Cardiovascular exercise, learning, memory, and cytokines: Results of a ten-week randomized controlled training study in young adults.

Physical exercise has been shown to enhance memory and to increase neuroplasticity. Rodent studies have revealed modulating effects of signaling molecules of the immune system (cytokines) on hippocampal plasticity and memory. Acute and chronic exercise have been both found to alter the number and function of immune cells. Thus, physical exercise might enhance neuroplasticity via an altered immune response. In this study we tested whether multiple repetitions of a vocabulary learning task combined with a bout of cardiovascular exercise enhances learning in humans and whether memory improvements correlated with acute exercise-induced cytokine changes. Data of 52 participants (20-40 years of age) who were randomly assigned to a cardiovascular exercise group (cycling) or a control group (stretching) were analyzed. During the 10-week treatment, participants completed 18 learning-exercise sessions. In each of these sessions, the vocabulary learning task was always performed immediately before exercising started. To assess acute exercise-induced changes in cytokine levels, blood sampling was performed at rest and immediately after exercising in two of the sessions. Learning success measured as increase in learning across all sessions and vocabulary retention four weeks after the treatment had ended did not differ between groups. The cycling group showed a relatively larger acute increase in IL-6, IL-1ra, IL-4, and IFN-γ compared to the stretching group. Exploratory analyses revealed significant positive associations between within-session learning and acute exercise-induced increases in IL-6 and IL-1ra in the cycling group only. These results suggest that the immune system may act as a mediator of exercise-induced cognitive benefits.

The Effects of Acute Cardiovascular Exercise on Memory and Its Associations With Exercise-Induced Increases in Neurotrophic Factors.

Due to increasing life expectancy, low-cost interventions to counteract age-related memory impairment have gained popularity. Physical activity has been shown to positively affect memory and hippocampal plasticity in rodents and humans. These effects have been proposed to be mediated by the release of neurotrophic factors. However, studies examining the effects of a single cardiovascular exercise session on human memory have yielded conflicting results. Moreover, it remains unclear whether exercise-induced memory enhancements are related to changes in peripheral neurotrophic factor concentrations. The present study tested whether one bout of cardiovascular exercise during an early phase of memory consolidation, compared to one bout of stretching and toning, positively affected memory. Furthermore, it was analyzed whether exercise-induced changes in the brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) were related to memory enhancement after a single bout of physical exercise. Fifty healthy participants (20-40 years) were randomly assigned to either a cycling group (BIKE) or a stretching and toning group (STRETCH). Participants performed an implicit vocabulary learning task which was immediately followed by physical exercise. Memory for the learned vocabulary was tested 1-2 weeks later. To measure exercise-induced changes in serum neurotrophic factor levels, blood samples were collected at rest (baseline) and immediately after the exercise session. Results did not show a significant difference in memory between the BIKE group and the STRETCH group. However, in the BIKE group, a larger increase in BDNF and VEGF levels was observed than in the STRETCH group. Moreover, the increase in BDNF and memory performance tended to be positively related in the BIKE group. We speculate that the correlation between exercise-increased BDNF levels and memory in the cycling group may indicate an involvement of BDNF in mediating memory processes after acute cardiovascular exercise.

Balance Expertise Is Associated with Superior Spatial Perspective-Taking Skills.

Balance training interventions over several months have been shown to improve spatial cognitive functions and to induce structural plasticity in brain regions associated with visual-vestibular self-motion processing. In the present cross-sectional study, we tested whether long-term balance practice is associated with better spatial cognition. To this end, spatial perspective-taking abilities were compared between balance experts (n = 40) practicing sports such as gymnastics, acrobatics or slacklining for at least four hours a week for the last two years, endurance athletes (n = 38) and sedentary healthy individuals (n = 58). The balance group showed better performance in a dynamic balance task compared to both the endurance group and the sedentary group. Furthermore, the balance group outperformed the sedentary group in a spatial perspective-taking task. A regression analysis across all participants revealed a positive association between individual balance performance and spatial perspective-taking abilities. Groups did not differ in executive functions, and individual balance performance did not correlate with executive functions, suggesting a specific association between balance skills and spatial cognition. The results are in line with theories of embodied cognition, assuming that sensorimotor experience shapes cognitive functions.

