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 No patients were withdrawn due to adverse events.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.

Right Hemispheric Homologous Language Pathways Negatively Predicts Poststroke Naming Recovery.

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

Predicting recovery in acute poststroke aphasia.

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

Distinguishing logopenic from semantic & nonfluent variant primary progressive aphasia: Patterns of linguistic and behavioral correlations.

While language characteristics of logopenic variant primary progressive aphasia (lvPPA) are well-defined, behavioral characteristics are less understood. We investigated correlations between language and behavioral scores across three variants of primary progressive aphasia (PPA) and found language performance and behavioral disturbances are correlated in lvPPA, but not other PPA subtypes. Results suggest that unlike other PPA variants, patients diagnosed with lvPPA do not develop negative behaviors until language deficits are severe. This is consistent with the underlying neuropathology of lvPPA, Alzheimer's Disease. Such findings are crucial to clinical prognosis, especially when considering the progressive nature of this disease.

Neural representation of word categories is distinct in the temporal lobe: An activation likelihood analysis.

The distinction between nouns and verbs is a language universal. Yet, functional neuroimaging studies comparing noun and verb processing have yielded inconsistent findings, ranging from a complete frontal(verb)-temporal(noun) dichotomy to a complete overlap in activation patterns. The current study addressed the debate about neural distinctions between nouns and verbs by conducting an activation likelihood estimation (ALE) meta-analysis of probabilistic cytoarchitectonic maps. Two levels of analysis were conducted: simple effects (Verbs vs. Baseline, Nouns vs. Baseline), and direct comparisons (Verbs vs. Nouns, Nouns vs. Verbs). Nouns were uniquely associated with a left medial temporal cluster (BA37). Activation foci for verbs included extensive inferior frontal (BA44-47) and mid-temporal (BA22, 21) regions in the left hemisphere. These findings confirm that the two grammatical classes have distinct neural architecture in supra-modal brain regions. Further, nouns and verbs overlapped in a small left lateral inferior temporal activation cluster (BA37), which is a region for modality-independent, grammatical class-independent lexical representations. These findings are most consistent with the view that as one acquires language, linguistic representations for a lexical category shift from the modality specific cortices which represent prototypical members of that category (e.g., motion for verbs) to abstract amodal representations in close proximity to modality specific cortices.

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.

Regional Brain Dysfunction Associated with Semantic Errors in Comprehension.

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.

Important considerations in lesion-symptom mapping: Illustrations from studies of word comprehension.

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.

Stroke of bad luck?

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.

Picturing the Size and Site of Stroke With an Expanded National Institutes of Health Stroke Scale.

BACKGROUND AND PURPOSE: The National Institutes of Health Stroke Scale (NIHSS) includes minimal assessment of cognitive function, particularly in right hemisphere (RH) stroke. Descriptions of the Cookie Theft picture from the NIHSS allow analyses that (1) correlate with aphasia severity and (2) identify communication deficits in RH stroke. We hypothesized that analysis of the picture description contributes valuable information about volume and location of acute stroke. METHODS: We evaluated 67 patients with acute ischemic stroke (34 left hemisphere [LH]; 33 RH) with the NIHSS, analysis of the Cookie Theft picture, and magnetic resonance imaging, compared with 35 sex- and age-matched controls. We evaluated descriptions for total content units (CU), syllables, ratio of left:right CU, CU/minute, and percent interpretive CU, based on previous studies. Lesion volume and percent damage to regions of interest were measured on diffusion-weighted imaging. Multivariable linear regression identified variables associated with infarct volume, independently of NIHSS score, age and sex. RESULTS: Patients with RH and LH stroke differed from controls, but not from each other, on CU, syllables/CU, and CU/minute. Left:right CU was lower in RH compared with LH stroke. CU, syllables/CU, and NIHSS each correlated with lesion volume in LH and RH stroke. Lesion volume was best accounted by a model that included CU, syllables/CU, NIHSS, left:right CU, percent interpretive CU, and age, in LH and RH stroke. Each discourse variable and NIHSS score were associated with percent damage to different regions of interest, independently of lesion volume and age. CONCLUSIONS: Brief picture description analysis complements NIHSS scores in predicting stroke volume and location.

The roles of occipitotemporal cortex in reading, spelling, and naming.

