Hypoxia has the potential to impair cognitive function; however, it is still uncertain which cognitive domains are adversely affected. We examined the effects of acute hypoxia (∼7 h) on central executive (Go/No-Go) and non-executive (memory) tasks and the extent to which impairment was potentially related to regional cerebral blood flow and oxygen delivery (CDO2 ). Twelve male participants performed cognitive tasks following 0, 2, 4 and 6 h of passive exposure to both normoxia and hypoxia (12% O2 ), in a randomized block cross-over single-blinded design. Middle cerebral artery (MCA) and posterior cerebral artery (PCA) blood velocities and corresponding CDO2 were determined using bilateral transcranial Doppler ultrasound. In hypoxia, MCA DO2 was reduced during the Go/No-Go task (P = 0.010 vs. normoxia, main effect), and PCA DO2 was attenuated during memorization (P = 0.005 vs. normoxia) and recall components (P = 0.002 vs. normoxia) in the memory task. The accuracy of the memory task was also impaired in hypoxia (P = 0.049 vs. normoxia). In contrast, hypoxia failed to alter reaction time (P = 0.19 vs. normoxia) or accuracy (P = 0.20 vs. normoxia) during the Go/No-Go task, indicating that selective attention and response inhibition were preserved. Hypoxia did not affect cerebral blood flow or corresponding CDO2 responses to cognitive activity (P > 0.05 vs. normoxia). Collectively, these findings highlight the differential sensitivity of cognitive domains, with memory being selectively vulnerable in hypoxia. NEW FINDINGS: What is the central question of this study? We sought to examine the effects of acute hypoxia on central executive (selective attention and response inhibition) and non-executive (memory) performance and the extent to which impairments are potentially related to reductions in regional cerebral blood flow and oxygen delivery. What is the main finding and its importance? Memory was impaired in acute hypoxia, and this was accompanied by a selective reduction in posterior cerebral artery oxygen delivery. In contrast, selective attention and response inhibition remained well preserved. These findings suggest that memory is selectively vulnerable to hypoxia.

Although the ergogenic effects of 3–6 mg/kg caffeine are widely accepted, the efficacy of low doses of caffeine has been discussed. However, it is unclear whether the ergogenic effects of caffeine on jump performance are dose responsive in a wide range of doses. This study aimed to examine the effect of very low (1 mg/kg) to moderate doses of caffeine, including commonly utilized ergogenic doses (i.e., 3 and 6 mg/kg), on vertical jump performance. A total of 32 well-trained collegiate sprinters and jumpers performed countermovement jumps and squat jumps three times each in a double-blind, counterbalanced, randomized, crossover design. Participants ingested a placebo or 1, 3, or 6 mg/kg caffeine 60 min before jumping. Compared with the placebo, 6 mg/kg caffeine significantly enhanced countermovement jump (p < .001) and squat jump (p = .012) heights; furthermore, 1 and 3 mg/kg of caffeine also significantly increased countermovement jump height (1 mg/kg: p = .002, 3 mg/kg: p < .001) but not squat jump height (1 mg/kg: p = .436, 3 mg/kg: p = .054). There were no significant differences among all caffeine doses in both jumps (all p > .05). In conclusion, even at a dose as low as 1 mg/kg, caffeine improved vertical jump performance in a dose-independent manner. This study provides new insight into the applicability and feasibility of 1 mg/kg caffeine as a safe and effective ergogenic strategy for jump performance.

New Findings: What is the central question of this study? What are the molecular, cerebrovascular and cognitive biomarkers of retired rugby union players with concussion history? What is the main finding and its importance? Retired rugby players compared with matched controls exhibited lower systemic nitric oxide bioavailability accompanied by lower middle cerebral artery velocity and mild cognitive impairment. Retired rugby players are more susceptible to accelerated cognitive decline. Abstract: Following retirement from sport, the chronic consequences of prior-recurrent contact are evident and retired rugby union players may be especially prone to accelerated cognitive decline. The present study sought to integrate molecular, cerebrovascular and cognitive biomarkers in retired rugby players with concussion history. Twenty retired rugby players aged 64 ± 5 years with three (interquartile range (IQR), 3) concussions incurred over 22 (IQR, 6) years were compared to 21 sex-, age-, cardiorespiratory fitness- and education-matched controls with no prior concussion history. Concussion symptoms and severity were assessed using the Sport Concussion Assessment Tool. Plasma/serum nitric oxide (NO) metabolites (reductive ozone-based chemiluminescence), neuron specific enolase, glial fibrillary acidic protein and neurofilament light-chain (ELISA and single molecule array) were assessed. Middle cerebral artery blood velocity (MCAv, doppler ultrasound) and reactivity to hyper/hypocapnia ((Figure presented.) / (Figure presented.)) were assessed. Cognition was determined using the Grooved Pegboard Test and Montreal Cognitive Assessment. Players exhibited persistent neurological symptoms of concussion (U = 109(41), P = 0.007), with increased severity compared to controls (U = 77(41), P < 0.001). Lower total NO bioactivity (U = 135(41), P = 0.049) and lower basal MCAv were apparent in players (F2,39 = 9.344, P = 0.004). This was accompanied by mild cognitive impairment (P = 0.020, 95% CI, −3.95 to −0.34), including impaired fine-motor coordination (U = 141(41), P = 0.021). Retired rugby union players with history of multiple concussions may be characterised by impaired molecular, cerebral haemodynamic and cognitive function compared to non-concussed, non-contact controls.

