Age-related decline in GABAergic intracortical inhibition can be counteracted by long-term learning of balance skills.

Ageing induces a decline in GABAergic intracortical inhibition, which seems to be associated not only with decremental changes in well-being, sleep quality, cognition and pain management but also with impaired motor control. So far, little is known regarding whether targeted interventions can prevent the decline of intracortical inhibition in the primary motor cortex in the elderly. Therefore, the present study investigated whether age-related cortical dis-inhibition could be reversed after 6 months of balance learning and whether improvements in postural control correlated with the extent of reversed dis-inhibition. The results demonstrated that intracortical inhibition can be upregulated in elderly subjects after long-term balance learning and revealed a correlation between changes in balance performance and intracortical inhibition. This is the first study to show physical activity-related upregulation of GABAergic inhibition in a population with chronic dis-inhibition and may therefore be seminal for many pathologies in which the equilibrium between inhibitory and excitatory neurotransmitters is disturbed. KEY POINTS: Ageing induces a decline in GABAergic intracortical inhibition. So far, little is known regarding whether targeted interventions can prevent the decline of intracortical inhibition in the primary motor cortex in the elderly. After 6 months of balance learning, intracortical inhibition can be upregulated in elderly subjects. The results of this study also revealed a correlation between changes in balance performance and intracortical inhibition. This is the first study to show physical activity-related upregulation of GABAergic inhibition in a population with chronic dis-inhibition.

Higher surface folding of the human premotor cortex is associated with better long-term learning capability.

The capacity to learn enabled the human species to adapt to various challenging environmental conditions and pass important achievements on to the next generation. A growing body of research suggests links between neocortical folding properties and numerous aspects of human behavior, but their impact on enhanced human learning capacity remains unexplored. Here we leverage three training cohorts to demonstrate that higher levels of premotor cortical folding reliably predict individual long-term learning gains in a challenging new motor task, above and beyond initial performance differences. Individual folding-related predisposition to motor learning was found to be independent of cortical thickness and intracortical microstructure, but dependent on larger cortical surface area in premotor regions. We further show that learning-relevant features of cortical folding occurred in close spatial proximity to practice-induced structural brain plasticity. Our results suggest a link between neocortical surface folding and human behavioral adaptability.

Changes in Cortical Microstructure of the Human Brain Resulting from Long-Term Motor Learning.

The mechanisms subserving motor skill acquisition and learning in the intact human brain are not fully understood. Previous studies in animals have demonstrated a causal relationship between motor learning and structural rearrangements of synaptic connections, raising the question of whether neurite-specific changes are also observable in humans. Here, we use advanced diffusion magnetic resonance imaging (MRI), sensitive to dendritic and axonal processes, to investigate neuroplasticity in response to long-term motor learning. We recruited healthy male and female human participants (age range 19-29) who learned a challenging dynamic balancing task (DBT) over four consecutive weeks. Diffusion MRI signals were fitted using Neurite Orientation Dispersion and Density Imaging (NODDI), a theory-driven biophysical model of diffusion, yielding measures of tissue volume, neurite density and the organizational complexity of neurites. While NODDI indices were unchanged and reliable during the control period, neurite orientation dispersion increased significantly during the learning period mainly in primary sensorimotor, prefrontal, premotor, supplementary, and cingulate motor areas. Importantly, reorganization of cortical microstructure during the learning phase predicted concurrent behavioral changes, whereas there was no relationship between microstructural changes during the control phase and learning. Changes in neurite complexity were independent of alterations in tissue density, cortical thickness, and intracortical myelin. Our results are in line with the notion that structural modulation of neurites is a key mechanism supporting complex motor learning in humans.SIGNIFICANCE STATEMENT The structural correlates of motor learning in the human brain are not fully understood. Results from animal studies suggest that synaptic remodeling (e.g., reorganization of dendritic spines) in sensorimotor-related brain areas is a crucial mechanism for the formation of motor memory. Using state-of-the-art diffusion magnetic resonance imaging (MRI), we found a behaviorally relevant increase in the organizational complexity of neocortical microstructure, mainly in primary sensorimotor, prefrontal, premotor, supplementary, and cingulate motor regions, following training of a challenging dynamic balancing task (DBT). Follow-up analyses suggested structural modulation of synapses as a plausible mechanism driving this increase, while colocalized changes in cortical thickness, tissue density, and intracortical myelin could not be detected. These results advance our knowledge about the neurobiological basis of motor learning in humans.