We evaluated the hypothesis that Brodmann's area (BA) 37 within left occipitotemporal cortex has at least two important functions in lexical processing. One role is the computation of case-, font-, location-, and orientation-independent grapheme descriptions for written word recognition and production (reading and spelling). This role may depend on the medial part of BA 37, in left midfusiform gyrus. The second role is in accessing modality-independent lexical representations for output, for naming and for reading and spelling of irregular or exception words. This role may depend on the lateral part of BA 37 in inferior temporal cortex. We tested these hypotheses in 234 participants with acute left hemisphere ischaemic stroke who underwent magnetic resonance imaging (MRI) and language testing within 48 hours of onset of stroke symptoms.

Protocol for Cerebellar Stimulation for Aphasia Rehabilitation (CeSAR): A randomized, double-blind, sham-controlled trial.

In this randomized, double-blind, sham-controlled trial of Cerebellar Stimulation for Aphasia Rehabilitation (CeSAR), we will determine the effectiveness of cathodal tDCS (transcranial direct current stimulation) to the right cerebellum for the treatment of chronic aphasia (>6 months post stroke). We will test the hypothesis that cerebellar tDCS in combination with an evidenced-based anomia treatment (semantic feature analysis, SFA) will be associated with greater improvement in naming untrained pictures (as measured by the change in Philadelphia Picture Naming Test), 1-week post treatment, compared to sham plus SFA. We will also evaluate the effects of cerebellar tDCS on naming trained items as well as the effects on functional communication, content, efficiency, and word-retrieval of picture description, and quality of life. Finally, we will identify imaging and linguistic biomarkers to determine the characteristics of stroke patients that benefit from cerebellar tDCS and SFA treatment. We expect to enroll 60 participants over five years. Participants will receive 15, 25-minute sessions of cerebellar tDCS (3-5 sessions per week) or sham tDCS combined with 1 hour of SFA treatment. Participants will be evaluated prior to the start of treatment, one-week post-treatment, 1-, 3-, and 6-months post treatment on primary and secondary outcome variables. The long-term aim of this study is to provide the basis for a Phase III randomized controlled trial of cerebellar tDCS vs sham with concurrent language therapy for treatment of chronic aphasia. Trial registration: The trial is registered with ClinicalTrials.gov NCT05093673.

Distinct mechanisms and timing of language recovery after stroke.

The "language network" is remarkably stable across language tasks but changes in response to injury to specific components or in response to "disconnection" of input to one component. We investigated network changes during language recovery, hypothesizing that language recovery takes place through distinct mechanisms: (a) reperfusion; (b) recovery from diaschisis; (c) recovery from structural disconnection; and (d) "reorganization" of language, whereby various components assume function of a damaged component. We also tested the hypothesis that "reorganization" depends on: the language task, level of performance, size and site of stroke, and time post onset. We tested these hypotheses in five participants who had structural, perfusion, and functional imaging utilizing spelling, reading, word generation, and picture naming tasks at acute and subsequent stages after ischaemic stroke. These cases illustrate different mechanisms of aphasia recovery or illustrate that reorganization of language acutely depends on individual variables in addition to size and site of stroke.

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.

Clinical Implementation of Noninvasive Brain Stimulation in an Outpatient Neurorehabilitation Program.

ABSTRACT: Motor, speech, and cognitive impairments are the most common consequences of neurological disorders. There has been an increasing interest in the use of noninvasive brain stimulation techniques such as transcranial direct current stimulation and transcranial magnetic stimulation to augment the effects of neurorehabilitation. Numerous research studies have shown that transcranial direct current stimulation and transcranial magnetic stimulation are highly promising neuromodulation tools that can work as adjuvants to standard neurorehabilitation services, including physical therapy, occupational therapy, and speech-language pathology. However, to date, there are vast differences in methodology in studies including noninvasive brain stimulation parameters, patient characteristics, time point of intervention after injury, and outcome measures, making it difficult to translate and implement transcranial direct current stimulation and transcranial magnetic stimulation in the clinical setting. Despite this, a series of principles are thought to underlie the effectiveness of noninvasive brain stimulation techniques. We developed a noninvasive brain stimulation rehabilitation program using these principles to provide best practices for applying transcranial direct current stimulation and/or transcranial magnetic stimulation as rehabilitation adjuvants in the clinical setting to help improve neurorehabilitation outcomes. This article outlines our approach, philosophy, and experience.

