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.

Neural Correlates of Mirror Visual Feedback-Induced Performance Improvements: A Resting-State fMRI Study.

Mirror visual feedback (MVF) is a promising approach to enhance motor performance without training in healthy adults as well as in patients with focal brain lesions. There is preliminary evidence that a functional modulation within and between primary motor cortices as assessed with transcranial magnetic stimulation (TMS) might be one candidate mechanism mediating the observed behavioral effects. Recently, studies using task-based functional magnetic resonance imaging (fMRI) have indicated that MVF-induced functional changes might not be restricted to the primary motor cortex (M1) but also include higher order regions responsible for perceptual-motor coordination and visual attention. However, aside from these instantaneous task-induced brain changes, little is known about learning-related neuroplasticity induced by MVF. Thus, in the present study, we assessed MVF-induced functional network plasticity with resting-state fMRI (rs-fMRI). We performed rs-fMRI of 35 right-handed, healthy adults before and after performing a complex ball-rotation task. The primary outcome measure was the performance improvement of the untrained left hand (LH) before and after right hand (RH) training with MVF (mirror group [MG], n = 17) or without MVF (control group [CG], n = 18). Behaviorally, the MG showed superior performance improvements of the untrained LH. In resting-state functional connectivity (rs-FC), an interaction analysis between groups showed changes in left visual cortex (V1, V2) revealing an increase of centrality in the MG. Within group comparisons showed further functional alterations in bilateral primary sensorimotor cortex (SM1), left V4 and left anterior intraparietal sulcus (aIP) in the MG, only. Importantly, a correlation analysis revealed a linear positive relationship between MVF-induced improvements of the untrained LH and functional alterations in left SM1. Our results suggest that MVF-induced performance improvements are associated with functional learning-related brain plasticity and have identified additional target regions for non-invasive brain stimulation techniques, a finding of potential interest for neurorehabilitation.

Anodal Transcranial Direct Current Stimulation Does Not Facilitate Dynamic Balance Task Learning in Healthy Old Adults.

Older adults frequently experience a decrease in balance control that leads to increased numbers of falls, injuries and hospitalization. Therefore, evaluating older adults' ability to maintain balance and examining new approaches to counteract age-related decline in balance control is of great importance for fall prevention and healthy aging. Non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) have been shown to beneficially influence motor behavior and motor learning. In the present study, we investigated the influence of tDCS applied over the leg area of the primary motor cortex (M1) on balance task learning of healthy elderly in a dynamic balance task (DBT). In total, 30 older adults were enrolled in a cross-sectional, randomized design including two consecutive DBT training sessions. Only during the first DBT session, either 20 min of anodal tDCS (a-tDCS) or sham tDCS (s-tDCS) were applied and learning improvement was compared between the two groups. Our data showed that both groups successfully learned to perform the DBT on both training sessions. Interestingly, between-group analyses revealed no difference between the a-tDCS and the s-tDCS group regarding their level of task learning. These results indicate that the concurrent application of tDCS over M1 leg area did not elicit DBT learning enhancement in our study cohort. However, a regression analysis revealed that DBT performance can be predicted by the kinematic profile of the movement, a finding that may provide new insights for individualized approaches of treating balance and gait disorders.

Transcranial Alternating Current Stimulation at Beta Frequency: Lack of Immediate Effects on Excitation and Interhemispheric Inhibition of the Human Motor Cortex.

Transcranial alternating current stimulation (tACS) is a form of noninvasive brain stimulation and is capable of influencing brain oscillations and cortical networks. In humans, the endogenous oscillation frequency in sensorimotor areas peaks at 20 Hz. This beta-band typically occurs during maintenance of tonic motor output and seems to play a role in interhemispheric coordination of movements. Previous studies showed that tACS applied in specific frequency bands over primary motor cortex (M1) or the visual cortex modulates cortical excitability within the stimulated hemisphere. However, the particular impact remains controversial because effects of tACS were shown to be frequency, duration and location specific. Furthermore, the potential of tACS to modulate cortical interhemispheric processing, like interhemispheric inhibition (IHI), remains elusive. Transcranial magnetic stimulation (TMS) is a noninvasive and well-tolerated method of directly activating neurons in superficial areas of the human brain and thereby a useful tool for evaluating the functional state of motor pathways. The aim of the present study was to elucidate the immediate effect of 10 min tACS in the ß-frequency band (20 Hz) over left M1 on IHI between M1s in 19 young, healthy, right-handed participants. A series of TMS measurements (motor evoked potential (MEP) size, resting motor threshold (RMT), IHI from left to right M1 and vice versa) was performed before and immediately after tACS or sham using a double-blinded, cross-over design. We did not find any significant tACS-induced modulations of intracortical excitation (as assessed by MEP size and RMT) and/or IHI. These results indicate that 10 min of 20 Hz tACS over left M1 seems incapable of modulating immediate brain activity or inhibition. Further studies are needed to elucidate potential aftereffects of 20 Hz tACS as well as frequency-specific effects of tACS on intracortical excitation and IHI.