New Findings: What is the central question of this study? High-intensity interval exercise (HIIE) is recommended for its favourable haemodynamic stimulation, but excessive haemodynamic fluctuations may stress the brain: is the cerebral vasculature protected against exaggerated systemic blood flow fluctuation during HIIE? What is the main finding and its importance? Time- and frequency-domain indices of aortic–cerebral pulsatile transition were lowered during HIIE. The findings suggest that the arterial system to the cerebral vasculature may attenuate pulsatile transition during HIIE as a defence mechanism against pulsatile fluctuation for the cerebral vasculature. Abstract: High-intensity interval exercise (HIIE) is recommended because it provides favourable haemodynamic stimulation, but excessive haemodynamic fluctuations may be an adverse impact on the brain. We tested whether the cerebral vasculature is protected against systemic blood flow fluctuation during HIIE. Fourteen healthy men (age 24 ± 2 years) underwent four 4-min exercises at 80–90% of maximal workload (Wmax) interspaced by 3-min active rest at 50–60% Wmax. Transcranial Doppler measured middle cerebral artery blood velocity (CBV). Systemic haemodynamics (Modelflow) and aortic pressure (AoP, general transfer function) were estimated from an invasively recorded brachial arterial pressure waveform. Using transfer function analysis, gain and phase between AoP and CBV (0.39–10.0 Hz) were calculated. Stroke volume, aortic pulse pressure and pulsatile CBV increased during exercise (time effect: P < 0.0001 for all), but a time-domain index of aortic–cerebral pulsatile transition (pulsatile CBV/pulsatile AoP) decreased throughout the exercise bouts (time effect: P < 0.0001). Furthermore, transfer function gain reduced, and phase increased throughout the exercise bouts (time effect: P < 0.0001 for both), suggesting the attenuation and delay of pulsatile transition. The cerebral vascular conductance index (mean CBV/mean arterial pressure; time effect: P = 0.296), an inverse index of cerebral vascular tone, did not change even though systemic vascular conductance increased during exercise (time effect: P < 0.0001). The arterial system to the cerebral vasculature may attenuate pulsatile transition during HIIE as a defence mechanism against pulsatile fluctuation for the cerebral vasculature.

Abstract: High-altitude (HA) hypoxia may alter the structural–functional integrity of the neurovascular unit (NVU). Herein, we compared male lowlanders (n = 9) at sea level (SL) and after 14 days acclimatization to 4300 m (chronic HA) in Cerro de Pasco (CdP), Péru (HA), against sex-, age- and body mass index-matched healthy highlanders (n = 9) native to CdP (lifelong HA). Venous blood was assayed for serum proteins reflecting NVU integrity, in addition to free radicals and nitric oxide (NO). Regional cerebral blood flow (CBF) was examined in conjunction with cerebral substrate delivery, dynamic cerebral autoregulation (dCA), cerebrovascular reactivity to carbon dioxide (CVRCO2) and neurovascular coupling (NVC). Psychomotor tests were employed to examine cognitive function. Compared to lowlanders at SL, highlanders exhibited elevated basal plasma and red blood cell NO bioavailability, improved anterior and posterior dCA, elevated anterior CVRCO2 and preserved cerebral substrate delivery, NVC and cognition. In highlanders, S100B, neurofilament light-chain (NF-L) and T-tau were consistently lower and cognition comparable to lowlanders following chronic-HA. These findings highlight novel integrated adaptations towards regulation of the NVU in highlanders that may represent a neuroprotective phenotype underpinning successful adaptation to the lifelong stress of HA hypoxia. (Figure presented.). Key points: High-altitude (HA) hypoxia has the potential to alter the structural–functional integrity of the neurovascular unit (NVU) in humans. For the first time, we examined to what extent chronic and lifelong hypoxia impacts multimodal biomarkers reflecting NVU structure and function in lowlanders and native Andean highlanders. Despite lowlanders presenting with a reduction in systemic oxidative–nitrosative stress and maintained cerebral bioenergetics and cerebrovascular function during chronic hypoxia, there was evidence for increased axonal injury and cognitive impairment. Compared to lowlanders at sea level, highlanders exhibited elevated vascular NO bioavailability, improved dynamic regulatory capacity and cerebrovascular reactivity, comparable cerebral substrate delivery and neurovascular coupling, and maintained cognition. Unlike lowlanders following chronic HA, highlanders presented with lower concentrations of S100B, neurofilament light chain and total tau. These findings highlight novel integrated adaptations towards the regulation of the NVU in highlanders that may represent a neuroprotective phenotype underpinning successful adaptation to the lifelong stress of HA hypoxia.