Differences in Decision-Making Behavior Between Elite and Amateur Team-Handball Players in a Near-Game Test Situation.

Athletic features distinguishing experts from non-experts in team sports are relevant for performance analyses, talent identification and successful training. In this respect, perceptual-cognitive factors like decision making have been proposed to be important predictor of talent but, however, assessing decision making in team sports remains a challenging endeavor. In particular, it is now known that decisions expressed by verbal reports or micro-movements in the laboratory differ from those actually made in on-field situations in play. To address this point, our study compared elite and amateur players' decision-making behavior in a near-game test environment including sport-specific sensorimotor responses. Team-handball players (N = 44) were asked to respond as quickly as possible to representative, temporally occluded attack sequences in a team-handball specific defense environment on a contact plate system. Specifically, participants had to choose and perform the most appropriate out of four prespecified, defense response actions. The frequency of responses and decision time were used as dependent variables representing decision-making behavior. We found that elite players responded significantly more often with offensive responses (p < 0.05, odds ratios: 2.76-3.00) in left-handed attack sequences. Decision time decreased with increasing visual information, but no expertise effect was found. We suppose that expertise-related knowledge and processing of kinematic information led to distinct decision-making behavior between elite and amateur players, evoked in a domain-specific and near-game test setting. Results also indicate that the quality of a decision might be of higher relevance than the required time to decide. Findings illustrate application opportunities in the context of performance analyses and talent identification processes.

Test-retest reliability of multi-parametric maps (MPM) of brain microstructure.

Multiparameter mapping (MPM) is a quantitative MRI protocol that is promising for studying microstructural brain changes in vivo with high specificity. Reliability values are an important prior knowledge for efficient study design and facilitating replicable findings in development, aging and neuroplasticity research. To explore longitudinal reliability of MPM we acquired the protocol in 31 healthy young subjects twice over a rescan interval of 4 weeks. We assessed the within-subject coefficient of variation (WCV), the between-subject coefficient of variation (BCV), and the intraclass correlation coefficient (ICC). Using these metrics, we investigated the reliability of (semi-) quantitative magnetization transfer saturation (MTsat), proton density (PD), transversal relaxation (R2*) and longitudinal relaxation (R1). To increase relevance for explorative studies in development and training-induced plasticity, we assess reliability both on local voxel- as well as ROI-level. Finally, we disentangle contributions and interplay of within- and between-subject variability to ICC and assess the optimal degree of spatial smoothing applied to the data. We reveal evidence that voxelwise ICC reliability of MPMs is moderate to good with median values in cortex (subcortical GM): MT: 0.789 (0.447) PD: 0.553 (0.264) R1: 0.555 (0.369) R2*: 0.624 (0.477). The Gaussian smoothing kernel of 2 to 4 mm FWHM resulted in optimal reproducibility. We discuss these findings in the context of longitudinal intervention studies and the application to research designs in neuroimaging field.

Brain Activation During Active Balancing and Its Behavioral Relevance in Younger and Older Adults: A Functional Near-Infrared Spectroscopy (fNIRS) Study.

