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Einleitung/Hintergrund
DC_TRAIN_APHASIA ist eine multizentrische, randomisiert-kontrollierte Studie, die seit November 2019 unter Federführung der Universitätsmedizin Greifswald durchgeführt wird (ClinicalTrials.gov Identifier: NCT03930121). Die Studie untersucht, ob adjuvante transkranielle Gleichstromstimulation („transcranial direct current stimulation“, tDCS) den Erfolg einer 3‑wöchigen intensiven Sprachtherapie bei chronischer Aphasie steigern kann.
Material und Methode
Bis Ende 2024 sollen bundesweit 130 Patient:innen eingeschlossen werden. Die Entwicklung innovativer Rekrutierungsstrategien stellt seit Beginn der Studie eine Herausforderung dar. Neben gängigen Rekrutierungsmethoden wie der direkten Ansprache von Menschen mit Aphasie in Kliniken, Logopädiepraxen, Rehabilitationseinrichtungen und Selbsthilfegruppen wurden Radiowerbespots, Fernsehbeiträge und Auftritte in sozialen Medien erprobt.
Zwischenergebnisse
Bis zum aktuellen Zeitpunkt konnten 110 Patient:innen in die Studie eingeschlossen werden. Zum größten kurzzeitigen Rücklauf führte die Rekrutierung über einen Fernseh- bzw. Radiobeitrag. Den größten langfristigen Rücklauf ergab die Rekrutierung über Logopädie- und Neurologiepraxen, Selbsthilfegruppen und soziale Medien. Teilnehmer:innen berichteten als „Testimonials“ positiv von der Sprachtherapie und der Anwendung von tDCS, die sich als gut verträglich erwies.
Diskussion
Die multizentrische Studie DC_TRAIN_APHASIA prüft die Wirksamkeit von tDCS als adjuvante Applikation für intensive Sprachtherapie bei chronischer Aphasie. Die vorliegende Übersicht soll künftigen Studien als Leitfaden zur Rekrutierung von Stichproben dienen, die Menschen mit eingeschränkten kommunikativen Fähigkeiten umfassen.
Manual sleep scoring for research purposes and for the diagnosis of sleep disorders is labor-intensive and often varies significantly between scorers, which has motivated many attempts to design automatic sleep stage classifiers. With the recent introduction of large, publicly available hand-scored polysomnographic data, and concomitant advances in machine learning methods to solve complex classification problems with supervised learning, the problem has received new attention, and a number of new classifiers that provide excellent accuracy. Most of these however have non-trivial barriers to use. We introduce the Greifswald Sleep Stage Classifier (GSSC), which is free, open source, and can be relatively easily installed and used on any moderately powered computer. In addition, the GSSC has been trained to perform well on a large variety of electrode set-ups, allowing high performance sleep staging with portable systems. The GSSC can also be readily integrated into brain-computer interfaces for real-time inference. These innovations were achieved while simultaneously reaching a level of accuracy equal to, or exceeding, recent state of the art classifiers and human experts, making the GSSC an excellent choice for researchers in need of reliable, automatic sleep staging.
Advances in spine surgery enable technically safe interventions in older patients with disabling spine disease, yet postoperative delirium (POD) poses a serious risk for postoperative recovery. This study investigates biomarkers of pro-neuroinflammatory states that may help objectively define the pre-operative risk for POD. This study enrolled patients aged ≥60 scheduled for elective spine surgery under general anesthesia. Biomarkers for a pro-neuroinflammatory state included S100 calcium-binding protein β (S100β), brain-derived neurotrophic factor (BDNF), Gasdermin D, and the soluble ectodomain of the triggering receptor expressed on myeloid cells 2 (sTREM2). Postoperative changes of Interleukin-6 (IL-6), Interleukin-1β (IL-1β), and C-reactive protein (CRP) were assessed as markers of systemic inflammation preoperatively, intraoperatively, and early postoperatively (up to 48 h). Patients with POD (n = 19, 75.7 ± 5.8 years) had higher pre-operative levels of sTREM2 (128.2 ± 69.4 pg/mL vs. 97.2 ± 52.0 pg/mL, p = 0.049) and Gasdermin D (2.9 ± 1.6 pg/mL vs. 2.1 ± 1.4 pg/mL, p = 0.29) than those without POD (n = 25, 75.6 ± 5.1 years). STREM2 was additionally a predictor for POD (OR = 1.01/(pg/mL) [1.00–1.03], p = 0.05), moderated by IL-6 (Wald-χ2 = 4.06, p = 0.04). Patients with POD additionally showed a significant increase in IL-6, IL-1β, and S100β levels on the first postoperative day. This study identified higher levels of sTREM2 and Gasdermin D as potential markers of a pro-neuroinflammatory state that predisposes to the development of POD. Future studies should confirm these results in a larger cohort and determine their potential as an objective biomarker to inform delirium prevention strategies.
