Neuroplasticity, the brain's capacity to reorganize itself by forming new neural connections, is central to modern neuroscience. Once believed to occur only during early development, research now shows that plasticity continues throughout the lifespan, supporting learning, memory, and recovery from injury or disease. Substantial progress has been made in understanding the mechanisms underlying neuroplasticity and their therapeutic applications. This overview article examines synaptic plasticity, structural remodeling, neurogenesis, and functional reorganization, highlighting both adaptive (beneficial) and maladaptive (harmful) processes across different life stages. Recent strategies to harness neuroplasticity, ranging from pharmacological agents and lifestyle interventions to cutting-edge technologies like brain-computer interfaces (BCIs) and targeted neuromodulation are evaluated in light of current empirical evidence. Contradictory findings in the literature are addressed, and methodological limitations that hamper widespread clinical adoption are discussed. The ethical and societal implications of deploying novel neuroplasticity-based interventions, including issues of equitable access, data privacy, and the blurred line between treatment and enhancement, are then explored in a structured manner. By integrating mechanistic insights, empirical data, and ethical considerations, the aim is to provide a comprehensive and balanced perspective for researchers, clinicians, and policymakers working to optimize brain health across diverse populations.

Identifying early predictors of cognitive decline and at-risk individuals is essential for timely intervention and prevention of dementia. This study aimed to detect neurobiological changes and factors related to cognitive performance in the Metropolit 1953 Danish male birth cohort. We analyzed data from 582 participants, aged 57-68 years, using machine learning techniques to group cognitive trajectories into four clusters differentiating high- and low-performing groups. These clusters were then evaluated with MRI, EEG, and lifestyle/familial risk factors to identify predictors of cognitive decline. Low education and occupation, alcohol consumption, and type 2 diabetes were associated with lower cognitive performance. Declines in neocortical volume and increases in frontotemporal alpha and temporoparietal gamma activity preceded clinical symptoms of cognitive decline. Neocortical atrophy and disruptions in network activity were prominent in lower-performing groups, with higher education and IQ scores and a lower prevalence of lifestyle factors moderating cognitive decline.

Exercise-induced adaptations, including neuroplasticity, are well studied for physical exercise that targets skeletal muscles. However, little is known about the neuroplastic potential of targeted speech and swallowing exercises. The current study aimed to gather preliminary data on molecular and functional changes associated with the neuroplastic effects of 4-week expiratory musculature-targeted resistance training in healthy young adults.

Five healthy young adult men aged between 19 and 35 years, M (SD) = 28.8 (2.68) years, underwent 4 weeks of expiratory muscle strength training (EMST). We measured changes in maximum expiratory pressure (MEP), serum brain-derived neurotrophic factor (BDNF), and insulin-like growth factor 1 (IGF-1) levels at baseline and posttraining conditions. Furthermore, functional and structural magnetic resonance images were obtained to investigate the neuroplastic effects of EMST. We analyzed the effects of training using a linear mixed model for each outcome, with fixed effects for baseline and posttraining.

MEP and serum BDNF levels significantly increased posttraining. However, this effect was not observed for IGF-1. A significant increase in functional activation in eight regions was also observed posttraining. However, we did not observe significant changes in the white matter microstructure.

Preliminary data from our study suggest targeted resistance training of expiratory muscles results in molecular and neuroplastic adaptations similar to exercise that targets skeletal muscles. Additionally, these results suggest that EMST could be a potential intervention to modulate (or prime) neurotrophic signaling pathways linked to functional strength gains and neuroplasticity.

Brain aging leads to a decline in cognitive function and a concomitant increase in the susceptibility to neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. A key question is how changes within individual cells of the brain give rise to age-related dysfunction. Developments in single-cell "omics" technologies, such as single-cell transcriptomics, have facilitated high-dimensional profiling of individual cells. These technologies have led to new and comprehensive characterizations of brain aging at single-cell resolution. Here, we review insights gleaned from single-cell omics studies of brain aging, starting with a cell-type-centric overview of age-associated changes and followed by a discussion of cell-cell interactions during aging. We highlight how single-cell omics studies provide an unbiased view of different rejuvenation interventions and comment on the promise of combinatorial rejuvenation approaches for the brain. Finally, we propose new directions, including models of brain aging and neural stem cells as a focal point for rejuvenation.

Chronic diseases linked with sedentary lifestyles and poor dietary habits are increasingly common in modern society. Exercise is widely acknowledged to have a plethora of health benefits, including its role in primary prevention of various chronic conditions like type 2 diabetes mellitus, obesity, cardiovascular disease, and several musculoskeletal as well as degenerative disorders. Regular physical activity induces numerous physiological adaptations that contribute to these positive effects, primarily observed in skeletal muscle but also impacting other tissues. There is a growing interest among researchers in developing pharmaceutical interventions that mimic the beneficial effects of exercise for therapeutic applications. Exercise mimetic medications have the potential to be helpful aids in enhancing functional outcomes for patients with metabolic dysfunction, neuromuscular and musculoskeletal disorders. Some of the potential targets for exercise mimetics include pathways involved in metabolism, mitochondrial function, inflammation, and tissue regeneration. The present review aims to provide an exhaustive overview of the current understanding of exercise physiology, the role of exerkines and biomolecular pathways, and the potential applications of exercise mimetic drugs for the treatment of several diseases.