Age-related deterioration of balance control is widely regarded as an important phenomenon influencing quality of life and longevity, such that a more comprehensive understanding of the neural mechanisms underlying this process is warranted. Specifically, previous studies have reported that older adults typically show higher neural activity during balancing as compared to younger counterparts, but the implications of this finding on balance performance remain largely unclear. Using functional near-infrared spectroscopy (fNIRS), differences in the cortical control of balance between healthy younger (n = 27) and older (n = 35) adults were explored. More specifically, the association between cortical functional activity and balance performance across and within age groups was investigated. To this end, we measured hemodynamic responses (i.e., changes in oxygenated and deoxygenated hemoglobin) while participants balanced on an unstable device. As criterion variables for brain-behavior-correlations, we also assessed postural sway while standing on a free-swinging platform and while balancing on wobble boards with different levels of difficulty. We found that older compared to younger participants had higher activity in prefrontal and lower activity in postcentral regions. Subsequent robust regression analyses revealed that lower prefrontal brain activity was related to improved balance performance across age groups, indicating that higher activity of the prefrontal cortex during balancing reflects neural inefficiency. We also present evidence supporting that age serves as a moderator in the relationship between brain activity and balance, i.e., cortical hemodynamics generally appears to be a more important predictor of balance performance in the older than in the younger. Strikingly, we found that age differences in balance performance are mediated by balancing-induced activation of the superior frontal gyrus, thus suggesting that differential activation of this region reflects a mechanism involved in the aging process of the neural control of balance. Our study suggests that differences in functional brain activity between age groups are not a mere by-product of aging, but instead of direct behavioral relevance for balance performance. Potential implications of these findings in terms of early detection of fall-prone individuals and intervention strategies targeting balance and healthy aging are discussed.

Priming cardiovascular exercise improves complex motor skill learning by affecting the trajectory of learning-related brain plasticity.

In recent years, mounting evidence from animal models and studies in humans has accumulated for the role of cardiovascular exercise (CE) in improving motor performance and learning. Both CE and motor learning may induce highly dynamic structural and functional brain changes, but how both processes interact to boost learning is presently unclear. Here, we hypothesized that subjects receiving CE would show a different pattern of learning-related brain plasticity compared to non-CE controls, which in turn associates with improved motor learning. To address this issue, we paired CE and motor learning sequentially in a randomized controlled trial with healthy human participants. Specifically, we compared the effects of a 2-week CE intervention against a non-CE control group on subsequent learning of a challenging dynamic balancing task (DBT) over 6 consecutive weeks. Structural and functional MRI measurements were conducted at regular 2-week time intervals to investigate dynamic brain changes during the experiment. The trajectory of learning-related changes in white matter microstructure beneath parieto-occipital and primary sensorimotor areas of the right hemisphere differed between the CE vs. non-CE groups, and these changes correlated with improved learning of the CE group. While group differences in sensorimotor white matter were already present immediately after CE and persisted during DBT learning, parieto-occipital effects gradually emerged during motor learning. Finally, we found that spontaneous neural activity at rest in gray matter spatially adjacent to white matter findings was also altered, therefore indicating a meaningful link between structural and functional plasticity. Collectively, these findings may lead to a better understanding of the neural mechanisms mediating the CE-learning link within the brain.

Making the rich richer: Frontoparietal tDCS enhances transfer effects of a single-session distractor inhibition training on working memory in high capacity individuals but reduces them in low capacity individuals.

Working memory (WM) performance depends on the ability to extract relevant while inhibiting irrelevant information from entering the WM storage. This distractor inhibition ability can be trained and is known to induce transfer effects on WM performance. Here we asked whether transfer on WM can be boosted by transcranial direct current stimulation (tDCS) during a single-session distractor inhibition training. As WM performance is ascribed to the frontoparietal network, in which prefrontal areas are associated with inhibiting distractors and posterior parietal areas with storing information, we placed the anode over the prefrontal and the cathode over the posterior parietal cortex during a single-session distractor inhibition training. This network-oriented stimulation protocol should enhance inhibition processes by shifting the neural activity from posterior to prefrontal regions. WM improved after a single-session distractor inhibition training under verum stimulation but only in subjects with a high WM capacity. In subjects with a low WM capacity, verum tDCS reduced the transfer effects on WM. We assume tDCS to strengthen the frontostriatal pathway in individuals with a high WM capacity leading to efficient inhibition of distractors. In contrast, the cathodal stimulation of the posterior parietal cortex might have hindered usual compensational mechanism in low capacity subjects, i.e. maintaining also irrelevant information in memory. Our results thus stress the need to adjust tDCS protocols to well-founded knowledge about neural networks and individual cognitive differences.

