Regional brain aging: premature aging of the domain general system predicts aphasia severity.

Premature brain aging is associated with poorer cognitive reserve and lower resilience to injury. When there are focal brain lesions, brain regions may age at different rates within the same individual. Therefore, we hypothesize that reduced gray matter volume within specific brain systems commonly associated with language recovery may be important for long-term aphasia severity. Here we show that individuals with stroke aphasia have a premature brain aging in intact regions of the lesioned hemisphere. In left domain-general regions, premature brain aging, gray matter volume, lesion volume and age were all significant predictors of aphasia severity. Increased brain age following a stroke is driven by the lesioned hemisphere. The relationship between brain age in left domain-general regions and aphasia severity suggests that degradation is possible to specific brain regions and isolated aging matters for behavior.

Dissociating reading and auditory comprehension in persons with aphasia.

Language comprehension is often affected in individuals with post-stroke aphasia. However, deficits in auditory comprehension are not fully correlated with deficits in reading comprehension and the mechanisms underlying this dissociation remain unclear. This distinction is important for understanding language mechanisms, predicting long-term impairments and future development of treatment interventions. Using comprehensive auditory and reading measures from a large cohort of individuals with aphasia, we evaluated the relationship between aphasia type and reading comprehension impairments, the relationship between auditory versus reading comprehension deficits and the crucial neuroanatomy supporting the dissociation between post-stroke reading and auditory deficits. Scores from the Western Aphasia Battery-Revised from 70 participants with aphasia after a left-hemisphere stroke were utilized to evaluate both reading and auditory comprehension of linguistically equivalent stimuli. Repeated-measures and univariate ANOVA were used to assess the relationship between auditory comprehension and aphasia types and correlations were employed to test the relationship between reading and auditory comprehension deficits. Lesion-symptom mapping was used to determine the dissociation of crucial brain structures supporting reading comprehension deficits controlling for auditory deficits and vice versa. Participants with Broca's or global aphasia had the worst performance on reading comprehension. Auditory comprehension explained 26% of the variance in reading comprehension for sentence completion and 44% for following sequential commands. Controlling for auditory comprehension, worse reading comprehension performance was independently associated with damage to the inferior temporal gyrus, fusiform gyrus, posterior inferior temporal gyrus, inferior occipital gyrus, lingual gyrus and posterior thalamic radiation. Auditory and reading comprehension are only partly correlated in aphasia. Reading is an integral part of daily life and directly associated with quality of life and functional outcomes. This study demonstrated that reading performance is directly related to lesioned areas in the boundaries between visual association regions and ventral stream language areas. This behavioural and neuroanatomical dissociation provides information about the neurobiology of language and mechanisms for potential future treatment interventions.

Dynamic network properties of the superior temporal gyrus mediate the impact of brain age gap on chronic aphasia severity.

Brain structure deteriorates with aging and predisposes an individual to more severe language impairments (aphasia) after a stroke. However, the underlying mechanisms of this relation are not well understood. Here we use an approach to model brain network properties outside the stroke lesion, network controllability, to investigate relations among individualized structural brain connections, brain age, and aphasia severity in 93 participants with chronic post-stroke aphasia. Controlling for the stroke lesion size, we observe that lower average controllability of the posterior superior temporal gyrus (STG) mediates the relation between advanced brain aging and aphasia severity. Lower controllability of the left posterior STG signifies that activity in the left posterior STG is less likely to yield a response in other brain regions due to the topological properties of the structural brain networks. These results indicate that advanced brain aging among individuals with post-stroke aphasia is associated with disruption of dynamic properties of a critical language-related area, the STG, which contributes to worse aphasic symptoms. Because brain aging is variable among individuals with aphasia, our results provide further insight into the mechanisms underlying the variance in clinical trajectories in post-stroke aphasia.

Predicting Outcomes of Language Rehabilitation: Prognostic Factors for Immediate and Long-Term Outcomes After Aphasia Therapy.

