Search

Abstract Kinematic data is a valuable source of movement information that provides insights into the health status, mental state, and motor skills of individuals. Additionally, kinematic data can serve as biometric data, enabling the identification of personal characteristics such as height, weight, and sex. In CeTI-Locomotion, four types of walking tasks and the 5 times sit-to-stand test (5RSTST) were recorded from 50 young adults wearing motion capture (mocap) suits equipped with Inertia-Measurement-Units (IMU). Our dataset is unique in that it allows the study of both intra- and inter-participant variability with high quality kinematic motion data for different motion tasks. Along with the raw kinematic data, we provide the source code for phase segmentation and the processed data, which has been segmented into a total of 4672 individual motion repetitions. To validate the data, we conducted visual inspection as well as machine-learning based identity and action recognition tests, achieving 97% and 84% accuracy, respectively. The data can serve as a normative reference of gait and sit-to-stand movements in healthy young adults and as training data for biometric recognition.

Abstract Digital technologies, such as virtual or augmented reality, can potentially support neurocognitive functions of the aging populations worldwide and complement existing intervention methods. However, aging-related declines in the frontal-parietal network and dopaminergic modulation which progress gradually across the later periods of the adult lifespan may affect the processing of multisensory congruence and expectancy based contextual plausibility. We assessed hemodynamic brain responses while middle-aged and old adults experienced car-riding virtual-reality scenarios where the plausibility of vibrotactile stimulations was manipulated by delivering stimulus intensities that were either congruent or incongruent with the digitalized audio-visual contexts of the respective scenarios. Relative to previous findings observed in young adults, although highly plausible vibrotactile stimulations confirming with contextual expectations also elicited higher brain hemodynamic responses in middle-aged and old adults, this effect was limited to virtual scenarios with extreme expectancy violations. Moreover, individual differences in plausibility-related frontal activity did not correlate with plausibility violation costs in the sensorimotor cortex, indicating less systematic frontal context-based sensory filtering in older ages. These findings have practical implications for advancing digital technologies to support aging societies.

Abstract Background Repeated sessions of training and non-invasive brain stimulation have the potential to enhance cognition in patients with cognitive impairment. We hypothesized that combining cognitive training with anodal transcranial direct current stimulation (tDCS) will lead to performance improvement in the trained task and yield transfer to non-trained tasks. Methods In our randomized, sham-controlled, double-blind study, 46 patients with cognitive impairment (60–80 years) were randomly assigned to one of two interventional groups. We administered a 9-session cognitive training (consisting of a letter updating and a Markov decision-making task) over 3 weeks with concurrent 1-mA anodal tDCS over the left dorsolateral prefrontal cortex (20 min in tDCS, 30 s in sham group). Primary outcome was trained task performance (letter updating task) immediately after training. Secondary outcomes included performance in tasks testing working memory (N-back task), decision-making (Wiener Matrices test) and verbal memory (verbal learning and memory test), and resting-state functional connectivity (FC). Tasks were administered at baseline, at post-assessment, and at 1- and 7-month follow-ups (FU). MRI was conducted at baseline and 7-month FU. Thirty-nine participants (85%) successfully completed the intervention. Data analyses are reported on the intention-to-treat (ITT) and the per-protocol (PP) sample. Results For the primary outcome, no difference was observed in the ITT (β = 0.1, 95%-CI [− 1.2, 1.3, p = 0.93] or PP sample (β = − 0.2, 95%-CI [− 1.6, 1.2], p = 0.77). However, secondary analyses in the N-back working memory task showed that, only in the PP sample, the tDCS outperformed the sham group (PP: % correct, β = 5.0, 95%-CI [− 0.1, 10.2], p = 0.06, d-prime β = 0.2, 95%-CI [0.0, 0.4], p = 0.02; ITT: % correct, β = 3.0, 95%-CI [− 3.9, 9.9], p = 0.39, d-prime β = 0.1, 95%-CI [− 0.1, 0.3], p = 0.5). Frontoparietal network FC was increased from baseline to 7-month FU in the tDCS compared to the sham group (p FDR

Transcranial direct current stimulation (tDCS) has been studied extensively for its potential to enhance human cognitive functions in healthy individuals and to treat cognitive impairment in various clinical populations. However, little is known about how tDCS modulates the neural networks supporting cognition and the complex interplay with mediating factors that may explain the frequently observed variability of stimulation effects within and between studies. Moreover, research in this field has been characterized by substantial methodological variability, frequent lack of rigorous experimental control and small sample sizes, thereby limiting the generalizability of findings and translational potential of tDCS. The present manuscript aims to delineate how these important issues can be addressed within a neuroimaging context, to reveal the neural underpinnings, predictors and mediators of tDCS-induced behavioral modulation. We will focus on functional magnetic resonance imaging (fMRI), because it allows the investigation of tDCS effects with excellent spatial precision and sufficient temporal resolution across the entire brain. Moreover, high resolution structural imaging data can be acquired for precise localization of stimulation effects, verification of electrode positions on the scalp and realistic current modeling based on individual head and brain anatomy. However, the general principles outlined in this review will also be applicable to other imaging modalities. Following an introduction to the overall state-of-the-art in this field, we will discuss in more detail the underlying causes of variability in previous tDCS studies. Moreover, we will elaborate on design considerations for tDCS-fMRI studies, optimization of tDCS and imaging protocols and how to assure high-level experimental control. Two additional sections address the pressing need for more systematic investigation of tDCS effects across the healthy human lifespan and implications for tDCS studies in age-associated disease, and potential benefits of establishing large-scale, multidisciplinary consortia for more coordinated tDCS research in the future. We hope that this review will contribute to more coordinated, methodologically sound, transparent and reproducible research in this field. Ultimately, our aim is to facilitate a better understanding of the underlying mechanisms by which tDCS modulates human cognitive functions and more effective and individually tailored translational and clinical applications of this technique in the future.

