Search

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

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

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

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

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

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

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

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

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

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

Background Characterizing productive language deficits following lesions to the right (RH) or left hemispheres (LH) is valuable in identifying appropriate therapeutic goals. While damage to the LH classically is associated with deficits in language, RH lesions also result in changed communication beyond prosody due to cognitive-linguistic effects. Cohesion, reference to introduced content across sentences within discourse, relies on a listener's clear and unambiguous understanding that a reference has occurred. To date, we are not aware of any prior work that has compared patterns of cohesive strategy between RH and LH lesioned individuals with cohesion deficits. Aims The purpose of the present study is to determine whether individuals with communication deficits following RH and LH lesions differ in the inclusion and clarity of cohesive markers. Methods & procedures Seventy-six RH samples and 145 LH samples were used for comparison of cohesion performance in a Cookie Theft picture description task. Cohesive ties were assessed following the protocol outlined in Liles and Coelho (1998). It was hypothesized that individuals with LH lesions would present a different pattern of cohesion behaviour than RH lesioned individuals when considered both acutely and chronically. Outcomes & results Overall, samples from LH and RH groups did not differ in word counts or cohesive marker usage. However, the patterns of markers they chose to employ were different. LH samples used conjunctions and personal pronouns more frequently and used lexical cohesive markers less frequently than RH samples. Acutely, patterns of cohesive marker use between LH and RH samples were more similar. Chronically, LH samples contained more personal pronouns and the differences in lexical cohesive markers remained unchanged. When cohesion was unsuccessful, LH and RH damage were associated with different patterns of error. LH samples tended to omit information needed to clarify the intended referent, resulting in incomplete cohesion errors. RH samples tended to sustain breakdowns in cohesion from sentence to sentence, not resolving incorrectly chosen pronouns or ambiguities left in their samples. Conclusions LH and RH lesions resulted in differing patterns of chosen cohesive markers and errors when cohesion was unsuccessful. This was particularly true in lexical cohesion, which has been far less studied than closed-class cohesive markers like referential pronouns. It was also noted that cohesive behavior did not appear to "recover" for either group, suggesting spontaneous recovery is minimal and present strategies for language therapy may not effectively address this linguistic function.

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

BACKGROUND: Naming impairment is commonly noted in individuals with aphasia. However, object naming receives more attention than action naming. Furthermore, most studies include participants with aphasia due to only one aetiology, commonly stroke. We developed a new assessment, the Hopkins Action Naming Assessment (HANA), to evaluate action naming impairments. AIMS: Our aims were to show that the HANA is a useful tool that can (1) identify action naming impairments and (2) be used to investigate the neural substrates underlying naming. We paired the HANA with the Boston Naming Test (BNT) to compare action and object naming. We considered participants with aphasia due to primary progressive aphasia (PPA) or acute left hemisphere stroke to provide a more comprehensive picture of brain-behaviour relationships critical for naming. Behaviourally, we hypothesised that there would be a double dissociation between object and action naming performance. Neuroanatomically, we hypothesised that different neural substrates would be implicated in object vs. action naming and that different lesion-deficit associations would be identified in participants with PPA vs. acute stroke. METHODS & PROCEDURES: Participants (N=138 with PPA, N=37 with acute stroke) completed the BNT and HANA. Behavioural performance was compared. A subset of participants (N=31 with PPA, N=37 with acute stroke) provided neuroimaging data. The whole brain was automatically segmented into regions of interest (ROIs). For participants with PPA, the image variables were the ROI volumes, normalised by the brain volume. For participants with acute stroke, the image variables were the percentage of each ROI affected by the lesion. The relationship between ROIs likely to be involved in naming performance was modelled with LASSO regression. OUTCOMES & RESULTS: Behavioural results showed a double dissociation in performance: in each group, some participants displayed intact performance relative to healthy controls on actions but not objects and/or significantly better performance on actions than objects, while others showed the opposite pattern. These results support the need to assess both objects and actions when evaluating naming deficits. Neuroimaging results identified different regions associated with object vs. action naming, implicating overlapping but distinct networks of regions. Furthermore, results differed for participants with PPA vs. acute stroke, indicating that critical information may be missed when only one aetiology is considered. CONCLUSIONS: Overall, the study provides a more comprehensive picture of the neural bases of naming, underscoring the importance of assessing both objects and actions and considering different aetiologies of damage. It demonstrates the utility of the HANA.