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

Advanced Brain Age and Chronic Poststroke Aphasia Severity.

BACKGROUND AND OBJECTIVES: Chronic poststroke language impairment is typically worse in older individuals or those with large stroke lesions. However, there is unexplained variance that likely depends on intact tissue beyond the lesion. Brain age is an emerging concept, which is partially independent from chronologic age. Advanced brain age is associated with cognitive decline in healthy older adults; therefore, we aimed to investigate the relationship with stroke aphasia. We hypothesized that advanced brain age is a significant factor associated with chronic poststroke language impairments, above and beyond chronologic age, and lesion characteristics. METHODS: This cohort study retrospectively evaluated participants from the Predicting Outcomes of Language Rehabilitation in Aphasia clinical trial (NCT03416738), recruited through local advertisement in South Carolina (US). Primary inclusion criteria were left hemisphere stroke and chronic aphasia (≥12 months after stroke). Participants completed baseline behavioral testing including the Western Aphasia Battery-Revised (WAB-R), Philadelphia Naming Test (PNT), Pyramids and Palm Trees Test (PPTT), and Wechsler Adult Intelligence Scale Matrices subtest, before completing 6 weeks of language therapy. The PNT was repeated 1 month after therapy. We leveraged modern neuroimaging techniques to estimate brain age and computed a proportional difference between chronologic age and estimated brain age. Multiple linear regression models were used to evaluate the relationship between proportional brain age difference (PBAD) and behavior. RESULTS: Participants (N = 93, 58 males and 35 females, average age = 61 years) had estimated brain ages ranging from 14 years younger to 23 years older than chronologic age. Advanced brain age predicted performance on semantic tasks (PPTT) and language tasks (WAB-R). For participants with advanced brain aging (n = 47), treatment gains (improvement on the PNT) were independently predicted by PBAD (T = -2.0474, p = 0.0468, 9% of variance explained). DISCUSSION: Through the application of modern neuroimaging techniques, advanced brain aging was associated with aphasia severity and performance on semantic tasks. Notably, therapy outcome scores were also associated with PBAD, albeit only among participants with advanced brain aging. These findings corroborate the importance of brain age as a determinant of poststroke recovery and underscore the importance of personalized health factors in determining recovery trajectories, which should be considered during the planning or implementation of therapeutic interventions.

Neural network bases of thematic semantic processing in language production.

Semantic processing is a central component of language and cognition. The anterior temporal lobe is postulated to be a key hub for semantic processing, but the posterior temporoparietal cortex is also involved in thematic associations during language. It is possible that these regions act in concert and depend on an anteroposterior network linking the temporal pole with posterior structures to support thematic semantic processing during language production. We employed connectome-based lesion-symptom mapping to examine the causal relationship between lesioned white matter pathways and thematic processing language deficits among individuals with post-stroke aphasia. Seventy-nine adults with chronic aphasia completed the Philadelphia Naming Test, and semantic errors were coded as either thematic or taxonomic to control for taxonomic errors. Controlling for nonverbal conceptual-semantic knowledge as measured by the Pyramids and Palm Trees Test, lesion size, and the taxonomic error rate, thematic error rate was associated with loss of white matter connections from the temporal pole traversing in peri-Sylvian regions to the posterior cingulate and the insula. These findings support the existence of a distributed network underlying thematic relationship processing in language as opposed to discrete cortical areas.

Brain age predicts long-term recovery in post-stroke aphasia.