Abstract The Tactile Internet aims to advance human-human and human-machine interactions that also utilize hand movements in real, digitized, and remote environments. Attention to elderly generations is necessary to make the Tactile Internet age inclusive. We present the first age-representative kinematic database consisting of various hand gesturing and grasping movements at individualized paces, thus capturing naturalistic movements. We make this comprehensive database of kinematic hand movements across the adult lifespan (CeTI-Age-Kinematic-Hand) publicly available to facilitate a deeper understanding of intra-individual–focusing especially on age-related differences–and inter-individual variability in hand kinematics. The core of the database contains participants’ hand kinematics recorded with wearable resistive bend sensors, individual static 3D hand models, and all instructional videos used during the data acquisition. Sixty-three participants ranging from age 20 to 80 years performed six repetitions of 40 different naturalistic hand movements at individual paces. This unique database with data recorded from an adult lifespan sample can be used to advance machine-learning approaches in hand kinematic modeling and movement prediction for age-inclusive applications.

Older adults demonstrate difficulties in sequential decision-making, which is partly attributed to under-recruitment of prefrontal networks. It is, therefore, important to understand the mechanisms that may improve this ability. This study investigated the effectiveness of an 18-sessions, home-based cognitive intervention and the neural mechanisms that underpin individual differences in intervention effects. Participants were required to learn sequential choices in a 3-stage Markov decision-making task that would yield the most rewards. Participants were assigned to better or worse responders group based on their performance at the last intervention session (T18). Better responders improved significantly starting from the fifth intervention session while worse responders did not improve across all training sessions. At post-intervention, only better responders showed condition-dependent modulation of the dorsolateral prefrontal cortex (DLPFC) as measured by fNIRS, with higher DLPFC activity in the delayed condition. Despite large individual differences, our data showed that value-based sequential-decision-making and its corresponding neural mechanisms can be remediated via home-based cognitive intervention in some older adults; moreover, individual differences in recruiting prefrontal activities after the intervention are associated with variations in intervention outcomes. Intervention-related gains were also maintained at three months after post-intervention. However, future studies should investigate the potential of combining other intervention methods such as non-invasive brain stimulation with cognitive intervention for older adults who do not respond to the intervention, thus emphasizing the importance of developing individualized intervention programs for older adults.

Abstract Forward planning is crucial to maximize outcome in complex sequential decision-making scenarios. In this cross-sectional study, we were particularly interested in age-related differences of forward planning. We presumed that especially older individuals would show a shorter planning depth to keep the costs of model-based decision-making within limits. To test this hypothesis, we developed a sequential decision-making task to assess forward planning in younger (age 60 years; n = 27) adults. By using reinforcement learning modelling, we inferred planning depths from participants' choices. Our results showed significantly shorter planning depths and higher response noise for older adults. Age differences in planning depth were only partially explained by well-known cognitive covariates such as working memory and processing speed. Consistent with previous findings, this indicates age-related shifts away from model-based behaviour in older adults. In addition to a shorter planning depth, our findings suggest that older adults also apply a variety of heuristical low-cost strategies.

Selective use of new information is crucial for adaptive decision-making. Combining a gamble bidding task with assessing cortical responses using functional near-infrared spectroscopy (fNIRS), we investigated potential effects of information valence on behavioral and neural processes of belief and value updating during uncertainty reduction in young adults. By modeling changes in the participants’ expressed subjective values using a Bayesian model, we dissociated processes of (i) updating beliefs about statistical properties of the gamble, (ii) updating values of a gamble based on new information about its winning probabilities, as well as (iii) expectancy violation. The results showed that participants used new information to update their beliefs and values about the gambles in a quasi-optimal manner, as reflected in the selective updating only in situations with reducible uncertainty. Furthermore, their updating was valence-dependent: information indicating an increase in winning probability was underweighted, whereas information about a decrease in winning probability was updated in good agreement with predictions of the Bayesian decision theory. Results of model-based and moderation analyses showed that this valence-dependent asymmetry was associated with a distinct contribution of expectancy violation, besides belief updating, to value updating after experiencing new positive information regarding winning probabilities. In line with the behavioral results, we replicated previous findings showing involvements of frontoparietal brain regions in the different components of updating. Furthermore, this study provided novel results suggesting a valence-dependent recruitment of brain regions. Individuals with stronger oxyhemoglobin responses during value updating was more in line with predictions of the Bayesian model while integrating new information that indicates an increase in winning probability. Taken together, this study provides first results showing expectancy violation as a contributing factor to sub-optimal valence-dependent updating during uncertainty reduction and suggests limitations of normative Bayesian decision theory.