BackgroundMild cognitive impairment is a common yet complex condition that is often underdiagnosed in the early stages. Miro Health is a mobile platform for the self-administration of sensor-based cognitive and behavioral assessments that was developed to measure factors typical of legacy neuropsychological tests in addition to behaviors that are currently left to subjective clinical impression such as eye movement, language, and processing speed.ObjectiveStudies were conducted to measure Miro Health’s concurrent validity, test-retest reliability, and amnestic MCI classification performance.MethodSpearman correlations were calculated to estimate the concurrent validity of Miro Health variables with legacy neuropsychological test variables using data from 160 study participants. Fifty-nine healthy controls were assessed at three time points to evaluate the test-retest reliability of Miro Health scores. Reliability was quantified with the scores’ intraclass correlations. Learning effects were measured as trends. In addition, a machine learning algorithm combined Miro Health variable scores into a Risk Score designed to distinguish 65 healthy controls (HC), 38 MCI participants (21 amnestic MCI (aMCI), and 17 non-amnestic MCI (naMCI)).ResultsSignificant correlations of Miro Health variables with legacy neuropsychological test variables were observed. Longitudinal studies show agreement of subsequent measurements and minimal learning effects. The Risk Score distinguished aMCI from healthy controls with an Area Under the Receiver Operator Curve (AUROC) of 0.97; the naMCI participants and controls were separated with an AUROC of 0.80, and the combined MCI group (aMCI + naMCI) was separated from healthy controls with an AUROC of 0.89.ConclusionMiro Health includes valid and reliable versions of variable scores that are analogous to legacy neuropsychological variable scores and a machine-learning derived risk score that effectively distinguishes HCs and individuals with MCI.

Difficulty recognizing affective prosody (receptive aprosodia) can occur following right hemisphere damage (RHD). Not all individuals spontaneously recover their ability to recognize affective prosody, warranting behavioral intervention. However, there is a dearth of evidence-based receptive aprosodia treatment research in this clinical population. The purpose of the current study was to investigate an explicit training protocol targeting affective prosody recognition in adults with RHD and receptive aprosodia. Eighteen adults with receptive aprosodia due to acute RHD completed affective prosody recognition before and after a short training session that targeted proposed underlying perceptual and conceptual processes. Behavioral impairment and lesion characteristics were investigated as possible influences on training effectiveness. Affective prosody recognition improved following training, and recognition accuracy was higher for pseudo- vs. real-word sentences. Perceptual deficits were associated with the most posterior infarcts, conceptual deficits were associated with frontal infarcts, and a combination of perceptual-conceptual deficits were related to temporoparietal and subcortical infarcts. Several right hemisphere ventral stream regions and pathways along with frontal and parietal hypoperfusion predicted training effectiveness. Explicit acoustic-prosodic-emotion training improves affective prosody recognition, but it may not be appropriate for everyone. Factors such as linguistic context and lesion location should be considered when planning prosody training.

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.

