Diabetes, brain health, and treatment gains in post-stroke aphasia.

Decision letter: Stage-dependent differential influence of metabolic and structural networks on memory across Alzheimer’s disease continuum

BackgroundStudies suggest that language recovery in aphasia may be improved by pairing speech-language therapy with transcranial direct current stimulation. However, results from many studies have been inconclusive regarding the impact transcranial direct current stimulation may have on language recovery in individuals with aphasia. An important factor that may impact the efficacy of transcranial direct current stimulation is its timing relative to speech-language therapy. Namely, online transcranial direct current stimulation (paired with speech-language therapy) and offline transcranial direct current stimulation (prior to or following speech-language therapy) may have differential effects on language recovery in post-stroke aphasia. Transcranial direct current stimulation provided immediately before speech-language therapy may prime the language system whereas stimulation provided immediately after speech-language therapy may aid in memory consolidation. The main aim of this study is to investigate the differential effects of offline and online transcranial direct stimulation on language recovery (i.e., conversation) in post-stroke aphasia.Methods/designThe study is a randomized, parallel-assignment, double-blind treatment study. Participants will be randomized to one of four treatment conditions and will participate in 15 treatment sessions. All groups receive speech-language therapy in the form of computer-based script practice. Three groups will receive transcranial direct current stimulation: prior to speech-language therapy, concurrent with speech-language therapy, or following speech-language therapy. One group will receive sham stimulation (speech-language therapy only). We aim to include 12 participants per group (48 total). We will use fMRI-guided neuronavigation to determine placement of transcranial direct stimulation electrodes on participants’ left angular gyrus. Participants will be assessed blindly at baseline, immediately post-treatment, and at 4 weeks and 8 weeks following treatment. The primary outcome measure is change in the rate and accuracy of the trained conversation script from baseline to post-treatment.DiscussionResults from this study will aid in determining the optimum timing to combine transcranial direct current stimulation with speech-language therapy to facilitate better language outcomes for individuals with aphasia. In addition, effect sizes derived from this study may also inform larger clinical trials investigating the impact of transcranial direct current stimulation on functional communication in individuals with aphasia.Trial registrationClinicalTrials.gov NCT03773406. December 12, 2018.

ObjectivesTo investigate the hypothesis that language recovery in post‐stroke aphasia is associated with structural brain changes.MethodsWe evaluated whether treatment‐induced improvement in naming is associated with reorganization of tissue microstructure within residual cortical regions. To this end, we performed a retrospective longitudinal treatment study using comprehensive language‐linguistic assessments and diffusion MRI sequences optimized for the assessment of complex microstructure (diffusional kurtosis imaging) to evaluate the relationship between language treatment response and cortical changes in 26 individuals with chronic stroke‐induced aphasia. We employed elastic net statistical models controlling for baseline factors including age, sex, and time since the stroke, as well as lesion volume.ResultsWe observed that improved naming accuracy (Philadelphia Naming Test) was statistically associated with increased post‐treatment microstructural integrity in the left posterior superior temporal gyrus. Moreover, increase in microstructural integrity in the left middle temporal gyrus and left inferior temporal gyrus was specifically associated with a decrease in semantic paraphasias. This longitudinal relationship between brain tissue integrity and language improvement was not observed in other non‐language related brain regions.InterpretationOur findings provide evidence that structural brain changes in the preserved left hemisphere regions are associated with treatment‐induced language recovery in aphasia and are part of the mechanisms supporting language and brain injury recovery.

Relationship between brain structural network integrity and emotional symptoms in youth with perinatally-acquired HIV