Longitudinal Reproducibility of Neurite Orientation Dispersion and Density Imaging (NODDI) Derived Metrics in the White Matter.

Diffusion-weighted magnetic resonance imaging (DWI) is undergoing constant evolution with the ambitious goal of developing in-vivo histology of the brain. A recent methodological advancement is Neurite Orientation Dispersion and Density Imaging (NODDI), a histologically validated multi-compartment model to yield microstructural features of brain tissue such as geometric complexity and neurite packing density, which are especially useful in imaging the white matter. Since NODDI is increasingly popular in clinical research and fields such as developmental neuroscience and neuroplasticity, it is of vast importance to characterize its reproducibility (or reliability). We acquired multi-shell DWI data in 29 healthy young subjects twice over a rescan interval of 4 weeks to assess the within-subject coefficient of variation (CVWS), between-subject coefficient of variation (CVBS) and the intraclass correlation coefficient (ICC), respectively. Using these metrics, we compared regional and voxel-by-voxel reproducibility of the most common image analysis approaches (tract-based spatial statistics [TBSS], voxel-based analysis with different extents of smoothing ["VBM-style"], ROI-based analysis). We observed high test-retest reproducibility for the orientation dispersion index (ODI) and slightly worse results for the neurite density index (NDI). Our findings also suggest that the choice of analysis approach might have significant consequences for the results of a study. Collectively, the voxel-based approach with Gaussian smoothing kernels of ≥4 mm FWHM and ROI-averaging yielded the highest reproducibility across NDI and ODI maps (CVWS mostly ≤3%, ICC mostly ≥0.8), respectively, whilst smaller kernels and TBSS performed consistently worse. Furthermore, we demonstrate that image quality (signal-to-noise ratio [SNR]) is an important determinant of NODDI metric reproducibility. We discuss the implications of these results for longitudinal and cross-sectional research designs commonly employed in the neuroimaging field.

Which Effects on Neuroanatomy and Path-Integration Survive? Results of a Randomized Controlled Study on Intensive Balance Training.

Balancing is a complex task requiring the integration of visual, somatosensory and vestibular inputs. The vestibular system is linked to the hippocampus, a brain structure crucial for spatial orientation. Here we tested the immediate and sustained effects of a one-month-long slackline training program on balancing and orientation abilities as well as on brain volumes in young adults without any prior experience in that skill. On the corrected level, we could not find any interaction effects for brain volumes, but the effect sizes were small to medium. A subsequent within-training-group analysis revealed volumetric increments within the somatosensory cortex and decrements within posterior insula, cerebellum and putamen remained stable over time. No significant interaction effects were observed on the clinical balance and the spatial orientation task two months after the training period (follow-up). We interpret these findings as a shift away from processes crucial for automatized motor output towards processes related to voluntarily controlled movements. The decrease in insular volume in the training group we propose to result from multisensory interaction of the vestibular with the visual and somatosensory systems. The discrepancy between sustained effects in the brain of the training group on the one hand and transient benefits in function on the other may indicate that for the latter to be retained a longer-term practice is required.

The Contribution of Functional Magnetic Resonance Imaging to the Understanding of the Effects of Acute Physical Exercise on Cognition.

The fact that a single bout of acute physical exercise has a positive impact on cognition is well-established in the literature, but the neural correlates that underlie these cognitive improvements are not well understood. Here, the use of neuroimaging techniques, such as functional magnetic resonance imaging (fMRI), offers great potential, which is just starting to be recognized. This review aims at providing an overview of those studies that used fMRI to investigate the effects of acute physical exercises on cerebral hemodynamics and cognition. To this end, a systematic literature survey was conducted by two independent reviewers across five electronic databases. The search returned 668 studies, of which 14 studies met the inclusion criteria and were analyzed in this systematic review. Although the findings of the reviewed studies suggest that acute physical exercise (e.g., cycling) leads to profound changes in functional brain activation, the small number of available studies and the great variability in the study protocols limits the conclusions that can be drawn with certainty. In order to overcome these limitations, new, more well-designed trials are needed that (i) use a more rigorous study design, (ii) apply more sophisticated filter methods in fMRI data analysis, (iii) describe the applied processing steps of fMRI data analysis in more detail, and (iv) provide a more precise exercise prescription.