The effect of trimodal visuo-audio-tactile stimulations on perceptual realism during vehicle riding simulations in virtual reality reveals that multisensory plausibility engages cortical activities in the frontal-parietal and sensorimotor regions.

Abstract Empirical evidence has shown that visually enhancing the saliency of reward probabilities can ease the cognitive demands of value comparisons and improve value-based decisions in old age. In the present study, we used a time-varying drift diffusion model that includes starting time parameters to better understand (1) how increasing the saliency of reward probabilities may affect the dynamics of value-based decision-making and (2) how these effects may interact with age. We examined choices made by younger and older adults in a mixed lottery choice task. On a subset of trials, we used a color-coding scheme to highlight the saliency of reward probabilities, which served as a decision-aid. The results showed that, in control trials, older adults started to consider probability relative to magnitude information sooner than younger adults, but that their evidence accumulation processes were less sensitive to reward probabilities than that of younger adults. This may indicate a noisier and more stochastic information accumulation process during value-based decisions in old age. The decision-aid increased the influence of probability information on evidence accumulation rates in both age groups, but did not alter the relative timing of accumulation for probability versus magnitude in either group.

Aging is associated with changes in spatial navigation behavior. In addition to an overall performance decline, older adults tend to rely more on proximal location cue information than on environmental boundary information during spatial navigation compared to young adults. The fact that older adults are more susceptible to errors during spatial navigation might be partly attributed to deficient dopaminergic modulation of hippocampal and striatal functioning. Hence, elevating dopamine levels might differentially modulate spatial navigation and memory performance in young and older adults. In this work, we administered levodopa (L-DOPA) in a double-blind within-subject, placebo-controlled design and recorded functional neuroimaging while young and older adults performed a 3D spatial navigation task in which boundary geometry or the position of a location cue were systematically manipulated. An age by intervention interaction on the neural level revealed an upregulation of brain responses in older adults and a downregulation of responses in young adults within the medial temporal lobe (including hippocampus and parahippocampus) and brainstem, during memory retrieval. Behaviorally, L-DOPA had no effect on older adults’ overall memory performance; however, older adults whose spatial memory improved under L-DOPA also showed a shift towards more boundary processing under L-DOPA. In young adults, L-DOPA induced a decline in spatial memory performance in task-naïve participants. These results are consistent with the inverted-U-shaped hypothesis of dopamine signaling and cognitive function and suggest that increasing dopamine availability improves hippocampus-dependent place learning in some older adults.

Abstract We recently showed that incentive motivation improves the precision of the Approximate Number System (ANS) in young adults. To shed light on the development of incentive motivation, the present study investigated whether this effect and its underlying mechanisms may also be observed in younger samples. Specifically, seven-year-old children (n = 23; 12 girls) and 14-year-old adolescents (n = 30; 15 girls) performed a dot comparison task with monetary reward incentives. Both age groups showed higher accuracy in a reward compared to a neutral condition and, similarly, higher processing efficiency as revealed by the drift rate parameter of the EZ-diffusion model. Furthermore, in line with the Incentive Salience Hypothesis, phasic pupil dilations—indicating the activation of the brain’s salience network—were greater in incentivized trials in both age groups. Together these finding suggest that incentive modulation improves numerosity discrimination in children and adolescents by enhancing the perceptual saliency of numerosity information. However, the observed reward anticipation effects were less pronounced in children relative to adolescents. Furthermore, unlike previous findings regarding young adults, the decision thresholds of children and adolescents were not raised by the monetary reward, which may indicate a more protracted development of incentive regulation of response caution than perceptual evidence accumulation.

Abstract While the importance of social affect and cognition is indisputable throughout the adult lifespan, findings of how empathy and prosociality develop and interact across adulthood are mixed and real-life data are scarce. Research using ecological momentary assessment recently demonstrated that adults commonly experience empathy in daily life. Furthermore, experiencing empathy was linked to higher prosocial behavior and subjective well-being. However, to date, it is not clear whether there are adult age differences in daily empathy and daily prosociality and whether age moderates the relationship between empathy and prosociality across adulthood. Here we analyzed experience-sampling data collected from participants across the adult lifespan to study age effects on empathy, prosocial behavior, and well-being under real-life circumstances. Linear and quadratic age effects were found for the experience of empathy, with increased empathy across the three younger age groups (18 to 45 years) and a slight decrease in the oldest group (55 years and older). Neither prosocial behavior nor well-being showed significant age-related differences. We discuss these findings with respect to (partially discrepant) results derived from lab-based and traditional survey studies. We conclude that studies linking in-lab experiments with real-life experience-sampling may be a promising venue for future lifespan studies.

