxy cases, 622 Lewy body dementia cases and 180 355 controls), we identified 1691 Parkinson's disease cases, 81 Lewy body dementia cases, 711 proxy cases and 7624 controls with a GBA variant (p.E326K, p.T369M or p.N370S). We performed a genome-wide association study and analysed the most recent Parkinson's disease-associated genetic risk score to detect genetic influences on GBA risk and age at onset. We attempted to replicate our findings in two independent datasets, including the personal genetics company 23andMe, Inc. and whole-genome sequencing data. Our analysis showed that the overall Parkinson's disease genetic risk score modifies risk for disease and decreases age at onset in carriers of GBA variants. Notably, this effect was consistent across all tested GBA risk variants. Dissecting this signal demonstrated that variants in close proximity to SNCA and CTSB (encoding cathepsin B) are the most significant contributors. Risk variants in the CTSB locus were identified to decrease mRNA expression of CTSB. Additional analyses suggest a possible genetic interaction between GBA and CTSB and GBA p.N370S induced pluripotent cell-derived neurons were shown to have decreased cathepsin B expression compared to controls. These data provide a genetic basis for modification of GBA-associated Parkinson's disease risk and age at onset, although the total contribution of common genetics variants is not large. We further demonstrate that common variability at genes implicated in lysosomal function exerts the largest effect on GBA associated risk for disease. Further, these results have implications for selection of GBA carriers for therapeutic interventions., (Published by Oxford University Press on behalf of the Guarantors of Brain 2019. This work is written by US Government employees and is in the public domain in the US.)

Background: Findings from several studies have indicated that participants with nfvPPA and participants with svPPA exhibit different patterns on action and object naming tasks, while other recent studies have found that neither participants with nfvPPA nor participants with svPPA show a significant difference in accuracy between object naming and action naming., Aims: The goal of this study was to test the hypothesis that relative action naming impairment is associated with grammatical ability in PPA, rather than a specific subtype of PPA., Methods & Procedures: Thirty-four participants with PPA completed the Boston Naming Test, the Action Naming subtest of the Boston Diagnostic Aphasia Examination, and the Northwestern Anagram Test, which was used to measure grammatical ability. Z -scores for the two naming tasks were calculated based on normative data from unimpaired controls. For each participant with PPA, the relative action naming impairment was calculated by subtracting the object naming z -score from the action naming z -score. Linear regression analysis was then used to evaluate the role of grammatical ability as a predictor of relative action naming impairment, while controlling for age, education, cognitive ability (as measured by the Montreal Cognitive Assessment), and semantic ability (as measured by the Pyramids and Palm Trees test). The interaction between grammatical ability and each control variable was also examined., Outcomes & Results: The main effect of grammatical ability was a significant predictor of relative action naming impairment, while none of the control variables was a significant predictor. However, the interaction between grammatical ability and semantic ability was also significant., Conclusions: Individuals who have both grammatical impairment and semantic impairment have the largest relative action naming impairment. These individuals may benefit from a treatment that focuses on the retrieval of verbs and their arguments.

MR Fingerprinting (MRF)-based Arterial-Spin-Labeling (ASL) has the potential to measure multiple parameters such as cerebral blood flow (CBF), bolus arrival time (BAT), and tissue T 1 in a single scan. However, the previous reports have only demonstrated a proof-of-principle of the technique but have not examined the performance of the sequence in the context of key imaging parameters. Furthermore, there has not been a study to directly compare the technique to clinically used perfusion method of dynamic-susceptibility-contrast (DSC) MRI. The present report consists of two studies. In the first study (N = 8), we examined the dependence of MRF-ASL sequence on TR time pattern. Ten different TR patterns with a range of temporal characteristics were examined by both simulations and experiments. The results revealed that there was a significance dependence of the sequence performance on TR pattern (p < 0.001), although there was not a single pattern that provided dramatically improvements. Among the TR patterns tested, a sinusoidal pattern with a period of 125 TRs provided an overall best estimation in terms of spatial consistency. These experimental observations were consistent with those of numerical simulations. In the second study (N = 8), we compared MRF-ASL results with those of DSC MRI. It was found that MRF-ASL and DSC MRI provided highly comparable maps of cerebral blood flow (CBF) and bolus-arrival-time (BAT), with spatial correlation coefficients of 0.79 and 0.91, respectively. However, in terms of quantitative values, BAT obtained with MRF-ASL was considerably lower than that from DSC (p < 0.001), presumably because of the differences in tracer characteristics in terms of diffusible versus intravascular tracers. Test-retest assessment of MRF-ASL MRI revealed that the spatial correlations of parametric maps were 0.997, 0.962, 0.746 and 0.863 for B 1 + , T 1 , CBF, and BAT, respectively. MRF-ASL is a promising technique for assessing multiple perfusion parameters simultaneously without contrast agent., (© 2019 John Wiley & Sons, Ltd.)