The neurogenic potential of the brain decreases during ageing, whereas the risk of neurodegenerative diseases and stroke rises. This creates a mismatch between the rate of neuron loss and the brain's capacity for replacement. Adult neurogenesis primarily occurs in the subgranular zone (SGZ) and the ventricular-subventricular zone (V-SVZ). Exercise enhances SGZ neurogenesis, and we previously showed that V-SVZ neurogenesis is induced by exercise via activation of the lactate receptor HCA1. Here, we investigated how high-intensity interval training (HIIT) and medium-intensity interval training (MIIT) affect neurogenesis in these niches. Wild-type (WT) and HCA1 knockout (KO) mice were randomized to sedentary, HIIT or MIIT (n = 5-8 per group) for 3 weeks. In the SGZ, HIIT increased the density of doublecortin (DCX)-positive cells in WT mice by 85% (5.77±1.76 vs. 3.12±1.54 cells/100 µm, P = 0.013) and KO mice (67% increase; 7.91±2.92 vs. 4.73±1.63 cells/100 µm, P = 0.004). MIIT did not alter the density of DCX-positive cells in either genotype. HIIT increased the density of Ki-67-positive cells only in KO mice (P = 0.038), whereas no differences in nestin-positive cells were observed. In the V-SVZ, HIIT increased the density of DCX-positive cells in WT mice by 155% (117.79±39.72 vs. 46.25±19.96 cells/100 µm, P < 0.001) and MIIT increased the density of DCX-positive cells by 80% (83.26±39.48 vs. 46.25±19.96 cells/100µm, P = 0.027). No exercise-induced changes were observed in KO mice. Similar patterns were noted for Ki-67 positive and DCX/Ki-67 double-positive cells in the V-SVZ. These findings suggest that HIIT enhances neurogenesis more robustly than MIIT in both niches, with HCA1 playing a crucial role in V-SVZ neurogenesis. KEY POINTS: The neurogenic potential of the brain decreases with age, whereas the risk of neurodegenerative diseases and stroke increases, highlighting a mismatch between neuronal loss and replacement capacity. Exercise enhances neurogenesis in both the subgranular zone and the ventricular-subventricular zone. High-intensity interval exercise is more effective than medium-intensity interval exercise at promoting neurogenesis in both the subgranular zone and the ventricular-subventricular zone of wild-type mice. The enhancement of neurogenesis in the ventricular-subventricular zone is dependent on the activation of the HCA1 receptor, as evidenced by the ability of medium- and high-intensity interval exercise to induce neurogenesis in wild-type mice and the lack of this effect in HCA1 knockout mice. By contrast, neurogenesis in the subgranular zone is independent on the activation of the HCA1 receptor, highlighting that neurogenesis in the two major neurogenic niches are regulated differently.

Children with intellectual disability tend to exhibit lower performance in fundamental movement skills, such as locomotor skills, object control skills, and balance, compared to their typically developing peers. Evidence suggests that physical activity programs tailored for individuals with intellectual disabilities can positively influence the development of their motor skills. Similar to typically developing children, physical activity in children with intellectual disabilities stimulates not only physical development, but also brain function, resulting in cognitive benefits. However, the extent of physical activity's impact on the cognitive functioning of this population remains insufficiently explored. The aim of our study was to assess the effectiveness of a motor exercise program based on the Bilateral Integration method implemented for pupils with moderate intellectual disabilities.

The sample consisted of 27 pupils with moderate intellectual disability (13 in the intervention group and 14 in the control group) from two special schools in Poland. Pupils in the intervention group participated in a modified version of the Bilateral Integration School Program - a 26-week physical activity program that included both individual and group sessions. The assessment of cognitive functioning, using the Fifth Edition of the Stanford-Binet Intelligence Subtests, was conducted over three time points in both groups: a pre-test before the intervention (T1), a post-test after the intervention phase end (T2) and a follow-up assessment three months after the post-test (T3).

Significant effects of the intervention compared to the control group were observed in certain cognitive variables. Repeated measures ANOVA revealed a significant group-by-time interaction for the Nonverbal Visual-Spatial Processing score, Nonverbal Working Memory score, as well as Verbal Fluid Reasoning.

The original program based on the Bilateral Integration method proved effective for pupils with moderate intellectual disability. Preliminary results indicate improvements in cognition, particularly in working memory and visual-spatial processing. Further studies are necessary to assess the program's efficacy comprehensively.

The study was designed to examine the effects of simultaneous combination of aerobic exercise and video game training on executive functions (EFs) and brain functional connectivity in older adults.

A four-armed, quasi-experimental study.

Community-dwelling adults aged 55 years and older.

A total of 97 older adults were divided into one of four groups: aerobic exercise (AE), video game (VG), combined intervention (CI), and passive control (PC). Participants in intervention groups received 32 sessions of training over a 4-month period at a frequency of twice a week. EFs was evaluated using a composite score derived from a battery of neuropsychological tests. The Montreal Cognitive Assessment (MoCA) was employed to evaluate overall cognitive function, while the 6-Minute Walking Test (6MWT) was utilized to gauge physical function. Additionally, the functional connectivity (FC) of the frontal-parietal networks (FPN) was examined as a neural indicator of cognitive processing and connectivity changes.

In terms of EFs, both VG and CI groups demonstrated improvement following the intervention. This improvement was particularly pronounced in the CI group, with a large effect size (Hedge's g = 0.83), while the VG group showed a medium effect size (Hedge's g = 0.56). A significant increase in MoCA scores was also observed in both the VG and CI groups, whereas a significant increase in 6MWT scores was observed in the AE and CI groups. Although there were no group-level changes observed in FC of the FPN, we found that changes in FC was behaviorally relevant as increased FC was associated with greater improvement in EFs.

The study offers preliminary evidence that both video game training and combined intervention could enhance EFs in older adults. Simultaneous combined intervention may hold greater potential for facilitating EFs gains. The initial evidence for correlated changes in brain connectivity and EFs provides new insights into understanding the neural basis underlying the training gains.

Endurance exercise leads to robust increases in memory and learning. Several exercise adaptations occur to mediate these improvements, including in both the hippocampus and in peripheral organs. Organ crosstalk has been becoming increasingly more present in exercise biology, and studies have shown that peripheral organs can communicate to the hippocampus and mediate hippocampal changes. Both learning and memory as well as other hippocampal functional-related changes such as neurogenesis, cell proliferation, dendrite morphology and synaptic plasticity are controlled by these exercise responsive peripheral proteins. These peripheral factors, also called exerkines, are produced by several organs including skeletal muscle, liver, adipose tissue, kidneys, adrenal glands and circulatory cells. Previous reviews have explored some of these exerkines including muscle-derived irisin and cathepsin B (CTSB), but a full picture of peripheral to hippocampus crosstalk with novel exerkines such as selenoprotein 1 (SEPP1) and platelet factor 4 (PF4), or old overlooked ones such as lactate and insulin-like growth factor 1 (IGF-1) is still missing. We provide 29 different studies of 14 different exerkines that crosstalk with the hippocampus. Thus, the purpose of this review is to explore peripheral exerkines that have shown to exert hippocampal function following exercise, demonstrating their particular effects and molecular mechanisms in which they could be inducing adaptations.

