Corticocerebellar White Matter Integrity Is Related to Naming Outcome in Post-Stroke Aphasia.

Studies have shown that the integrity of white matter tracts connecting different regions in the left cerebral hemisphere is important for aphasia recovery after stroke. However, the impact of the underlying structural connection between the cortex and the cerebellum in post-stroke aphasia is poorly understood. We studied the microstructural integrity of the cerebellum and the corticocerebellar connections and their role in picture naming. Fifty-six patients with left cerebral infarcts (sparing the cerebellum) underwent diffusion tensor imaging (DTI) and Boston Naming Test. We compared the fractional anisotropy (FA) and mean diffusivity (MD) values of the right and the left cerebellum (lobular gray and white matter structures) and cerebellocortical connections. Recursive feature elimination and Spearman correlation analyses were performed to evaluate the relationship between naming performance and the corticocerebellar connections. We found that the right, relative to left, cerebellar structures and their connections with the left cerebrum showed lower FA and higher MD values, both reflecting lower microstructural integrity. This trend was not observed in the healthy controls. Higher MD values of the right major cerebellar outflow tract were associated with poorer picture naming performance. Our study provides the first DTI data demonstrating the critical importance of ascending and descending corticocerebellar connections for naming outcomes after stroke.

When words first fail: Predicting the emergence of primary progressive aphasia variants from unclassifiable anomic performance in early disease.

Background: The majority of patients with primary progressive aphasia (PPA) can be distinguished into one of three variants: semantic, non-fluent/agrammatic, or logopenic. However, many do not meet criteria for any one variant. Aim: To identify aspects of cognitive-linguistic performance that yield an early unclassifiable PPA designation that predicted the later emergence of a given variant. Methods & Procedures: Of 256 individuals with PPA evaluated, 19 initially were unclassifiable and later met criteria for a variant. Receiver operating characteristic curves were used to evaluate the binary ability of a given task to predict eventual classification as a given variant. Tasks with a high area under the curve were examined using regression analyses to determine their ability to predict variant. Outcomes & Results: High mean predictive value was observed for multiple naming assessments targeting nouns and verbs. The Boston Naming Test (BNT) was the only test that, in isolation, resulted in a significant model and high classification accuracy. Conclusions: Although naming impairment is common across PPA variants, very low initial BNT scores emerged as a uniquely accurate basis for predicting eventual semantic variant, and normal BNT scores predicted eventual nonfluent/agrammatic variant. High performance on picture-verb verification was useful in identifying future lvPPA.

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

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

Association of Regional Atrophy With Naming Decline in Primary Progressive Aphasia.

BACKGROUND AND OBJECTIVES: Primary progressive aphasia (PPA) is a neurodegenerative condition that predominantly impairs language. Most investigations of how focal atrophy affects language consider 1 time point compared with healthy controls. However, true atrophy quantification requires comparing individual brains over time. In this observational cohort study, we identified areas where focal atrophy was associated with contemporaneous decline in naming in the same individuals. METHODS: Cross-sectional analyses-related Boston Naming Test (BNT) performance and volume in 22 regions of interests (ROIs) at each time point using Least Absolute Shrinkage and Selection Operator (LASSO) regression. Longitudinal analysis evaluated changes in BNT performance and change in volume in the same ROIs. RESULTS: Participants (N = 62; 50% female; mean age = 66.8 ± 7.4 years) with PPA completed the BNT and MRI twice (mean = 343.9 ± 209.0 days apart). In cross-sectional left inferior frontal gyrus pars opercularis, superior temporal pole, middle temporal gyrus, and inferior temporal gyrus were identified as critical for naming at all time points. Longitudinal analysis revealed that increasing atrophy in the left supramarginal gyrus and middle temporal pole predicted greater naming decline, as did female sex and longer intervals between time points. DISCUSSION: Although cross-sectional analyses identified classic language areas that were consistently related to poor performance at multiple time points, it was not increasing atrophy in these areas that lead to further decline: longitudinal analysis of each person's atrophy over time instead identified nearby but distinct regions where increased atrophy was related to decreasing performance. The results demonstrate that directly examining atrophy (in each individual) over time furthers understanding of decline in PPA and reveal the importance of left supramarginal gyrus and middle temporal pole in maintaining naming when areas normally critical for language degenerate. The novel results provide insight into how the underlying disease progresses to result in the clinical decline in naming, the deficit most common among all 3 PPA variants.