Purpose No study has assessed the acute effect of caffeine supplementation on 100-m sprint running in athletics and caffeine's net ergogenicity on 100-m sprint running remains unclear. We investigated the acute effects of caffeine supplementation on 100-m sprint running performance in a field test. Methods Thirteen male collegiate sprinters were subjected to 100-m sprint running time trials (TT) after the ingestion of 6 mg·kg-1 body weight caffeine or placebo supplementation in a double-blind, counterbalanced, randomized, and crossover design. Sprint velocity was measured with a laser system, and sprint time was calculated from the data in which the effects of environmental factors that would act as confounding factors on sprint time during TT were eliminated. Results The corrected 100-m sprint time was significantly shortened by 0.14 s with caffeine supplementation compared with placebo (placebo: 11.40 ± 0.39 s, caffeine: 11.26 ± 0.33 s; P = 0.007, g = -0.33). The corrected sprint time up to 60 m during TT was also significantly shorter with caffeine supplementation than with placebo (P = 0.002). Furthermore, the mean sprint velocity for splits of 0-10 and 10-20 m was significantly increased by caffeine supplementation (all P < 0.05). Conclusions Acute caffeine supplementation enhanced the corrected 100-m sprint time by improving the sprint performance in the first 60 m after more explosive acceleration in the early stage of the acceleration phase. Thus, for the first time, we directly demonstrated caffeine's ergogenicity on 100-m sprint performance in athletics.

The speed and accuracy of decision-making (i.e., executive function (EF) domains) is an integral factor in many sports. At rest, prolonged cognitive load (pCL) impairs reaction time (RT). In contrast, exercise improves RT and EF. We hypothesized that RT and EF during exercise would be diminished by prolonged ‘dual tasking’ as a consequence of pCL. To test the hypothesis, twenty healthy male participants performed four conditions [resting control (Rest), pCL only (pCLRest), exercise only (EX), and pCL + exercise (pCLEX)] in a randomized-crossover design. Both exercise conditions utilized a 50-min cycling exercise protocol (60% VO2 peak) and the pCL was achieved via a 50-min colour-word Stroop task (CWST). Compared with Rest, pCLRest caused a slowed CWST RT (P < 0.05) and a large SD (i.e., intraindividual variability) of CWST RT (P < 0.01). Similarly, compared with EX, the slowed CWST RT (P < 0.05) and large SD of CWST RT (P < 0.01) were also observed in pCLEX. Whereas the reverse-Stroop interference was not affected in pCLRest (P = 0.46), it was larger (i.e., declined EF) in pCLEX than EX condition (P < 0.05). These observations provide evidence that the effort of pCL impairs RT and EF even during exercise.

Emergent evidence suggests that cyclic intermittent hypoxia increases cerebral arterial shear rate and endothelial function, whereas continuous exposure decreases anterior cerebral oxygen (O2) delivery. To examine to what extent continuous hypoxia impacts cerebral shear rate, cerebral endothelial function, and consequent cerebral O2 delivery (CDO2), eight healthy males were randomly assigned single-blind to 7 h passive exposure to both normoxia (21% O2) and hypoxia (12% O2). Blood flow in the brachial and internal carotid arteries were determined using Duplex ultrasound and included the combined assessment of systemic and cerebral endothelium-dependent flow-mediated dilatation. Systemic (brachial artery) flow-mediated dilatation was consistently lower during hypoxia (P = 0.013 vs. normoxia), whereas cerebral flow-mediated dilation remained preserved (P = 0.927 vs. normoxia) despite a reduction in internal carotid artery antegrade shear rate (P = 0.002 vs. normoxia) and CDO2 (P < 0.001 vs. normoxia). Collectively, these findings indicate that the reduction in CDO2 appears to be independent of cerebral endothelial function and contrasts with that observed during cyclic intermittent hypoxia, highlighting the regulatory importance of (hypoxia) dose duration and flow/shear rate phenotype.

Recurrent contact and concussion in rugby union remains a significant public health concern given the potential increased risk of neurodegeneration in later life. This study determined to what extent prior-recurrent contact impacts molecular-hemodynamic biomarkers underpinning cognition in current professional rugby union players with a history of concussion. Measurements were performed in 20 professional rugby union players with an average of 16 (interquartile range [IQR] 13–19) years playing history reporting 3 (IQR 1–4) concussions. They were compared to 17 sex-age-physical activity-and education-matched non-contact controls with no prior history of self-reported concussion. Venous blood was assayed directly for the ascorbate free radical (A•− electron paramagnetic resonance spectroscopy) nitric oxide metabolites (NO reductive ozone-based chemiluminescence) and select biomarkers of neurovascular unit integrity (NVU chemiluminescence/ELISA). Middle cerebral artery blood flow velocity (MCAv doppler ultrasound) was employed to determine basal perfusion and cerebrovascular reactivity (CVR) to hyper/hypocapnia ((Formula presented.)). Cognition was assessed by neuropsychometric testing. Elevated systemic oxidative-nitrosative stress was confirmed in the players through increased A•− (p < 0.001) and suppression of NO bioavailability (p < 0.001). This was accompanied by a lower CVR range ((Formula presented.); p = 0.045) elevation in neurofilament light-chain (p = 0.010) and frontotemporal impairments in immediate-memory (p = 0.001) delayed-recall (p = 0.048) and fine-motor coordination (p < 0.001). Accelerated cognitive decline subsequent to prior-recurrent contact and concussion history is associated with a free radical-mediated suppression of CVR and neuronal injury providing important mechanistic insight that may help better inform clinical management.