Abstract Antenatal synthetic glucocorticoid (sGC) treatment is a potent modifier of the hypothalamic-pituitary-adrenal (HPA) axis. In this context, epigenetic modifications are discussed as potential regulators explaining how prenatal exposure to GCs might translate into persistent changes of HPA axis “functioning”. The purpose of this study was to investigate whether DNA methylation and gene expression profiles of stress-associated genes (NR3C1; FKBP5; SLC6A4) may mediate the persistent effects of sGC on cortisol stress reactivity that have been previously observed. In addition, hair cortisol concentrations (hairC) were investigated as a valid biomarker of long-term HPA axis activity. This cross-sectional study comprised 108 term-born children and adolescents, including individuals with antenatal GC treatment and controls. From whole blood, DNA methylation was analyzed by targeted deep bisulfite sequencing. Relative mRNA expression was determined by RT-qPCR experiments and qBase analysis. Acute stress reactivity was assessed by the Trier Social Stress Test (TSST) measuring salivary cortisol by ELISA and hairC concentrations were determined from hair samples by liquid chromatography coupled with tandem mass spectrometry. First, no differences in DNA methylation and mRNA expression levels of the stress-associated genes between individuals treated with antenatal sGC compared to controls were found. Second, DNA methylation and mRNA expression levels were neither associated with cortisol stress reactivity nor with hairC. These findings do not corroborate the belief that DNA methylation and mRNA expression profiles of stress-associated genes (NR3C1; FKBP5; SLC6A4) play a key mediating role of the persistent effects of sGC on HPA axis functioning.

Mechanisms underlying perceptual processing and inference undergo substantial changes across the lifespan. If utilized properly, technologies could support and buffer the relatively more limited neurocognitive functions in the still developing or aging brains. Over the past decade, a new type of digital communication infrastructure, known as the “Tactile Internet (TI),” is emerging in the fields of telecommunication, sensor and actuator technologies and machine learning. A key aim of the TI is to enable humans to experience and interact with remote and virtual environments through digitalized multimodal sensory signals that also include the haptic (tactile and kinesthetic) sense. Besides their applied focus, such technologies may offer new opportunities for the research tapping into mechanisms of digitally embodied perception and cognition as well as how they may differ across age cohorts. However, there are challenges in translating empirical findings and theories about neurocognitive mechanisms of perception and lifespan development into the day-to-day practices of engineering research and technological development. On the one hand, the capacity and efficiency of digital communication are affected by signal transmission noise according to Shannon’s (1949) Information Theory. On the other hand, neurotransmitters, which have been postulated as means that regulate the signal-to-noise ratio of neural information processing (e.g., Servan-Schreiber et al., 1990), decline substantially during aging. Thus, here we highlight neuronal gain control of perceptual processing and perceptual inference to illustrate potential interfaces for developing age-adjusted technologies to enable plausible multisensory digital embodiments for perceptual and cognitive interactions in remote or virtual environments.

Abstract The abilities to monitor one’s actions and novel information in the environment are crucial for behavioural and cognitive control. This study investigated the development of error and novelty monitoring and their electrophysiological correlates by using a combined flanker with novelty-oddball task in children (7–12 years) and adolescents (14–18 years). Potential moderating influences of prenatal perturbation of steroid hormones on these performance monitoring processes were explored by comparing individuals who were prenatally exposed and who were not prenatally exposed to synthetic glucocorticoids (sGC). Generally, adolescents performed more accurately and faster than children. However, behavioural adaptations to error or novelty, as reflected in post-error or post-novelty slowing, showed different developmental patterns. Whereas post-novelty slowing could be observed in children and adolescents, error-related slowing was absent in children and was marginally significant in adolescents. Furthermore, the amplitude of error-related negativity was larger in adolescents, whereas the amplitude of novelty-related N2 was larger in children. These age differences suggest that processes involving top-down processing of task-relevant information (for instance, error monitoring) mature later than processes implicating bottom-up processing of salient novel stimuli (for instance, novelty monitoring). Prenatal exposure to sGC did not directly affect performance monitoring but initial findings suggest that it might alter brain-behaviour relation, especially for novelty monitoring.

Previous studies indicate a role of dopamine in spatial navigation. Although neural representations of direction are an important aspect of spatial cognition, it is not well understood whether dopamine directly affects these representations, or only impacts other aspects of spatial brain function. Moreover, both dopamine and spatial cognition decline sharply during age, raising the question which effect dopamine has on directional signals in the brain of older adults. To investigate these questions, we used a double-blind cross-over L-DOPA/Placebo intervention design in which 43 younger and 37 older adults navigated in a virtual spatial environment while undergoing functional magnetic resonance imaging (fMRI). We studied the effect of L-DOPA, a dopamine precursor, on fMRI activation patterns that encode spatial walking directions that have previously been shown to lose specificity with age. This was done in predefined regions of interest, including the early visual cortex, retrosplenial cortex, and hippocampus. Classification of brain activation patterns associated with different walking directions was improved across all regions following L-DOPA administration, suggesting that dopamine broadly enhances neural representations of direction. No evidence for differences between regions was found. In the hippocampus these results were found in both age groups, while in the retrosplenial cortex they were only observed in younger adults. Taken together, our study provides evidence for a link between dopamine and the specificity of neural responses during spatial navigation. Significance Statement: The sense of direction is an important aspect of spatial navigation, and neural representations of direction can be found throughout a large network of space-related brain regions. But what influences how well these representations track someone’s true direction? Using a double-blind cross-over L-DOPA/Placebo intervention design, we find causal evidence that the neurotransmitter dopamine impacts the fidelity of direction selective neural representations in the human hippocampus and retrosplenial cortex. Interestingly, the effect of L-DOPA was either equally present or even smaller in older adults, despite the well-known age related decline of dopamine. These results provide novel insights into how dopamine shapes the neural representations that underlie spatial navigation.