The association between age and language recovery in stroke remains unclear. Here, we used neuroimaging data to estimate brain age, a measure of structural integrity, and examined the extent to which brain age at stroke onset is associated with (i) cross-sectional language performance, and (ii) longitudinal recovery of language function, beyond chronological age alone. A total of 49 participants (age: 65.2 ± 12.2 years, 25 female) underwent routine clinical neuroimaging (T1) and a bedside evaluation of language performance (Bedside Evaluation Screening Test-2) at onset of left hemisphere stroke. Brain age was estimated from enantiomorphically reconstructed brain scans using a machine learning algorithm trained on a large sample of healthy adults. A subsample of 30 participants returned for follow-up language assessments at least 2 years after stroke onset. To account for variability in age at stroke, we calculated proportional brain age difference, i.e. the proportional difference between brain age and chronological age. Multiple regression models were constructed to test the effects of proportional brain age difference on language outcomes. Lesion volume and chronological age were included as covariates in all models. Accelerated brain age compared with age was associated with worse overall aphasia severity (F(1, 48) = 5.65, P = 0.022), naming (F(1, 48) = 5.13, P = 0.028), and speech repetition (F(1, 48) = 8.49, P = 0.006) at stroke onset. Follow-up assessments were carried out ≥2 years after onset; decelerated brain age relative to age was significantly associated with reduced overall aphasia severity (F(1, 26) = 5.45, P = 0.028) and marginally failed to reach statistical significance for auditory comprehension (F(1, 26) = 2.87, P = 0.103). Proportional brain age difference was not found to be associated with changes in naming (F(1, 26) = 0.23, P = 0.880) and speech repetition (F(1, 26) = 0.00, P = 0.978). Chronological age was only associated with naming performance at stroke onset (F(1, 48) = 4.18, P = 0.047). These results indicate that brain age as estimated based on routine clinical brain scans may be a strong biomarker for language function and recovery after stroke.

Predictors of Therapy Response in Chronic Aphasia: Building a Foundation for Personalized Aphasia Therapy.

Chronic aphasia, a devastating impairment of language, affects up to a third of stroke survivors. Speech and language therapy has consistently been shown to improve language function in prior clinical trials, but few clinicially applicable predictors of individual therapy response have been identified to date. Consequently, clinicians struggle substantially with prognostication in the clinical management of aphasia. A rising prevalence of aphasia, in particular in younger populations, has emphasized the increasing demand for a personalized approach to aphasia therapy, that is, therapy aimed at maximizing language recovery of each individual with reference to evidence-based clinical recommendations. In this narrative review, we discuss the current state of the literature with respect to commonly studied predictors of therapy response in aphasia. In particular, we focus our discussion on biographical, neuropsychological, and neurobiological predictors, and emphasize limitations of the literature, summarize consistent findings, and consider how the research field can better support the development of personalized aphasia therapy. In conclusion, a review of the literature indicates that future research efforts should aim to recruit larger samples of people with aphasia, including by establishing multisite aphasia research centers.

Genetics in aphasia recovery.

Considerable research efforts have been exerted toward understanding the mechanisms underlying recovery in aphasia. However, predictive models of spontaneous and treatment-induced recovery remain imprecise. Some of the hitherto unexplained variability in recovery may be accounted for with genetic data. A few studies have examined the effects of the BDNF val66met polymorphism on aphasia recovery, yielding mixed results. Advances in the study of stroke genetics and genetics of stroke recovery, including identification of several susceptibility genes through candidate-gene or genome-wide association studies, may have implications for the recovery of language function. The current chapter discusses both the direct and indirect evidence for a genetic basis of aphasia recovery, the implications of recent findings within the field, and potential future directions to advance understanding of the genetics-recovery associations.

Individualized response to semantic versus phonological aphasia therapies in stroke.

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 (R 2 = 0.188). Severity of stroke symptoms emerged as the strongest predictor of phonological treatment response (R 2 = 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.

Machine learning-based multimodal prediction of language outcomes in chronic aphasia.