Transcranial direct current stimulation (tDCS) over primary motor cortex leg area promotes dynamic balance task performance.

OBJECTIVE: The aim of the study was to investigate the effects of facilitatory anodal tDCS (a-tDCS) applied over the leg area of the primary motor cortex on learning a complex whole-body dynamic balancing task (DBT). We hypothesized that a-tDCS during DBT enhances learning performance compared to sham tDCS (s-tDCS). METHODS: In a randomized, parallel design, we applied either a-tDCS (n=13) or s-tDCS (n=13) in a total of 26 young subjects while they perform the DBT. Task performance and error rates were compared between groups. Additionally, we investigated the effect of tDCS on the relationship between performance and kinematic variables capturing different aspects of task execution. RESULTS: A-tDCS over M1 leg area promotes balance performance in a DBT relative to s-tDCS, indicated by higher performance and smaller error scores. Furthermore, a-tDCS seems to mediate the relationship between DBT performance and the kinematic variable velocity. CONCLUSIONS: Our findings provide novel evidence for the ability of tDCS to improve dynamic balance learning, a fact, particularly important in the context of treating balance and gait disorders. SIGNIFICANCE: TDCS facilitates dynamic balance performance by strengthening the inverse relationship of performance and velocity, thus making tDCS one potential technique to improve walking ability or help to prevent falls in patients in the future.

Augmenting mirror visual feedback-induced performance improvements in older adults.

Previous studies have indicated that age-related behavioral alterations are not irreversible but are subject to amelioration through specific training interventions. Both training paradigms and non-invasive brain stimulation (NIBS) can be used to modulate age-related brain alterations and thereby influence behavior. It has been shown that mirror visual feedback (MVF) during motor skill training improves performance of the trained and untrained hands in young adults. The question remains of whether MVF also improves motor performance in older adults and how performance improvements can be optimised via NIBS. Here, we sought to determine whether anodal transcranial direct current stimulation (a-tDCS) can be used to augment MVF-induced performance improvements in manual dexterity. We found that older adults receiving a-tDCS over the right primary motor cortex (M1) during MVF showed superior performance improvements of the (left) untrained hand relative to sham stimulation. An additional control experiment in participants receiving a-tDCS over the right M1 only (without MVF/motor training of the right hand) revealed no significant behavioral gains in the left (untrained) hand. On the basis of these findings, we propose that combining a-tDCS with MVF might be relevant for future clinical studies that aim to optimise the outcome of neurorehabilitation.

Mirror Visual Feedback-Induced Performance Improvement and the Influence of Hand Dominance.

Mirror visual feedback (MVF) is a promising technique in clinical settings that can be used to augment performance of an untrained limb. Several studies with healthy volunteers and patients using transcranial magnetic stimulation (TMS) or functional magnetic resonance imaging (fMRI) indicate that functional alterations within primary motor cortex (M1) might be one candidate mechanism that could explain MVF-induced changes in behavior. Until now, most studies have used MVF to improve performance of the non-dominant hand (NDH). The question remains if the behavioral effect of MVF differs according to hand dominance. Here, we conducted a study with two groups of young, healthy right-handed volunteers who performed a complex ball-rotation task while receiving MVF of the dominant (n = 16, group 1, MVFDH) or NDH (n = 16, group 2, MVFNDH). We found no significant differences in baseline performance of the untrained hand between groups before MVF was applied. Furthermore, there was no significant difference in the amount of performance improvement between MVFDH and MVFNDH indicating that the outcome of MVF seems not to be influenced by hand dominance. Thus our findings might have important implications in neurorehabilitation suggesting that patients suffering from unilateral motor impairments might benefit from MVF regardless of the dominance of the affected limb.