Human dopaminergic system in the exercise-cognition link.

While the dopaminergic system is important for cognitive processes, it is also sensitive to the influence of physical activity (PA). We summarize current evidence on whether PA-related changes in the human dopaminergic system are associated with alterations in cognitive performance, discuss recent advances, and highlight challenges and opportunities for future research.

Creatine supplementation research fails to support the theoretical basis for an effect on cognition: Evidence from a systematic review.

Creatine supplementation has been put forward as a possible aid to cognition, particularly for vegans, vegetarians, the elderly, sleep deprived and hypoxic individuals. However, previous narrative reviews have only provided limited support for these claims. This is despite the fact that research has shown that creatine supplementation can induce increased brain concentrations of creatine, albeit to a limited extent. We carried out a systematic review to examine the current state of affairs. The review supported claims that creatine supplementation can increases brain creatine content but also demonstrated somewhat equivocal results for effects on cognition. It does, however, provide evidence to suggest that more research is required with stressed populations, as supplementation does appear to significantly affect brain content. Issues with research design, especially supplementation regimens, need to be addressed. Future research must include measurements of creatine brain content.

The neuromodulatory role of dopamine in improved reaction time by acute cardiovascular exercise.

Acute cardiovascular physical exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Here, using positron emission tomography (PET) with [11 C]raclopride, in a multi-experiment study we investigated whether acute exercise releases endogenous dopamine (DA) in the brain. We hypothesized that acute exercise augments the brain DA system, and that RT improvement is correlated with this endogenous DA release. The PET study (Experiment 1: n = 16) demonstrated that acute physical exercise released endogenous DA, and that endogenous DA release was correlated with improvements in RT of the Go/No-Go task. Thereafter, using two electrical muscle stimulation (EMS) studies (Experiments 2 and 3: n = 18 and 22 respectively), we investigated what triggers RT improvement. The EMS studies indicated that EMS with moderate arm cranking improved RT, but RT was not improved following EMS alone or EMS combined with no load arm cranking. The novel mechanistic findings from these experiments are: (1) endogenous DA appears to be an important neuromodulator for RT improvement and (2) RT is only altered when exercise is associated with central signals from higher brain centres. Our findings explain how humans rapidly alter their behaviour using neuromodulatory systems and have significant implications for promotion of cognitive health. KEY POINTS: Acute cardiovascular exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Using the neurochemical specificity of [11 C]raclopride positron emission tomography, we demonstrated that acute supine cycling released endogenous dopamine (DA), and that this release was correlated with improved RT. Additional electrical muscle stimulation studies demonstrated that peripherally driven muscle contractions (i.e. exercise) were insufficient to improve RT. The current study suggests that endogenous DA is an important neuromodulator for RT improvement, and that RT is only altered when exercise is associated with central signals from higher brain centres.

Habituation of the cold shock response: A systematic review and meta-analysis.

Cold water immersion (CWI) evokes the life-threatening reflex cold shock response (CSR), inducing hyperventilation, increasing cardiac arrhythmias, and increasing drowning risk by impairing safety behaviour. Repeated CWI induces CSR habituation (i.e., diminishing response with same stimulus magnitude) after ∼4 immersions, with variation between studies. We quantified the magnitude and coefficient of variation (CoV) in the CSR in a systematic review and meta-analysis with search terms entered to Medline, SportDiscus, PsychINFO, Pubmed, and Cochrane Central Register. Random effects meta-analyses, including effect sizes (Cohen's d) from 17 eligible groups (k), were conducted for heart rate (HR, n = 145, k = 17), respiratory frequency (fR, n = 73, k = 12), minute ventilation (Ve, n = 106, k = 10) and tidal volume (Vt, n = 46, k=6). All CSR variables habituated (p < 0.001) with large or moderate pooled effect sizes: ΔHR -14 (10) bt. min-1 (d: -1.19); ΔfR -8 (7) br. min-1 (d: -0.78); ΔVe, -21.3 (9.8) L. min-1 (d: -1.64); ΔVt -0.4 (0.3) L -1. Variation was greatest in Ve (control vs comparator immersion: 32.5&24.7%) compared to Vt (11.8&12.1%). Repeated CWI induces CSR habituation potentially reducing drowning risk. We consider the neurophysiological and behavioural consequences.