Resting state correlates of picture description informativeness in left vs. right hemisphere chronic stroke.

Introduction: Despite a growing emphasis on discourse processing in clinical neuroscience, relatively little is known about the neurobiology of discourse production impairments. Individuals with a history of left or right hemisphere stroke can exhibit difficulty with communicating meaningful discourse content, which implies both cerebral hemispheres play a role in this skill. However, the extent to which successful production of discourse content relies on network connections within domain-specific vs. domain-general networks in either hemisphere is unknown. Methods: In this study, 45 individuals with a history of either left or right hemisphere stroke completed resting state fMRI and the Cookie Theft picture description task. Results: Participants did not differ in the total number of content units or the percentage of interpretative content units they produced. Stroke survivors with left hemisphere damage produced significantly fewer content units per second than individuals with right hemisphere stroke. Intrinsic connectivity of the left language network was significantly weaker in the left compared to the right hemisphere stroke group for specific connections. Greater efficiency of communication of picture scene content was associated with stronger left but weaker right frontotemporal connectivity of the language network in patients with a history of left hemisphere (but not right hemisphere) stroke. No significant relationships were found between picture description measures and connectivity of the dorsal attention, default mode, or salience networks or with connections between language and other network regions. Discussion: These findings add to prior behavioral studies of picture description skills in stroke survivors and provide insight into the role of the language network vs. other intrinsic networks during discourse production.

Transcranial Direct Current Stimulation Paired With Verb Network Strengthening Treatment Improves Verb Naming in Primary Progressive Aphasia: A Case Series.

PURPOSE: There are few evidence-based treatments for language deficits in primary progressive aphasia (PPA). PPA treatments are often adopted from the poststroke aphasia literature. The poststroke aphasia literature has shown promising results using Verb Network Strengthening Treatment (VNeST), a behavioral therapy that focuses on improving naming by producing verbs and their arguments in phrases and sentences. Emerging research in poststroke aphasia and PPA has shown promising results pairing behavioral language therapy with transcranial direct current stimulation (tDCS). METHOD: This study used a double-blind, within-subjects, sham-controlled crossover design to study the effect of anodal tDCS applied to left inferior frontal gyrus (IFG) plus VNeST versus VNeST plus sham stimulation in two individuals with nonfluent variant PPA and one individual with logopenic variant PPA. Participants received two phases of treatment, each with 15 1-hr sessions of VNeST. One phase paired VNeST with tDCS stimulation, and one with sham. For each phase, language testing was conducted at baseline, and at 1 week and 8 weeks posttreatment conclusion. For each participant, treatment efficacy was evaluated for each treatment phase by comparing the mean change in accuracy between baseline and the follow-up time points for naming trained verbs (primary outcome measure), untrained verbs, and nouns on the Object and Action Naming Battery. Mean change from baseline was also directly compared between tDCS and sham phases at each time point. RESULTS: Results revealed a different pattern of outcomes for each of the participants. A tDCS advantage was not found for trained verbs for any participant. Two participants with nonfluent variant PPA had a tDCS advantage for generalization to naming of untrained verbs, which was apparent at 1 week and 8 weeks posttreatment. One participant with nonfluent variant also showed evidence of generalization to sentence production in the tDCS phase. CONCLUSION: VNeST plus anodal tDCS stimulation of left IFG shows promising results for improving naming in PPA.

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.

Diagnosing and managing post-stroke aphasia.

Introduction: Aphasia is a debilitating language disorder and even mild forms of aphasia can negatively affect functional outcomes, mood, quality of life, social participation, and the ability to return to work. Language deficits after post-stroke aphasia are heterogeneous. Areas covered: The first part of this manuscript reviews the traditional syndrome-based classification approach as well as recent advances in aphasia classification that incorporate automatic speech recognition for aphasia classification. The second part of this manuscript reviews the behavioral approaches to aphasia treatment and recent advances such as noninvasive brain stimulation techniques and pharmacotherapy options to augment the effectiveness of behavioral therapy. Expert opinion: Aphasia diagnosis has largely evolved beyond the traditional approach of classifying patients into specific syndromes and instead focuses on individualized patient profiles. In the future, there is a great need for more large scale randomized, double-blind, placebo-controlled clinical trials of behavioral treatments, noninvasive brain stimulation, and medications to boost aphasia recovery.

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.