Converging patterns of aging-associated brain volume loss and tissue microstructure differences.

Given the worldwide increasing socioeconomic burden of aging-associated brain diseases, there is pressing need to gain in-depth knowledge about the neurobiology of brain anatomy changes across the life span. Advances in quantitative magnetic resonance imaging sensitive to brain's myelin, iron, and free water content allow for a detailed in vivo investigation of aging-related changes while reducing spurious morphometry differences. Main aim of our study is to link previous morphometry findings in aging to microstructural tissue properties in a large-scale cohort (n = 966, age range 46-86 y). Addressing previous controversies in the field, we present results obtained with different approaches to adjust local findings for global effects. Beyond the confirmation of age-related atrophy, myelin, and free water decreases, we report proportionally steeper volume, iron, and myelin decline in sensorimotor and subcortical areas paralleled by free water increase. We demonstrate aging-related white matter volume, myelin, and iron loss in frontostriatal projections. Our findings provide robust evidence for spatial overlap between volume and tissue property differences in aging that affect predominantly motor and executive networks.

Colocalized White Matter Plasticity and Increased Cerebral Blood Flow Mediate the Beneficial Effect of Cardiovascular Exercise on Long-Term Motor Learning.

Cardiovascular exercise (CE) is a promising intervention strategy to facilitate cognition and motor learning in healthy and diseased populations of all ages. CE elevates humoral parameters, such as growth factors, and stimulates brain changes potentially relevant for learning and behavioral adaptations. However, the causal relationship between CE-induced brain changes and human's ability to learn remains unclear. We tested the hypothesis that CE elicits a positive effect on learning via alterations in brain structure (morphological changes of gray and white matter) and function (functional connectivity and cerebral blood flow in resting state). We conducted a randomized controlled trial with healthy male and female human participants to compare the effects of a 2 week CE intervention against a non-CE control group on subsequent learning of a challenging new motor task (dynamic balancing; DBT) over 6 consecutive weeks. We used multimodal neuroimaging [T1-weighted magnetic resonance imaging (MRI), diffusion-weighted MRI, perfusion-weighted MRI, and resting state functional MRI] to investigate the neural mechanisms mediating between CE and learning. As expected, subjects receiving CE subsequently learned the DBT at a higher rate. Using a modified nonparametric combination approach along with multiple mediator analysis, we show that this learning boost was conveyed by CE-induced increases in cerebral blood flow in frontal brain regions and changes in white matter microstructure in frontotemporal fiber tracts. Our study revealed neural mechanisms for the CE-learning link within the brain, probably allowing for a higher flexibility to adapt to highly novel environmental stimuli, such as learning a complex task.SIGNIFICANCE STATEMENT It is established that cardiovascular exercise (CE) is an effective approach to promote learning and memory, yet little is known about the underlying neural transfer mechanisms through which CE acts on learning. We provide evidence that CE facilitates learning in human participants via plasticity in prefrontal white matter tracts and a colocalized increase in cerebral blood flow. Our findings are among the first to demonstrate a transfer potential of experience-induced brain plasticity. In addition to practical implications for health professionals and coaches, our work paves the way for future studies investigating effects of CE in patients suffering from prefrontal hypoperfusion or white matter diseases.

Intrinsic Connectivity Changes Mediate the Beneficial Effect of Cardiovascular Exercise on Sustained Visual Attention.