Maintaining good health is crucial, and exercise plays a vital role in achieving this goal. It offers a range of positive benefits for cognitive function, regardless of age. However, as our population ages and life expectancy increases, cognitive impairment has become a prevalent issue, often coexisting with age-related neurodegenerative conditions. This can result in devastating consequences such as memory loss, difficulty speaking, and confusion, greatly hindering one's ability to lead an ordinary life. In addition, the decrease in mental capacity has a significant effect on an individual's physical and emotional well-being, greatly reducing their overall level of contentment and causing a significant financial burden for communities. While most current approaches aim to slow the decline of cognition, exercise offers a non-pharmacological, safe, and accessible solution. Its effects on cognition are intricate and involve changes in the brain's neural plasticity, mitochondrial stability, and energy metabolism. Moreover, exercise triggers the release of cytokines, playing a significant role in the body-brain connection and its impact on cognition. Additionally, exercise can influence gene expression through epigenetic mechanisms, leading to lasting improvements in brain function and behavior. Herein, we summarized various genetic and epigenetic mechanisms that can be modulated by exercise in cognitive dysfunction.

Major depressive disorder (MDD) is currently the most common psychiatric disorder in the world. It characterized by a high incidence of disease with the symptoms like depressed mood, slowed thinking, and reduced cognitive function. Without timely intervention, there is a 20-30% risk of conversion to treatment-resistant depression (TRD) and a high burden for the patient, family and society. Numerous studies have shown that physical activity (PA) is a non-pharmacological treatment that can significantly improve the mental status of patients with MDD and has positive effects on cognitive function, sleep status, and brain plasticity. However, the physiological and psychological effects of different types of PA on individuals vary, and the dosage profile of PA in improving symptoms in patients with MDD has not been elucidated. In most current studies of MDD, PA can be categorized as continuous endurance training (ECT), explosive interval training (EIT), resistance strength training (RST), and mind-body training (MBT), and the effects on patients' depressive symptoms, cognitive function, and sleep varied. Therefore, the present study was based on a narrative review and included a large number of existing studies to investigate the characteristics and differences in the effects of different PA interventions on MDD. The study also investigated the characteristics and differences of different PA interventions in MDD, and explained the neural mechanisms through the results of multimodal brain function monitoring, including the intracranial environment and brain structure. It aims to provide exercise prescription and theoretical reference for future research in neuroscience and clinical intervention in MDD.

Physical exercise is suggested to promote hippocampal neuroplasticity by increasing circulating neurotrophic and anti-inflammatory factors. Our aim was to explore the interplay between the effect of progressive resistance exercise on blood biomarker levels, hippocampal neurometabolite levels and hippocampal volume in older adults with a low compared to a high risk of mild cognitive impairment (MCI). Seventy apparently healthy male/female older adults (aged 60-85 years old) were randomly allocated to a 12 week lower limb progressive resistance or no intervention, stratified for low (< 26/30) or high (≥ 26/30) Montreal Cognitive Assessment (MoCA) score, indicating MCI risk. Outcome measures were blood levels of insulin-like growth factor-1 (IGF-1), interleukin-6 (IL-6) or kynurenine (KYN); hippocampal total and subfield volumes of the cornu ammonis 1 (CA1) and 4 (CA4), subiculum, presubiculum, and dentate gyrus measured with magnetic resonance imaging (MRI); and hippocampus neurometabolites including total N-acetylaspartate (NAA), myo-inositol (mIns), and total creatine (Cr) measured with proton magnetic resonance spectroscopy (1H-MRS). We evaluated the intervention effect, cognitive status effect, their interaction and the bivariate relationship between exercise-induced changes between the outcome measures. Higher kynurenine levels (p = 0.015) and lower subiculum volumes (p = 0.043) were found in older adults with high MCI risk compared to older adults with low MCI risk. Exercise-induced CA1 volume changes were negatively correlated with hippocampal tNAA/mIns level changes (r = -0.605, p = 0.006). This study provides valuable insight in the multifactorial processes related to resistance training in older adults with low or high MCI risk.

Alzheimer's disease threatens the health of older adults, particularly by disrupting executive and memory functions, and many studies have shown that aerobic exercise prevents and improves the symptoms associated with the disease.

The objective was to systematically review the effects of aerobic exercise on executive and memory functions in patients with Alzheimer's disease and to determine the effect factors and mechanisms of the design of aerobic exercise intervention programs.

Relevant literature was searched in three databases (PubMed, Web of Science, and EBSCO) from January 1, 2014 to March 1, 2023, using a subject-word search method. Data on 10 items, including author and country, were extracted from the literature after screening. The quality of the literature was evaluated using the Physiotherapy Evidence Database scale, and a systematic review was performed.

Twelve papers from seven countries were ultimately included, embodying 11 randomized controlled trials and one study with a repeated-measures design. The overall quality of the studies was good as 657 study participants, aged 45 years and older who had varying degrees of Alzheimer's disease and significant symptoms, were included. Aerobic exercise was found to have a significant positive impact on executive and memory functions in people with Alzheimer's disease.

The effects of aerobic exercise on aspects of executive function were mainly characterized by improvements in inhibitory control, working memory, and cognitive flexibility, whereas the effects on aspects of memory function were mainly characterized by improvements in logical memory, situational memory, and short-term memory.

Motoric cognitive risk syndrome (MCR) is a pre-dementia syndrome characterized by subjective memory complaints and gait impairments that may be related to lower prefrontal cortex (PFC) function. Acute bouts of aerobic exercise are shown to improve PFC function, however, the acute effects of exercise on PFC oxygenation have not yet been examined in MCR. This study aims to characterize the PFC oxygenation responses during acute exercise in older adults with MCR. Nineteen older adults with MCR performed a submaximal cycling exercise protocol. Functional near-infrared spectroscopy (fNIRS) is used to measure concentrations of oxygenated (OxyHb) and deoxygenated (DeoxyHb) hemoglobin from the PFC. There is a trend for increased OxyHb concentrations and decreased DeooxyHb concentrations during exercise. Exercise also induced significant increases in ratings of perceived exertion (RPEs) and heart rate. A significant, positive correlation between PFC OxyHb and RPEs during the cycling exercise are also observed. The findings reveal that PFC oxygenation increases during exercise in an intensity-dependent manner and the subjective perception of exertion is associated with the magnitude of PFC oxygenation. These results suggest that moderate-intensity cycling exercise may have beneficial effects on increasing cerebral blood flow in the PFC of older adults with MCR.