Task shielding is an important executive control demand in dual-task performance enabling the segregation of stimulus–response translation processes in each task to minimize between-task interference. Although neuroimaging studies have shown activity in left dorsolateral prefrontal cortex (dlPFC) during various multitasking performances, the specific role of dlPFC in task shielding, and whether non-invasive brain stimulation (NIBS) may facilitate task shielding remains unclear. We therefore applied a single-blind, crossover sham-controlled design in which 34 participants performed a dual-task experiment with either anodal transcranial direct current stimulation (atDCS, 1 mA, 20 min) or sham tDCS (1 mA, 30 s) over left dlPFC. Task shielding was assessed by the backward-crosstalk effect, indicating the extent of between-task interference in dual tasks. Between-task interference was largest at high temporal overlap between tasks, i.e., at short stimulus onset asynchrony (SOA). Most importantly, in these conditions of highest multitasking demands, atDCS compared to sham stimulation significantly reduced between-task interference in error rates. These findings extend previous neuroimaging evidence and support modulation of successful task shielding through a conventional tDCS setup with anodal electrode over the left dlPFC. Moreover, our results demonstrate that NIBS can improve shielding of the prioritized task processing, especially in conditions of highest vulnerability to between-task interference.
The combination of repeated behavioral training with transcranial direct current stimulation (tDCS) holds promise to exert beneficial effects on brain function beyond the trained task. However, little is known about the underlying mechanisms. We performed a monocenter, single-blind randomized, placebo-controlled trial comparing cognitive training to concurrent anodal tDCS (target intervention) with cognitive training to concurrent sham tDCS (control intervention), registered at ClinicalTrial.gov (Identifier NCT03838211). The primary outcome (performance in trained task) and secondary behavioral outcomes (performance on transfer tasks) were reported elsewhere. Here, underlying mechanisms were addressed by pre-specified analyses of multimodal magnetic resonance imaging before and after a three-week executive function training with prefrontal anodal tDCS in 48 older adults. Results demonstrate that training combined with active tDCS modulated prefrontal white matter microstructure which predicted individual transfer task performance gain. Training-plus-tDCS also resulted in microstructural grey matter alterations at the stimulation site, and increased prefrontal functional connectivity. We provide insight into the mechanisms underlying neuromodulatory interventions, suggesting tDCS-induced changes in fiber organization and myelin formation, glia-related and synaptic processes in the target region, and synchronization within targeted functional networks. These findings advance the mechanistic understanding of neural tDCS effects, thereby contributing to more targeted neural network modulation in future experimental and translation tDCS applications.
Deteriorations in slow wave sleep (SWS) have been linked to brain aging and Alzheimer’s disease (AD), possibly due to its key role in clearance of amyloid-beta and tau (Aß/tau), two pathogenic hallmarks of AD. Spermidine administration has been shown to improve sleep quality in animal models. So far, the association between spermidine levels in humans and parameters of SWS physiology are unknown but may be valuable for therapeutic strategies. Data from 216 participants (age range 50–81 years) of the population-based Study of Health in Pomerania TREND were included in our analysis. We investigated associations between spermidine plasma levels, key parameters of sleep macroarchitecture and microarchitecture that were previously associated with AD pathology, and brain health measured via a marker of structural brain atrophy (AD score). Higher spermidine levels were significantly associated with lower coupling between slow oscillations and spindle activity. No association was evident for SWS, slow oscillatory, and spindle activity throughout non-rapid eye movement sleep. Furthermore, elevated spermidine blood levels were significantly associated with a higher AD score, while sleep markers revealed no association with AD score. The association between higher spermidine levels and brain health was not mediated by coupling between slow oscillations and spindle activity. We report that higher spermidine blood levels are associated not only with deteriorated brain health but also with less advantageous markers of sleep quality in older adults. Future studies need to evaluate whether sleep, spermidine, and Aß/tau deposition are interrelated and whether sleep may play a mediating role.
Introduction
With the worldwide increase of life expectancy leading to a higher proportion of older adults experiencing age-associated deterioration of cognitive abilities, the development of effective and widely accessible prevention and therapeutic measures has become a priority and challenge for modern medicine. Combined interventions of cognitive training and transcranial direct current stimulation (tDCS) have shown promising results for counteracting age-associated cognitive decline. However, access to clinical centres for repeated sessions is challenging, particularly in rural areas and for older adults with reduced mobility, and lack of clinical personnel and hospital space prevents extended interventions in larger cohorts. A home-based and remotely supervised application of tDCS would make the treatment more accessible for participants and relieve clinical resources. So far, studies assessing feasibility of combined interventions with a focus on cognition in a home-based setting are rare. With this study, we aim to provide evidence for the feasibility and the effects of a multisession home-based cognitive training in combination with tDCS on cognitive functions of healthy older adults.