Balance, gait, and navigation performance are related to physical exercise in blind and visually impaired children and adolescents.

Self-motion perception used for locomotion and navigation requires the integration of visual, vestibular, and proprioceptive input. In the absence of vision, postural stability and locomotor tasks become more difficult. Previous research has suggested that in visually deprived children, postural stability and levels of physical activity are overall lower than in sighted controls. Here we hypothesized that visually impaired and blind children and adolescents differ from sighted controls in postural stability and gait parameters, and that physically active individuals outperform sedentary peers in postural stability and gait parameters as well as in navigation performance. Fourteen blind and visually impaired children and adolescents (8-18 years of age) and 14 matched sighted individuals took part. Assessments included postural sway, single-leg stance time, parameters of gait variability and stability, self-reported physical activity, and navigation performance. Postural sway was larger and single-leg stance time was lower in blind and visually impaired participants than in blindfolded sighted individuals. Physical activity was higher in the sighted group. No differences between the group of blind and visually impaired and blindfolded sighted participants were observed for gait parameters and navigation performance. Higher levels of physical activity were related to lower postural sway, longer single-leg stance time, higher gait stability, and superior navigation performance in blind and visually impaired participants. The present data suggest that physical activity may enhance postural stability and gait parameters, and thereby promote navigation performance in blind and visually impaired children and adolescents.

Improved balance performance accompanied by structural plasticity in blind adults after training.

Postural control requires the sensory integration of visual, vestibular, and proprioceptive signals. In the absence of vision, either by blindfolding or in blind individuals, balance performance is typically poorer than with sight. Previous research has suggested that despite showing compensatory vestibular and proprioceptive processing during upright standing, balance performance in blind individuals is overall lower than in sighted controls with eyes open. The present study tested whether balance training, which places demands on vestibular and proprioceptive self-motion perception, improves balance performance in blind adults, and whether we find similar structural correlates in cortical and subcortical brain areas as have been reported in sighted individuals. Fourteen congenitally or late blind adults were randomly assigned to either a balance or a relaxation group and exercised twice a week for 12 weeks. Assessments prior to and after training included balance tests and the acquisition of T1-weighted MRI images. The blind balance group significantly improved in dynamic, static, and functional balance performance compared to the blind relaxation group. The balance performance improvement did not differ from that of age- and gender matched sighted adults after balance training. Cortical thickness increased in the left parahippocampus and decreased in the inferior insula bilaterally in the blind balance group compared to the blind relaxation group. Thickness decreases in the insula were related to improved static and functional balance. Gray matter volume was reduced in the left hippocampus proper and increased in the right subiculum in the blind balance group. The present data suggest that impaired balance performance in blind adults can be significantly improved by a training inducing plasticity in brain regions associated with vestibular and proprioceptive self-motion processing.

Author Correction: Balance training improves memory and spatial cognition in healthy adults.

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Effects of barefoot and footwear conditions on learning of a dynamic balance task: a randomized controlled study.

PURPOSE: Although barefoot balancing has shown to be more challenging compared to shod balancing, it is still unclear whether this may also influence the balance learning effects. The purpose of this study was to explore the impact of barefoot and shod exercising on learning of a dynamic balance task. METHODS: Sixty healthy and physically active adults (mean age 25.3 ± 3.4 years) were randomly allocated into one of three groups (barefoot, shod and controls). The barefoot and shod intervention groups exercised once weekly over 7 weeks on a stability platform with an unstable surface. Each training session included 15 trials over 30 s. Before and after the intervention period, all participants completed two balance tests (stability platform and Balance Error Scoring System = BESS) under barefoot and shod conditions. Group effects in stability gains (pre to post-test differences) were analysed using ANOVA. Development of balance learning curves during the intervention period was analysed using a mixed effects model. RESULTS: Balance times improved in both intervention groups (p < 0.001, 95% CI barefoot 5.82-9.22 s, shod 7.51-10.92 s) compared to controls. The barefoot intervention group showed a significantly less sloped balance learning curve compared to the shod intervention group (p = 0.033). No changes over time or differences between groups were found for the BESS test. CONCLUSIONS: Improvements in the dynamic balance task did not differ between individuals exercising barefoot or with footwear although the progression was slower in the barefoot group. The lack of changes in the BESS supports the task-specificity of balance learning effects.