Neural regions underlying object and action naming: Complementary evidence from acute stroke and primary progressive aphasia.

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.

Neural correlates of syntactic comprehension: A longitudinal study.

Broca's area is frequently implicated in sentence comprehension but its specific role is debated. Most lesion studies have investigated deficits at the chronic stage. We aimed (1) to use acute imaging to predict which left hemisphere stroke patients will recover sentence comprehension; and (2) to better understand the role of Broca's area in sentence comprehension by investigating acute deficits prior to functional reorganization. We assessed comprehension of canonical and noncanonical sentences in 15 patients with left hemisphere stroke at acute and chronic stages. LASSO regression was used to conduct lesion symptom mapping analyses. Patients with more severe word-level comprehension deficits and a greater proportion of damage to supramarginal gyrus and superior longitudinal fasciculus were likely to experience acute deficits prior to functional reorganization. Broca's area was only implicated in chronic deficits. We propose that when temporoparietal regions are damaged, intact Broca's area can support syntactic processing after functional reorganization occurs.

Task performance to discriminate among variants of primary progressive aphasia.

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.

Stroke Recurrence and Its Relationship With Language Abilities.

Purpose Many factors influence poststroke language recovery, yet little is known about the influence of previous stroke(s) on language after left hemisphere stroke. In this prospective longitudinal study, we investigated the role of prior stroke on language abilities following an acute left hemisphere ischemic stroke, while controlling for demographic and stroke-related factors, and examined if earlier stroke impacted language recovery at a chronic time point. Method Participants (n = 122) with acute left hemisphere ischemic stroke completed language evaluation and clinical neuroimaging. They were divided into two groups: single stroke (SS; n = 79) or recurrent stroke (RS; n = 43). A subset of participants (n = 31) completed chronic-stage re-evaluation. Factors studied included age, education, diabetes and hypertension diagnoses, lesion volume and broad location, group status, aphasia prevalence, and language scores. Results Groups did not differ in language performance across time points. The only significant group differences were that participants with RS were older, had smaller acute lesions, and were less educated. Stroke group membership (SS vs. RS) was not associated with language performance at either time point. In patients with prior stroke, large acute lesion volumes were associated with acute language performance, whereas both large acute and chronic volumes influenced recovery. Conclusions History of prior stroke in itself may not significantly influence language impairment after an additional acute left hemisphere stroke, unless it contributes substantially to the total volume of infarcted brain tissue. Chronic and acute lesion volumes should be accounted for in studies investigating poststroke language performance and recovery. Supplemental Material https://doi.org/10.23641/asha.14669715.

Thalamic Nuclei and Thalamocortical Pathways After Left Hemispheric Stroke and Their Association with Picture Naming.

Background: Previous studies utilized lesion-centric approaches to study the role of the thalamus in language. In this study, we tested the hypotheses that non-lesioned dorsomedial and ventral anterior nuclei (DMVAC) and pulvinar lateral posterior nuclei complexes (PLC) of the thalamus and their projections to the left hemisphere show secondary effects of the strokes, and that their microstructural integrity is closely related to language-related functions. Methods: Subjects with language impairments after a left-hemispheric cortical and/or subcortical, early stroke (n = 31, ≤6 months) or late stroke (n = 30, ≥12 months) sparing thalamus underwent the Boston Naming Test (BNT) and diffusion tensor imaging (DTI). The tissue integrity of DMVAC, PLC, and their cortical projections was quantified with DTI. The right-left asymmetry profiles of these structures were evaluated in relation to the time since stroke. The association between microstructural integrity and BNT score was investigated in relation to stroke chronicity with partial correlation analyses adjusted for confounds. Results: In both early stroke and late stroke groups, left-sided tracts showed significantly higher mean diffusivities (MDs), which were likely due to Wallerian degeneration. Higher MD values of the cortical projections from the left PLC (r = -0.5, p = 0.005) and DMVAC (r = -0.53, p = 0.002) were correlated with lower BNT score in the late stroke but not early stroke group. Conclusion: Nonlesioned thalamic nuclei and thalamocortical pathways show rightward lateralization of the microstructural integrity after a left hemispheric stroke, and this pattern is associated with poorer naming. Impact statement To the best of our knowledge, our study is the first diffusion tensor imaging study suggesting that the thalamic nuclei and pathways of the left hemisphere spared by direct ischemic insult undergo secondary degeneration over time that is associated with poorer picture naming. Our study may pave the way for targeted interventions such as invasive or noninvasive brain stimulation techniques that engage these spared pathways to prevent secondary degeneration and lead to better outcomes in poststroke aphasia.