Attempts to personalize aphasia treatment to the extent where it is possible to reliably predict individual response to a particular treatment have yielded inconclusive results. The current study aimed to (i) compare the effects of phonologically versus semantically focussed naming treatment and (ii) examine biographical and neuropsychological baseline factors predictive of response to each treatment. One hundred and four individuals with chronic post-stroke aphasia underwent 3 weeks of phonologically focussed treatment and 3 weeks of semantically focussed treatment in an unblinded cross-over design. A linear mixed-effects model was used to compare the effects of treatment type on proportional change in correct naming across groups. Correlational analysis and stepwise regression models were used to examine biographical and neuropsychological predictors of response to phonological and semantic treatment across all participants. Last, chi-square tests were used to explore the association between treatment response and phonological and semantic deficit profiles. Semantically focussed treatment was found to be more effective at the group-level, independently of treatment order (P = 0.041). Overall, milder speech and language impairment predicted good response to semantic treatment (r range: 0.256–0.373) across neuropsychological tasks. The Western Aphasia Battery-Revised Spontaneous Speech score emerged as the strongest predictor of semantic treatment response (R2 = 0.188). Severity of stroke symptoms emerged as the strongest predictor of phonological treatment response (R2 = 0.103). Participants who showed a good response to semantic treatment were more likely to present with fluent speech compared to poor responders (P = 0.005), whereas participants who showed a good response to phonological treatment were more likely to present with apraxia of speech (P = 0.020). These results suggest that semantic treatment may be more beneficial to the improvement of naming performance in aphasia than phonological treatment, at the group-level. In terms of personalized predictors, participants with relatively mild impairments and fluent speech responded better to semantic treatment, while phonological treatment benefitted participants with more severe impairments and apraxia of speech., Kristinsson et al. found superior effects of semantic versus phonological therapy in a group of 104 participants with chronic aphasia. Personalized predictors of semantic therapy response included mild language impairment and fluent speech, whereas more severe language impairment and presence of apraxia of speech predicted response to phonological therapy., Graphical Abstract Graphical Abstract

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.

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

Author(s): Staffaroni, Adam M; Weintraub, Sandra; Rascovsky, Katya; Rankin, Katherine P; Taylor, Jack; Fields, Julie A; Casaletto, Kaitlin B; Hillis, Argye E; Lukic, Sladjana; Gorno-Tempini, Maria Luisa; Heuer, Hilary; Teylan, Merilee A; Kukull, Walter A; Miller, Bruce L; Boeve, Bradley F; Rosen, Howard J; Boxer, Adam L; Kramer, Joel H | Abstract: IntroductionThe Frontotemporal Lobar Degeneration Module (FTLD-MOD) includes a neuropsychological battery designed to assess the clinical features of FTLD, although much is unknown about its utility. We investigated FTLD-MOD and Uniform Data Set 3.0 (UDS) language tests for differential diagnosis and disease monitoring.MethodsLinear regressions compared baseline performances in 1655 National Alzheimer's Coordinating Center participants (behavioral variant frontotemporal dementia (bvFTD, nn=n612), semantic variant primary progressive aphasia (svPPA, nn=n168), non-fluent/agrammatic variant PPA (nfvPPA, nn=n168), logopenic variant PPA (lvPPA, nn=n109), and controls (nn=n581)). Sample sizes to detect treatment effects were estimated using longitudinal data.ResultsAmong PPAs, the FTLD-MOD language tasks and UDS Multilingual Naming Test accurately discriminated svPPA. Number Span Forward best discriminated lvPPA; Phonemic:Semantic Fluency ratio was excellent for nfvPPA classification. UDS fluency and naming measures required the smallest sample size to detect meaningful change.DiscussionThe FTLD-MOD and UDS differentiated among PPA subtypes. UDS 3.0 measures performed best for longitudinal monitoring.

Lesion and imaging studies have shown that the left inferior frontal gyrus (IFG) is involved in selective semantic retrieval of information from the temporal lobes. However, causal, i.e., interventional, evidence is sparse. In the present study we addressed this question by testing whether transcranial direct current stimulation (tDCS) over the left IFG in a group of individuals with primary progressive aphasia may improve semantic fluency, a task that relies to selective semantic retrieval. Semantic fluency improved significantly more in the tDCS vs. sham condition immediately post-treatment and improvement lasted up to 2 months. We further addressed the question of who will benefit most from such an intervention by testing possible demographic, clinical and functional connectivity variables that may predict the behavioral tDCS effect. We found that patients with stronger baseline functional connectivity between the subareas of the left IFG opercularis and triangularis, and between the middle temporal pole and superior temporal gyrus. were the most likely to benefit from tDCS over the left IFG. We thus provided causal evidence that the left IFG is the neural substrate of selective semantic retrieval and tDCS over the left IFG may improve semantic fluency in individuals with stronger baseline functional connectivity.

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.