Exercise-induced neuroplasticity: Balance training increases cortical thickness in visual and vestibular cortical regions.

Physical exercise has been shown to induce structural plasticity in the human brain and to enhance cognitive functions. While previous studies focused on aerobic exercise, suggesting a link between increased cardiorespiratory fitness and exercise-induced neuroplasticity, recent findings have suggested that whole-body exercise with minor metabolic demands elicits beneficial effects on brain structure as well. In the present study, we tested if balance training, challenging the sensory-motor system and vestibular self-motion perception, induces structural plasticity. Thirty-seven healthy adults aged 19-65 years were randomly assigned to either a balance training or a relaxation training group. All participants exercised twice a week for 12 weeks. Assessments before and after the training included a balance test and the acquisition of high-resolution T1-weighted images to analyze morphological brain changes. Only the balance group significantly improved balance performance after training. Cortical thickness was increased in the superior temporal cortex, in visual association cortices, in the posterior cingulate cortex, in the superior frontal sulcus, and in the precentral gyri in the balance group, compared to the relaxation group. Moreover, there was evidence that the balance training resulted in decreased putamen volume. Improved balance performance correlated with the increase of precentral cortical thickness and the decrease in putamen volume. The results suggest that balance training elicits neuroplasticity in brain regions associated with visual and vestibular self-motion perception. As these regions are known for their role in spatial orienting and memory, stimulating visual-vestibular pathways during self-motion might mediate beneficial effects of physical exercise on cognition.

Balance training improves memory and spatial cognition in healthy adults.

Physical exercise has been shown to improve cognitive functions. However, it is still unknown which type of exercise affects cognition. In the present study, we tested the hypothesis that a demanding balance training program improves memory and spatial cognition. Forty healthy participants aged 19-65 years were randomly assigned to either a balance or relaxation training intervention. Each group exercised twice a week for a total of 12 weeks. Pre- and posttests assessed balance performance, cardiorespiratory fitness, memory, spatial cognition, and executive functions. Only the balance group significantly increased in balance performance from pre- to posttest, while cardiorespiratory fitness remained unchanged in both groups. Moreover, the balance group significantly improved in memory and spatial cognition. Effects on executive functions were not observed. These results suggest that balance training is capable of improving particularly memory and spatial cognition. Therefore, an increase in cardiorespiratory fitness does not seem to be necessary to induce beneficial effects of physical exercise on cognition. It might be speculated that stimulating the vestibular system during balance training induces changes of the hippocampus and parietal cortex possibly via direct pathways between the vestibular system and these brain regions.

The Effects of Acute Physical Exercise on Memory, Peripheral BDNF, and Cortisol in Young Adults.

In animals, physical activity has been shown to induce functional and structural changes especially in the hippocampus and to improve memory, probably by upregulating the release of neurotrophic factors. In humans, results on the effect of acute exercise on memory are inconsistent so far. Therefore, the aim of the present study was to assess the effects of a single bout of physical exercise on memory consolidation and the underlying neuroendocrinological mechanisms in young adults. Participants encoded a list of German-Polish vocabulary before exercising for 30 minutes with either high intensity or low intensity or before a relaxing phase. Retention of the vocabulary was assessed 20 minutes after the intervention as well as 24 hours later. Serum BDNF and salivary cortisol were measured at baseline, after learning, and after the intervention. The high-intensity exercise group showed an increase in BDNF and cortisol after exercising compared to baseline. Exercise after learning did not enhance the absolute number of recalled words. Participants of the high-intensity exercise group, however, forgot less vocabulary than the relaxing group 24 hours after learning. There was no robust relationship between memory scores and the increase in BDNF and cortisol, respectively, suggesting that further parameters have to be taken into account to explain the effects of exercise on memory in humans.

