Rapid stimulation of human dentate gyrus function with acute mild exercise.

Physical exercise has beneficial effects on neurocognitive function, including hippocampus-dependent episodic memory. Exercise intensity level can be assessed according to whether it induces a stress response; the most effective exercise for improving hippocampal function remains unclear. Our prior work using a special treadmill running model in animals has shown that stress-free mild exercise increases hippocampal neuronal activity and promotes adult neurogenesis in the dentate gyrus (DG) of the hippocampus, improving spatial memory performance. However, the rapid modification, from mild exercise, on hippocampal memory function and the exact mechanisms for these changes, in particular the impact on pattern separation acting in the DG and CA3 regions, are yet to be elucidated. To this end, we adopted an acute-exercise design in humans, coupled with high-resolution functional MRI techniques, capable of resolving hippocampal subfields. A single 10-min bout of very light-intensity exercise (30%[Formula: see text]) results in rapid enhancement in pattern separation and an increase in functional connectivity between hippocampal DG/CA3 and cortical regions (i.e., parahippocampal, angular, and fusiform gyri). Importantly, the magnitude of the enhanced functional connectivity predicted the extent of memory improvement at an individual subject level. These results suggest that brief, very light exercise rapidly enhances hippocampal memory function, possibly by increasing DG/CA3-neocortical functional connectivity.

The effectiveness of exercise intervention for academic achievement, cognitive function, and physical health among children in Mongolia: a cluster RCT study protocol.

BACKGROUND: Many studies have demonstrated positive effects of physical activity on children's health such as improved cardiorespiratory function and decreased obesity. Physical activity has also been found to have positive effects on academic achievement and cognitive function. However, there are few high quality RCT studies on this topic at present and the findings remain controversial. METHODS: This protocol describes cluster randomized controlled trials assessing the impact of school-based exercise intervention among children in Mongolia. The intervention consists of 3-min sessions of high intensity interval training combined with music implemented two times a week at school during study periods. The participants are children in the fourth grade in public elementary schools in the Sukhbaatar district in Ulaanbaatar, Mongolia. The participants are cluster randomized by school and allocated either to the intervention or control group. The primary outcome is academic achievement. Secondary outcomes are obesity/overweight, physical fitness function, lifestyle, mental health, and cognitive function. DISCUSSION: This cluster-RCT is designed and implemented to assess the effectiveness of exercise intervention on academic achievement, cognitive function, and physical and mental health among school-age children in Mongolia. This study will provide evidence to promote physical activities among children in low- and middle- income countries. TRIAL REGISTRATION: UMIN: UMIN000031062 . Registered on 1st February 2018.

Neural basis for reduced executive performance with hypoxic exercise.

While accumulating evidence suggests positive effects of exercise on executive function, such effects vary with environment. In particular, exercise in a hypoxic environment (hypobaric or normobaric hypoxia), leading to decreased oxygen supply, may dampen or cancel such effects. Thus, we further explore the relation between the effects of hypoxic exercise on executive function and their underlying neural mechanisms by monitoring changes of cortical activation patterns using functional near-infrared spectroscopy (fNIRS). Fifteen healthy participants performed color-word Stroop tasks (CWST) before and after a 10 min bout of moderate-intensity exercise (50%V̇O2peak) under normoxic and hypoxic conditions (fraction of inspired oxygen (FIO2) = 0.135). During the CWST, we monitored prefrontal activation using fNIRS. CWST performance under hypoxic conditions decreased compared with normoxic conditions. In addition, CWST-related activation in the left dorsolateral prefrontal cortex (DLPFC) was reduced after a bout of hypoxic exercise. There was statistically significant association between decreased CWST performance and activation in the left DLPFC. These results suggest that moderate exercise under normobaric hypoxic conditions has negative effects on executive function by reducing task-related activations in the DLPFC.

A transferable high-intensity intermittent exercise improves executive performance in association with dorsolateral prefrontal activation in young adults.