Cardiovascular exercise (CE) is an evidence-based healthy lifestyle strategy. Yet, little is known about its effects on brain and cognition in young adults. Furthermore, evidence supporting a causal path linking CE to human cognitive performance via neuroplasticity is currently lacking. To understand the brain networks that mediate the CE-cognition relationship, we conducted a longitudinal, controlled trial with healthy human participants to compare the effects of a 2-week CE intervention against a non-CE control group on cognitive performance. Concomitantly, we used structural and functional magnetic resonance imaging to investigate the neural mechanisms mediating between CE and cognition. On the behavioral level, we found that CE improved sustained attention, but not processing speed or short-term memory. Using graph theoretical measures and statistical mediation analysis, we found that a localized increase in eigenvector centrality in the left middle frontal gyrus, probably reflecting changes within an attention-related network, conveyed the effect of CE on cognition. Finally, we found CE-induced changes in white matter microstructure that correlated with intrinsic connectivity changes (intermodal correlation). These results suggest that CE is a promising intervention strategy to improve sustained attention via brain plasticity in young, healthy adults.

Interindividual differences in gray and white matter properties are associated with early complex motor skill acquisition.

Brain circuits mediate but also constrain experience-induced plasticity and corresponding behavioral changes. Here we tested whether interindividual behavioral differences in learning a challenging new motor skill correlate with variations in brain anatomy. Young, healthy participants were scanned using structural magnetic resonance imaging (T1-weighted MPRAGE, n = 75 and/or diffusion-weighted MRI, n = 59) and practiced a complex whole-body balancing task on a seesaw-like platform. Using conjunction tests based on the nonparametric combination (NPC) methodology, we found that gray matter volume (GMV) in the right orbitrofrontal cortex was positively related to the subjects' initial level of proficiency and their ability to improve performance during practice. Similarly, we obtained a strong trend toward a positive correlation between baseline fractional anisotropy (FA) in commissural prefrontal fiber pathways and later motor learning. FA results were influenced more strongly by radial than axial diffusivity. However, we did not find unique anatomical correlates of initial performance and learning to rate. Our findings reveal structural predispositions for successful motor skill performance and acquisition in frontal brain structures and underlying frontal white matter tracts. Together with previous results, these findings support the view that structural constraints imposed by the brain determine subsequent behavioral success and underline the importance of structural brain network constitution before learning starts.

Physical Exercise as Personalized Medicine for Dementia Prevention?

Accumulating evidence mainly from observational studies supports the notion that lifestyle factors such as regular physical activity can modulate potential risk factors of dementia. Regarding a potential mechanism for this interaction, results from intervention studies show that exercising can induce neuroplastic changes in the human brain. However, a detailed look at the study results reveals a wide interindividual variability in the observed effects. This heterogeneity may originate from the fact that there are "responders" and "non-responders" with respect to the impact of physical exercise on physiological outcome parameters (i.e., VO2 peak) and the brain. From this, it follows that recommendations for physical exercise programs should not follow a "one size fits all" approach. Instead, we propose that the exercises should be tailored to an individual in order to maximize the potential neuroplastic and preventive effects of regular exercise. These adaptations should take the individual performance levels into account and impact both the quality (i.e., type) and the quantity of exercises (i.e., intensity, duration, and volume).

Brain Gray Matter Volume Is Modulated by Visual Input and Overall Learning Success but Not by Time Spent on Learning a Complex Balancing Task.

To better understand the process of neuroplasticity, this study assesses brain changes observed by voxel-based morphometry (VBM) in response to two different learning conditions. Twenty-two young, healthy subjects learned slacklining, a complex balancing task, with either their eyes open (EO, n = 11) or their eyes closed (EC, n = 11). The learning took place three times per week for four weeks, with learning periods of 1 hour, providing a total of 12 hours of learning. The scanning and testing protocols were applied at three time-points: (1) immediately before learning (baseline), (2) immediately afterwards (post-test), and (3) two months afterwards (follow-up). The EO group performed better on the task-specific test. Significant group*time interaction effects were found in sensory-motor areas at the post-test, with increases in the EO group only. The results suggest that VBM-observed brain changes in response to learning a complex balancing task vary depending on the learning success and the availability of visual input, and not solely on the amount of time spent on learning. These findings should be taken into account by future studies using similar methodologies.

Vestibulo-Hippocampal Function Is Enhanced and Brain Structure Altered in Professional Ballet Dancers.