The effects of sleep deprivation, acute hypoxia, and exercise on cognitive performance: A multi-experiment combined stressors study.

INTRODUCTION: Both sleep deprivation and hypoxia have been shown to impair executive function. Conversely, moderate intensity exercise is known to improve executive function. In a multi-experiment study, we tested the hypotheses that moderate intensity exercise would ameliorate any decline in executive function after i) three consecutive nights of partial sleep deprivation (PSD) (Experiment 1) and ii) the isolated and combined effects of a single night of total sleep deprivation (TSD) and acute hypoxia (Experiment 2). METHODS: Using a rigorous randomised controlled crossover design, 12 healthy participants volunteered in each experiment (24 total, 5 females). In both experiments seven executive function tasks (2-choice reaction time, logical relations, manikin, mathematical processing, 1-back, 2-back, 3-back) were completed at rest and during 20 min semi-recumbent, moderate intensity cycling. Tasks were completed in the following conditions: before and after three consecutive nights of PSD and habitual sleep (Experiment 1) and in normoxia and acute hypoxia (FIO2 = 0.12) following one night of habitual sleep and one night of TSD (Experiment 2). RESULTS: Although the effects of three nights of PSD on executive functions were inconsistent, one night of TSD (regardless of hypoxic status) reduced executive functions. Significantly, regardless of sleep or hypoxic status, executive functions are improved during an acute bout of moderate intensity exercise. CONCLUSION: These novel data indicate that moderate intensity exercise improves executive function performance after both PSD and TSD, regardless of hypoxic status. The key determinants and/or mechanism(s) responsible for this improvement still need to be elucidated. Future work should seek to identify these mechanisms and translate these significant findings into occupational and skilled performance settings.

The effects of acute high-intensity aerobic exercise on cognitive performance: A structured narrative review.

It is well established that acute moderate-intensity exercise improves cognitive performance. However, the effects of acute high-intensity aerobic exercise on cognitive performance have not been well characterized. In this review, we summarize the literature investigating the exercise-cognition interaction, especially focusing on high-intensity aerobic exercise. We discuss methodological and physiological factors that potentially mediate cognitive performance in response to high-intensity exercise. We propose that the effects of high-intensity exercise on cognitive performance are primarily affected by the timing of cognitive task (during vs. after exercise, and the time delay after exercise). In particular, cognitive performance is more likely to be impaired during high-intensity exercise when both cognitive and physiological demands are high and completed simultaneously (i.e., the dual-task paradigm). The effects may also be affected by the type of cognitive task, physical fitness, exercise mode/duration, and age. Second, we suggest that interactions between changes in regional cerebral blood flow (CBF), cerebral oxygenation, cerebral metabolism, neuromodulation by neurotransmitters/neurotrophic factors, and a variety of psychological factors are promising candidates that determine cognitive performance in response to acute high-intensity exercise. The present review has implications for recreational, sporting, and occupational activities where high cognitive and physiological demands are required to be completed concurrently.

The acute exercise-cognition interaction: From the catecholamines hypothesis to an interoception model.

An interoception model for the acute exercise-cognition interaction is presented. During exercise following the norepinephrine threshold, interoceptive feedback induces increased tonic release of extracellular catecholamines, facilitating phasic release hence better cognitive performance of executive functions. When exercise intensity increases to maximum, the nature of task-induced norepinephrine release from the locus coeruleus is dependent on interaction between motivation, perceived effort costs and perceived availability of resources. This is controlled by interaction between the rostral and dorsolateral prefrontal cortices, orbitofrontal cortex, anterior cingulate cortex and anterior insula cortex. If perceived available resources are sufficient to meet predicted effort costs and reward value is high, tonic release from the locus coeruleus is attenuated thus facilitating phasic release, therefore cognition is not inhibited. However, if perceived available resources are insufficient to meet predicted effort costs or reward value is low, tonic release from the locus coeruleus is induced, attenuating phasic release. As a result, cognition is inhibited, although long-term memory and tasks that require switching to new stimuli-response couplings are probably facilitated.