Although growing attention has been drawn to attainable, high-intensity intermittent exercise (HIE)-based intervention, which can improve cardiovascular and metabolic health, for sedentary individuals, there is limited information on the impact and potential benefit of an easily attainable HIE intervention for cognitive health. We aimed to reveal how acute HIE affects executive function focusing on underlying neural substrates. To address this issue, we examined the effects of acute HIE on executive function using the color-word matching Stroop task (CWST), which produces a cognitive conflict in the decision-making process, and its neural substrate using functional near infrared spectroscopy (fNIRS). Twenty-five sedentary young adults (mean age: 21.0 ± 1.6 years; 9 females) participated in two counter-balanced sessions: HIE and resting control. The HIE session consisted of two minutes of warm-up exercise (50 W load at 60 rpm) and eight sets of 30 s of cycling exercise at 60% of maximal aerobic power (mean: 127 W ± 29.5 load at 100 rpm) followed by 30 s of rest on a recumbent-ergometer. Participants performed a CWST before and after the 10-minute exercise session, during both of which cortical hemodynamic changes in the prefrontal cortex were monitored using fNIRS. Acute HIE led to improved Stroop performance reflected by a shortening of the response time related to Stroop interference. It also evoked cortical activation related to Stroop interference on the left-dorsal-lateral prefrontal cortex (DLPFC), which corresponded significantly with improved executive performance. These results provide the first empirical evidence using a neuroimaging method, to our knowledge, that acute HIE improves executive function, probably mediated by increased activation of the task-related area of the prefrontal cortex including the left-DLPFC.

Acute moderate exercise improves mnemonic discrimination in young adults.

Increasing evidence suggests that regular moderate exercise increases neurogenesis in the dentate gyrus (DG) of the hippocampus and improves memory functions in both humans and animals. The DG is known to play a role in pattern separation, which is the ability to discriminate among similar experiences, a fundamental component of episodic memory. While long-term voluntary exercise improves pattern separation, there is little evidence of alterations in DG function after an acute exercise session. Our previous studies showing acute moderate exercise-enhanced DG activation in rats, and acute moderate exercise-enhanced prefrontal activation and executive function in humans, led us to postulate that acute moderate exercise may also activate the hippocampus, including more specifically the DG, thus improving pattern separation. We thus investigated the effects of a 10-min moderate exercise (50% V̇O2peak ) session, the recommended intensity for health promotion, on mnemonic discrimination (a behavioral index of pattern separation) in young adults. An acute bout of moderate exercise improved mnemonic discrimination performance in high similarity lures. These results support our hypothesis that acute moderate exercise improves DG-mediated pattern separation in humans, proposing a useful human acute-exercise model for analyzing the neuronal substrate underlying acute and regular exercise-enhanced episodic memory based on the hippocampus. © 2016 Wiley Periodicals, Inc.

The association between aerobic fitness and cognitive function in older men mediated by frontal lateralization.

Previous studies have shown that higher aerobic fitness is related to higher cognitive function and higher task-related prefrontal activation in older adults. However, a holistic picture of these factors has yet to be presented. As a typical age-related change of brain activation, less lateralized activity in the prefrontal cortex during cognitive tasks has been observed in various neuroimaging studies. Thus, this study aimed to reveal the relationship between aerobic fitness, cognitive function, and frontal lateralization. Sixty male older adults each performed a submaximal incremental exercise test to determine their oxygen intake (V·O2) at ventilatory threshold (VT) in order to index their aerobic fitness. They performed a color-word Stroop task while prefrontal activation was monitored using functional near infrared spectroscopy. As an index of cognitive function, Stroop interference time was analyzed. Partial correlation analyses revealed significant correlations among higher VT, shorter Stroop interference time and greater left-lateralized dorsolateral prefrontal cortex (DLPFC) activation when adjusting for education. Moreover, mediation analyses showed that left-lateralized DLPFC activation significantly mediated the association between VT and Stroop interference time. These results suggest that higher aerobic fitness is associated with cognitive function via lateralized frontal activation in older adults.

Effects of exercise on cognitive function: the possible strategy for anti-aging.