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., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

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 50 th percentile versus lower 50 th 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., Competing Interests: Declaration of Interest Statement The authors have no potential conflicts of interest to report.

Background: Individuals with primary progressive aphasia (PPA) develop visuospatial deficits over time, and those with logopenic variant (lvPPA) are at greatest risk of developing such deficits. However, not all previous studies of visuospatial deficits in PPA have ensured equivalent duration of disease across variants and few have measured deficits longitudinally., Aims: The aims of our study were to: 1) investigate differences in baseline visuomotor figure construction, visual figure delayed recall, and figure recognition in PPA variants with similar symptom duration at baseline, and 2) explore patterns of decline in these areas., Methods & Procedures: Ninety-three individuals with PPA [39 lvPPA, 24 nonfluent agrammatic PPA (nfaPPA), and 30 semantic variant PPA (svPPA)] were administered the Benson Complex Figure Copy, Benson Complex Figure Delay (Recall), and Benson Figure Recognition. Thirty individuals completed this testing 3 to 47 months post baseline., Outcome & Results: Participants with lvPPA and svPPA showed lower mean scores than those with nfaPPA on visual figure delayed recall at baseline, even though there were no differences in estimated time from disease onset or correlation with disease severity as reflected by naming performance, F (2, 90) = 5.78, p < .004. Those with nfaPPA performed significantly better than those with lvPPA, Tukey HSD p < .05, and those with svPPA, Tukey HSD p < .01. There were no differences between variants in rate of decline in visuomotor figure construction, visual figure delayed recall, and figure recognition., Conclusions: These findings revealed relatively spared visuospatial memory in nfaPPA, which may aid in the differential diagnosis of PPA and contribute to designing therapy or compensatory strategies., Competing Interests: Disclosure Statement No potential conflict of interest was reported by the authors.