Background and Objective: Life-long balance training has been shown to affect brain structure, including the hippocampus. Data are missing in this respect on professional ballet dancers of both genders. It is also unknown whether transfer effects exist on general balancing as well as spatial orientation abilities, a function mainly supported by the hippocampus. We aimed to assess differences in gray matter (GM) structure, general balancing skills, and spatial orientation skills between professional ballet dancers and non-dancers. Methods: Nineteen professional ballet dancers aged 18-35 (27.5 ± 4.1 years; 10 females) and nineteen age-matched non-dancers (26.5 ± 2.1 years; 10 females) were investigated. Main outcomes assessed were the score of a 30-item clinical balance test (CBT), the average error distance (in centimeters) on triangle completion task, and difference in GM density as seen by voxel-based morphometric analysis (VBM, SPM). Results: Ballet group performed significantly better on all conditions of the CBT and in the wheelchair (vestibular-dependent) condition of the spatial orientation test. Larger GM volumes for ballet dancers were observed in the right hippocampus, parahippocampal gyrus, insula, and cingulate motor cortex, whereas both larger and smaller volumes were detected within cerebellum bilaterally in comparison to non-dancers. Conclusion: Our results indicate that life-long ballet training could lead to better clinically relevant balancing abilities as well as vestibular-dependent spatial orientation capabilities; both of the benefits might be caused by positive influence of ballet training on the vestibular system function, and-possibly-its connectivity with temporal lobe regions responsible for vestibular-dependent orienting in space.

Physical Exercise and Spatial Training: A Longitudinal Study of Effects on Cognition, Growth Factors, and Hippocampal Plasticity.

Physical exercise has been suggested to improve cognitive performance through various neurobiological mechanisms, mediated by growth factors such as BDNF, IGF-I, and VEGF. Moreover, animal research has demonstrated that combined physical and cognitive stimulation leads to increased adult neurogenesis as compared to either experimental condition alone. In the present study, we therefore investigated whether a sequential combination of physical and spatial training in young, healthy adults elicits an additive effect on training and transfer gains. To this end, we compared the effects of (i) eight 20-minute sessions of cycling, (ii) sixteen 30-minute sessions of spatial training, (iii) a combination of both, and included (iv) a passive control cohort. We assessed longitudinal changes in cognitive performance, growth factor levels, and T1 relaxation of hippocampal subfields (acquired with 7 T MRI). While substantial physical and spatial training gains were elicited in all trained groups, longitudinal transfer changes did not differ between these groups. Notably, we found no evidence for an additive effect of sequential physical and spatial training. These results challenge the extrapolation from the findings reported in animals to young, healthy adults.

Remote Effects of Non-Invasive Cerebellar Stimulation on Error Processing in Motor Re-Learning.

BACKGROUND: While concurrent transcranial direct current stimulation (tDCS) affects motor memory acquisition and long-term retention, it is unclear how behavioral interference modulates long-term tDCS effects. Behavioral interference can be introduced through a secondary task learned in-between motor memory acquisition and later recall of the original task. OBJECTIVE/HYPOTHESIS: The cerebellum is important for the processing of errors if movements should be adapted to external perturbations (motor memory acquisition). We hypothesized that concurrent cerebellar tDCS during adaptation influences both memory acquisition and re-acquisition if motor errors are enlarged due to behavioral interference. METHODS: In a sham-controlled and double-blinded study, we applied anodal and cathodal tDCS to the ipsilateral cerebellum while subjects adapted reaching movements to an external, clockwise force field perturbation (acquisition task A) with their dominant right arm. Behavioral interference by an oppositely oriented, counter-clockwise perturbation (secondary task B) was introduced in between the acquisition and re-acquisition (24 h later) sessions. RESULTS: Learning task B disrupted memory retention of A and re-increased motor errors in the re-acquisition session. Anodal but not sham or cathodal tDCS impaired motor memory acquisition and, additionally, increased motor errors during re-acquisition of the original motor memory. CONCLUSION(S): Behavioral interference disrupted motor memory retention but tDCS delivered online during memory acquisition induced lasting and robust effects on re-acquisition performance one day later. Our data also suggest different error-processing mechanisms at work during motor memory acquisition and re-acquisition.