Aging is one of the major factors which decline cognitive function associated with hippo- campus and prefrontal cortex, so it is an urgent issue to develop the practical treatment for aging brain. Since many researchers show that physical exercise can increase hippocampal neurogenesis and gray matter volume of prefrontal cortex, physical exercise is a potential candidate for preventing cognitive decline. Recently, we have reported that mild intensity exercise training enhances neurogenesis in rodents. In addition, we found long term inter- vention of mild exercise has beneficial effects on prefrontal gray matter volume and cognitive function in older adults. Based on these facts, mild exercise could be optimal strategy for anti-aging of brain.

Positive effect of acute mild exercise on executive function via arousal-related prefrontal activations: an fNIRS study.

Despite the practical implication of mild exercise, little is known about its influence on executive function and its neural substrates. To address these issues, the present study examined the effect of an acute bout of mild exercise on executive function and attempted to identify potential neural substrates using non-invasive functional near-infrared spectroscopy (fNIRS). Twenty-five young individuals performed a color-word matching Stroop task (CWST) and a two-dimensional scale to measure changes of psychological mood states both before and after a 10-minute exercise session on a cycle ergometer at light intensity (30% v(·)o2peak) and, for the control session, without exercise. Cortical hemodynamic changes in the prefrontal area were monitored with fNIRS during the CWST in both sessions. The acute bout of mild exercise led to improved Stroop performance, which was positively correlated with increased arousal levels. It also evoked cortical activations regarding Stroop interference on the left dorsolateral prefrontal cortex and frontopolar area. These activations significantly corresponded with both improved cognitive performance and increased arousal levels. Concurrently, this study provides empirical evidence that an acute bout of mild exercise improves executive function mediated by the exercise-induced arousal system, which intensifies cortical activation in task-related prefrontal sub-regions.

Mild exercise improves executive function with increasing neural efficiency in the prefrontal cortex of older adults.

This study examined whether a 3-month mild-exercise intervention could improve executive function in healthy middle-aged and older adults in a randomized control trial. Ultimately, a total of 81 middle-aged and older adults were randomly assigned to either an exercise group or a control group. The exercise group received 3 months of mild cycle exercise intervention (3 sessions/week, 30-50 min/session). The control group was asked to behave as usual for the intervention period. Before and after the intervention, participants did color-word matching Stroop tasks (CWST), and Stroop interference (SI)-related reaction time (RT) was assessed as an indicator of executive function. During the CWST, prefrontal activation was monitored using functional near-infrared spectroscopy (fNIRS). SI-related oxy-Hb changes and SI-related neural efficiency (NE) scores were assessed to examine the underlying neural mechanism of the exercise intervention. Although the mild-exercise intervention significantly decreased SI-related RT, there were no significant effects of exercise intervention on SI-related oxy-Hb changes or SI-related NE scores in prefrontal subregions. Lastly, changes in the effects of mild exercise on NE with advancing age were examined. The 81 participants were divided into two subgroups (younger-aged subgroup [YA], older-aged subgroup [OA], based on median age [68 years.]). Interestingly, SI-related RT significantly decreased, and SI-related NE scores in all ROIs of the prefrontal cortex significantly increased only in the OA subgroup. These results reveal that a long-term intervention of very light-intensity exercise has a positive effect on executive function especially in older adults, possibly by increasing neural efficiency in the prefrontal cortex.

Improvement of mnemonic discrimination with acute light exercise is mediated by pupil-linked arousal in healthy older adults.

Physical exercise has positive impacts on hippocampal memory decline with aging. One of the postulated neurobiological mechanisms of the decline is reduced catecholaminergic projections from the locus coeruleus to the hippocampus. Recent human studies revealed that very light exercise rapidly enhances memory and pupil diameter, which suggests that light exercise may improve memory via neural circuits involved in the ascending arousal system, including the locus coeruleus, even in older adults. Thus, we aimed to clarify the effects of a single bout of light-intensity exercise (60% ventilatory threshold) on mnemonic discrimination performance, an index of hippocampal memory function, in healthy older adults using a randomized crossover design. Pupil diameter was measured during exercise as a physiological marker of the ascending arousal system. Discrimination of highly similar stimuli to the targets improved after exercise when compared to the resting control performance. Importantly, causal mediation analysis showed that pupil dilation during exercise mediated the memory improvement. These results suggest that brief light exercise rapidly enhances memory, possibly by upregulating the ascending arousal system.