Levothyroxine (LEV) monotherapy cannot completely improve cognitive and behavioral impairments induced by hypothyroidism, whereas a combination therapy of exercise and LEV may ameliorate these deficits. This study aimed to determine the effects of mild-intensity forced exercise and LEV treatment on the anxiety profile and cognitive functions in male offspring of hypothyroid dams.

Twenty-four female rats (mothers) were randomly divided into sham (healthy) and hypothyroidism groups and then placed with male rats to mate. The presence of vaginal plaque confirmed pregnancy (gestational day, GD 0). 6-propyl-2-thiouracil (PTU, 100 ppm) was added to the drinking water of the hypothyroidism group from GD 6 to the 21st postnatal day (PND). The sham group received tap water. On PND 21, serum T4 levels of mothers, and 10 pups were measured to confirm hypothyroidism. Sixty-four male pups were left undisturbed for 30 days and then were divided into eight groups that received saline or LEV (50 μg/kg, i.p.) with or without forced mild-intensity exercise. After 14 days of interventions, anxiety-like behaviors, spatial learning and memory, and hippocampal brain-derived neurotrophic factor (BDNF) levels were evaluated.

A pre and postnatal PTU-induced model of hypothyroidism increased anxiety-like behaviors, impaired spatial learning and memory, and decreased hippocampal BDNF levels in male offspring rats. LEV alone increased BDNF levels and improved spatial learning. Exercise alone increased BDNF levels, improved spatial learning and memory, and decreased anxiety-like behaviors. Exercise plus LEV more effectively improved anxiety-like behaviors and spatial learning than exercise or LEV alone.

Practically, these pre-clinical findings highlight the importance of the combination of exercise and LEV regimen in treating patients with hyperthyroidism.

Sleep disorders often accompany neurological injuries, significantly impacting patient recovery and quality of life.The efficacy and adherence of traditional treatment methods have certain limitations. Exercise has been found to be a highly beneficial treatment method, capable of preventing and alleviating neurological injuries and sleep disorders. This article reviews relevant research findings from both domestic and international sources over the past few decades, systematically summarizing and analyzing the application of exercise therapy in sleep disorders,strategy of exercise intervention program and the potential molecular mechanisms by which exercise therapy improves sleep disorders. Shortcomings in current research and suggestions are presented, providing a reference for future in-depth studies on exercise interventions for sleep disorders.

Epidemiological studies show that modifiable risk factors account for approximately 40% of the population variability in risk of developing dementia, including sporadic Alzheimer's disease (AD). Recent findings suggest that these factors may also modify disease trajectories of people with autosomal-dominant AD. With positron emission tomography imaging, it is now possible to study the disease many years before its clinical onset. Such studies can provide key knowledge regarding pathways for either the prevention of pathology or the postponement of its clinical expression. The former "resistance pathway" suggests that modifiable risk factors could affect amyloid and tau burden decades before the appearance of cognitive impairment. Alternatively, the resilience pathway suggests that modifiable risk factors may mitigate the symptomatic expression of AD pathology on cognition. These pathways are not mutually exclusive and may appear at different disease stages. Here, in a narrative review, we present neuroimaging evidence that supports both pathways in sporadic AD and autosomal-dominant AD. We then propose mechanisms for their protective effect. Among possible mechanisms, we examine neural and vascular mechanisms for the resistance pathway. We also describe brain maintenance and functional compensation as bases for the resilience pathway. Improved mechanistic understanding of both pathways may suggest new interventions.

Objectives: The present study aimed to investigate the effect of corrective exercise intervention (corrective exercise reminding and training software) on musculoskeletal disorders (MSDs), fatigue, posture and working memory among office workers. Methods: A total of 66 office workers participated in the present study. Data collection was carried out using questionnaires (including the Nordic musculoskeletal questionnaire, multidimensional fatigue inventory and Borg rating scale), direct observations of work postures using rapid upper limb assessment (RULA) and rapid office strain assessment, and the n-back test. Results: There was a significant difference between the two groups (intervention and control) in terms of the severity of musculoskeletal discomfort after the intervention. There was a significant decrease in the mean score of trunk posture and the total RULA score in the intervention group after the intervention. The severity of perceived discomfort in all areas except the knee declined during the intervention. There was also a significant difference in physical and mental fatigue scores before and after the intervention. There was a significant difference in the accuracy score of office workers after the intervention compared to before the intervention. Conclusions: Overall, the results confirm the effectiveness of this low-cost, simple and easy-to-use ergonomic intervention.

Ramps facilitate earlier access to complex environments and increase early life voluntary exercise, which may positively affect the cognitive development of chickens. This study focused on quantifying individual differences in ramp use and its impact on spatial cognition of laying hen pullets. Sixteen identical pens were housed with Lohmann Selected Leghorn (LSL) chicks of which eight chicks from each pen were colour marked from one day of age (DoA) to serve as focal birds. We quantified overall ramp use (walk/run, wing-assisted incline running, and jump/fly to and from ramps) by scan sampling recorded videos for 6, 10, 12, 20, 27, 41, and 55 DoA for all focal birds. From 56 to 95 DoA, long and short-term spatial memory of three focal birds per pen were assessed in a holeboard test in three consecutive phases: cued, uncued and reversal. Mixed model analysis showed that the spatial cognitive abilities of the birds were linked to differences in ramp use frequency averaged across all observation days. Birds with higher ramp use made fewer reference (Estimate ± Confidence Interval = 0.94 [0.88, 0.99], p = 0.08) and working memory errors (Est ± CI = 0.77 [0.59, 1.00], p = 0.06) in the cued phase than birds with lower ramp use. In contrast, birds with higher ramp use made more reference memory errors (Est ± CI = 1.10 [1.01, 1.20], p = 0.05) in the reversal phase. Birds with higher ramp use also made more reference memory errors compared to birds with lower ramp use as the phases changed from cued to uncued (p = 0.001). Our results indicate that there might be a relationship between early life ramp use and spatial cognition of laying hens.