Non-fluent speech is one of the most common impairments in post-stroke aphasia. The rehabilitation of non-fluent speech in aphasia is particularly challenging as patients are rarely able to produce and practice fluent speech production. Speech entrainment is a behavioural technique that enables patients with non-fluent aphasia to speak fluently. However, its mechanisms are not well understood and the level of improved fluency with speech entrainment varies among individuals with non-fluent aphasia. In this study, we evaluated the behavioural and neuroanatomical factors associated with better speech fluency with the aid of speech entrainment during the training phase of speech entrainment. We used a lesion-symptom mapping approach to define the relationship between chronic stroke location on MRI and the number of different words per second produced during speech entrainment versus picture description spontaneous speech. The behavioural variable of interest was the speech entrainment/picture description ratio, which, if ≥1, indicated an increase in speech output during speech entrainment compared to picture description. We used machine learning (shallow neural network) to assess the statistical significance and out-of-sample predictive accuracy of the neuroanatomical model, and its regional contributors. We observed that better assisted speech (higher speech entrainment/picture description ratio) was achieved by individuals who had preservation of the posterior middle temporal gyrus, inferior fronto-occipital fasciculus and uncinate fasciculus, while exhibiting lesions in areas typically associated with non-fluent aphasia, such as the superior longitudinal fasciculus, precentral, inferior frontal, supramarginal and insular cortices. Our findings suggest that individuals with dorsal stream damage but preservation of ventral stream structures are more likely to achieve more fluent speech with the aid of speech entrainment compared to spontaneous speech. This observation provides insight into the mechanisms of non-fluent speech in aphasia and has potential implications for future research using speech entrainment for rehabilitation of non-fluent aphasia., (© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We sought to determine the underlying pathophysiology relating white matter hyperintensities to chronic aphasia severity. We hypothesized that: (i) white matter hyperintensities are associated with damage to fibres of any length, but to a higher percentage of long-range compared to mid- and short-range intracerebral white matter fibres; and (ii) the number of long-range fibres mediates the relationship between white matter hyperintensities and chronic post-stroke aphasia severity. We measured the severity of periventricular and deep white matter hyperintensities and calculated the number and percentages of short-, mid- and long-range white matter fibres in 48 individuals with chronic post-stroke aphasia. Correlation and mediation analyses were performed to assess the relationship between white matter hyperintensities, connectome fibre-length measures and aphasia severity as measured with the aphasia quotient of the Western Aphasia Battery-Revised (WAB-AQ). We found that more severe periventricular and deep white matter hyperintensities correlated with a lower proportion of long-range fibres (r = -0.423, P = 0.003 and r = -0.315, P = 0.029, respectively), counterbalanced by a higher proportion of short-range fibres (r = 0.427, P = 0.002 and r = 0.285, P = 0.050, respectively). More severe periventricular white matter hyperintensities also correlated with a lower proportion of mid-range fibres (r = -0.334, P = 0.020), while deep white matter hyperintensities did not correlate with mid-range fibres (r = -0.169, P = 0.250). Mediation analyses revealed: (i) a significant total effect of periventricular white matter hyperintensities on WAB-AQ (standardized beta = -0.348, P = 0.008); (ii) a non-significant direct effect of periventricular white matter hyperintensities on WAB-AQ (P > 0.05); (iii) significant indirect effects of more severe periventricular white matter hyperintensities on worse aphasia severity mediated in parallel by fewer long-range fibres (effect = -6.23, bootstrapping: standard error = 2.64, 95%CI: -11.82 to -1.56) and more short-range fibres (effect = 4.50, bootstrapping: standard error = 2.59, 95%CI: 0.16 to 10.29). We conclude that small vessel brain disease seems to affect chronic aphasia severity through a change of the proportions of long- and short-range fibres. This observation provides insight into the pathophysiology of small vessel brain disease, and its relationship with brain health and chronic aphasia severity., (© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

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 (r 2  = 0.91, p = 0.006) measured at two time points, as well as between control CVR (r 2  = 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 (r 2  = 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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.

Agrammatism in aphasia is not a homogeneous syndrome, but a characterization of a nonuniform set of language behaviors in which grammatical markers and complex syntactic structures are omitted, simplified, or misinterpreted. In a sample of 71 left-hemisphere stroke survivors, syntactic processing was quantified with the Northwestern Assessment of Verbs and Sentences (NAVS). Classification analyses were used to assess the relation between NAVS performance and morphosyntactically reduced speech in picture descriptions. Voxel-based and connectivity-based lesion-symptom mapping were applied to investigate neural correlates of impaired syntactic processing. Despite a nonrandom correspondence between NAVS performance and morphosyntactic production deficits, there was variation in individual patterns of syntactic processing. Morphosyntactically reduced production was predicted by lesions to left-hemisphere inferior frontal cortex. Impaired verb argument structure production was predicted by damage to left-hemisphere posterior superior temporal and angular gyrus, as well as to a ventral pathway between temporal and frontal cortex. Damage to this pathway was also predictive of impaired sentence comprehension and production, particularly of noncanonical sentences. Although agrammatic speech production is primarily predicted by lesions to inferior frontal cortex, other aspects of syntactic processing rely rather on regional integrity in temporoparietal cortex and the ventral stream., (© 2019 Wiley Periodicals, Inc.)