Recent studies have combined multiple neuroimaging modalities to gain further understanding of the neurobiological substrates of aphasia. Following this line of work, the current study uses machine learning approaches to predict aphasia severity and specific language measures based on a multimodal neuroimaging dataset. A total of 116 individuals with chronic left-hemisphere stroke were included in the study. Neuroimaging data included task-based functional magnetic resonance imaging (fMRI), diffusion-based fractional anisotropy (FA)-values, cerebral blood flow (CBF), and lesion-load data. The Western Aphasia Battery was used to measure aphasia severity and specific language functions. As a primary analysis, we constructed support vector regression (SVR) models predicting language measures based on (i) each neuroimaging modality separately, (ii) lesion volume alone, and (iii) a combination of all modalities. Prediction accuracy across models was subsequently statistically compared. Prediction accuracy across modalities and language measures varied substantially (predicted vs. empirical correlation range: r = .00-.67). The multimodal prediction model yielded the most accurate prediction in all cases (r = .53-.67). Statistical superiority in favor of the multimodal model was achieved in 28/30 model comparisons (p-value range: <.001-.046). Our results indicate that different neuroimaging modalities carry complementary information that can be integrated to more accurately depict how brain damage and remaining functionality of intact brain tissue translate into language function in aphasia.

Translation, adaptation and psychometric properties of the Icelandic stroke and aphasia quality of life scale-39g.

BACKGROUND: The overarching aim of aphasia rehabilitation is to improve people's quality of life. The most commonly used quality of life measure developed for use with individuals with aphasia is the Stroke and Aphasia Quality of Life Scale-39 (SAQOL-39g). AIMS: We aimed to translate and adapt the SAQOL-39g into Icelandic, and examine its psychometric properties. Furthermore, this study aimed to gather preliminary information on the health-related quality of life (HRQOL) of stroke patients in Iceland. METHOD: A traditional back-translation approach was applied to translate the SAQOL-39g into Icelandic. We recruited 20 poststroke patients, thereof ten with aphasia, for evaluation of the psychometric properties of the translated instrument. Acceptability was based on missing data, and floor and ceiling effects, internal consistency was measured by Cronbach's α and correlation between test items and overall score, and test-retest reliability was measured by intraclass correlation coefficient (ICC) for overall and domain scores. RESULTS: The back-translation led to reviewing of eight test items for the final translation. No test items required cultural adaptation. The acceptability of the translation met criteria for both proportion of missing data (0%) and floor and ceiling effects for test items and domains (<80%). Internal consistency also met criteria, both for overall score (α = 0.94) and domains: physical domain (α = 0.93), psychosocial domain (α = 0.93) and communication domain (α = 0.89). Correlation between test items and overall score ranged from 0.30 to 0.82. Test-retest reliability met criteria both for overall score (0.95) and domains: physical domain (0.94), psychosocial domain (0.95), and communication domain (0.95). The mean total score was significantly lower for participants with aphasia compared to participants without aphasia (3.73 vs. 4.20; p < 05). CONCLUSIONS: The Icelandic SAQOL-39g demonstrated good psychometric properties. Preliminary evidence suggests that the HRQOL of people with aphasia is significantly worse than of people without aphasia after stroke.

The recovery rate of early stuttering.

PURPOSE: Across studies there is great variability in reported rates of stuttering recovery. This study examined the impact that different definitions of recovery had on calculation of recovery rates and factors associated with recovery within the same sample of children. METHOD: Speech samples and parents and child reports of their experiences of stuttering were collected from 38 children who stuttered aged 2-5 years of age (Occassion-1) and again at 9-13 years of age (Occassion-2). Four different criteria for recovery that were developed representing variations in criteria reported in previous research were applied to data from these children. RESULTS: . The majority of the participants (82%) showed very little disfluent speech (<1% syllables stuttered) at Occasion 2. Recovery rate varied greatly depending on the criteria used, ranging from 13.2%-94.7%. Definitions ordered from least to greatest recovery that were (a) parent and clinician report no stuttering and no stuttering observed (13.2 %); (b) ≤1% syllables stuttered; severity rated at ≤1; parent, clinician, and child report recovery (55.3 %); (c) ≤1% syllables stuttered; severity rated at ≤1; parent and clinician report recovery (71.1 %); (d) <3.0 % syllables stuttered (94.7 %). Five participants were considered recovered and two were considered persistent stutters across all criteria. Different factors were associated with recovery from stuttering depending on the criterion used. CONCLUSION: The concept of recovery from stuttering is complex and estimations of recovery rate are likely to be greatly affected by differences in definitions and measurement across studies. This has a flow-on effect in determining the factors associated with recovery from stuttering.