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

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

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

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

Lesion-deficit association studies are important as they can reveal brain regions essential for specific functions, but sometimes appear to yield conflicting results. We aimed to show how pitfalls of lesions studies can be avoided, and converging results obtained, illustrating from studies of the role of posterior superior temporal gyrus in auditory word comprehension. We review published lesion studies on auditory comprehension and present new data from both acute and chronic stroke that address weaknesses in some previous studies. Results demonstrate how convergence of positive results from diverse lesion studies provides strong evidence for the role of a particular region in a given behavior. This article is protected by copyright. All rights reserved.

Lesion-symptom mapping is an important method of identifying networks of brain regions critical for functions. However, results might be influenced substantially by the imaging modality and timing of assessment. We tested the hypothesis that brain regions found to be associated with acute language deficits depend on (1) timing of behavioral measurement, (2) imaging sequences utilized to define the "lesion" (structural abnormality only or structural plus perfusion abnormality), and (3) power of the study. We studied 191 individuals with acute left hemisphere stroke with MRI and language testing to identify areas critical for spoken word comprehension. We use the data from this study to examine the potential impact of these three variables on lesion-symptom mapping. We found that only the combination of structural and perfusion imaging within 48 h of onset identified areas where more abnormal voxels was associated with more severe acute deficits, after controlling for lesion volume and multiple comparisons. The critical area identified with this methodology was the left posterior superior temporal gyrus, consistent with other methods that have identified an important role of this area in spoken word comprehension. Results have implications for interpretation of other lesion-symptom mapping studies, as well as for understanding areas critical for auditory word comprehension in the healthy brain. We propose that lesion-symptom mapping at the acute stage of stroke addresses a different sort of question about brain-behavior relationships than lesion-symptom mapping at the chronic stage, but that timing of behavioral measurement and imaging modalities should be considered in either case. Hum Brain Mapp 38:2990-3000, 2017. © 2017 Wiley Periodicals, Inc.

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

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

The story of a hereditary vulnerability of the left hemisphere language network as the basis for both developmental and degenerative language deficits has been unfolding for some time. It has long been recognized that developmental dyslexia and other developmental language impairments can reflect cortical anomalies in the left hemisphere, including the planum temporale.1 A genetic basis for some developmental language disorders such as FOXP2 mutations was also identified nearly 2 decades ago.2 We have also known for some time that people with the neurodegenerative language disorder of primary progressive aphasia (PPA) have cortical atrophy in the left hemisphere.3 But a link between developmental and neurodegenerative language deficits has been discovered more recently,4,5 and a FOXP2 -driven network has recently been implicated in both developmental and neurodegenerative disease.6

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 < .001). 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).

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., Highlights • A brain mechanism for tDCS over the left IFG in PPA is proposed. • Functional connectivity changes only between the stimulated and temporal areas. • Changes in functional connectivity correlate with language therapy outcomes. • This is the first study providing evidence for tDCS mechanisms in PPA.

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

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.

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.

Purpose: The neural mechanisms that support aphasia recovery are not yet fully understood. Our goal was to evaluate longitudinal changes in naming recovery in participants with posterior cerebral artery (PCA) stroke using a case-by-case analysis. Methods: Using task based and resting state functional magnetic resonance imaging (fMRI) and detailed language testing, we longitudinally studied the recovery of the naming network in four participants with PCA stroke with naming deficits at the acute (0 week), sub acute (3–5 weeks), and chronic time point (5–7 months) post stroke. Behavioral and imaging analyses (task related and resting state functional connectivity) were carried out to elucidate longitudinal changes in naming recovery. Results: Behavioral and imaging analysis revealed that an improvement in naming accuracy from the acute to the chronic stage was reflected by increased connectivity within and between left and right hemisphere “language” regions. One participant who had persistent moderate naming deficit showed weak and decreasing connectivity longitudinally within and between left and right hemisphere language regions. Conclusions: These findings emphasize a network view of aphasia recovery, and show that the degree of inter- and intra- hemispheric balance between the language-specific regions is necessary for optimal recovery of naming, at least in participants with PCA stroke.