Abnormal cognitive and sensorial properties have been reported in patients with psychiatric and neurodevelopmental conditions, such as attention deficit hyperactivity disorder (ADHD). ADHD patients exhibit impaired dopaminergic signaling and plasticity in brain areas related to cognitive and sensory processing. The spontaneous hypertensive rat (SHR), in comparison to the Wistar Kyoto rat (WKY), is the most used genetic animal model to study ADHD. Brain neurotrophic factor (BDNF), critical for midbrain and hippocampal dopaminergic neuron survival and differentiation, is reduced in both ADHD subjects and SHR. Physical exercise (e.g. swimming) promotes neuroplasticity and improves cognition by increasing BDNF and irisin. Here we investigate the effects of gestational swimming on sensorial and behavioral phenotypes, striatal dopaminergic parameters, and hippocampal FNDC5/irisin and BDNF levels observed in WKY and SHR. Gestational swimming improved nociception in SHR rats (p = 0.006) and increased hippocampal BDNF levels (p = 0.02) in a sex-dependent manner in adolescent offspring. Sex differences were observed in hippocampal FNDC5/irisin levels (p = 0.002), with females presenting lower levels than males. Our results contribute to the notion that swimming during pregnancy is a promising alternative to improve ADHD phenotypes in the offspring.

There is significant interest in uncovering the mechanisms through which exercise enhances cognition, memory, and mood, and lowers the risk of neurodegenerative diseases. In this study, we utilize forced treadmill running and distance-matched voluntary wheel running, coupled with light sheet 3D brain imaging and c-Fos immunohistochemistry, to generate a comprehensive atlas of exercise-induced brain activation in mice.

To investigate the effects of exercise on brain activity, we compared whole-brain activation profiles of mice subjected to treadmill running with mice subjected to distance-matched wheel running. Male mice were assigned to one of four groups: a) an acute bout of voluntary wheel running, b) confinement to a cage with a locked running wheel, c) forced treadmill running, or d) placement on an inactive treadmill. Immediately following each exercise or control intervention, blood samples were collected for plasma analysis, and brains were collected for whole-brain c-Fos quantification.

Our dataset reveals 255 brain regions activated by acute exercise in mice, the majority of which have not previously been linked to exercise. We find a broad response of 140 regulated brain regions that are shared between voluntary wheel running and treadmill running, while 32 brain regions are uniquely regulated by wheel running and 83 brain regions uniquely regulated by treadmill running. In contrast to voluntary wheel running, forced treadmill running triggers activity in brain regions associated with stress, fear, and pain.

Our findings demonstrate a significant overlap in neuronal activation signatures between voluntary wheel running and distance-matched forced treadmill running. However, our analysis also reveals notable differences and subtle nuances between these two widely used paradigms. The comprehensive dataset is accessible online at www.neuropedia.dk, with the aim of enabling future research directed towards unraveling the neurobiological response to exercise.

Chronic stress is a major risk factor for neuropsychiatric conditions such as depression. Adult hippocampal neurogenesis (AHN) has emerged as a promising target to counteract stress-related disorders given the ability of newborn neurons to facilitate endogenous plasticity. Recent data sheds light on the interaction between cannabinoids and neurotrophic factors underlying the regulation of AHN, with important effects on cognitive plasticity and emotional flexibility. Since physical exercise (PE) is known to enhance neurotrophic factor levels, we hypothesised that PE could engage with cannabinoids to influence AHN and that this would result in beneficial effects under stressful conditions. We therefore investigated the actions of modulating cannabinoid type 2 receptors (CB2R), which are devoid of psychotropic effects, in combination with PE in chronically stressed animals. We found that CB2R inhibition, but not CB2R activation, in combination with PE significantly ameliorated stress-evoked emotional changes and cognitive deficits. Importantly, this combined strategy critically shaped stress-induced changes in AHN dynamics, leading to a significant increase in the rates of cell proliferation and differentiation of newborn neurons, overall reduction in neuroinflammation, and increased hippocampal levels of BDNF. Together, these results show that CB2Rs are crucial regulators of the beneficial effects of PE in countering the effects of chronic stress. Our work emphasises the importance of understanding the mechanisms behind the actions of cannabinoids and PE and provides a framework for future therapeutic strategies to treat stress-related disorders that capitalise on lifestyle interventions complemented with endocannabinoid pharmacomodulation.

Obesity has been linked to a range of pathologies, including dementia. In contrast, regular physical activity is associated with the prevention or reduced progression of neurodegeneration. Specifically, physical activity can improve memory and spatial cognition, reduce age-related cognitive decline, and preserve brain volume, but the mechanisms are not fully understood. Accordingly, we investigated whether any detrimental effects of high-fat diet (HFD)-induced obesity on cognition, motor behavior, adult hippocampal neurogenesis, and brain-derived neurotrophic factor (BDNF) could be mitigated by voluntary exercise training in male C57Bl/6 mice. HFD-induced impairment of motor function was not reversed by exercise. Importantly, voluntary wheel running improved long-term memory and increased hippocampal neurogenesis, suggesting that regular physical activity may prevent cognitive decline in obesity.

Prior physical activity reduces the risk of future stress-related mental health disorders including depression, anxiety, and post-traumatic stress disorder. Rodents allowed to engage in voluntary wheel running are similarly protected from behavioral consequences of stress. The present review summarizes current knowledge on mechanisms underlying exercise-induced stress resistance. A conceptual framework involving the development (during exercise) and expression (during stress) of stress resistance from exercise is proposed. During the development of stress resistance, adaptations involving multiple exercise signals and molecular mediators occur within neural circuits orchestrating various components of the stress response, which then respond differently to stress during the expression of stress resistance. Recent data indicate that the development and expression of stress resistance from exercise involve multiple independent mechanisms that depend on sex, stressor severity, and behavioral outcome. Recent insight into the role of the prefrontal cortex in exercise-induced stress resistance illustrates these multiple mechanisms. This knowledge has important implications for the design of future experiments aimed at identifying the mechanisms underlying exercise-induced stress resistance.