Background: Gilles de la Tourette Syndrome (GTS) is a neurodevelopmental disorder with a peak of symptom severity around late childhood and early adolescence. Previous findings in adult GTS suggest that changes in perception-action integration, as conceptualized in the theory of event coding framework, are central for the understanding of GTS. However, the neural mechanisms underlying these processes in adolescence are elusive. Methods: A total of 59 children/adolescents aged 9 to 18 years (n = 32 with GTS, n = 27 typically developing youths) were examined using a perception-action integration task (event file task) derived from the theory of event coding. Event-related electroencephalogram recordings (theta and beta band activity) were analyzed using electroencephalogram–beamforming methods. Results: Behavioral data showed robust event file binding effects in both groups without group differences. Neurophysiological data showed that theta and beta band activity were involved in event file integration in both groups. However, the functional neuroanatomical organization was markedly different for theta band activity between the groups. The typically developing group mainly relied on superior frontal regions, whereas the GTS group engaged parietal and inferior frontal regions. A more consistent functional neuroanatomical activation pattern was observed for the beta band, engaging inferior parietal and temporal regions in both groups. Conclusions: Perception-action integration processes lag behind in persisting GTS but not in the GTS population as a whole, underscoring differences in developmental trajectories and the importance of longitudinal investigations for the understanding of GTS. The findings corroborate known differences in the functional/structural brain organization in GTS and suggest an important role of theta band activity in these patients.

Abstract Spatial learning can be based on intramaze cues and environmental boundaries. These processes are predominantly subserved by striatal- and hippocampal-dependent circuitries, respectively. Maturation and aging processes in these brain regions may affect lifespan differences in their contributions to spatial learning. We independently manipulated an intramaze cue or the environment’s boundary in a navigation task in 27 younger children (6–8 years), 30 older children (10–13 years), 29 adolescents (15–17 years), 29 younger adults (20–35 years) and 26 older adults (65–80 years) to investigate lifespan age differences in the relative prioritization of either information. Whereas learning based on an intramaze cue showed earlier maturation during the progression from younger to later childhood and remained relatively stable across adulthood, maturation of boundary-based learning was more protracted towards peri-adolescence and showed strong aging-related decline. Furthermore, individual differences in prioritizing intramaze cue- over computationally more demanding boundary-based learning was positively associated with cognitive processing fluctuations and this association was partially mediated by spatial working memory capacity during adult, but not during child development. This evidence reveals different age gradients of two modes of spatial learning across the lifespan, which seem further influenced by individual differences in cognitive processing fluctuations and working memory, particularly during aging.

Transcranial direct current stimulation (tDCS) has been studied extensively for its potential to enhance human cognitive functions in healthy individuals and to treat cognitive impairment in various clinical populations. However, little is known about how tDCS modulates the neural networks supporting cognition and the complex interplay with mediating factors that may explain the frequently observed variability of stimulation effects within and between studies. Moreover, research in this field has been characterized by substantial methodological variability, frequent lack of rigorous experimental control and small sample sizes, thereby limiting the generalizability of findings and translational potential of tDCS. The present manuscript aims to delineate how these important issues can be addressed within a neuroimaging context, to reveal the neural underpinnings, predictors and mediators of tDCS-induced behavioral modulation. We will focus on functional magnetic resonance imaging (fMRI), because it allows the investigation of tDCS effects with excellent spatial precision and sufficient temporal resolution across the entire brain. Moreover, high resolution structural imaging data can be acquired for precise localization of stimulation effects, verification of electrode positions on the scalp and realistic current modeling based on individual head and brain anatomy. However, the general principles outlined in this review will also be applicable to other imaging modalities. Following an introduction to the overall state-of-the-art in this field, we will discuss in more detail the underlying causes of variability in previous tDCS studies. Moreover, we will elaborate on design considerations for tDCSfMRI studies, optimization of tDCS and imaging protocols and how to assure high-level experimental control. Two additional sections address the pressing need for more systematic investigation of tDCS effects across the healthy human lifespan and implications for tDCS studies in age-associated disease, and potential benefits of establishing large-scale, multidisciplinary consortia for more coordinated tDCS research in the future. We hope that this review will contribute to more coordinated, methodologically sound, transparent and reproducible research in this field. Ultimately, our aim is to facilitate a better understanding of the underlying mechanisms by which tDCS modulates human cognitive functions and more effective and individually tailored translational and clinical applications of this technique in the future. [ABSTRACT FROM AUTHOR]