Background. Brain-derived neurotrophic factor (BDNF) is assumed to play a role in mediating neuroplasticity after stroke. Carriers of the function-limiting Val66Met (rs6265) single nucleotide polymorphism (SNP) may have a downregulation in BDNF secretion, which may lead to a poorer prognosis after stroke compared to noncarriers in motor learning and motor function recovery. The present study investigates whether this polymorphism may also affect the recovery of poststroke aphasia (ie, language impairment). Objective. To study the influence of the BDNF Val66Met polymorphism on the recovery of poststroke aphasia. Methods. We included 53 patients with poststroke aphasia, all participating in an inpatient rehabilitation program with speech and language therapy. All patients were genotyped for the Val66Met SNP and subdivided into carriers (at least one Met allele) and noncarriers (no Met allele). Primary outcome measures included the improvement over rehabilitation time on the Amsterdam-Nijmegen Everyday Language Test (ANELT) and the Boston Naming Test (BNT). Results. The outcome measures showed a large variability in the improvement scores on both the ANELT and BNT. There was no significant difference between noncarriers and carriers in the primary outcome measures. Conclusion. This study investigated the effect of the BDNF Val66Met polymorphism on clinical recovery of poststroke aphasia. In contrast to earlier studies describing a reducing effect of this polymorphism on motor function recovery after stroke, the present study does not support a reduction in language recovery for carriers compared to noncarriers with poststroke aphasia.

Brain health imaging markers, post-stroke aphasia and Cognition: A scoping review

Objectives: In this pilot study we investigated the effects of transcranial direct current stimulation (tDCS) on language recovery in the subacute stage of post-stroke aphasia using clinical parameters and diffusion imaging with constrained spherical deconvolution-based tractography. Methods: The study included 21 patients with subacute post-stroke aphasia. Patients were randomly classified into two groups with a ratio of 2:1 to receive real tDCS or sham tDCS as placebo control. Patients received 10 sessions (5/week) bi-hemispheric tDCS treatments over the left affected Broca’s area (anodal electrode) and over the right unaffected Broca’s area (cathodal stimulation). Aphasia score was assessed clinically using the language section of the Hemispheric Stroke Scale (HSS) before and after treatment sessions. Diffusion imaging and tractography were performed for seven patients of the real group, both before and after the 10th session. Dissection of language-related white matter tracts was achieved, and diffusion measures were extracted. A paired Student’s t-test was used to compare the clinical recovery and diffusion measures of the dissected tracts both pre- and post- treatment. The partial correlation between changes in diffusion measures and the language improvements was calculated. Results: At baseline assessment, there were no significant differences between groups in demographic and clinical HSS language score. No significant clinical recovery in HSS was evident in the sham group. However, significant improvements in the different components of HSS were only observed in patients receiving real tDCS. Associated significant increase in the fractional anisotropy of the right uncinate fasciculus and a significant reduction in the mean diffusivity of the right frontal aslant tract were reported. A significant positive correlation was found between the changes in the right uncinate fasciculus and fluency improvement. Conclusions: Aphasia recovery after bi-hemispheric transcranial direct current stimulation was associated with contralesional right-sided white matter changes at the subacute stage. These changes probably reflect neuroplasticity that could contribute to the recovery. Both the right uncinate fasciculus and right frontal aslant tract seem to be involved in aphasia recovery.

Repetitive transcranial magnetic stimulation (rTMS) is a promising intervention for language recovery in post-stroke aphasia, yet the efficacy of different frequency protocols remains to be fully understood. This study aims to explore the efficacy of high versus low-frequency rTMS on language recovery in post-stroke aphasia. In this retrospective cohort study, 194 patients with post-stroke aphasia who underwent rTMS treatment from December 2019 to December 2022 were analyzed. Patients were categorized into 2 groups based on the frequency of rTMS received: low frequency (≤1 Hz, n = 101) and high frequency (≥5 Hz, n = 93). National Institutes of Health Stroke Scale scores were recorded to quantify overall neurological deficits at baseline. Language outcomes were assessed using the Western Aphasia Battery-Aphasia Quotient (WAB-AQ) and the Boston Naming Test (BNT) at baseline, immediately post-treatment, and 2 months later. Adverse events were also recorded. One day post-treatment, the low-frequency rTMS group showed significantly greater improvements in WAB-AQ scores compared to the high-frequency group (P < .001), with significant enhancements in spontaneous speech, auditory comprehension, repetition, and naming (all P < .001). BNT scores also improved significantly in the low-frequency group (P = .025). At the 2-month follow-up, both groups exhibited continued improvement, but the low-frequency group maintained significantly greater gains in WAB-AQ (P < .001), BNT (P = .032), spontaneous speech (P < .001), auditory comprehension (P = .003), repetition (P = .041), and naming (P = .019). Linear mixed model analysis confirmed that low-frequency rTMS facilitated superior language recovery, with significant Time*Group interactions observed for WAB-AQ (P < .001), spontaneous speech (P < .001), auditory comprehension (P < .001), and naming (P = .034). High-frequency rTMS was associated with a higher frequency of headaches (P = .018) and scalp dysesthesia (P < .001). Serious adverse events were significantly less frequent in the low-frequency group (P < .001). Low-frequency rTMS is more effective and safer than high-frequency rTMS in improving language recovery for patients with post-stroke aphasia. These findings suggest a potential preference for low-frequency rTMS in clinical settings.