Engaging in regular physical activity and establishing exercise habits is known to have multifaceted benefits extending beyond physical health to cognitive and mental well-being. This study explores the intricate relationship between exercise habits, brain imaging markers, and mental health outcomes. While extensive evidence supports the positive impact of exercise on cognitive functions and mental health, recent advancements in multimodal imaging techniques provide a new dimension to this exploration. By using a cross-sectional multimodal brain-behavior statistic in participants with different exercise habits, we aim to unveil the intricate mechanisms underlying exercise's influence on cognition and mental health, including the status of depression, anxiety, and quality of life. This integration of exercise science and imaging promises to substantiate cognitive benefits on mental health and uncover functional and structural changes underpinning these effects. This study embarks on a journey to explore the significance of multimodal imaging metrics (i.e., structural and functional metrics) in deciphering the intricate interplay between exercise habits and mental health, enhancing the comprehension of how exercise profoundly shapes psychological well-being. Our analysis of group comparisons uncovered a strong association between regular exercise habits and improved mental well-being, encompassing factors such as depression, anxiety levels, and overall life satisfaction. Additionally, individuals who engaged in exercise displayed enhanced brain metrics across different modalities. These metrics encompassed greater gray matter volume within the left frontal regions and hippocampus, improved white matter integrity in the frontal-occipital fasciculus, as well as more robust functional network configurations in the anterior segments of the default mode network. The interplay between exercise habits, brain adaptations, and mental health outcomes underscores the pivotal role of an active lifestyle in nurturing a resilient and high-functioning brain, thus paving the way for tailored interventions and improved well-being.

Changes in gene expression are involved in many brain functions. Epigenetic processes modulate gene expression by histone modification and DNA methylation or RNA-mediated processes, which is important for brain function. Consequently, epigenetic changes are also a part of brain diseases such as mental illness and addiction. Understanding the role of different factors on the brain epigenome may help us understand the function of the brain. This review discussed the effects of caffeine, lipids, addictive substances, physical activity, and pollutants on the epigenetic changes in the brain and their modulatory effects on brain function.

As the global population ages, the prevalence of neurodegenerative diseases is surging. These disorders have a multifaceted pathogenesis, entwined with genetic and environmental factors. Emerging research underscores the profound influence of diet on the development and progression of health conditions. Intermittent fasting (IF), a dietary pattern that is increasingly embraced and recommended, has demonstrated potential in improving neurophysiological functions and mitigating pathological injuries with few adverse effects. Although the precise mechanisms of IF's beneficial impact are not yet completely understood, gut microbiota and their metabolites are believed to be pivotal in mediating these effects. This review endeavors to thoroughly examine current studies on the shifts in gut microbiota and metabolite profiles prompted by IF, and their possible consequences for neural health. It also highlights the significance of dietary strategies as a clinical consideration for those with neurological conditions.

Because chronic difficulties with cognition and well-being are common after mild traumatic brain injury (mTBI) and aerobic physical activity and exercise (PAE) is a potential treatment and mitigation strategy, we sought to determine their relationship in a large sample with remote mTBI.

The Long-Term Impact of Military-Relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium prospective longitudinal study is a national multicenter observational study of combat-exposed service members and veterans. Study participants with positive mTBI histories (n = 1,087) were classified as "inactive" (23%), "insufficiently active" (46%), "active" (19%), or "highly active" (13%) based on the aerobic PAE level. The design was a cross-sectional analysis with multivariable regression. PAE was reported on the Behavioral Risk Factor Surveillance System. Preselected primary outcomes were seven well-validated cognitive performance tests of executive function, learning, and memory: The California Verbal Learning Test-Second Edition Long-Delay Free Recall and Total Recall, Brief Visuospatial Memory Test-Revised Total Recall, Trail-Making Test-Part B, and NIH Toolbox for the Assessment of Neurological Behavior and Function Cognition Battery Picture Sequence Memory, Flanker, and Dimensional Change Card Sort tests. Preselected secondary outcomes were standardized self-report questionnaires of cognitive functioning, life satisfaction, and well-being.

Across the aerobic activity groups, cognitive performance tests were not significantly different. Life satisfaction and overall health status scores were higher for those engaging in regular aerobic activity. Exploratory analyses also showed better working memory and verbal fluency with higher aerobic activity levels.

An association between the aerobic activity level and the preselected primary cognitive performance outcome was not demonstrated using this study sample and methods. However, higher aerobic activity levels were associated with better subjective well-being. This supports a clinical recommendation for regular aerobic exercise among persons with chronic or remote mTBI. Future longitudinal analyses of the exercise-cognition relationship in chronic mTBI populations are recommended.

Physically active pupils may be better and more resilient learners. However, it is unclear whether walking or cycling to school yields similar educational and school-related mental health benefits as leisure-time physical activity. We examined the associations of active school transport and leisure-time moderate-to-vigorous physical activity with perceived academic performance, competency in academic skills, school burnout and school enjoyment.

We included 34 103 Finnish adolescents (mean age 15.4 years; 53% girls) from the 2015 School Health Promotion study cohort. For the analyses, we used logistic regression, adjusting for major sociodemographic, environmental, lifestyle and physical activity covariates.

Active school transport was positively associated with educational outcomes and school enjoyment, but not with school burnout. For example, compared with non-active transport, 10-30 min of daily active school transport was linked to 30% [odds ratio (OR) 1.30, 95% confidence interval (CI) 1.21-1.40] and 17% (OR 1.17, 95% CI 1.08-1.27) higher odds of high perceived academic performance and high reading competency, respectively. Leisure-time physical activity was robustly associated with all outcomes. For example, compared with the inactive, the most physically active adolescents had 86% higher odds of high perceived academic performance (OR 1.86, 95% CI 1.66-2.08), 57% higher odds of high competency in mathematics (OR 1.57, 95% CI 1.39-1.77) and 40% lower odds of school burnout (OR 0.60, 95% CI 0.52-0.69).

Compared with active school transport, leisure-time physical activity was more strongly associated with educational and school-related mental health outcomes. Nevertheless, walking or cycling to school might lead to improvements in classroom performance and school enjoyment.

Physical activity (PA) promotes brain health in a variety of domains including cognition, mood, and neuroplasticity. At the neurochemical level, the mechanisms underlying these effects in the brain are not fully understood. With proton Magnetic Resonance Spectroscopy (1H-MRS), it is possible to non-invasively quantify metabolite concentrations, enabling studies to obtain measures of exercise-induced neurochemical changes. This systematic review aimed to examine the existing literature on acute effects of PA on brain metabolites as measured by 1H-MRS. Four databases (Cochrane Central Register of Controlled Trials, PubMed, Embase, and PsycINFO) were searched, identifying 2965 studies, of which 9 met the inclusion criteria. Across studies, Gamma-AminoButyric Acid (GABA) and lactate tended to increase after exercise, while no significant changes in choline were reported. For glutamine/glutamate (Glx), studies were inconclusive. Conclusions were limited by the lack of consensus on 1H-MRS data processing and exercise protocols. To reduce inter-study differences, future studies are recommended to (1): apply a standardized exercise index (2), consider the onset time of MRS scans, and (3) follow standardized MRS quantification methods.