Molecular genetic research provides unprecedented opportunities to examine genotype-phenotype correlations underlying complex syndromes. To investigate pathogenic mutations and genotype-phenotype relationships in diverse neurodegenerative conditions, we performed a rare variant analysis of damaging mutations in autopsy-confirmed neurodegenerative cases from the Johns Hopkins Brain Resource Center (n = 1243 patients). We used NeuroChip genotyping and C9orf72 hexanucleotide repeat analysis to rapidly screen our cohort for disease-causing mutations. In total, we identified 42 individuals who carried a pathogenic mutation in LRRK2, GBA, APP, PSEN1, MAPT, GRN, C9orf72, SETX, SPAST, or CSF1R, and we provide a comprehensive description of the diverse clinicopathological features of these well-characterized cases. Our study highlights the utility of high-throughput genetic screening arrays to establish a molecular diagnosis in individuals with complex neurodegenerative syndromes, to broaden disease phenotypes and to provide insights into unexpected disease associations., (Published by Elsevier Inc.)

Purpose Our goal was to evaluate an updated version of the "Cookie Theft" picture by obtaining norms based on picture descriptions by healthy controls for total content units (CUs), syllables per CU, and the ratio of left-right CUs. In addition, we aimed to compare these measures from healthy controls to picture descriptions obtained from individuals with poststroke aphasia and primary progressive aphasia (PPA) to assess whether these measures can capture impairments in content and efficiency of communication. Method Using an updated version of this picture, we analyzed descriptions from 50 healthy controls to develop norms for numbers of syllables, total CUs, syllables per CU, and left-right CU. We provide preliminary data from 44 individuals with aphasia (19 with poststroke aphasia and 25 with PPA). Results A total of 96 CUs were established based on the written transcriptions of spoken picture descriptions of the 50 control participants. There was a significant effect of group on total CUs, syllables, syllables per CU, and left-right CUs. The poststroke participants produced significantly fewer total CU and syllables than those with PPA. Each aphasic group produced significantly fewer total CUs, fewer syllables, more syllables per CU, and lower left-right CUs (indicating a right-sided bias) compared to controls. Conclusions Results show that the measures of numbers of syllables, total CUs, syllables per CU, and left-right CUs can distinguish language output of individuals with aphasia from controls and capture impairments in content and efficiency of communication. A limitation of this study is that we evaluated only 44 individuals with aphasia. In the future, we will evaluate other measures, such as CUs per minute, lexical variability, grammaticality, and ratio of nouns to verbs. Supplemental Material https://doi.org/10.23641/asha.7015223.