It has been well established in epidemiological studies and randomized controlled trials that habitual exercise is beneficial for brain health, such as cognition and mental health. Generally, it may be reasonable to say that the physiological benefits of acute exercise can prevent brain disorders in late life if such exercise is habitually/chronically conducted. However, the mechanisms of improvement in brain function via chronic exercise remain incompletely understood because such mechanisms are assumed to be multifactorial, such as the adaptation of repeated acute exercise. This review postulates that cerebral metabolism may be an important physiological factor that determines brain function. Among metabolites, the provision of lactate to meet elevated neural activity and regulate the cerebrovascular system and redox states in response to exercise may be responsible for exercise-enhanced brain health. Here, we summarize the current knowledge regarding the influence of exercise on brain health, particularly cognitive performance, with the underlying mechanisms by means of lactate. Regarding the influence of chronic exercise on brain function, the relevance of exercise intensity and modality, particularly high-intensity interval exercise, is acknowledged to induce "metabolic myokine" (i.e., lactate) for brain health.

Football players are at increased risk of neurodegeneration, the likely consequence of repetitive mechanical trauma caused by heading the ball. However, to what extent a history of heading the ball affects cerebral blood flow (CBF) regulation and its potential relationship to cognitive impairment is unknown. To address this, we recruited 16 concussion-free male amateur football players (age: 25 ± 6 y) with a history of heading the ball (18 ± 6 y) and 18 sex, age, education, and activity-matched controls with no prior history of contact sport participation or concussion. Cerebral perfusion was measured at rest and in response to both hyper/hypocapnia to determine cerebrovascular reactivity to carbon dioxide (CVRCO2HYPER/HYPO) using transcranial Doppler ultrasound and capnography, with the sum reflecting the cerebral vasomotor range. Cognition and visuomotor coordination were assessed using the Montreal cognitive assessment (MoCA) and the Grooved Pegboard Dexterity Test (GPD), respectively. While no differences in cerebral perfusion were observed (p = 0.938), CVRCO2HYPER/HYPO (p = 0.038/p = 0.025), cerebral vasomotor range (p = 0.002), MoCA (p = 0.027), and GPD performance (dominant hand, P ≤ 0.001) were consistently lower in the players compared to controls. These findings are the first to demonstrate that CBF regulation and cognition are collectively impaired in male football players with history of heading the ball, which may contribute to neurodegeneration.

New Findings: What is the central question of this study? How does recurrent contact incurred across a season of professional rugby union impact molecular, cerebrovascular and cognitive function? What is the main findings and its importance? A single season of professional rugby union increases systemic oxidative–nitrosative stress (OXNOS) confirmed by a free radical-mediated suppression in nitric oxide bioavailability. Forwards encountered a higher frequency of contact events compared to backs, exhibiting elevated OXNOS and lower cerebrovascular function and cognition. Collectively, these findings provide mechanistic insight into the possible cause of reduced cognition in rugby union subsequent to impairment in the redox regulation of cerebrovascular function. Abstract: Contact events in rugby union remain a public health concern. We determined the molecular, cerebrovascular and cognitive consequences of contact events during a season of professional rugby. Twenty-one male players aged 25 (mean) ± 4 (SD) years were recruited from a professional rugby team comprising forwards (n = 13) and backs (n = 8). Data were collected across the season. Pre- and post-season, venous blood was assayed for the ascorbate free radical (A•–, electron paramagnetic resonance spectroscopy) and nitric oxide (NO, reductive ozone-based chemiluminescence) to quantify oxidative–nitrosative stress (OXNOS). Middle cerebral artery velocity (MCAv, Doppler ultrasound) was measured to assess cerebrovascular reactivity (CVR), and cognition was assessed using the Montreal Cognitive Assessment (MoCA). Notational analysis determined contact events over the season. Forwards incurred more collisions (Mean difference [MD] 7.49; 95% CI, 2.58–12.40; P = 0.005), tackles (MD 3.49; 95% CI, 0.42–6.56; P = 0.028) and jackals (MD 2.21; 95% CI, 0.18–4.24; P = 0.034). Forwards suffered five concussions while backs suffered one concussion. An increase in systemic OXNOS, confirmed by elevated A•– (F2,19 = 10.589, P = 0.004) and corresponding suppression of NO bioavailability (F2,19 = 11.492, P = 0.003) was apparent in forwards and backs across the season. This was accompanied by a reduction in cerebral oxygen delivery ((Formula presented.), F2,19 = 9.440, P = 0.006) and cognition (F2,19 = 4.813, P = 0.041). Forwards exhibited a greater decline in the cerebrovascular reactivity range to changes in PETCO2 ((Formula presented.) compared to backs (MD 1.378; 95% CI, 0.74–2.02; P < 0.001).

