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 No patients were withdrawn due to adverse events.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.

Enhanced Imaging and Language Assessments for Primary Progressive Aphasia.

BACKGROUND AND OBJECTIVES: It is widely agreed that primary progressive aphasia (PPA) is a clinical syndrome with at least 3 distinct variants that differ in phenotype, areas of atrophy, and most common underlying neurodegenerative disease. The distinction between logopenic variant PPA (lvPPA) and other variants is important for prognosis and medical management. However, differentiating logopenic from nonfluent agrammatic variant can be difficult. We aimed to identify a novel behavioral assessment that (1) distinguishes logopenic from the other variants with a high degree of accuracy and (2) correlates with left superior temporal-inferior parietal atrophy (previously shown to be associated with this variant). The location of atrophy was measured using a novel, clinically useful imaging analysis. METHODS: In this observational cohort study of 227 individuals with PPA, participants were administered sentence reading and repetition subtests from a standard battery. A subset of 41 participants were administered enhanced reading and repetition subtests with 5 longer sentences, of which 13 had brain imaging. Ratios of word-level and sentence-level accuracy in reading:repetition were calculated. We used one-way analysis of variance (ANOVA) to determine whether either or both ratios of reading:repetition independently discriminated between variants and t test to determine whether the ratios distinguished between nonfluent and logopenic variants. We identified receiver operating characteristics and Pearson correlations between the reading:repetition ratios and ratio of left:right superior temporal-inferior parietal volume. RESULTS: The sentence reading:repetition ratio using the new stimuli significantly differed across the 3 variants (p < 0.00001) and differed between nonfluent and logopenic variants (t(27) = 4.1; p = 0.0003). The area under the curve for distinguishing logopenic from other variants was 0.85 (0.71-0.99), and the diagnostic accuracy was 87.5%. The sentence reading:repetition ratio correlated with left:right superior temporal-inferior parietal volume (r = 0.69; p = 0.0087), but not with left:right volume of regions of interest associated with other variants. DISCUSSION: Results provide an efficient and reliable clinical assessment, and a novel imaging analysis, to distinguish the clinical syndrome of logopenic variant from other variants of PPA. Results also support the proposal that lvPPA reflects a defect in phonological short-term memory caused by atrophy in the superior temporal-inferior parietal cortex. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that the sentence reading:repetition ratio distinguished logopenic PPA from other PPA variants.

Dysfunctional Tissue Correlates of Unrelated Naming Errors in Acute Left Hemisphere Stroke.

Most naming error lesion-symptom mapping (LSM) studies have focused on semantic and/or phonological errors. Anomic individuals also produce unrelated word errors, which may be linked to semantic or modality-independent lexical deficits. To investigate the neural underpinnings of rarely-studied unrelated errors, we conducted LSM analyses in 100 individuals hospitalized with a left hemisphere stroke who completed imaging protocols and language assessments. We used least absolute shrinkage and selection operator regression to capture relationships between naming errors and dysfunctional brain tissue metrics (regional damage or hypoperfusion in vascular territories) in two groups: participants with and without impaired single-word auditory comprehension. Hypoperfusion-particularly within the parietal lobe-was an important error predictor, especially for the unimpaired group. In both groups, higher unrelated error proportions were associated with primarily ventral stream damage, the language route critical for processing meaning. Nonetheless, brain metrics implicated in unrelated errors were distinct from semantic error correlates.