Effects of a cognitive training on spatial learning and associated functional brain activations.

BACKGROUND: Both cognitive and physical exercise have been discussed as promising interventions for healthy cognitive aging. The present study assessed the effects of cognitive training (spatial vs. perceptual training) and physical training (endurance training vs. non-endurance training) on spatial learning and associated brain activation in 33 adults (40-55 years). Spatial learning was assessed with a virtual maze task, and at the same time neural correlates were measured with functional magnetic resonance imaging (fMRI). RESULTS: Only the spatial training improved performance in the maze task. These behavioral gains were accompanied by a decrease in frontal and temporal lobe activity. At posttest, participants of the spatial training group showed lower activity than participants of the perceptual training group in a network of brain regions associated with spatial learning, including the hippocampus and parahippocampal gyrus. No significant differences were observed between the two physical intervention groups. CONCLUSIONS: Functional changes in neural systems associated with spatial navigation can be induced by cognitive interventions and seem to be stronger than effects of physical exercise in middle-aged adults.

Beneficial effects of physical exercise on neuroplasticity and cognition.

The human brain adapts to changing demands by altering its functional and structural properties ("neuroplasticity") which results in learning and acquiring skills. Convergent evidence from both human and animal studies suggests that physical activity facilitates neuroplasticity of certain brain structures and as a result cognitive functions. Animal studies have identified an enhancement of neurogenesis, synaptogenesis, angiogenesis and the release of neurotrophins as neural mechanisms mediating beneficial cognitive effects of physical exercise. This review summarizes behavioral consequences and neural correlates at the system level following physical exercise interventions in humans of different ages. The results suggest that physical exercise may trigger processes facilitating neuroplasticity and, thereby, enhances an individual's capacity to respond to new demands with behavioral adaptations. Indeed, some recent studies have suggested that combining physical and cognitive training might result in a mutual enhancement of both interventions. Moreover, new data suggest that to maintain the neuro-cognitive benefits induced by physical exercise, an increase in the cardiovascular fitness level must be maintained.

Cardiovascular fitness modulates brain activation associated with spatial learning.

Aerobic exercise has beneficial effects on cognitive functioning in aging humans, especially on executive functions associated with frontal brain regions. In rodents, exercise has been shown to induce structural and neurophysiological changes especially in the hippocampus and to improve spatial learning. The present study investigated the relationship between cardiovascular fitness, spatial learning and associated patterns of brain activation cross-sectionally and longitudinally in a sample of middle-aged men and women (40-55 years) that took part in a six-month exercise intervention and an additional spatial training. Spatial learning capacities before and after the interventions were measured with a virtual maze task. During this task, participants were repeatedly moved through a virtual town and were instructed to infer the spatial layout of the environment. Brain activations during encoding of the virtual town were assessed with functional magnetic resonance imaging (fMRI). The fMRI data revealed that brain activations during successful spatial learning were modulated by the individual fitness level in a neural network, comprising the hippocampus, retrosplenial cortex, cuneus, precuneus, parahippocampal gyrus, caudate nucleus, insula, putamen, and further frontal, temporal, occipital and cingulate regions. Moreover, physical exercising induced changes in cardiovascular fitness that correlated positively with changes in brain activations in the medial frontal gyrus and the cuneus. However, overall spatial learning performance did not vary with cardiovascular fitness. These data suggest that cardiovascular fitness has an impact on brain regions associated with spatial learning in humans and hence, could be a potent intervention to prevent age-related cognitive decline.

Differential cognitive effects of cycling versus stretching/coordination training in middle-aged adults.