Cognitive Fatigue Effects on Physical Performance: The Role of Interoception.

The consensus of opinion, with regard to the effect of cognitive fatigue on subsequent physical performance, is that there is a small, negative effect, but there is no consensus regarding the mechanisms involved. When glucose levels are normal, undertaking cognitive tasks does not induce energy or neurotransmitter depletion. The adenosine hypothesis is questioned as cognitively induced increases in adenosine release are phasic and transient, while persistent effects of adenosine are tonic. Thus, the most likely explanation for a negative effect of cognitive fatigue would appear to be changes in perceptions of effort, for which there is some evidence from subjective participant feedback, while interoceptive theory would suggest a role for motivation levels. Cognitive fatigue and physical fatigue are dependent on interoceptive mechanisms, in particular the interactions between top-down predictions of effort from the dorsolateral prefrontal cortex (PFC) to the insula cortex, anterior cingulate cortex, ventromedial and ventrolateral PFC, and bottom-up feedback from the lamina I spinothalamic pathway, and the vagal and glossopharyngeal medullothalamic pathway. The dopaminergic mesocorticolimbic and the locus coeruleus-noradrenaline pathways are also vital. It would appear that cognitive fatigue leads to different predictions of the expected sensory consequences of undertaking the exercise than in the control condition and there is some evidence that motivation can overcome this. Much more research, in which motivation levels are manipulated, is necessary as the effects are small and the reasons for cognitive fatigue causing changes in predictions of sensory consequences are not clear.

Cognitive performance is associated with cerebral oxygenation and peripheral oxygen saturation, but not plasma catecholamines, during graded normobaric hypoxia.

NEW FINDINGS: What is the central question of this study? What are the mechanisms responsible for the decline in cognitive performance following exposure to acute normobaric hypoxia? What are the main findings and their importance? We found that (1) performance of a complex central executive task (n-back) was reduced at FIO2 0.12; (2) there was a strong correlation between performance of the n-back task and reductions in SpO2 and cerebral oxygenation; and (3) plasma adrenaline, noradrenaline, cortisol and copeptin were not correlated with cognitive performance. ABSTRACT: It is well established that hypoxia impairs cognitive function; however, the physiological mechanisms responsible for these effects have received relatively little attention. This study examined the effects of graded reductions in fraction of inspired oxygen ( FIO2 ) on oxygen saturation ( SpO2 ), cerebral oxygenation, cardiorespiratory variables, activity of the sympathoadrenal system (adrenaline, noradrenaline) and hypothalamic-pituitary-adrenal axis (cortisol, copeptin), and cognitive performance. Twelve healthy males [mean (SD), age: 22 (4) years, height: 178 (5) cm, mass: 75 (9) kg, FEV1 /FVC ratio: 85 (5)%] completed a four-task battery of cognitive tests to examine inhibition, selective attention (Eriksen flanker), executive function (n-back) and simple and choice reaction time (Deary-Liewald). Tests were completed before and following 60 min of exposure to FIO2 0.2093, 0.17, 0.145 and 0.12. Following 60 min of exposure, response accuracy in the n-back task was significantly reduced in FIO2 0.12 compared to baseline [82 (9) vs. 93 (5)%; P < 0.001] and compared to all other conditions at the same time point [ FIO2 0.2093: 92 (3)%; FIO2 0.17: 91 (6)%; FIO2 0.145: 85 (10)%; FIO2 12: 82 (9)%; all P < 0.05]. The performance of the other tasks was maintained. Δaccuracy and Δreaction time of the n-back task was correlated with both Δ SpO2 [r(9) = 0.66, P < 0.001 and r(9) = -0.36, P = 0.037, respectively] and Δcerebral oxygenation [r(7) = 0.55, P < 0.001 and r(7) = -0.38, P = 0.045, respectively]. Plasma adrenaline, noradrenaline, cortisol and copeptin were not significantly elevated in any condition or correlated with any of the tests of cognitive performance. These findings suggest that reductions in peripheral oxygen saturation and cerebral oxygenation, and not increased activity of the sympathoadrenal system and hypothalamic-pituitary-adrenal axis, as previously speculated, are responsible for a decrease in cognitive performance during normobaric hypoxia.