NEW FINDINGS: What is the central question of this study? To what extent do hypoxia-induced changes in the peripheral and central respiratory chemoreflex modulate anterior and posterior cerebral oxygen delivery, with corresponding implications for susceptibility to acute mountain sickness? What is the main finding and its importance? We provide evidence for site-specific regulation of cerebral blood flow in hypoxia that preserves oxygen delivery in the posterior but not the anterior cerebral circulation, with minimal contribution from the central respiratory chemoreflex. External carotid artery vasodilatation might prove to be an alternative haemodynamic risk factor that predisposes to acute mountain sickness. ABSTRACT: The aim of the present study was to determine the extent to which hypoxia-induced changes in the peripheral and central respiratory chemoreflex modulate anterior and posterior cerebral blood flow (CBF) and oxygen delivery (CDO2 ), with corresponding implications for the pathophysiology of the neurological syndrome, acute mountain sickness (AMS). Eight healthy men were randomly assigned single blind to 7 h of passive exposure to both normoxia (21% O2 ) and hypoxia (12% O2 ). The peripheral and central respiratory chemoreflex, internal carotid artery, external carotid artery (ECA) and vertebral artery blood flow (duplex ultrasound) and AMS scores (questionnaires) were measured throughout. A reduction in internal carotid artery CDO2 was observed during hypoxia despite a compensatory elevation in perfusion. In contrast, vertebral artery and ECA CDO2 were preserved, and the former was attributable to a more marked increase in perfusion. Hypoxia was associated with progressive activation of the peripheral respiratory chemoreflex (P < 0.001), whereas the central respiratory chemoreflex remained unchanged (P > 0.05). Symptom severity in participants who developed clinical AMS was positively related to ECA blood flow (Lake Louise score, r = 0.546-0.709, P = 0.004-0.043; Environmental Symptoms Questionnaires-Cerebral symptoms score, r = 0.587-0.771, P = 0.001-0.027, n = 4). Collectively, these findings highlight the site-specific regulation of CBF in hypoxia that maintains CDO2 selectively in the posterior but not the anterior cerebral circulation, with minimal contribution from the central respiratory chemoreflex. Furthermore, ECA vasodilatation might represent a hitherto unexplored haemodynamic risk factor implicated in the pathophysiology of AMS.

This study compared the effects of low-intensity resistance exercise with slow movement and tonic force generation (ST-LRE) and high-intensity resistance exercise (HRE) on post-exercise improvements in cognitive inhibitory control (IC). Sixteen young males completed ST-LRE and HRE sessions in a crossover design. Bilateral knee extensor ST-LRE and HRE (8 repetitions/set, 6 sets) were performed with 50% of one-repetition maximum with slow contractile speed and 80% of one-repetition maximum with normal contractile speed, respectively. The IC was assessed using the color-word Stroop task at six time points: baseline, pre-exercise, immediate post-exercise, and every 10 min during the 30-min post-exercise recovery period. The blood lactate response throughout the experimental session did not differ between ST-LRE and HRE (condition × time interaction P = 0.396: e.g., mean ± standard error of the mean; 8.1 ± 0.5 vs. 8.1 ± 0.5 mM, respectively, immediately after exercise, P = 0.983, d = 0.00). Large-sized decreases in the reverse-Stroop interference scores, which represent improved IC, compared to those before exercise (i.e., baseline and pre-exercise) were observed throughout the 30 min post-exercise recovery period for both ST-LRE and HRE (decreasing rate ≥ 38.8 and 41.4%, respectively, all ds ≥ 0.95). The degree of post-exercise IC improvements was similar between the two protocols (condition × time interaction P = 0.998). These findings suggest that despite the application of a lower exercise load, ST-LRE improves post-exercise IC similarly to HRE, which may be due to the equivalent blood lactate response between the two protocols, in healthy young adults.