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., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Deficits in lexical retrieval are commonly observed in individuals with post-stroke aphasia. Successful lexical retrieval is related to lexical diversity, lexical sophistication, and phonological word properties; however, the crucial brain regions supporting these different features are not fully understood. We performed MRI-based lesion symptom mapping in 58 individuals with a chronic left hemisphere stroke to assess how regional damage relates to spoken discourse-extracted measures of lexical diversity, lexical sophistication, and phonological word properties. For discourse transcription and word feature analysis, we used the Computerized Language Analysis (CLAN) program, Stanford Core Natural Language Processing, Irvine Phonotactic Online Dictionary, Lexical Complexity Analyzer, and Gramulator. Lesions involving the left posterior insula and supramarginal gyri and inferior fronto-occipital fasciculus were significant predictors of utterances with, on average, lower lexical diversity. Low lexical sophistication was associated with damage to the left pole of the superior temporal gyrus. Production of words with lower phonological complexity (fewer phonemes, higher phonological similarity) was associated with damage to the left supramarginal gyrus. Our findings indicate that discourse-extracted features of lexical retrieval depend on the integrity of specific brain regions involving insular and peri-Sylvian areas. The identified regions provide insight into potentially underlying mechanisms of lexically diverse, sophisticated and phonologically complex words produced during discourse., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Transcranial magnetic stimulation (TMS) is an accessible, non-invasive technique to study cortical function in vivo. TMS studies have provided important pathophysiological insights across a range of neurodegenerative disorders and enhanced our understanding of brain reorganisation after stroke. In neurodegenerative disease, TMS has provided novel insights into the function of cortical output cells and the related intracortical interneuronal networks. Characterisation of cortical hyperexcitability in amyotrophic lateral sclerosis and altered motor cortical function in frontotemporal dementia, demonstration of cholinergic deficits in Alzheimer's disease and Parkinson's disease are key examples where TMS has led to advances in understanding of disease pathophysiology and potential mechanisms of propagation, with the potential for diagnostic applications. In stroke, TMS methodology has facilitated the understanding of cortical reorganisation that underlie functional recovery. These insights are critical to the development of effective and targeted rehabilitation strategies in stroke. The present review will provide an overview of cortical function measures obtained using TMS and how such measures may provide insight into brain function. Through an improved understanding of cortical function across a range of neurodegenerative disorders, and identification of changes in neural structure and function associated with stroke that underlie clinical recovery, more targeted therapeutic approaches may now be developed in an evolving era of precision medicine., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Speech and swallowing utilize overlapping anatomy and are thus inherently related processes. We sought to identify common neural mechanisms between risk of swallowing dysfunction and apraxia of speech (AOS). This was a retrospective analysis using data from a prospectively collected cohort. Left hemisphere stroke patients (68 subjects) tested with the Apraxia Battery for Adults II, a swallow screen, and MRI were included in the study. Main outcome measure was the presence of AOS or aspiration risk after stroke. We identified a significant association between AOS measures and increased aspiration risk (defined by failed swallow screen; p = 0.04; OR 5.2). Lesions in pars opercularis of Broca's area (BA 44) were associated with both AOS (p = 0.044; OR 9.7) and increased aspiration risk (p = 0.04; OR 5) but deficits rarely co-occurred in the same cases. Lesions in left premotor cortex (BA 6) were not significantly associated with increased aspiration risk (p = 0.06; OR 3.3) but were significantly associated with AOS (p = 0.008; OR 7). Impaired swallowing function was also associated with lesions in Wernicke's area (BA 22; p = 0.05; OR 3.5) and pars triangularis (BA 45; p = 0.02; OR 6.8). AOS and risk of aspiration are associated in patients with acute left hemisphere stroke. Acute infarct in the pars opercularis of Broca's area is associated with both deficits, though they rarely co-occur in the same individual. The co-occurrence of AOS and risk of aspiration likely reflects dependence on closely related neural structures.

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.

Introduction: Transcranial direct current stimulation (tDCS) has been recently shown to improve language outcomes in primary progressive aphasia (PPA) but most studies are small and the influence of PPA variant is unknown., Methods: Thirty-six patients with PPA participated in a randomized, sham-controlled, double-blind, within-subject crossover design for 15 daily sessions of stimulation coupled with written naming/spelling therapy. Outcome measures were letter accuracy of treated and untreated words immediately after and at 2 weeks and 2 months posttreatment., Results: tDCS treatment was more effective than sham: gains for treated words were maintained 2 months posttreatment; gains from tDCS also generalized to untreated words and were sustained 2 months posttreatment. Different effects were obtained for each PPA variant, with no tDCS advantage for semantic variant PPA., Discussion: The study supports using tDCS as an adjunct to written language interventions in individuals with logopenic or nonfluent/agrammatic PPA seeking compensatory treatments in clinical settings.

Objective: To 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., Methods: In 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 χ 2 tests., Results: Severity 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., Conclusion: Naming 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., (© 2018 American Academy of Neurology.)

The intent and feelings of the speaker are often conveyed less by what they say than by how they say it, in terms of the affective prosody - modulations in pitch, loudness, rate, and rhythm of the speech to convey emotion. Here we propose a cognitive architecture of the perceptual, cognitive, and motor processes underlying recognition and generation of affective prosody. We developed the architecture on the basis of the computational demands of the task, and obtained evidence for various components by identifying neurologically impaired patients with relatively specific deficits in one component. We report analysis of performance across tasks of recognizing and producing affective prosody by four patients (three with right hemisphere stroke and one with frontotemporal dementia). Their distinct patterns of performance across tasks and quality of their abnormal performance provides preliminary evidence that some of the components of the proposed architecture can be selectively impaired by focal brain damage., (Copyright © 2018 Elsevier Inc. All rights reserved.)