Effects of physical activity interventions on cognitive and academic performance in children and adolescents: a novel combination of a systematic review and recommendations from an expert panel.

OBJECTIVE: To summarise the current evidence on the effects of physical activity (PA) interventions on cognitive and academic performance in children, and formulate research priorities and recommendations. DESIGN: Systematic review (following PRISMA guidelines) with a methodological quality assessment and an international expert panel. We based the evaluation of the consistency of the scientific evidence on the findings reported in studies rated as of high methodological quality. DATA SOURCES: PubMed, PsycINFO, Cochrane Central, Web of Science, ERIC, and SPORTDiscus. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: PA-intervention studies in children with at least one cognitive or academic performance assessment. RESULTS: Eleven (19%) of 58 included intervention studies received a high-quality rating for methodological quality: four assessed effects of PA interventions on cognitive performance, six assessed effects on academic performance, and one on both. All high-quality studies contrasted the effects of additional/adapted PA activities with regular curriculum activities. For cognitive performance 10 of 21 (48%) constructs analysed showed statistically significant beneficial intervention effects of PA, while for academic performance, 15 of 25 (60%) analyses found a significant beneficial effect of PA. Across all five studies assessing PA effects on mathematics, beneficial effects were reported in six out of seven (86%) outcomes. Experts put forward 46 research questions. The most pressing research priority cluster concerned the causality of the relationship between PA and cognitive/academic performance. The remaining clusters pertained to PA characteristics, moderators and mechanisms governing the 'PA-performance' relationship and miscellaneous topics. CONCLUSION: There is currently inconclusive evidence for the beneficial effects of PA interventions on cognitive and overall academic performance in children. We conclude that there is strong evidence for beneficial effects of PA on maths performance.The expert panel confirmed that more 'high-quality' research is warranted. By prioritising the most important research questions and formulating recommendations we aim to guide researchers in generating high-quality evidence. Our recommendations focus on adequate control groups and sample size, the use of valid and reliable measurement instruments for physical activity and cognitive performance, measurement of compliance and data analysis. PROSPERO REGISTRATION NUMBER: CRD42017082505.

Central fatigue theory and endurance exercise: Toward an interoceptive model.

We propose a model of exercise-induced central fatigue based on interoception and motivation. Predictions of the expected sensory feedback are fed forward by the dorsolateral (DL) prefrontal cortex (PFC) to the anterior insula cortex (AIC). During exercise, the AIC receives feedback from lamina Ⅰ lateral spinothalamic and nucleus tractus solitarii medullothalamic pathways. The feedback is compared to the predictions in order to generate a current awareness state, which is forwarded to the anterior cingulate cortex (ACC), ventromedial (VM)PFC and lateral (L)PFC. The LPFC integrates the information and makes a decision as to whether to continue or stop. The decision is dependent upon interaction with the substantia nigra pars compacta and ventral tegmental area dopamine (DA), and locus coeruleus (LC)-norepinephrine (NE) systems. Phasic activation of DA and NE neurons appears to be necessary for maintenance of goal-related action but the VMPFC and ACC, which project to the LC, induce tonic NE activity when the rewards are thought to be not worth the cost thus fatigue is perceived.

Acute Anxiety Predicts Components of the Cold Shock Response on Cold Water Immersion: Toward an Integrated Psychophysiological Model of Acute Cold Water Survival.