The length of rest interval between sets (i.e., inter-set rest interval) is an important variable for resistance exercise program. However, the impact of the inter-set rest interval on improvements in cognitive function following resistance exercise remains unknown. In this study, we compared the effect of short rest interval (SRI) vs. long rest interval (LRI) protocols on post-exercise cognitive inhibitory control (IC) improvements induced by low-intensity resistance exercise. Twenty healthy, young males completed both SRI and LRI sessions in a crossover design. The bilateral knee extensor low-intensity resistance exercise was programed for six sets with 10 repetitions per set using 40% of one-repetition maximum. The inter-set rest interval lengths for SRI and LRI protocols were set for 1 and 3min, respectively. The color-word Stroop task (CWST) was administrated at six time points: baseline, pre-exercise, immediate post-exercise, and every 10min during the 30-min post-exercise recovery period. The levels of blood lactate, which may be an important determinant for improving IC, throughout the 30-min post-exercise recovery period were significantly higher following SRI protocol than following LRI protocol (p=0.002 for interaction effect). In line with this result, large-sized decreases in the reverse-Stroop interference score, which represent improved IC, were observed immediately after SRI protocol (d=0.94 and 0.82, respectively, vs. baseline and pre-exercise) as opposed to the moderate-sized decreases immediately after LRI protocol (d=0.62 and 0.66, respectively, vs. baseline and pre-exercise). Moreover, significant decreases in the reverse-Stroop interference score were observed from 10 to 30min after SRI protocol (all ps<0.05 vs. baseline and/or pre-exercise), whereas no such decrease was observed after LRI protocol. Furthermore, the degree of decreases in the reverse-Stroop interference score throughout the 30-min post-exercise recovery period was significantly greater in SRI protocol than in LRI protocol (p=0.046 for interaction effect). We suggest that the SRI protocol is more useful in improving post-exercise IC, potentially via greater circulating lactate levels, compared to the LRI protocol. Therefore, the inter-set rest interval length may be an important variable for determining the degree of cognitive function improvements following resistance exercise in healthy young males.

We examined the acute impact of both low- and high-glycemic index (GI) breakfasts on plasma brain-derived neurotrophic factor (BDNF) and dynamic cerebral autoregulation (dCA) compared with breakfast omission. Ten healthy men (age 24 ± 1 yr) performed three trials in a randomized crossover order; omission and Low-GI (GI = 40) and High-GI (GI = 71) breakfast conditions. Middle cerebral artery velocity (transcranial Doppler ultrasonography) and arterial pressure (finger photoplethysmography) were continuously measured for 5 min before and 120 min following breakfast consumption to determine dCA using transfer function analysis. After these measurements of dCA, venous blood samples for the assessment of plasma BDNF were obtained. Moreover, blood glucose was measured before breakfast and every 30 min thereafter. The area under the curve of 2 h postprandial blood glucose in the High-GI trial was higher than the Low-GI trial (P < 0.01). The GI of the breakfast did not affect BDNF. In addition, both very-low (VLF) and low-frequency (LF) transfer function phase or gains were not changed during the omission trial. In contrast, LF gain (High-GI P < 0.05) and normalized gain (Low-GI P < 0.05) were decreased by both GI trials, while a decrease in VLF phase was observed in only the High-GI trial (P < 0.05). These findings indicate that breakfast consumption augmented dCA in the LF range but High-GI breakfast attenuated cerebral blood flow regulation against slow change (i.e., the VLF range) in arterial pressure. Thus we propose that breakfast and glycemic control may be an important strategy to optimize cerebrovascular health.

We previously determined that improvement in cognitive inhibitory control (IC) immediately after localized resistance exercise was greater for high-intensity resistance exercise (HRE) than for low-intensity resistance exercise (LRE). However, our previous study used the same total repetitions (i.e., same repetitions per set) between HRE and LRE; therefore, the difference in postexercise IC improvement might be due to a difference in work volume (i.e., intensity × total repetitions). In this study, we compared the effect of high-volume (HV)-LRE to that of volume-matched HRE on postexercise IC improvements. Twenty-two healthy, young males performed both HV-LRE and HRE in a crossover design. Exercise loads for HV-LRE and HRE were set at 35% and 70% of one-repetition maximum, respectively. The bilateral knee extension exercises for HV-LRE and HRE were programmed for six sets with 20 and 10 repetitions, respectively, per set. IC was measured using the color-word Stroop task (CWST) at six time points; baseline, pre-exercise, immediate postexercise, and every 10 min during the 30-min postexercise recovery period. The reverse-Stroop interference score decreased significantly immediately after HV-LRE and HRE compared with that before each exercise (decreasing rate >34 and >38%, respectively, vs. baseline and pre-exercise; all ps < .05), and the decreased score remained significant until 20 min after both protocols (decreasing rate >40 and >38%, respectively, vs. baseline and pre-exercise; all ps < .05). The degree of the postexercise IC improvements did not differ significantly between the two protocols. These findings suggest that HV-LRE improves IC in a similar manner to volume-matched HRE.

PURPOSE: Blood flow restriction (BFR) walking is recognized as a beneficial strategy for increasing skeletal muscle mass and strength. No study has examined the effect of BFR exercise on cognitive functions, including executive function (EF). In this study, we examined the effect of BFR walking on EF. METHODS: We performed two studies, at rest and exercise, with BFR or non-BFR (NBFR) in a crossover design. Sitting rest was performed for 15 min (study 1, n = 8). Exercise was programed at five sets of 2-min walking at 5 km/h with 1-min rest intervals (study 2, n = 16). The BFR condition was achieved using 200 mmHg pressure cuffs placed around the proximal region of the thighs. The NBFR condition involved no pressure cuffs. EF was assessed using the color-word Stroop task before and after each condition. RESULTS: In study 1, there were no significant effects on EF parameters for both BFR and NBFR conditions, suggesting that BFR alone does not improve EF. In study 2, incongruent reaction time shortened after BFR walking compared to that before walking (P = 0.001). Furthermore, the reverse-Stroop interference score decreased after BFR walking compared to that before walking (P < 0.001). CONCLUSION: These findings suggest that, even with a mild exercise, BFR walking improves EF independently of the effect of BFR alone or walking alone.