Abstract Background Given the growing older population worldwide, and the associated increase in age-related diseases, such as Alzheimer’s disease (AD), investigating non-invasive methods to ameliorate or even prevent cognitive decline in prodromal AD is highly relevant. Previous studies suggest transcranial direct current stimulation (tDCS) to be an effective method to boost cognitive performance, especially when applied in combination with cognitive training in healthy older adults. So far, no studies combining tDCS concurrent with an intense multi-session cognitive training in prodromal AD populations have been conducted. Methods The AD-Stim trial is a monocentric, randomized, double-blind, placebo-controlled study, including a 3-week tDCS-assisted cognitive training with anodal tDCS over left DLPFC (target intervention), compared to cognitive training plus sham (control intervention). The cognitive training encompasses a letter updating task and a three-stage Markov decision-making task. Forty-six participants with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) will be randomized block-wise to either target or control intervention group and participate in nine interventional visits with additional pre- and post-intervention assessments. Performance in the letter updating task after training and anodal tDCS compared to sham stimulation will be analyzed as primary outcome. Further, performance on the second training task and transfer tasks will be investigated. Two follow-up visits (at 1 and 7 months post-training) will be performed to assess possible maintenance effects. Structural and functional magnetic resonance imaging (MRI) will be applied before the intervention and at the 7-month follow-up to identify possible neural predictors for successful intervention. Significance With this trial, we aim to provide evidence for tDCS-induced improvements of multi-session cognitive training in participants with SCD and MCI. An improved understanding of tDCS effects on cognitive training performance and neural predictors may help to develop novel approaches to counteract cognitive decline in participants with prodromal AD. Trial registration ClinicalTrials.gov , NCT04265378 . Registered on 07 February 2020. Retrospectively registered. Protocol version: Based on BB 004/18 version 1.2 (May 17, 2019). Sponsor: University Medicine Greifswald.

Abstract 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.

The ability to perceive differences in depth is important in many daily life situations. It is also of relevance in laparoscopic surgical procedures that require the extrapolation of three-dimensional visual information from two-dimensional planar images. Besides visual-motor coordination, laparoscopic skills and binocular depth perception are demanding visual tasks for which learning is important. This study explored potential relations between binocular depth perception and individual variations in performance gains during laparoscopic skill acquisition in medical students naïve of such procedures. Individual differences in perceptual learning of binocular depth discrimination when performing a random dot stereogram (RDS) task were measured as variations in the slope changes of the logistic disparity psychometric curves from the first to the last blocks of the experiment. The results showed that not only did the individuals differ in their depth discrimination; the extent with which this performance changed across blocks also differed substantially between individuals. Of note, individual differences in perceptual learning of depth discrimination are associated with performance gains from laparoscopic skill training, both with respect to movement speed and an efficiency score that considered both speed and precision. These results indicate that learning-related benefits for enhancing demanding visual processes are, in part, shared between these two tasks. Future studies that include a broader selection of task-varying monocular and binocular cues as well as visual-motor coordination are needed to further investigate potential mechanistic relations between depth perceptual learning and laparoscopic skill acquisition. A deeper understanding of these mechanisms would be important for applied research that aims at designing behavioral interventions for enhancing technology-assisted laparoscopic skills.

Humans differ in their capacity for integrating perceived events and related actions. The “Theory of event coding” (TEC) conceptualizes how stimuli and actions are cognitively bound into a common functional representation (or “code”), known as the “event file”. To date, however, the neural processes underlying the development of event file coding mechanisms across age are largely unclear. We investigated age-related neural changes of event file coding from late childhood to early adulthood, using EEG signal decompositions methods. We included a group of healthy participants (n = 91) between 10 and 30 years, performing an event file paradigm. Results of this study revealed age-related effects on event file coding processes both at the behavioural and the neurophysiological level. Performance accuracy data showed that event file unbinding und rebinding processes become more efficient from late childhood to early adulthood. These behavioural effects are reflected by age-related effects in two neurophysiological subprocesses associated with the superior parietal cortex (BA7) as revealed in the analyses using EEG signal decomposition. The first process entails mapping and association processes between stimulus and response; whereas, the second comprises inhibitory control subprocesses subserving the selection of the relevant motor programme amongst competing response options.

Anticipating population ageing to reach a historically unprecedented level in this century and considering the public goal of promoting well-being until old age, research in many fields has started to focus on processes and factors that contribute to healthy ageing. Since human interactions have a tremendous impact on our mental and physical well-being, scientists are increasingly investigating the basic processes that enable successful social interactions such as social affect (empathy, compassion) and social cognition (Theory of Mind). However, regarding the replication crisis in psychological science it is crucial to probe the reproducibility of findings revealed by each specific method. To this end, we aimed to replicate the effect of age on empathy, compassion and Theory of Mind observed in Reiter and colleagues' study (Reiter et al. 2017 Sci. Rep. 7, 11046 (doi:10.1038/s41598-017-10669-4)) by using the same ecologically valid paradigm in an independent sample with similar age ranges. We were able to replicate the previously observed results of a preservation or even enhancement in socio-affective processes, but a decline in socio-cognitive processes for older adults. Our findings add to the understanding of how social affect and cognition change across the adult lifespan and may suggest targets for intervention studies aiming to foster successful social interactions and well-being until advanced old age.

Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article.