Introduction: Drowning is a leading cause of accidental death. In cold-water, sudden skin cooling triggers the life-threatening cold shock response (CSR). The CSR comprises tachycardia, peripheral vasoconstriction, hypertension, inspiratory gasp, and hyperventilation with the hyperventilatory component inducing hypocapnia and increasing risk of aspirating water to the lungs. Some CSR components can be reduced by habituation (i.e., reduced response to stimulus of same magnitude) induced by 3-5 short cold-water immersions (CWI). However, high levels of acute anxiety, a plausible emotion on CWI: magnifies the CSR in unhabituated participants, reverses habituated components of the CSR and prevents/delays habituation when high levels of anxiety are experienced concurrent to immersions suggesting anxiety is integral to the CSR. Purpose: To examine the predictive relationship that prior ratings of acute anxiety have with the CSR. Secondly, to examine whether anxiety ratings correlated with components of the CSR during immersion before and after induction of habituation. Methods: Forty-eight unhabituated participants completed one (CON1) 7-min immersion in to cold water (15°C). Of that cohort, twenty-five completed four further CWIs that would ordinarily induce CSR habituation. They then completed two counter-balanced immersions where anxiety levels were increased (CWI-ANX) or were not manipulated (CON2). Acute anxiety and the cardiorespiratory responses (cardiac frequency [fc], respiratory frequency [fR], tidal volume [VT ], minute ventilation [ E]) were measured. Multiple regression was used to identify components of the CSR from the most life-threatening period of immersion (1st minute) predicted by the anxiety rating prior to immersion. Relationships between anxiety rating and CSR components during immersion were assessed by correlation. Results: Anxiety rating predicted the fc component of the CSR in unhabituated participants (CON1; p < 0.05, r = 0.536, r2= 0.190). After habituation immersions (i.e., cohort 2), anxiety rating predicted the fR component of the CSR when anxiety levels were lowered (CON2; p < 0.05, r = 0.566, r2= 0.320) but predicted the fc component of the CSR (p < 0.05, r = 0.518, r2= 0.197) when anxiety was increased suggesting different drivers of the CSR when anxiety levels were manipulated; correlation data supported these relationships. Discussion: Acute anxiety is integral to the CSR before and after habituation. We offer a new integrated model including neuroanatomical, perceptual and attentional components of the CSR to explain these data.

Cognitive fatigue effects on physical performance: A systematic review and meta-analysis.

Recent research has examined the effect that undertaking a cognitively fatiguing task for ≤90 min has on subsequent physical performance. Cognitive fatigue is claimed to affect subsequent physical performance by inducing energy depletion in the brain, depletion of brain catecholamine neurotransmitters or changes in motivation. Observation of the psychophysiology and neurochemistry literature questions the ability of 90 min' cognitive activity to deplete energy or catecholamine resources. The purpose of this study, therefore, was to examine the evidence for cognitive fatigue having an effect on subsequent physical performance. A systematic, meta-analytic review was undertaken. We found a small but significant pooled effect size based on comparison between physical performance post-cognitive fatigue compared to post-control (g = -0.27, SE = -0.12, 95% CI -0.49 to -0.04, Z(10) = -2.283, p < 0.05). However, the results were not heterogenous (Q(10) = 2.789, p > 0.10, Τ2 < 0.001), suggesting that the pooled effect size does not amount to a real effect and differences are due to random error. No publication bias was evident (Kendall's τ = -0.07, p > 0.05). Thus, the results are somewhat contradictory. The pooled effect size shows a small but significant negative effect of cognitive fatigue, however tests of heterogeneity show that the results are due to random error. Future research should use neuroscientific tests to ensure that cognitive fatigue has been achieved.

The Effect of Head-to-Head Competition on Behavioural Thermoregulation, Thermophysiological Strain and Performance During Exercise in the Heat.