OBJECTIVE: Physical exercise has been linked to higher cognitive functioning and enhanced brain plasticity in aging humans. The most consistent positive effects have been reported for executive functions associated with frontal brain regions. In rodents, however, running has been shown to induce functional and structural changes in the hippocampus, a brain region known to be important for memory. It is still a matter of debate which cognitive functions are susceptible to exercise and whether an increase in cardiovascular fitness is beneficial for cognitive functioning. Moreover, little is known about the impact of exercise on cognition in middle-aged humans. METHOD: Sixty-eight sedentary men and women between 40 and 56 years of age were randomly assigned to one of two training programs: aerobic endurance training (cycling) or nonendurance training (stretching/coordination). Both groups exercised twice a week for six months. Additionally, a sedentary control group was tested. At baseline and after six months, episodic memory, perceptual speed, executive functions, and spatial reasoning were assessed with standardized psychometric tests, and all participants underwent a cardiovascular fitness test. RESULTS: Significant improvements in memory were observed in both the cycling and the stretching/coordination group as compared with the sedentary control group. The improvement in episodic memory correlated positively with the increase in cardiovascular fitness. The stretching/coordination training particularly improved selective attention as compared with the cycling training. CONCLUSIONS: The results suggest that cardiovascular fitness has beneficial effects even in high-functioning middle-aged participants, but that these benefits are very specific to memory functions rather than a wider range of cognitive functions.

Long-term effects of physical exercise on verbal learning and memory in middle-aged adults: results of a one-year follow-up study.

A few months of physical exercise have been shown to increase cognition and to modulate brain functions in previously sedentary, mainly older adults. However, whether the preservation of newly gained cognitive capacities requires an active maintenance of the achieved fitness level during the intervention is not yet known. The aim of the present study was to test whether cardiovascular fitness one year after an exercise intervention was linked to cognitive variables. Twenty-five healthy participants (42-57 years of age) took part in a follow-up assessment one year after the end of a supervised exercise intervention. Measurements included a cardiovascular fitness test, psychometric tests of verbal learning and memory and selective attention as well as questionnaires assessing physical activity and self-efficacy beliefs. Recognition scores of participants with higher cardiovascular fitness at follow-up did not change significantly during the follow-up period; however, the scores of participants with lower cardiovascular fitness decreased. One year after the end of the physical training intervention, previously sedentary participants spent more hours exercising than prior to the intervention. The time participants spent exercising correlated with their self-efficacy beliefs. These results demonstrate a direct link between verbal learning and cardiovascular fitness and show that positive effects of physical interventions on learning and memory do need an active maintenance of cardiovascular fitness.

Early visual deprivation affects the development of face recognition and of audio-visual speech perception.

PURPOSE: The investigation of patients treated for bilateral congenital cataracts allows to study the development of visual and multisensory functions after a period of visual deprivation in early infancy. In the present study, cataract patients were tested for their capability to recognize faces and to integrate auditory and visual speech information. METHODS: In Experiment 1, 12 cataract patients were tested with the Benton Facial Recognition Test. In Experiment 2, a McGurk paradigm was used that investigated audio-visual interaction and lip-reading capabilities. Here, fifteen cataract patients participated and were compared to normally sighted controls and to visually impaired controls. RESULTS: In the Benton Facial Recognition Test, cataract patients' performance was unimpaired when target and test face were identical. By contrast, they performed worse than a normally sighted control group when head orientation and/or lighting conditions of the test faces were changed. In the McGurk paradigm, cataract patients displayed impaired lip-reading abilities and a reduced audio-visual interaction compared to normally sighted controls. The latter deficit prevailed even in a sub-group matched for lip-reading capacities with a normally sighted control sub-group. CONCLUSION: These results suggest that visual input in early infancy is a prerequisite for a normal development of visual and multisensory functions.

Long-term versus short-term memory deficits for faces in temporal lobe and generalized epilepsy patients.