Groove Rhythm Enhances Exercise Impact on Prefrontal Cortex Function in Groove Enjoyers.

A positive affective response modulates the effects of aerobic exercise on prefrontal executive function (EF). Groove rhythm (GR), eliciting the feeling of wanting to move to music, is useful for inducing positive affective response during exercise. Three minutes of listening to GR activated the left dorsolateral prefrontal cortex (l-DLPFC) and enhanced EF in participants who had higher psychological responses to GR. This finding prompted us to test the hypothesis that the combination of GR and exercise (GREX) induces positive psychological responses that enhance PFC function through entrainment of body movements and musical beats. 41 participants were administered two experimental conditions: three min of very light-intensity (30% V̇ O2peak) exercise combined with GR and combined with a white-noise metronome (WMEX). Before and after exercise, participants performed a Stroop task and were monitored for l-DLPFC activity with functional near-infrared spectroscopy. GREX enhanced EF and l-DLPFC activity in participants who experienced greater subjective feelings of audiomotor entrainment and increased excitement with GREX. These psychological responses were predictive of the impact of GREX on l-DLPFC activity and EF. These findings, together with previous results, support the hypothesis that GR allows us to boost the cognitive benefits of exercise via l-DLPFC activity only in those who enjoy groove, and suggest that subjective audiomotor entrainment is a key mechanism of this boosting effect.

A possible contribution of the locus coeruleus to arousal enhancement with mild exercise: evidence from pupillometry and neuromelanin imaging.

Acute mild exercise has been observed to facilitate executive function and memory. A possible underlying mechanism of this is the upregulation of the ascending arousal system, including the catecholaminergic system originating from the locus coeruleus (LC). Prior work indicates that pupil diameter, as an indirect marker of the ascending arousal system, including the LC, increases even with very light-intensity exercise. However, it remains unclear whether the LC directly contributes to exercise-induced pupil-linked arousal. Here, we examined the involvement of the LC in the change in pupil dilation induced by very light-intensity exercise using pupillometry and neuromelanin imaging to assess the LC integrity. A sample of 21 young males performed 10 min of very light-intensity exercise, and we measured changes in the pupil diameters and psychological arousal levels induced by the exercise. Neuromelanin-weighted magnetic resonance imaging scans were also obtained. We observed that pupil diameter and psychological arousal levels increased during very light-intensity exercise, which is consistent with previous findings. Notably, the LC contrast, a marker of LC integrity, predicted the magnitude of pupil dilation and psychological arousal enhancement with exercise. These relationships suggest that the LC-catecholaminergic system is a potential a mechanism for pupil-linked arousal induced by very light-intensity exercise.

Groove rhythm stimulates prefrontal cortex function in groove enjoyers.

Hearing a groove rhythm (GR), which creates the sensation of wanting to move to the music, can also create feelings of pleasure and arousal in people, and it may enhance cognitive performance, as does exercise, by stimulating the prefrontal cortex. Here, we examined the hypothesis that GR enhances executive function (EF) by acting on the left dorsolateral prefrontal cortex (l-DLPFC) while also considering individual differences in psychological responses. Fifty-one participants underwent two conditions: 3 min of listening to GR or a white-noise metronome. Before and after listening, participants performed the Stroop task and were monitored for l-DLPFC activity with functional near-infrared spectroscopy. Our results show that GR enhanced EF and l-DLPFC activity in participants who felt a greater groove sensation and a more feeling clear-headed after listening to GR. Further, these psychological responses predict the impact of GR on l-DLPFC activity and EF, suggesting that GR enhances EF via l-DLPFC activity when the psychological response to GR is enhanced.

Cognitive fatigue due to exercise under normobaric hypoxia is related to hypoxemia during exercise.