Physical exercise has beneficial effects on adult hippocampal neurogenesis (AHN) and cognitive processes, including learning. Although it is not known if anaerobic resistance training and high-intensity interval training, which involve alternating brief bouts of highly intense anaerobic activity with rest periods, have comparable effects on AHN. Also, while less thoroughly investigated, individual genetic diversity in the overall response to physical activity is likely to play a key role in the effects of exercise on AHN. Physical exercise has been shown to improve health on average, although the benefits may vary from person to person, perhaps due to genetic differences. Maximal aerobic capacity and metabolic health may improve significantly with aerobic exercise for some people, while the same amount of training may have little effect on others. This review discusses the AHN's capability for peripheral nervous system (PNS) regeneration and central nervous system (CNS) control via physical exercise. Exercise neurogenicity, effective genes, growth factors, and the neurotrophic factors involved in PNS regeneration and CNS control were discussed. Also, some disorders that could be affected by AHN and physical exercise are summarized.

Schizophrenia psychoses can be treated much better today due to the introduction of antipsychotics about 70 years ago in conjunction with the implementation of specific psychotherapies. However, current treatment options are still limited in the area of negative symptoms and disease-associated cognitive deficits. In the last 15 years, randomised controlled trials (RCTs) have been able to show that physical training and especially endurance training could represent a comprehensive complementary treatment approach and could lead to a significant improvement in positive, but especially also in negative symptoms and cognitive deficits. As a result, sports therapy for schizophrenia psychoses has found its way not only into the national treatment guidelines of the German Society for Psychiatry, Psychotherapy, Psychosomatics and Neurology (DGPPN), but also into European recommendations such as those of the European Psychiatric Association (EPA). With the introduction of the "Living guideline" format (here an update takes place at least once a year), a broader implementation in health care will be easier in the future. Based on a narrative review, this paper describes the process of implementing sports therapy for schizophrenia psychoses from its beginnings to its incorporation into guidelines and can be applied analogously to other forms of therapy.

Executive function is a core deficit in children with attention deficit hyperactivity disorder (ADHD). This study systematically reviewed the evidence for the effects of physical activity (PA) interventions on executive function in children and adolescents with ADHD and explored the moderating effects of key variables of PA on executive function.

Relevant literature in four electronic databases, Pubmed, Web of Science, Cochrane Library, and Embase, were systematically searched. Revman 5.4 was used for data analysis, and combined effect sizes, heterogeneity tests, subgroup analyses, and sensitivity analyses were calculated. Egger's test in Stata 15.0 was used for publication bias testing.

A total of 24 articles with 914 participants were included. Meta-analysis showed that PA interventions improved inhibitory control (SMD = -0.50, 95%CI [-0.71, -0.29], P < 0.00001), working memory (SMD = -0.50, 95%CI [-0.83, -0.16], P = 0.004) and cognitive flexibility in children and adolescents with ADHD (SMD = -0.45, 95%CI [-0.81, -0.09], P = 0.01). Subgroup analysis revealed a moderating effect of intervention intensity, motor skill type, sessions of PA, and weekly exercise volume on executive function.

PA interventions had positive effects on improvements in core executive functions in children and adolescents with ADHD and were influenced by intervention intensity, type of motor skill, sessions of PA, and amount of exercise. This has practical implications for the formulation of PA interventions programs.

Mnemonic discrimination is very vulnerable to aging. Previous studies have reported that aerobic exercise and enriched cognitive stimulation (e.g., video games) could improve mnemonic discrimination in older adults. The animal model suggested that combining the 2 training methods could result in a larger improvement. However, there is limited evidence on the potential superior efficacy of combined intervention with human participants. Moreover, the neural basis of this potential superior is poorly understood.

We conducted a 16-week intervention trial with 98 community-dwelling older adults assigned to one of the four groups (combined training, aerobic cycling alone, video game alone, or passive control). Mnemonic discrimination was measured as the primary behavioral outcome, hippocampal volume, and functional connectivity of the default mode network (DMN) were measured as neural indicators.

Participants receiving the combined intervention demonstrated the largest effect size of mnemonic discrimination improvement. Magnetic resonance image results indicated aerobic exercising increased left hippocampal volume, while video-game training counteracted the decline of DMN functional connectivity with aging. The synergy of hippocampal structural and functional plasticity observed in the combined training group explained why the largest intervention benefits were obtained by this group.

Despite the nonrandomized design (i.e., likely self-selection bias), our results provide new evidence that combined intervention of exercise and cognitive training is more effective than single intervention for older adults. Parallel to animal studies, aerobic exercise and the video game with enriched cognitive stimulation could induce hippocampal plasticity through separate structural and functional pathways.

ChiCTR1900022702.

In the last decades, important progress has been achieved in the understanding of the neurotrophic effects of intermittent fasting (IF), calorie restriction (CR) and exercise. Improved neuroprotection, synaptic plasticity and adult neurogenesis (NSPAN) are essential examples of these neurotrophic effects. The importance in this respect of the metabolic switch from glucose to ketone bodies as cellular fuel has been highlighted. More recently, calorie restriction mimetics (CRMs; resveratrol and other polyphenols in particular) have been investigated thoroughly in relation to NSPAN. In the narrative review sections of this manuscript, recent findings on these essential functions are synthesized and the most important molecules involved are presented. The most researched signaling pathways (PI3K, Akt, mTOR, AMPK, GSK3β, ULK, MAPK, PGC-1α, NF-κB, sirtuins, Notch, Sonic hedgehog and Wnt) and processes (e.g., anti-inflammation, autophagy, apoptosis) that support or thwart neuroprotection, synaptic plasticity and neurogenesis are then briefly presented. This provides an accessible entry point to the literature. In the annotated bibliography section of this contribution, brief summaries are provided of about 30 literature reviews relating to the neurotrophic effects of interest in relation to IF, CR, CRMs and exercise. Most of the selected reviews address these essential functions from the perspective of healthier aging (sometimes discussing epigenetic factors) and the reduction of the risk for neurodegenerative diseases (Alzheimer's disease, Huntington's disease, Parkinson's disease) and depression or the improvement of cognitive function.