A double dissociation between plural and possessive "s": Evidence from the Morphosyntactic Generation test.

People with aphasia demonstrate impaired production of bound inflectional morphemes, such as noun plurals and possession. They often show greater difficulty in marking possession versus plurality. Using a new tool for eliciting language, 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. Performance of the plural was stronger than possessive in group analyses. However, some individuals demonstrated the inverse pattern of performance. These participants provide counter-evidence to the theory that difficulty with marking possessives is purely the result of their greater cognitive-linguistic complexity and support a functional double dissociation between possessives and plurals. The deficits resulted from morphosyntactic impairment. Future work is needed to understand why plural and possessive markers were differently sensitive to neurological disorders of language.

Neuromodulation in post-stroke aphasia treatment.

PURPOSE OF REVIEW: This paper aims to review non-invasive brain stimulation (NIBS) methods to augment speech and language therapy (SLT) for patients with post-stroke aphasia. RECENT FINDINGS: In the past five years there have been more than 30 published studies assessing the effect of transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) for improving aphasia in people who have had a stroke. Different approaches to NIBS treatment have been used in post-stroke aphasia treatment including different stimulation locations, stimulation intensity, number of treatment sessions, outcome measures, type of aphasia treatment, and time post-stroke. SUMMARY: This review of NIBS for post-stroke aphasia shows that both tDCS and TMS can be beneficial for improving speech and language outcomes for patients with stroke. Prior to translating NIBS to clinical practice, further studies are needed to determine optimal tDCS and TMS parameters as well as the mechanisms underlying tDCS and TMS treatment outcomes.

White Matter Hyperintensities Contribute to Language Deficits in Primary Progressive Aphasia.

OBJECTIVE: To determine the contribution of white matter hyperintensities (WMH) to language deficits while accounting for cortical atrophy in individuals with primary progressive aphasia (PPA). METHOD: Forty-three individuals with PPA completed neuropsychological assessments of nonverbal semantics, naming, and sentence repetition plus T2-weighted and fluid-attenuated inversion recovery scans. Using three visual scales, we rated WMH and cerebral ventricle size for both scan types. We used Spearman correlations to evaluate associations between the scales and scans. To test whether visual ratings-particularly of WMH-are associated with language, we compared a base model (including gray matter component scores obtained via principal component analysis, age, and days between assessment and MRI as independent variables) with full models (ie, the base model plus visual ratings) for each language variable. RESULTS: Visual ratings were significantly associated within and between scans and were significantly correlated with age but not with other vascular risk factors. Only the T2 scan ratings were associated with language abilities. Specifically, controlling for other variables, poorer naming was significantly related to larger ventricles (P = 0.033) and greater global (P = 0.033) and periventricular (P = 0.049) WMH. High global WMH (P = 0.034) were also correlated with worse sentence repetition skills. CONCLUSION: Visual ratings of global brain health were associated with language deficits in PPA independent of cortical atrophy and age. While WMH are not unique to PPA, measuring WMH in conjunction with cortical atrophy may elucidate more accurate brain structure-behavior relationships in PPA than cortical atrophy measures alone.