Females are more prone to cognitive decline, stroke and neurodegenerative disease, possibly due to more marked reductions in cerebral blood flow and cerebrovascular reactivity to CO2 (CVRCO2HYPER) in later life. To what extent regular exercise confers selective neuroprotection in females remains unestablished. To examine this, 73 adults were prospectively assigned to 1 of 4 groups based on sex (male, ♂ vs. female, ♀) and physical activity status (trained, ≥150 min of moderate-vigorous intensity aerobic exercise/week; n = 18♂ vs. 18♀ vs. untrained, no formal exercise; n = 18♂ vs. 19♀). Middle cerebral artery velocity (MCAv, transcranial Doppler ultrasound), mean arterial pressure (MAP, finger photoplethysmography) and end-tidal CO2 (capnography) were assessed at rest during normocapnea and hypercapnea (5% CO2) enabling CVRCO2HYPER to be assessed. Cerebrovascular resistance/conductance indices (CVRi/CVCi) were calculated as MAP/MCAv and MCAv/MAP. Maximal oxygen uptake (VO2MAX) was determined during incremental semi-recumbent cycling ergometry to volitional exhaustion. Despite having a lower VO2MAX, females were characterized by selective elevations in MCAv, CVRCO2HYPER and lower CVRi (P < 0.05), but the training responses were similar across sexes. Linear relationships were observed between VO2MAX and CVRCO2HYPER (pooled untrained and trained data; ♂ r = 0.70, ♀ r = 0.51; both P < 0.05) with a consistent elevation in the latter equivalent to ∼1.50%.mmHg-1 compared to males across the spectrum of cardiorespiratory fitness. These findings indicate that despite having comparatively lower levels of cardiorespiratory fitness, the neuroprotective benefits of regular exercise translate into females and may help combat cerebrovascular disease in later life.

INTRODUCTION: High-intensity interval exercise (HIIE) is more effective at increasing metabolic and cardiovascular health compared with moderate-intensity continuous exercise for patients with cardiovascular disease, but exhaustive high-intensity continuous exercise attenuates dynamic cerebral autoregulation (CA). This study assessed the effect of HIIE on dynamic CA. METHODS: Nine healthy men (age, 24 ± 3 yr; mean ± SD) warmed up at 50%-60% maximal workload (Wmax) for 5 min before HIIE including four 4-min bouts of exercise at 80%-90% Wmax interspaced by four 3-min bouts at 50% to 60% Wmax. Transcranial Doppler determined middle cerebral artery mean blood velocity (MCA Vmean), and brachial artery catheterization determined mean arterial pressure (MAP). Dynamic CA was evaluated by transfer function analysis of changes in MAP and MCA Vmean. RESULTS: The HIIE increased MAP (from 92 ± 9 to 104 ± 10 mm Hg; P < 0.0125), whereas MCA Vmean did not change. Transfer function phase increased and coherence decreased during HIIE (P < 0.0125 vs rest, respectively), whereas gain was unchanged. CONCLUSIONS: The results suggest that dynamic CA is unaffected during HIIE, indicating that the brain is protected from fluctuations in MAP. Thus, we propose that HIIE may be beneficial for brain-related health as maintenance of cerebral perfusion in contrast to high-intensity continuous exercise.

Acute aerobic exercise improves inhibitory control (IC). This improvement is often associated with increases in perceived exertion during exercise. However, listening to music during aerobic exercise mitigates an exercise-induced increase in perceived exertion. Thus, it is hypothesized that such effects of music may interfere with exercise-induced improvements in IC. To test this hypothesis, we examined the effect of music on post-exercise IC improvements that were induced by moderate-intensity exercise. Fifteen healthy young men performed cycle ergometer exercise with music or non-music. The exercise was performed using a moderate-intensity of 60% of VO2 peak for 30 min. The music condition was performed while listening to self-selected music. The non-music condition involved no music. To evaluate IC, the Stroop task was administered before exercise, immediately after exercise, and during the 30-min post-exercise recovery period. The rate of perceived exertion immediately before moderate-intensity exercise completed was significantly lower in music condition than in non-music condition. The IC significantly improved immediately after exercise and during the post-exercise recovery period compared to before exercise in both music and non-music conditions. The post-exercise IC improvements did not significantly differ between the two conditions. These findings indicate that self-selected music-induced mitigation of the increase in perceived exertion during moderate-intensity exercise dose not interfere with exercise-induced improvements in IC. Therefore, we suggest that listening to music may be a beneficial strategy in mitigating the increase in perceived exertion during aerobic exercise without decreasing the positive effects on IC.