Accumulating studies suggest that neuroinflammation characterized by microglial overactivation plays a pivotal role in the pathogenesis of Parkinson’s disease. As such, inhibition of microglial overactivation might be a promising treatment strategy to delay the onset or slow the progression of Parkinson’s disease. Ginsenoside Rb1, the most active ingredient of ginseng, reportedly exerts neuroprotective effects by suppressing inflammation in vitro. The present study aimed to evaluate the neuroprotective and anti-inflammatory effects of ginsenoside Rb1 in a lipopolysaccharide-induced rat Parkinson’s disease model. Rats were divided into four groups. In the control group, sham-operated rats were intraperitoneally administered normal saline for 14 consecutive days. In the ginsenoside Rb1 group, ginsenoside Rb1 (20 mg/kg) was intraperitoneally injected for 14 consecutive days after sham surgery. In the lipopolysaccharide group, a single dose of lipopolysaccharide was unilaterally microinjected into the rat substantial nigra to establish the Parkinson’s disease model. Lipopolysaccharide-injected rats were treated with normal saline for 14 consecutive days. In the ginsenoside Rb1 + lipopolysaccharide group, lipopolysaccharide was unilaterally microinjected into the rat substantial nigra. Subsequently, ginsenoside Rb1 was intraperitoneally injected for 14 consecutive days. To investigate the therapeutic effects of ginsenoside Rb1, behavioral tests were performed on day 15 after lipopolysaccharide injection. We found that ginsenoside Rb1 treatment remarkably reduced apomorphine-induced rotations in lipopolysaccharide-treated rats compared with the lipopolysaccharide group. To investigate the neurotoxicity of lipopolysaccharide and potential protective effect of ginsenoside Rb1, contents of dopamine and its metabolites in the striatum were measured by high-performance liquid chromatography. Compared with the lipopolysaccharide group, ginsenoside Rb1 obviously attenuated the lipopolysaccharide-induced depletion of dopamine and its metabolites in the striatum. To further explore the neuroprotective effect of ginsenoside Rb1 against lipopolysaccharide-induced neurotoxicity, immunohistochemistry and western blot assay of tyrosine hydroxylase were performed to evaluate dopaminergic neuron degeneration in the substantial nigra par compacta. The results showed that lipopolysaccharide injection caused a large loss of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra and a significant decrease in overall tyrosine hydroxylase expression. However, ginsenoside Rb1 noticeably reversed these changes. To investigate whether the neuroprotective effect of ginsenoside Rb1 was associated with inhibition of lipopolysaccharide-induced microglial activation, we examined expression of the microglia marker Iba-1. Our results confirmed that lipopolysaccharide injection induced a significant increase in Iba-1 expression in the substantia nigra; however, ginsenoside Rb1 effectively suppressed lipopolysaccharide-induced microglial overactivation. To elucidate the inhibitory mechanism of ginsenoside Rb1, we examined expression levels of inflammatory mediators (tumor necrosis factor-α, interleukin-1β, inducible nitric oxide synthase, and cyclooxygenase 2) and phosphorylation of nuclear factor kappa B signaling-related proteins (IκB, IKK) in the substantia nigra with enzyme-linked immunosorbent and western blot assays. Our results revealed that compared with the control group, phosphorylation and expression of inflammatory mediators IκB and IKK in the substantia nigra of lipopolysaccharide group rats were significantly increased; whereas, ginsenoside Rb1 obviously reduced lipopolysaccharide-induced changes on the lesioned side of the substantial nigra par compacta. These findings confirm that ginsenoside Rb1 can inhibit inflammation induced by lipopolysaccharide injection into the substantia nigra and protect dopaminergic neurons, which may be related to its inhibition of the nuclear factor kappa B signaling pathway. This study was approved by the Experimental Animal Ethics Committee of Shandong University of China in April 2016 (approval No. KYLL-2016-0148).

The ability to learn sequential contingencies of actions for predicting future outcomes is indispensable for flexible behavior in many daily decision-making contexts. It remains open whether such ability may be enhanced by transcranial direct current stimulation (tDCS). The present study combined tDCS with functional near-infrared spectroscopy (fNIRS) to investigate potential tDCS-induced effects on sequential decision-making and the neural mechanisms underlying such modulations. Offline tDCS and sham stimulation were applied over the left and right dorsolateral prefrontal cortex (dlPFC) in young male adults (N = 29, mean age = 23.4 years, SD = 3.2) in a double-blind between-subject design using a three-state Markov decision task. The results showed (i) an enhanced dlPFC hemodynamic response during the acquisition of sequential state transitions that is consistent with the findings from a previous functional magnetic resonance imaging (fMRI) study; (ii) a tDCS-induced increase of the hemodynamic response in the dlPFC, but without accompanying performance-enhancing effects at the behavioral level; and (iii) a greater tDCS-induced upregulation of hemodynamic responses in the delayed reward condition that seems to be associated with faster decision speed. Taken together, these findings provide empirical evidence for fNIRS as a suitable method for investigating hemodynamic correlates of sequential decision-making as well as functional brain correlates underlying tDCS-induced modulation. Future research with larger sample sizes for carrying out subgroup analysis is necessary in order to decipher interindividual differences in tDCS-induced effects on sequential decision-making process at the behavioral and brain levels.

Cognitive function is associated with health and important life outcomes. Here, the authors perform a genome-wide association study for general cognitive function in 300,486 individuals and identify genetic loci that implicate neural and cell developmental pathways in this trait.

Numerous technological solutions have been proposed to promote piano learning and teaching, but very few with market success. We are convinced that users’ needs should be the starting point for an effective and transdisciplinary development process of piano-related Tactile Internet with Human-in-the-Loop (TaHIL) applications. Thus, we propose to include end users in the initial stage of technology development. We gathered insights from adult piano teachers and students through an online survey and digital interviews. Three potential literature-based solutions have been visualized as scenarios to inspire participants throughout the interviews. Our main findings indicate that potential end users consider posture and body movements, teacher–student communication, and self-practice as crucial aspects of piano education. Further insights resulted in so-called acceptance requirements for each scenario, such as enabling meaningful communication in distance teaching, providing advanced data on a performer’s body movement for increased well-being, and improving students’ motivation for self-practice, all while allowing or even promoting artistic freedom of expression and having an assisting instead of judging character. By putting the users in the center of the fuzzy front end of technology development, we have gone a step further toward concretizing TaHIL applications that may contribute to the routines of piano teaching and learning.