We previously found that a 10-min bout of moderate-intensity exercise (50% maximal oxygen uptake) under normobaric and hypoxic conditions (fraction of inspired oxygen [[Formula: see text]] = 0.135) reduced executive performance and neural activity in the left dorsolateral prefrontal cortex (DLPFC). To examine whether this cognitive fatigue is due to a decrease in SpO2 during exercise, we compared executive performance and related prefrontal activation between two experimental conditions, in which the participants inhaled normobaric hypoxic gas ([Formula: see text]= 0.135) (hypoxic exercise [HE]) or hypoxic gas adjusted so that SpO2 during exercise remained at the resting level (milder hypoxic exercise [ME]). ME condition showed that reaction time in executive performance decreased (t[13] = 2.228, P < 0.05, d = 0.34, paired t-test) and left DLPFC activity increased (t[13] = -2.376, P < 0.05, d = 0.63, paired t-test) after exercise compared with HE condition. These results showed that the HE-induced reductions in the left DLPFC activity and executive performance were both suppressed in the ME condition, supporting the hypothesis that exercise-induced cognitive fatigue under hypoxic environment is due to hypoxemia during exercise. This may lead to the development of a method of coping with cognitive fatigue due to exercise that causes hypoxemia.

Pupil-linked arousal with very light exercise: pattern of pupil dilation during graded exercise.

Although it has been hypothesized that moderate to vigorous exercise immediately modulates cognition via ascending arousal system activation, such activation during very-light to light exercise has remained uncertain. Here, we aimed to uncover the exact exercise intensity necessary for ascending arousal system activation using pupillometry. The pupil diameter, psychological arousal, and ventilation during graded exercise of 26 young males were analyzed based on %[Formula: see text]. Pupils dilated with very-light exercise compared to rest, stabilized, and then drastically increased again with moderate exercise and above. Pupil dilation with very-light exercise was positively correlated with increases in psychological arousal. Thus, we have shown that there are two phases of pupil dilation during graded exercise: one with very-light exercise coinciding with psychological arousal response, and the other with moderate exercise or above similar to the ventilation increase pattern. This unique pupil dilation pattern provides physiological evidence of ascending arousal system activation with very-light exercise.

Comparison Between the Effects of Continuous and Intermittent Light-Intensity Aerobic Dance Exercise on Mood and Executive Functions in Older Adults.

There is a growing body of evidence suggesting that one bout of moderate-intensity exercise enhances executive functions in older adults. However, in terms of safety, feasibility, and continuity, older individuals prefer light, easy, and fun exercises to moderate and stressful exercises for improving executive functions. Therefore, light-intensity aerobic dance exercise (LADE) could be suitable if it produces potential benefits related to executive functions. As for continuous vs. intermittent exercise, intermittent exercise has received a lot of attention, as it results in greater effects on mood and executive functions than continuous exercise; however, its effects in older adults remain uncertain. Thus, in this study, we aimed to examine the acute effects of intermittent LADE (I-LADE) in comparison with those of continuous LADE (C-LADE) on mood and executive functions. Fifteen healthy older adults participated in 10-min I-LADE and C-LADE conditions on separate days. Perceived enjoyment following exercise was assessed using the Physical Activity Enjoyment Scale (PACES). The pleasantness of the mood during exercise and pleasure and arousal levels after exercise were assessed using the Feeling Scale and Two-Dimensional Mood Scale, respectively. Executive function was assessed using the Stroop task before and after exercise. As a result, pleasantness of the mood during exercise and exercise enjoyment levels were greater in I-LADE than in C-LADE. Arousal and pleasure levels and Stroop task performance increased after both LADEs and did not differ between the two exercise conditions. These findings suggest that although enhancement of mood and executive functions after exercise did not differ between C-LADE and I-LADE, I-LADE could be more enjoyable and fun than C-LADE. This study will help in the development of exercise conditions that can enable the elderly to enhance their executive functions in a fun way.

Positive Mood while Exercising Influences Beneficial Effects of Exercise with Music on Prefrontal Executive Function: A Functional NIRS Study.