Facing an unrelenting rise in dementia cases worldwide, researchers are exploring non-pharmacological ways to ameliorate cognitive decline in later life. Twenty older adults completed assessments before and after a single bout of interactive physical and cognitive exercise, by playing a neuro-exergame that required pedaling and steering to control progress in a tablet-based video game tailored to impact executive function (the interactive Physical and Cognitive Exercise System; iPACES v2). This study explored the cognitive and biomarker outcomes for participants with mild cognitive impairment (MCI) and normative older adults after 20 min of pedal-to-play exercise. Neuropsychological and salivary assessments were performed pre- and post-exercise to assess the impact. Repeated-measures ANOVAs revealed significant interaction effects, with MCI participants experiencing greater changes in executive function and alpha-amylase levels than normative older adults; within-group changes were also significant. This study provides further data regarding cognitive effects and potential mechanisms of action for exercise as an intervention for MCI.

The volume of the hippocampus and its subfields is known to be affected by aging, disease, and physical training. In regard to training, the differential effects of aerobic exercise and dance training on the subfield volume suggest that balance function may be involved. However, the relationship between balance function and the volume of the hippocampus and its subfields remains unclear.

Subjects were 30 cognitively intact individuals. They underwent balance tests, cognitive tests and structural MRI scans. The balance index measured was the index of postural stability (IPS) under a visual block condition and/or a proprioception block condition. MR images acquired using a 3-tesla system and three-dimensional T1-weighted images were segmented in the hippocampal subfield with Freesurfer 6.0.0. The relationship between the IPS and hippocampal volume was evaluated.

A positive correlation was observed only between the IPS closed eyes/soft surface condition and whole hippocampal volume ratio. In the subfields, positive correlations were found between the IPS and molecular layer of the hippocampus, granule cell layer of the dentate gyrus (GC-ML-DG), and cornu ammonis areas (CA)3 and CA4. These correlations were stronger under the closed eyes/soft surface condition than under the other conditions.

A correlation between balance function and the volume of the hippocampus and subfields was found in healthy elderly subjects. The balance function may be involved in the volume of the whole hippocampus and specific subfields. The IPS closed eyes/soft surface condition is considered to reflect vestibular function. Thus, IPS may be useful in evaluations of the relationship between the vestibular system function via the hippocampus and balance.

People with a Fontan circulation are at risk of neurodevelopmental delay and disability, and cognitive dysfunction, that has significant implications for academic and occupational attainment, psychosocial functioning, and overall quality of life. Interventions for improving these outcomes are lacking. This review article discusses current intervention practices and explores the evidence supporting exercise as a potential intervention for improving cognitive functioning in people living with a Fontan circulation. Proposed pathophysiological mechanisms underpinning these associations are discussed in the context of Fontan physiology and avenues for future research are recommended.

An inaugural workshop supported by "The Leo and Anne Albert Charitable Trust," was held October 4-7, 2019 in Scottsdale, Arizona, to focus on the effects of exercise on the brain and to discuss how physical activity may prevent or delay the onset of aging-related neurodegenerative conditions. The Scientific Program Committee (led by Dr. Jeff Burns) assembled translational, clinical, and basic scientists who research various aspects of the effects of exercise on the body and brain, with the overall goal of gaining a better understanding as to how to delay or prevent neurodegenerative diseases. In particular, research topics included the links between cardiorespiratory fitness, the cerebrovasculature, energy metabolism, peripheral organs, and cognitive function, which are all highly relevant to understanding the effects of acute and chronic exercise on the brain. The Albert Trust workshop participants addressed these and related topics, as well as how other lifestyle interventions, such as diet, affect age-related cognitive decline associated with Alzheimer's and other neurodegenerative diseases. This report provides a synopsis of the presentations and discussions by the participants, and a delineation of the next steps towards advancing our understanding of the effects of exercise on the aging brain.

Physical exercise in cancer patients is a promising intervention to improve cognition and increase brain volume, including hippocampal volume. We investigated whether a 6-month exercise intervention primarily impacts total hippocampal volume and additionally hippocampal subfield volumes, cortical thickness and grey matter volume in previously physically inactive breast cancer patients. Furthermore, we evaluated associations with verbal memory.

Chemotherapy-exposed breast cancer patients (stage I-III, 2-4 years post diagnosis) with cognitive problems were included and randomized in an exercise intervention (n = 70, age = 52.5 ± 9.0 years) or control group (n = 72, age = 53.2 ± 8.6 years). The intervention consisted of 2x1 hours/week of supervised aerobic and strength training and 2x1 hours/week Nordic or power walking. At baseline and at 6-month follow-up, volumetric brain measures were derived from 3D T1-weighted 3T magnetic resonance imaging scans, including hippocampal (subfield) volume (FreeSurfer), cortical thickness (CAT12), and grey matter volume (voxel-based morphometry CAT12). Physical fitness was measured with a cardiopulmonary exercise test. Memory functioning was measured with the Hopkins Verbal Learning Test-Revised (HVLT-R total recall) and Wordlist Learning of an online cognitive test battery, the Amsterdam Cognition Scan (ACS Wordlist Learning). An explorative analysis was conducted in highly fatigued patients (score of ≥ 39 on the symptom scale 'fatigue' of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire), as previous research in this dataset has shown that the intervention improved cognition only in these patients.

Multiple regression analyses and voxel-based morphometry revealed no significant intervention effects on brain volume, although at baseline increased physical fitness was significantly related to larger brain volume (e.g., total hippocampal volume: R = 0.32, B = 21.7 mm3, 95 % CI = 3.0 - 40.4). Subgroup analyses showed an intervention effect in highly fatigued patients. Unexpectedly, these patients had significant reductions in hippocampal volume, compared to the control group (e.g., total hippocampal volume: B = -52.3 mm3, 95 % CI = -100.3 - -4.4)), which was related to improved memory functioning (HVLT-R total recall: B = -0.022, 95 % CI = -0.039 - -0.005; ACS Wordlist Learning: B = -0.039, 95 % CI = -0.062 - -0.015).

No exercise intervention effects were found on hippocampal volume, hippocampal subfield volumes, cortical thickness or grey matter volume for the entire intervention group. Contrary to what we expected, in highly fatigued patients a reduction in hippocampal volume was found after the intervention, which was related to improved memory functioning. These results suggest that physical fitness may benefit cognition in specific groups and stress the importance of further research into the biological basis of this finding.