It is still an open question whether short-term and long-term memory are two anatomically dissociable memory systems working in parallel or whether they are represented by neural circuits within similar cortical areas. Epilepsy may be used as a model to study these memory processes. We hypothesized that a double dissociation of short-term and long-term memory exists in temporal lobe epilepsy (TLE) and idiopathic generalized epilepsy (IGE). Immediate and 24-hour face recognition was tested in 10 TLE patients, 9 IGE patients, and 10 healthy controls. TLE patients' immediate recognition was unimpaired, but their memory scores were reduced as compared to healthy controls after 24 hours. In IGE patients, memory was already reduced during immediate recognition. These results are in line with the idea that short-term memory is a transient trace that requires consolidation supported by the medial temporal lobe to change into a more stable status of long-term memory.

Unimodal and crossmodal gradients of spatial attention: Evidence from event-related potentials.

Behavioral and event-related potential (ERP) studies have shown that spatial attention is gradually distributed around the center of the attentional focus. The present study compared uni- and crossmodal gradients of spatial attention to investigate whether the orienting of auditory and visual spatial attention is based on modality specific or supramodal representations of space. Auditory and visual stimuli were presented from five speaker locations positioned in the right hemifield. Participants had to attend to the innermost or outmost right position in order to detect either visual or auditory deviant stimuli. Detection rates and event-related potentials (ERPs) indicated that spatial attention is distributed as a gradient. Unimodal spatial ERP gradients correlated with the spatial resolution of the modality. Crossmodal spatial gradients were always broader than the corresponding unimodal spatial gradients. These results suggest that both modality specific and supramodal spatial representations are activated during orienting attention in space.

Auditory and auditory-tactile processing in congenitally blind humans.

Studying blind humans is an excellent opportunity to investigate how experience might shape auditory processing. In everyday life, blind humans rely more on auditory information than sighted humans to recognize people, localize events, or process language. A growing number of studies have provided evidence that the increased use of the auditory system results in compensatory behavior in the blind. Blind humans perform better in perceptual auditory tasks, like pitch or duration discrimination, and in auditory language and memory tasks. Neural plasticity at different levels of the auditory processing stream has been linked to these behavioral benefits. In everyday life, many events stimulate more than one sensory system. Multisensory research has cumulated evidence that the integration of information across modalities facilitates perception and action control. Neurophysiological correlates of multisensory interactions have been described for various subcortical and cortical areas. There is evidence that vision plays a pivotal role in setting up multisensory functions during ontogeny. This article summarizes evidence for a reorganization of multisensory brain areas and reduced crossmodal interactions on the behavioral level following congenital visual deprivation.

Neural correlates of cross-modally induced changes in tactile awareness.

When a single tactile stimulus is presented together with two tones, participants often report perceiving two touches. It is a matter of debate whether this cross-modal effect of audition on touch reflects the interplay between modalities at early perceptual or at later processing stages, and which brain processes determine what in the end is consciously perceived. Event-related brain potentials (ERPs) were recorded while rare single tactile stimuli accompanied by two tones (1T2A) were presented among frequent tactile double stimuli accompanied by two tones (2T2A). Although participants were instructed to ignore the tones and to respond to single tactile stimuli only, they often failed to respond to 1T2A stimuli ("illusory double touches," 1T2A(i)). ERPs to "illusory double touches" versus "real double touches" (2T2A) differed 50 msec after the (missing) second touch. This suggests that at an early sensory stage, illusory and real touches are processed differently. On the other hand, although similar stimuli elicited a tactile mismatch negativity (MMN) between 100 and 200 msec in a unisensory tactile experiment, no MMN was observed for the 1T2A(i) stimuli in the multisensory experiment. "Tactile awareness" was associated with a negativity at 250 msec, which was enhanced in response to correctly identified deviants as compared to physically identical deviants that elicited an illusion. Thus, auditory stimuli seem to alter neural mechanisms associated with automatic tactile deviant detection. The present findings contribute to the debate of which processing step in the brain determines what is consciously perceived.