Much attention has been focused on physical exercise benefits to mental health such as mood and cognitive function. Our recent studies have consistently shown that a single bout of exercise elicits increased task-related brain activation mainly in the dorsolateral part of the prefrontal cortex (DLPFC), which results in improved executive performance. As the DLPFC is associated with the modulation of mood as well as executive function, it is tempting to hypothesize that exercising while in a positive mood would facilitate the beneficial effects of exercise on executive function via DLPFC activation. Thus, we conceived an experiment that used music to elicit a positive mood during exercise. Thirty-three young adults performed ten minutes of moderate-intensity (50% V.O2peak) pedaling exercise with two experimental conditions: listening to music and listening to beeps at a steady tempo. Mood and executive function were respectively assessed using the Two-Dimensional Mood Scale and a color-word-matching Stroop task before and after the exercise sessions. Prefrontal activation during the Stroop task was monitored using functional near-infrared spectroscopy. Exercise with music elicited greater enhancement of a positive mood (vitality) than did exercise with beeps. Contrary to our hypothesis, there were no significant differences between conditions in improvement in Stroop task performance and task-related cortical activation in the left-DLPFC. The correlation analyses, however, revealed significant correlations among increased vitality, shortened Stroop interference time and increased activation in the left-DLPFC. These results support the hypothesis that positive mood while exercising influences the benefit of exercise on prefrontal activation and executive performance.

Benefit of human moderate running boosting mood and executive function coinciding with bilateral prefrontal activation.

Running, compared to pedaling is a whole-body locomotive movement that may confer more mental health via strongly stimulating brains, although running impacts on mental health but their underlying brain mechanisms have yet to be determined; since almost the mechanistic studies have been done with pedaling. We thus aimed at determining the acute effect of a single bout of running at moderate-intensity, the most popular condition, on mood and executive function as well as their neural substrates in the prefrontal cortex (PFC). Twenty-six healthy participants completed both a 10-min running session on a treadmill at 50%[Formula: see text] and a resting control session in randomized order. Executive function was assessed using the Stroop interference time from the color-word matching Stroop task (CWST) and mood was assessed using the Two-Dimensional Mood Scale, before and after both sessions. Prefrontal hemodynamic changes while performing the CWST were investigated using functional near-infrared spectroscopy. Running resulted in significant enhanced arousal and pleasure level compared to control. Running also caused significant greater reduction of Stroop interference time and increase in Oxy-Hb signals in bilateral PFCs. Besides, we found a significant association among pleasure level, Stroop interference reaction time, and the left dorsolateral PFCs: important brain loci for inhibitory control and mood regulation. To our knowledge, an acute moderate-intensity running has the beneficial of inducing a positive mood and enhancing executive function coinciding with cortical activation in the prefrontal subregions involved in inhibitory control and mood regulation. These results together with previous findings with pedaling imply the specificity of moderate running benefits promoting both cognition and pleasant mood.

Spontaneous Eye Blink Rate Connects Missing Link between Aerobic Fitness and Cognition.

PURPOSE: Higher aerobic fitness, a physiological marker of habitual physical activity, is likely to predict higher executive function based on the prefrontal cortex (PFC), according to current cross-sectional studies. The exact biological link between the brain and the brawn remains unclear, but the brain dopaminergic system, which acts as a driving force for physical activity and exercise, can be hypothesized to connect the missing link above. Recently, spontaneous eye blink rate (sEBR) was proposed and has been used as a potential, noninvasive marker of brain dopaminergic activity in the neuroscience field. To address the hypothesis above, we sought to determine whether sEBR is a mediator of the association between executive function and aerobic fitness. METHODS: Thirty-five healthy young males (18-24 yr old) had their sEBR measured while staring at a fixation cross while at rest. They underwent an aerobic fitness assessment using a graded exercise test to exhaustion and performed a color-word Stroop task as an index of executive function. Stroop task-related cortical activation in the left dorsolateral PFC (l-DLPFC) was monitored using functional near-infrared spectroscopy. RESULTS: Correlation analyses revealed significant correlations among higher aerobic fitness, less Stroop interference, and higher sEBR. Moreover, mediation analyses showed that sEBR significantly mediated the association between aerobic fitness and Stroop interference. In addition, higher sEBR was correlated with higher neural efficiency of the l-DLPFC (i.e., executive function was high, and the corresponding l-DLPFC activation was relatively low). CONCLUSION: These results indicate that the sEBR mediates the association between aerobic fitness and executive function through prefrontal neural efficiency, which clearly supports the hypothesis that brain dopaminergic function works to connect, at least in part, the missing link between aerobic fitness and executive function.