Brain Damage Associated with Impaired Sentence Processing in Acute Aphasia.

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, for example, Broca's area, anterior temporal areas, and temporo-parietal areas. We examined the association between damage to specific language-related ROIs 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. One hundred four individuals with acute aphasia (<20 days poststroke) were included in the study. Structural MRI scans were obtained, and all participants completed a 45-item sentence-picture matching task. We performed an ROI-based stepwise regression analyses to examine the relation between cortical brain damage and impaired comprehension of canonical and noncanonical sentences. Damage to the posterior middle temporal gyrus was the strongest predictor for overall task performance and performance on noncanonical sentences. Damage to the angular gyrus was the strongest predictor for performance on canonical sentences, and damage to the posterior superior temporal gyrus predicted noncanonical scores when performance on canonical sentences was included as a cofactor. Overall, our models showed that damage to temporo-parietal and posterior temporal areas was associated with impaired syntactic comprehension. Our results indicate that the temporo-parietal area is crucially implicated in complex syntactic processing, whereas the role of Broca's area may be complementary.

Brain-Derived Neurotrophic Factor Genotype-Specific Differences in Cortical Activation in Chronic Aphasia.

Purpose The brain-derived neurotrophic factor (BDNF) gene has been shown to be important for synaptic plasticity in animal models. Human research has suggested that BDNF genotype may influence stroke recovery. Some studies have suggested a genotype-specific motor-related brain activation in stroke recovery. However, recovery from aphasia in relation to BDNF genotype and language-related brain activation has received limited attention. We aimed to explore functional brain activation by BDNF genotype in individuals with chronic aphasia. Consistent with findings in healthy individuals and individuals with poststroke motor impairment, we hypothesized that, among individuals with aphasia, the presence of the Met allele of the BDNF gene is associated with reduced functional brain activation compared to noncarriers of the Met allele. Method Eighty-seven individuals with chronic stroke-induced aphasia performed a naming task during functional magnetic resonance imaging scanning and submitted blood or saliva samples for BDNF genotyping. The mean number of activated voxels was compared between groups, and group-based activation maps were directly compared. Neuropsychological testing was conducted to compare language impairment between BDNF genotype groups. The Western Aphasia Battery Aphasia Quotient (Kertesz, 2007) was included as a covariate in all analyses. Results While lesion size was comparable between groups, the amount of activation, quantified as the number of activated voxels, was significantly greater in noncarriers of the Met allele (whole brain: 98,500 vs. 28,630, p < .001; left hemisphere only: 37,209 vs. 7,000, p < .001; right hemisphere only: 74,830 vs. 30,630, p < .001). This difference was most strongly expressed in the right hemisphere posterior temporal area, pre- and postcentral gyrus, and frontal lobe, extending into the white matter. Correspondingly, the atypical BDNF genotype group was found to have significantly less severe aphasia (Western Aphasia Battery Aphasia Quotient of 64.2 vs. 54.3, p = .033) and performed better on a naming task (Philadelphia Naming Test [Roach, Schwartz, Martin, Grewal, & Brecher, 1996] score of 74.7 vs. 52.8, p = .047). A region of interest analysis of intensity of activation revealed no group differences, and a direct comparison of average activation maps across groups similarly yielded null results. Conclusion BDNF genotype mediates cortical brain activation in individuals with chronic aphasia. Correspondingly, individuals carrying the Met allele present with more severe aphasia compared to noncarriers. These findings warrant further study into the effects of BDNF genotype in aphasia. Supplemental Material https://doi.org/10.23641/asha.10073147 Presentation Video https://doi.org/10.23641/asha.10257581.