BackgroundWith increasing aging populations worldwide, developing interventions against age-associated cognitive decline is particularly important. Evidence suggests that combination of brain stimulation with cognitive training intervention may enhance training effects in terms of performance gain or transfer to untrained domains. This protocol describes a Phase IIb clinical trial that investigates the intervention effects of training combined with brain stimulation in older adults.MethodsThe TrainStim-Cog study is a monocentric, randomized, single-blind, placebo-controlled intervention. The study will investigate cognitive training with concurrent anodal transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (target intervention) compared to cognitive training with sham stimulation (control intervention) over nine sessions in 3 weeks, consisting of a letter updating task, and a three-stage Markov decision-making task. Fifty-six older adults will be recruited from the general population. Baseline assessment will be performed including neuropsychological screening and performance on training tasks. Participants will be allocated to one of the two study arms using block-wise randomization stratified by age and baseline performance with a 1:1 allocation ratio. Primary outcome is performance in the letter updating task after training under anodal tDCS compared to sham stimulation. Secondary outcomes include performance changes in the decision-making task and transfer tasks, as well as brain structure and functional networks assessed by structural, and functional magnetic resonance imaging (MRI) that are acquired pre- and post-intervention.SignificanceThe main aim of the TrainStim-Cog study is to provide evidence for behavioral and neuronal effects of tDCS-accompanied cognitive training and to elucidate the underlying mechanisms in older adults. Our findings will contribute toward developing efficient interventions for age-associated cognitive decline.Trial registrationThis trial was retrospectively registered at Clinicaltrials.gov Identifier: NCT03838211 at February 12, 2019, https://clinicaltrials.gov/ct2/show/NCT03838211.Protocol versionBased on BB 004/18 version 1.2 (May 17, 2019).

Aging and dopamine modulation have both been independently shown to influence the functional connectivity of brain networks during rest. Dopamine modulation is known to decline during the course of aging. Previous evidence also shows that the dopamine transporter gene (DAT1) influences the re-uptake of dopamine and the anyA9 genotype of this gene is associated with higher striatal dopamine signaling. Expanding these two lines of prior research, we investigated potential interactive effects between aging and individual variations in the DAT1 gene on the modular organization of brain acvitiy during rest. The graph-theoretic metrics of modularity, betweenness centrality and participation coefficient were assessed in 41 younger (age 20-30 years) and 37 older (age 60-75 years) adults. Age differences were only observed in the participation coefficient in carriers of the anyA9 genotype of the DAT1 gene and this effect was most prominently observed in the default mode network. Furthermore, we found that individual differences in the values of the participation coefficient correlated with individual differences in fluid intelligence and a measure of executive control in the anyA9 carriers. The correlation between participation coefficient and fluid intelligence was mainly shared with age-related differences, whereas the correlation with executive control was independent of age. These findings suggest that DAT1 genotype moderates age differences in the functional integration of brain networks as well as the relation between network characteristics and cognitive abilities.

A hallmark of all primary and metastatic tumours is their high rate of glucose uptake and glycolysis. A consequence of the glycolytic phenotype is the accumulation of metabolic acid; hence, tumour cells experience considerable intracellular acid stress. To compensate, tumour cells upregulate acid pumps, which expel the metabolic acid into the surrounding tumour environment, resulting in alkalization of intracellular pH and acidification of the tumour microenvironment. Nevertheless, we have only a limited understanding of the consequences of altered intracellular pH on cell physiology, or of the genes and pathways that respond to metabolic acid stress. We have used yeast as a genetic model for metabolic acid stress with the rationale that the metabolic changes that occur in cancer that lead to intracellular acid stress are likely fundamental. Using a quantitative systems biology approach we identified 129 genes required for optimal growth under conditions of metabolic acid stress. We identified six highly conserved protein complexes with functions related to oxidative phosphorylation (mitochondrial respiratory chain complex III and IV), mitochondrial tRNA biosynthesis [glutamyl-tRNA(Gln) amidotransferase complex], histone methylation (Set1C–COMPASS), lysosome biogenesis (AP-3 adapter complex), and mRNA processing and P-body formation (PAN complex). We tested roles for two of these, AP-3 adapter complex and PAN deadenylase complex, in resistance to acid stress using a myeloid leukaemia-derived human cell line that we determined to be acid stress resistant. Loss of either complex inhibited growth of Hap1 cells at neutral pH and caused sensitivity to acid stress, indicating that AP-3 and PAN complexes are promising new targets in the treatment of cancer. Additionally, our data suggests that tumours may be genetically sensitized to acid stress and hence susceptible to acid stress-directed therapies, as many tumours accumulate mutations in mitochondrial respiratory chain complexes required for their proliferation.

The ability to learn decreases with old age especially in a dynamically changing environment, however the precise nature of this decline is not understood. Nassar and colleagues report that older adults show a reduced ability to learn from uncertain outcomes compared to younger adults.