At least three distinct variants of primary progressive aphasia (PPA) have been described, but they are difficult to distinguish early in the course, when individuals experience primarily anomia. People with svPPA are often the hardest to care for, because they have impaired comprehension of words and objects and often have negative changes in comportment. We sought to identify an early marker of semantic variant primary progressive aphasia (svPPA) and to enhance the understanding of the semantic deficit in svPPA. We hypothesized that the pattern of eye tracking in a word picture matching task can differentiate svPPA from other variants and can predict which participants with unclassifiable PPA will progress to svPPA. We tested 19 individuals with PPA on a word picture matching task with eye tracking. We found that individuals with svPPA were less accurate than other variants when the foils were semantic coordinates (horse-cow) or schematically related (horse-saddle), but not when they were thematically related (saw-horse) or unrelated. Moreover, even in the condition in which they were highly accurate (unrelated foils) they looked much more often to the foils and for longer, than other variants or controls. Unclassifiable PPA participants who eventually developed svPPA showed the same pattern. This abnormal pattern was associated with atrophy in bilateral temporal poles., (Copyright © 2018. Published by Elsevier Ltd.)

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.

Impaired expression of emotion through pitch, loudness, rate, and rhythm of speech (affective prosody) is common and disabling after right hemisphere (RH) stroke. These deficits impede all social interactions. Previous studies have identified cortical areas associated with impairments of expression, recognition, or repetition of affective prosody, but have not identified critical white matter tracts. We hypothesized that: (1) differences across patients in specific acoustic features correlate with listener judgment of affective prosody and (2) these differences are associated with infarcts of specific RH gray and white matter regions. To test these hypotheses, 41 acute ischemic RH stroke patients had MRI diffusion weighted imaging and described a picture. Affective prosody of picture descriptions was rated by 21 healthy volunteers. We identified percent damage (lesion load) to each of seven regions of interest previously associated with expression of affective prosody and two control areas that have been associated with recognition but not expression of prosody. We identified acoustic features that correlated with listener ratings of prosody (hereafter "prosody acoustic measures") with Spearman correlations and linear regression. We then identified demographic variables and brain regions where lesion load independently predicted the lowest quartile of each of the "prosody acoustic measures" using logistic regression. We found that listener ratings of prosody positively correlated with four acoustic measures. Furthermore, the lowest quartile of each of these four "prosody acoustic measures" was predicted by sex, age, lesion volume, and percent damage to the seven regions of interest. Lesion load in pars opercularis, supramarginal gyrus, or associated white matter tracts (and not control regions) predicted lowest quartile of the four "prosody acoustic measures" in logistic regression. Results indicate that listener perception of reduced affective prosody after RH stroke is due to reduction in specific acoustic features caused by infarct in right pars opercularis or supramarginal gyrus, or associated white matter tracts.

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.