BackgroundCardiovascular risk factor burden in the absence of clinical or radiological “events” is associated with mild cognitive impairment. Magnetic resonance imaging techniques exploring the integrity of neuronal fiber connectivity within white matter networks supporting cognitive processing could be used to measure the impact of cardiovascular disease on brain health and be used beyond bedside neuropsychological tests to detect subclinical changes and select or stratify participants for entry into clinical trials.Methods and ResultsWe assessed the relationship between verbal IQ and brain network integrity and the effect of cardiovascular risk factors on network integrity by constructing whole‐brain structural connectomes from magnetic resonance imaging diffusion images (N=60) from people with various degrees of cardiovascular risk factor burden. We measured axonal integrity by calculating network density and determined the effect of fiber loss on network topology and efficiency, using graph theory. Multivariate analyses were used to evaluate the relationship between cardiovascular risk factor burden, physical activity, age, education, white matter integrity, and verbal IQ. Reduced network density, resulting from a disproportionate loss of long‐range white matter fibers, was associated with white matter network fragmentation (r=−0.52, P<10−4), lower global efficiency (r=0.91, P<10−20), and decreased verbal IQ (adjusted R 2=0.23, P<10−4).ConclusionsCardiovascular risk factors may mediate negative effects on brain health via loss of energy‐dependent long‐range white matter fibers, which in turn leads to disruption of the topological organization of the white matter networks, lowered efficiency, and reduced cognitive function.

Language recovery in aphasia following implicit structural priming

Obstructive sleep apnea is highly prevalent in the post-stroke population, and has been shown to affect cognitive, neurological, and functional status. Continuous positive airway pressure (CPAP) treatment is one of the most effective interventions for obstructive sleep apnea, but compliance is often low due to confounding effects of co-occurring conditions, side effects of treatment titration procedures, and individual patient personality characteristics, perceptions, and social factors. Current research suggests that CPAP treatment for obstructive sleep apnea is not associated with significant risk and can subsequently improve post-stroke motor and neurocognitive function. However, effects of CPAP treatment on post-stroke speech and language recovery remain unclear. Post-stroke communication disorders (e.g., aphasia, dysarthria, and apraxia) are also highly prevalent in this population. Knowledge of the potential positive impact of CPAP on language recovery could contribute to patients’ motivation to comply with CPAP treatment and provide incentive for speech-language pathologists to refer patients to sleep medicine specialists. In this review of the literature, we examine the question of what effect CPAP treatment may have on post-stroke speech and language function and recovery, as well as summarize the current knowledge on cognitive, neurological, and functional effects. While this review of the literature found CPAP to have varying effects on different cognitive domains, there was not sufficient evidence to determine effects on language recovery. Further research is necessary to determine the potential effects of CPAP treatment on speech and language recovery among stroke patients.

The role of the hippocampus in statistical learning and language recovery in persons with post stroke aphasia