BACKGROUND: It has been suggested that pacing is a thermoregulatory behaviour. We investigated the effect of competition on pacing, performance and thermophysiological strain during exercise in the heat and the psychological factors mediating competition effects. METHOD: Eighteen males (maximum oxygen uptake [V O 2max] 3.69 [0.44] L min-1) undertook a preliminary 20-km cool (wet-bulb globe temperature [WBGT] 12 °C) cycling time trial (TT) and three experimental 20-km trials (balanced order): (i) cool TT (CoolSolo); (ii) hot (WBGT 26 °C) TT (HotSolo); (iii) hot head-to-head competition (HotH2H). During TTs, an avatar of the participant's performance was visible. During HotH2H, participants believed they were competing against another participant, but the competitor's avatar replicated their own preliminary (cool) TT. RESULTS: TTs (min:sec [SD]) slowed with increased ambient temperature [CoolSolo 35:31 (2:11) versus HotSolo 36:10 (2:26); p = 0.011]. This effect was negated by competition; performances were not different between HotH2H [35:17 (1:52)] and CoolSolo (p = 0.160) and were quicker in HotH2H versus HotSolo (p = 0.001). End-exercise rectal temperature, mean body temperature and physiological strain index were (p < 0.05) higher in HotH2H than either solo condition. Despite faster performance and greater thermophysiological strain, rating of perceived exertion (RPE), thermal comfort and sensation, and perceptual strain index were not different between HotH2H and HotSolo. The difference in end-exercise rectal temperature between HotH2H and HotSolo was related to pre-exercise anticipatory heart rate response (r = 0.608, p = 0.010) and participants' propensity for deliberate risk-taking (B = 0.12, p < 0.001), whereas self-reported resilience predicted change in performance times between HotH2H versus HotSolo (B = - 9.40, p = 0.010). CONCLUSION: Competition changes the relationship between perceived and actual thermophysiological state, altering behavioural thermoregulation and increasing thermophysiological strain; this could increase heat-illness risk. Psychophysiological and psychological measures may identify susceptible individuals.

Effect of acute hypoxia on cognition: A systematic review and meta-regression analysis.

A systematic meta-regression analysis of the effects of acute hypoxia on the performance of central executive and non-executive tasks, and the effects of the moderating variables, arterial partial pressure of oxygen (PaO2) and hypobaric versus normobaric hypoxia, was undertaken. Studies were included if they were performed on healthy humans; within-subject design was used; data were reported giving the PaO2 or that allowed the PaO2 to be estimated (e.g. arterial oxygen saturation and/or altitude); and the duration of being in a hypoxic state prior to cognitive testing was ≤6days. Twenty-two experiments met the criteria for inclusion and demonstrated a moderate, negative mean effect size (g=-0.49, 95% CI -0.64 to -0.34, p<0.001). There were no significant differences between central executive and non-executive, perception/attention and short-term memory, tasks. Low (35-60mmHg) PaO2 was the key predictor of cognitive performance (R2=0.45, p<0.001) and this was independent of whether the exposure was in hypobaric hypoxic or normobaric hypoxic conditions.

Developing the catecholamines hypothesis for the acute exercise-cognition interaction in humans: Lessons from animal studies.

The catecholamines hypothesis for the acute exercise-cognition interaction in humans fails to adequately explain the interaction between peripherally circulating catecholamines and brain concentrations; how different exercise intensities×durations affect different cognitive tasks; and how brain catecholamines, glucocorticoids, BDNF and 5-hydroxytryptamine interact. A review of the animal literature was able to clarify many of the issues. Rodent studies showed that facilitation of cognition during short to moderate duration (SMD), moderate exercise could be accounted for by activation of the locus coeruleus via feedback from stretch reflexes, baroreceptors and, post-catecholamines threshold, ß-adrenoceptors on the vagus nerve. SMD, moderate exercise facilitates all types of task by stimulation of the reticular system by norepinephrine (NE) but central executive tasks are further facilitated by activation of α2A-adrenoceptors and D1-dopaminergic receptors in the prefrontal cortex, which increases the signal to 'noise' ratio. During long-duration, moderate exercise and heavy exercise, brain concentrations of glucocorticoids and 5-hydroxytryptamine, the latter in moderate exercise only, also increase. This further increases catecholamines release. This results in increased activation of D1-receptors and α1-adrenoceptors, in the prefrontal cortex, which dampens all neural activity, thus inhibiting central executive performance. However, activation of ß- and α1-adrenoceptors can positively affect signal detection in the sensory cortices, hence performance of perception/attention and autonomous tasks can be facilitated. Animal studies also show that during long-duration, moderate exercise and heavy exercise, NE activation of ß-adrenoceptors releases cAMP, which modulates the signaling and trafficking of the BDNF receptor Trk B, which facilitates long-term potentiation.