Purpose: The purpose of this study was to describe the linguistic environment of phonological paraphasias in 3 variants of primary progressive aphasia (semantic, logopenic, and nonfluent) and to describe the profiles of paraphasia production for each of these variants., Method: Discourse samples of 26 individuals diagnosed with primary progressive aphasia were investigated for phonological paraphasias using the criteria established for the Philadelphia Naming Test (Moss Rehabilitation Research Institute, 2013). Phonological paraphasias were coded for paraphasia type, part of speech of the target word, target word frequency, type of segment in error, word position of consonant errors, type of error, and degree of change in consonant errors., Results: Eighteen individuals across the 3 variants produced phonological paraphasias. Most paraphasias were nonword, followed by formal, and then mixed, with errors primarily occurring on nouns and verbs, with relatively few on function words. Most errors were substitutions, followed by addition and deletion errors, and few sequencing errors. Errors were evenly distributed across vowels, consonant singletons, and clusters, with more errors occurring in initial and medial positions of words than in the final position of words. Most consonant errors consisted of only a single-feature change, with few 2- or 3-feature changes. Importantly, paraphasia productions by variant differed from these aggregate results, with unique production patterns for each variant., Conclusions: These results suggest that a system where paraphasias are coded as present versus absent may be insufficient to adequately distinguish between the 3 subtypes of PPA. The 3 variants demonstrate patterns that may be used to improve phenotyping and diagnostic sensitivity. These results should be integrated with recent findings on phonological processing and speech rate. Future research should attempt to replicate these results in a larger sample of participants with longer speech samples and varied elicitation tasks., Supplemental Materials: https://doi.org/10.23641/asha.5558107.

Objective: Many stroke patients show remarkable recovery of language after initial severe impairment, but it is difficult to predict which patients will show good recovery. We aimed to identify patient and lesion characteristics that together predict the best naming outcome in 4 studies., Methods: We report 2 longitudinal studies that identified 2 variables at onset that were strongly associated with good recovery of naming (the most common residual deficit in aphasia) in the first 6 months after stroke: damage to left posterior superior temporal gyrus (pSTG) and/or superior longitudinal fasciculus/arcuate fasciculus (SLF/AF), and selective serotonin reuptake inhibitor (SSRI) use. We then tested these variables in 2 independent cohorts of chronic left hemisphere stroke patients, using chi-square tests and multivariate logistic regression for dichotomous outcomes and t tests for continuous outcomes., Results: Lesion load in left pSTG and SLF/AF was associated with poorer naming outcome. Preservation of these areas and use of SSRIs were associated with naming recovery, independent of lesion volume, time since stroke, and depression. Patients with damage to these critical areas showed better naming outcome if they took SSRIs for 3 months after stroke. Those with preservation of these critical areas achieved good recovery of naming regardless of SSRI use., Interpretation: Lesion load in left pSTG and SLF/AF at onset predicts later naming performance. Although based on a small number of patients, our preliminary results suggest outcome might be modulated by SSRIs, but these associations need to be confirmed in a larger randomized controlled trial. Ann Neurol 2018;83:612-622., (© 2018 American Neurological Association.)

Background: An increasing body of research suggests that acute stroke patients who are dehydrated may have worsened functional outcomes. We sought to explore the relationship between a volume contracted state (VCS) at the time of ischemic stroke and hospital outcomes as compared with euvolemic patients., Methods: We enrolled a consecutive series of ischemic stroke patients from a single academic stroke center within 12 hours from stroke onset. VCS was defined via surrogate markers (blood urea nitrogen/creatinine ratio >15 and urine specific gravity >1.010). The primary outcome was change in NIH Stroke Scale (NIHSS) score from admission to discharge. Multivariable analyses included adjustment for demographics and infarct size., Results: Over an 11-month study period, 168 patients were eligible for inclusion. Of the126 with complete laboratory and MRI data, 44% were in a VCS at the time of admission. Demographics were similar in both the VCS and euvolemic groups, as were baseline NIHSS scores (6.7 vs 7.3; p = 0.63) and infarct volumes (12 vs 16 mL; p = 0.48). However, 42% of patients in a VCS demonstrated early clinical worsening, compared with 17% of the euvolemic group ( p = 0.02). A VCS remained a significant predictor of worsening NIHSS in adjusted models (odds ratio 4.34; 95% confidence interval 1.75-10.76)., Conclusions: Acute stroke patients in a VCS demonstrate worse short-term outcomes compared to euvolemic patients, independent of infarct size. Results suggest an opportunity to explore current hydration practices.