The insula has been implicated in many sequelae of stroke. It is the area most commonly infarcted in people with post-stroke arrhythmias, loss of thermal sensation, hospital acquired pneumonia, and apraxia of speech. We hypothesized that some of these results reflect the fact that: (1) ischemic strokes that involve the insula are larger than strokes that exclude the insula (and therefore are associated with more common and persistent deficits); and (2) insular involvement is a marker of middle cerebral artery (MCA) occlusion. We analyzed MRI scans of 861 patients with acute ischemic hemispheric strokes unselected for functional deficits, and compared infarcts involving the insula to infarcts not involving the insula using t-tests for continuous variables and chi square tests for dichotomous variables. Mean infarct volume was larger for infarcts including the insula (n = 232) versus excluding the insula (n = 629): 65.8 ± 78.8 versus 10.2 ± 15.9 cm3 (p, Highlights • The insula is the most commonly infarcted area in patients with a wide range of deficits. • In 861 acute ischemic hemispheric strokes, mean infarct volume was much larger when infarct included the insula (p

Language recovery following acute left hemisphere (LH) stroke is notoriously difficult to predict. Global language measures (e.g., overall aphasia severity) and gross lesion metrics (e.g., size) provide incomplete recovery predictions. In this study, we test the hypothesis that the types of naming errors patients produce, combined with dysfunctional brain tissue metrics, can provide additional insight into recovery following acute LH stroke. One hundred forty-eight individuals who were hospitalized with a new LH stroke completed clinical neuroimaging and assessments of naming and global language skills. A subset of participants again completed language testing at subacute, early (5–7 months post-stroke), and late (≥11 months post-stroke) chronic phases. At each time point, we coded naming errors into four types (semantic, phonological, mixed and unrelated) and determined error type totals and proportions. Dysfunctional tissue measures included the percentage of damage to language network regions and hypoperfusion in vascular territories. A higher proportion of semantic errors was associated with better acute naming, but higher proportions of other error types was related to poorer accuracy. Naming and global language skills significantly improved over time , but naming error profiles did not change. Fewer acute unrelated errors and less damage to left angular gyrus resulted in optimal naming and language recovery by the final testing time point, yet patients with more acute errors and damage to left middle temporal gyrus demonstrated the greatest increases in language over time. These results illustrate that naming error profiles, particularly unrelated errors, add power to predictions of language recovery after stroke., Highlights • In acute stroke, a high proportion of semantic errors was related to better naming. • Higher proportions of other errors were related to lower acute naming skills. • Over time, naming and global language improved, but error patterns did not change. • The strongest recovery predictors were unrelated errors and temporoparietal integrity.

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.

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.

Background Functional neuroimaging techniques can provide a unique window into the neural basis of language recovery after a stroke. The functional neuroimaging literature on post-stroke language recovery is complex; multiple factors such as the time post-stroke, degree of initial impairment, nature of the task, and lesion location and size, influence recovery patterns. Some of these factors may not be applicable across different stroke participants, and therefore, influence recovery trajectories in vastly different manners across patients. Aims The aim of this paper is to examine longitudinal changes in brain activation patterns of reading and naming recovery in participants with posterior cerebral artery (PCA) strokes with varying degrees of initial language impairment. Methods & procedures Five participants with PCA strokes and 5 healthy controls underwent language testing and functional MRI with a covert reading task and an overt picture-naming task. Stroke participants underwent language testing and scanning at the three time points: 2-5 weeks (T1, subacute phase), 4-7 months (T2, chronic phase), and 11-13 months (T3, chronic phase). Healthy controls underwent language testing and fMRI once. Outcomes & results Language testing indicated that there were varying degrees of reading and naming recovery or decline from the subacute to the chronic phase. With regard to task-based fMRI, we found that for most participants, naming consistently activated a diffuse bilateral network of frontal, temporal, parietal, and occipital regions across the three time points. In contrast, for the reading task, functional activation across the three time points was more left lateralized with a right to left shift in peak activation from the subacute to the chronic phase. Conclusions These results indicate that the patterns of activation during language processing is highly dependent on the task and phase of recovery, and these results may have implications for neurally targeted non-invasive brain stimulation techniques.

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.

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.

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.

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

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.