Background: Stroke, a global health concern, often leads to language impairment (aphasia). In Egypt, with a high stroke prevalence, aphasia affects a significant number of survivors. Noninvasive techniques like repetitive transcranial magnetic stimulation (rTMS) show promise in rehabilitation. Cultural variations in test results emphasize the need for region-specific considerations in standardized assessments for post-stroke care. Aim of the work: To evaluate the role of low frequency rTMS to speed up the recovery of post-stroke aphasia for a better quality of life. Patients and Methods: This randomized clinical trial investigates the effects of (rTMS) on post-stroke aphasia. Patients with post-stroke non-fluent aphasia were divided into two groups, with one receiving inhibitory rTMS and the other sham sessions. Inclusion criteria involve adults with a single left hemisphere stroke, while exclusion criteria include prior strokes. The study includes comprehensive assessments for aphasia, and depression. The stimulation protocol involves 20 minutes of daily rTMS for ten days, targeting the right inferior frontal gyrus. The study aims to evaluate the rTMS impact on language recovery. Results: The study evaluated low-frequency rTMS for post-stroke aphasia recovery in 30 patients, comparing TMS and sham groups. No significant demographic or cerebrovascular risk factor differences were found. While rTMS group showed improvement in depression, there were no significant differences between TMS and sham groups in aphasia improvement. Conclusion: Low-frequency rTMS demonstrated no significant superiority over sham stimulation in post-stroke aphasia recovery. Both groups exhibited improved depression without notable distinctions.

Modulation of activity in language networks using repetitive transcranial magnetic stimulation (rTMS) may possibly support recovery from poststroke aphasia. Case series and feasibility studies seem to indicate a therapeutic effect; however, randomized sham-controlled, proof-of-principle studies relating clinical effects to activation patterns are missing. Twenty-four patients with subacute poststroke aphasia were randomized to a 10-day protocol of 20-minute inhibitory 1 Hz rTMS over the right triangular part of the posterior inferior frontal gyrus or sham stimulation, followed by 45 minutes of speech and language therapy. Activity in language networks was measured with O-15-water positron emission tomography during verb generation before and after treatment. Language performance was assessed using the Aachen Aphasia Test battery. The primary outcome measure, global Aachen Aphasia Test score change, was significantly higher in the rTMS group (t test, P=0.003). Increases were largest for subtest naming (P=0.002) and tended to be higher for comprehension, token test, and writing (P<0.1). Patients in the rTMS group activated proportionally more voxels in the left hemisphere after treatment than before (difference in activation volume index) compared with sham-treated patients (t test, P=0.002).There was a moderate but significant linear relationship between activation volume index change and global Aachen Aphasia Test score change (r2=0.25; P=0.015). Ten sessions of inhibitory rTMS over the right posterior inferior frontal gyrus, in combination with speech and language therapy, significantly improve language recovery in subacute ischemic stroke and favor recruitment of left-hemispheric language networks.

Background Aphasia, a common consequence of stroke, significantly impairs language function, necessitating rehabilitation strategies that leverage neuroplasticity for effective recovery. Insights into the neural underpinnings of language recovery are vital for optimizing therapeutic approaches. Objective This scoping review synthesizes empirical findings on the modulation of resting-state functional connectivity (rsFC) following speech and language therapy (SLT) in individuals with post-stroke aphasia (PWA), in order to better understand and add to attempts to map the neural trajectory of recovery. Methods A comprehensive search was conducted in the PubMed and Web of Science databases to identify relevant studies. Covidence Systematic Review Software, 2022 was employed to manage the initial and full-text screening process. Following PRISMA guidelines, we systematically reviewed studies examining rsFC changes after SLT in PWA. We included studies that utilized rsfMRI in addition to behavioral assessments to ascertain the neural correlates of therapeutic intervention. Results Eleven studies were reviewed, highlighting an overall increase in intra-hemispheric connectivity, particularly within the left hemisphere, and a complex pattern of inter-hemispheric connectivity changes post-treatment. Increased connectivity within language-specific and domain-general regions suggests a dynamic neural reorganization towards a more efficient network configuration. Graph theory analysis illuminates the balance between network segregation and integration, with implications for the “small-world” characteristics of optimal brain function during recovery. Conclusion Our review indicates that SLT fosters significant neuroplastic changes in rsFC associated with language recovery in PWA. These changes reflect the adaptive reorganization of both language-specific and domain-general networks. However, the variability in treatment modalities, analytic methods, and the need for standardized approaches in rsfMRI research limit generalizability. Future research should focus on the refinement and systemization of methods and should aim to elucidate the roles of intra- and inter-hemispheric connectivity in aphasia recovery and refine rsfMRI’s potential as a biomarker for treatment outcomes.