Objective: Individuals with "minor stroke" lack a dense hemiparesis or aphasia; however, commonly endorse persistent cognitive and motor problems despite low NIHSS scores. They also report problems with mood, energy, and the ability to think clearly that are less well characterized. Socioeconomic factors and stroke severity can influence patient-reported outcomes. In this study we explore patient-reported outcomes and the influence of these factors after minor stroke., Patients and Methods: Patients returning to clinic post-stroke with an NIHSS of ≤ 4 were administered a scale to quantify problems with daily activities and resulting functional burden, along with measures of fatigue and depression. T-tests, chi square analysis, and linear regression were used to compare functional outcomes of patients to controls (TIA or stroke mimic (n = 40)), and evaluate the association between patient-reported outcomes, stroke characteristics, and socioeconomic factors., Results: 151 stroke patients were seen a mean 83.6 days post-infarct. Patients reported more problems (11.7 versus 6.9, p = 0.02), resulting in higher functional burden (26.5 versus 12.3, p = 0.01), increased depression (p = 0.07), and greater fatigue (p = 0.02) compared to controls. There was no relationship between stroke characteristics (other than NIHSS), baseline education, income, marital status, or living situation and perception of recovery; however, those actively working prior to their stroke reported better outcomes across all categories (p for each <0.02), and differences persisted in multivariable regression models., Conclusion: Prior occupational status may represent an important prognostic indicator for patients with minor stroke. Individuals working at the time of their infarct report better functional outcomes irrespective of age or stroke severity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Despite its basic and translational importance, the neural circuitry supporting the perception of emotional faces remains incompletely understood. Functional imaging studies and chronic lesion studies indicate distinct roles of the amygdala and insula in recognition of fear and disgust in facial expressions, whereas intracranial encephalography studies, which are not encumbered by variations in human anatomy, indicate a somewhat different role of these structures. In this article, we leveraged lesion-mapping techniques in individuals with acute right hemisphere stroke to investigate lesions associated with impaired recognition of prototypic emotional faces before significant neural reorganization can occur during recovery from stroke. Right hemisphere stroke patients were significantly less accurate than controls on a test of emotional facial recognition for both positive and negative emotions. Patients with right amygdala or anterior insula lesions had significantly lower scores than other right hemisphere stroke patients on recognition of angry and happy faces. Lesion volume within several regions, including the right amygdala and anterior insula, each independently contributed to the error rate in recognition of individual emotions. Results provide additional support for a necessary role of the right amygdala and anterior insula within a network of regions underlying recognition of facial expressions, particularly those that have biological importance or motivational relevance and have implications for clinical practice., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

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., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Individuals with primary progressive aphasia (PPA) and their caregivers want to know what to expect so that they can plan support appropriately. The ability to predict decline in naming and semantic knowledge, and advise individuals with PPA and their caregivers regarding future planning, would be invaluable clinically., Aims: The aims of this study were to investigate patterns of decline in naming and semantic knowledge in each of the clinical variants of PPA (logopenic variant PPA, lvPPA; nonfluent agrammatic PPA, nfaPPA; and semantic variant PPA, svPPA) and to examine the effects of other variables on rate of decline. We hypothesized that speech-language rehabilitation, higher education, and higher baseline test scores would be associated with slower decline, and older age with faster decline., Methods and Procedures: A total of ninety-four participants with PPA underwent language testing, including thirty six participants with lvPPA, thirty-one participants with nfaPPA, and twenty-seven participants with svPPA. All participant groups were similar in age and education. We focused on decline on three tests: the short form of the Boston Naming Test (BNT), the Hopkins Assessment of Naming Actions (HANA), and the short form of the Pyramids and Palm Trees Test (PPTT)., Outcome and Results: Across language tests, the most precipitous rates of decline (loss of points per month) occurred in nfaPPA, followed by svPPA, then lvPPA. Female sex, longer symptom duration, higher baseline test score, and speech-language rehabilitation were associated with slower decline., Conclusions: PPA variants were distinguishable by rapidity of decline, with nfaPPA having the most precipitous decline. As hypothesized, higher baseline test scores and speech-language rehabilitation were associated with slower decline. Surprisingly, age and education were not important prognostically for individuals in this study. Further study of prognostically-relevant variables in PPA is indicated in this population.