Methods and analysis
The TrainStim-Home trial is a monocentric, randomised, double-blind, placebo-controlled study. Thirty healthy participants, aged 60–80 years, will receive 2 weeks of combined cognitive training and anodal tDCS over left dorsolateral prefrontal cortex (target intervention), compared with cognitive training plus sham stimulation. The cognitive training will comprise a letter updating task, and the participants will be stimulated for 20 min with 1.5 mA. The intervention sessions will take place at the participants’ home, and primary outcome will be the feasibility, operationalised by two-thirds successfully completed sessions per participant. Additionally, performance in the training task and an untrained task will be analysed.
Ethics and dissemination
Ethical approval was granted by the ethics committee of the University Medicine Greifswald. Results will be available through publications in peer-reviewed journals and presentations at national and international conferences.Trial registration numberNCT04817124.
Metrological methods for word learning list tests can be developed with an information theoretical approach extending earlier simple syntax studies. A classic Brillouin entropy expression is applied to the analysis of the Rey’s Auditory Verbal Learning Test RAVLT (immediate recall), where more ordered tasks—with less entropy—are easier to perform. The findings from three case studies are described, including 225 assessments of the NeuroMET2 cohort of persons spanning a cognitive spectrum from healthy older adults to patients with dementia. In the first study, ordinality in the raw scores is compensated for, and item and person attributes are separated with the Rasch model. In the second, the RAVLT IR task difficulty, including serial position effects (SPE), particularly Primacy and Recency, is adequately explained (Pearson’s correlation R=0.80) with construct specification equations (CSE). The third study suggests multidimensionality is introduced by SPE, as revealed through goodness-of-fit statistics of the Rasch analyses. Loading factors common to two kinds of principal component analyses (PCA) for CSE formulation and goodness-of-fit logistic regressions are identified. More consistent ways of defining and analysing memory task difficulties, including SPE, can maintain the unique metrological properties of the Rasch model and improve the estimates and understanding of a person’s memory abilities on the path towards better-targeted and more fit-for-purpose diagnostics.
Neural mechanisms of behavioral improvement induced by repeated transcranial direct current stimulation (tDCS) combined with cognitive training are yet unclear. Previously, we reported behavioral effects of a 3-day visuospatial memory training with concurrent anodal tDCS over the right temporoparietal cortex in older adults. To investigate intervention-induced neural alterations we here used functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) datasets available from 35 participants of this previous study, acquired before and after the intervention. To delineate changes in whole-brain functional network architecture, we employed eigenvector centrality mapping. Gray matter alterations were analyzed using DTI-derived mean diffusivity (MD). Network centrality in the bilateral posterior temporooccipital cortex was reduced after anodal compared to sham stimulation. This focal effect is indicative of decreased functional connectivity of the brain region underneath the anodal electrode and its left-hemispheric homolog with other “relevant” (i.e., highly connected) brain regions, thereby providing evidence for reorganizational processes within the brain's network architecture. Examining local MD changes in these clusters, an interaction between stimulation condition and training success indicated a decrease of MD in the right (stimulated) temporooccipital cluster in individuals who showed superior behavioral training benefits. Using a data-driven whole-brain network approach, we provide evidence for targeted neuromodulatory effects of a combined tDCS-and-training intervention. We show for the first time that gray matter alterations of microstructure (assessed by DTI-derived MD) may be involved in tDCS-enhanced cognitive training. Increased knowledge on how combined interventions modulate neural networks in older adults, will help the development of specific therapeutic interventions against age-associated cognitive decline.
Introduction
Given rapid global population aging, developing interventions against age-associated cognitive decline is an important medical and societal goal. We evaluated a cognitive training protocol combined with transcranial direct current stimulation (tDCS) on trained and non-trained functions in non-demented older adults.
Methods
Fifty-six older adults (65–80 years) were randomly assigned to one of two interventional groups, using age and baseline performance as strata. Both groups performed a nine-session cognitive training over 3 weeks with either concurrent anodal tDCS (atDCS, 1 mA, 20 minutes) over the left dorsolateral prefrontal cortex (target intervention) or sham stimulation (control intervention). Primary outcome was performance on the trained letter updating task immediately after training. Secondary outcomes included performance on other executive and memory (near and far transfer) tasks. All tasks were administered at baseline, post-intervention, and at 1- and 7-month follow-up assessments. Prespecified analyses to investigate treatment effects were conducted using mixed-model analyses.
Results
No between-group differences emerged in the trained letter updating and Markov decision-making tasks at post-intervention and at follow-up timepoints. Secondary analyses revealed group differences in one near-transfer task: Superior n-back task performance was observed in the tDCS group at post-intervention and at follow-up. No such effects were observed for the other transfer tasks. Improvements in working memory were associated with individually induced electric field strengths.
Discussion
Cognitive training with atDCS did not lead to superior improvement in trained task performance compared to cognitive training with sham stimulation. Thus, our results do not support the immediate benefit of tDCS-assisted multi-session cognitive training on the trained function. As the intervention enhanced performance in a near-transfer working memory task, we provide exploratory evidence for effects on non-trained working memory functions in non-demented older adults that persist over a period of 1 month.