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

BACKGROUND: It is estimated that ∼30% of stroke survivors have aphasia, a language disorder resulting from damage to left-hemisphere language networks. In acute care settings, efficient identification of aphasia is critical, but there is a paucity of efficient bedside assessments. OBJECTIVE: To determine whether objective measures on a picture description task administered within 48 hours post stroke (a) predict language recovery, (b) estimate left-hemisphere lesion volume and location, and (c) correlate with other bedside language assessments. METHOD: Behavioral data were scored at acute and chronic time points. Neuroimaging data were used to determine associations between the picture description task, other language assessments, and lesion volume and location. RESULTS: Acute content units, age, and total lesion volume predicted communication recovery; F3,18 = 3.98, P = 0.024; r = 0.40. Significant correlations were found between the picture description task and lesion volume and location. Picture description outcomes were also associated with other clinical language assessments. DISCUSSION: This picture description task quickly predicted the language performance (communication recovery and outcome) for patients who suffered a left-hemisphere stroke. Picture description task measures correlated with damage in the left hemisphere and with other, more time-consuming and cumbersome language assessments that are typically administered acutely at bedside. CONCLUSION: The predictive value of this picture description task and correlations with existing language assessments substantiate the clinical importance of a reliable yet rapid bedside measure for acute stroke patients that can be administered by a variety of health care professionals.

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

OBJECTIVE: To determine whether right ventral stream and limbic structures (including posterior superior temporal gyrus [STG], STG, temporal pole, inferior frontal gyrus pars orbitalis, orbitofrontal cortex, amygdala, anterior cingulate, gyrus, and the sagittal stratum) are implicated in emotional prosody identification. METHODS: Patients with MRI scans within 48 hours of unilateral right hemisphere ischemic stroke were enrolled. Participants were presented with 24 sentences with neutral semantic content spoken with happy, sad, angry, afraid, surprised, or bored prosody and chose which emotion the speaker was feeling based on tone of voice. Multivariable linear regression was used to identify individual predictors of emotional prosody identification accuracy from a model, including percent damage to proposed right hemisphere structures, age, education, and lesion volume across all emotions (overall emotion identification) and 6 individual emotions. Patterns of recovery were also examined at the chronic stage. RESULTS: The overall emotion identification model was significant (adjusted r 2 = 0.52; p = 0.043); greater damage to right posterior STG (p = 0.038) and older age (p = 0.009) were individual predictors of impairment. The model for recognition of fear was also significant (adjusted r 2 = 0.77; p = 0.002), with greater damage to right amygdala (p = 0.047), older age (p < 0.001), and less education (p = 0.005) as individual predictors. Over half of patients with chronic stroke had residual impairments. CONCLUSIONS: Right posterior STG in the right hemisphere ventral stream is critical for emotion identification in speech. Patients with stroke with damage to this area should be assessed for emotion identification impairment.

Neural processing critical for distinguishing between speech sounds.

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

Learning in complex, multi-component cognitive systems: Different learning challenges within the same system.

Using word learning as an example of a complex system, we investigated how differences in the structure of the subcomponents in which learning occurs can have significant consequences for the challenge of integrating new information within such systems. Learning a new word involves integrating information into the two key stages/subcomponents of processing within the word production system. In the first stage, multiple semantic features are mapped onto a single word. Conversely, in the second stage, a single word is mapped onto multiple segmental features. We tested whether the unitary goal of word learning leads to different local outcomes in these two stages because of their reversed mapping patterns. Neurotypical individuals (N = 17) learned names and semantic features for pictures of unfamiliar objects presented in semantically related, segmentally related and unrelated blocks. Both similarity types interfered with word learning. However, feature learning was differentially affected within the two subcomponents of word production. Semantic similarity facilitated learning distinctive semantic features (i.e., features unique to each item), whereas segmental similarity facilitated learning shared segmental features (i.e., features common to several items in a block). These results are compatible with an incremental learning model in which learning not only strengthens certain associations but also weakens others according to the local goals of each subcomponent. More generally, they demonstrate that the same overall learning goal can lead to opposite learning outcomes in the subcomponents of a complex system. The general principles uncovered may extend beyond word learning to other complex systems with multiple subcomponents. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Contributions of Neuroimaging to Understanding Language Deficits in Acute Stroke.

Advances in structural and functional imaging techniques have provided new insights into our understanding of brain and language relationships. In this article, we review the various structural and functional imaging methods currently used to study language deficits in acute stroke. We also discuss the advantages and the limitations of each imaging modality and the applications of each modality in the clinical and research settings in the study of language deficits.