High-intensity interval exercise (HIIE) improves cerebral executive function (EF), but the improvement in EF is attenuated after repeated HIIE, perhaps because of lower lactate availability for the brain. This investigation examined whether improved EF after exercise relates to brain lactate uptake. Fourteen healthy, male subjects performed 2HIIEprotocols separatedby 60min of rest.Blood sampleswere obtained fromthe right internal jugular venous bulb and from the brachial artery to determine arterial-venous differences across the brain for lactate (a-v difflactate), glucose (a-v diffglucose), oxygen (a-v diffoxygen), and brain-derived neurotrophic factor (BDNF
a-v diffBDNF). EF was evaluated by the color-word Stroop task. The first HIIE improved EF for 40 min, whereas the second HIIE improved EF only immediately after exercise. The a-v diffglucose was unchanged, whereas the a-v diffBDNF increased similarly after both HIIEs, and the a-v difflactate increased, but the increase was attenuated after the secondHIIE, compared with the firstHIIE (P &lt
0.05).The EF after HIIE correlatedwith the a-v difflactate (r2=0.62
P &lt
0.01). We propose that attenuated improvement in EF after repeated HIIE relates to reduced cerebral lactate metabolism and is, thereby, linked to systemic metabolism as an example of the lactate shuttle mechanism.

Objective Aerobic exercise is known to acutely improve cognitive functions, such as executive function (EF) and memory function (MF). Additionally, consumption of flavanol-rich cocoa has been reported to acutely improve cognitive function. The aim of this study was to determine whether high cocoa flavanol (CF
HCF) consumption would enhance exercise-induced improvement in cognitive function. To test this hypothesis, we examined the combined effects of HCF consumption and moderate-intensity exercise on EF and MF during postexercise recovery. Methods Ten healthy young men received either an HCF (563 mg of CF) or energy-matched low CF (LCF
38 mg of CF) beverage 70 min before exercise in a single-blind counterbalanced manner. The men then performed moderate-intensity cycling exercise at 60% of peak oxygen uptake for 30 min. The participants performed a color-word Stroop task and face-name matching task to evaluate EF and MF, respectively, during six time periods throughout the experimental session. Results EF significantly improved immediately after exercise compared with before exercise in both conditions. However, EF was higher after HCF consumption than after LCF consumption during all time periods because HCF consumption improved EF before exercise. In contrast, HCF consumption and moderate-intensity exercise did not improve MF throughout the experiment. Conclusion The present findings demonstrated that HCF consumption before moderate-intensity exercise could enhance exercise-induced improvement in EF, but not in MF. Therefore, we suggest that the combination of HCF consumption and aerobic exercise may be beneficial for improving EF.

The positive effect of acute resistance exercise on executive function, such as inhibitory control (IC), is poorly understood. Several previous studies have demonstrated this effect using whole-body resistance exercise. However, it remains unclear whether localized resistance exercise performed using only limited muscle groups could also acutely improve IC. Thus, the present study examined the effect of an acute bout of localized resistance exercise on IC. Twelve healthy men performed a color-word Stroop task (CWST) before and immediately after the experimental conditions, which consisted of 2 resistance exercises and a resting control (CON). Bilateral knee extension was used to create 2 resistance exercise conditions: light-intensity resistance exercise (LRE) and high-intensity resistance exercise (HRE) conditions, which were 40% and 80% of one-repetition maximum, respectively. The resistance exercise session was programmed for 6 sets with 10 repetitions per set. The CWST-measured IC was significantly improved immediately after both LRE and HRE, but it did not improve immediately after CON. However, the improved IC was significantly greater in HRE than in LRE. The present findings showed that IC could be rapidly improved by an acute bout of localized resistance exercise, especially with high-intensity. Therefore, we suggest that in addition to whole-body resistance exercise, localized resistance exercise performed using limited muscle groups may be sufficient for improving IC.

Purpose: The effect of exercise volume represented by exercise intensity and duration on postexercise executive function (EF) improvement remains unclear. In the present study, involving two volume-controlled evaluations, we aimed to compare acute exercise protocols with differing intensities and durations to establish an effective exercise protocol for improving EF. Methods: In study 1, 12 healthy male subjects performed cycle ergometer exercise, based on a low-intensity (LI) protocol for 20 min (LI20), moderate-intensity (MI) protocol for 20 min (MI20), and MI20 volume-matched LI protocol for 40 min (LI40). The exercise intensities for the LI and MI were set at 30% and 60% of peak oxygen consumption, respectively. In study 2, 15 healthy male subjects performed MI exercise for 10 min (MI10), MI20, and 40 min (MI40). To evaluate the EF, the color-word Stroop task was administrated before exercise, immediately after exercise, and during the 30-min postexercise recovery. Results: In study 1, postexercise EF improvement was sustained for a longer duration after MI20 than after LI40 and was sustained for a longer duration after LI40 than after LI20. In study 2, although there was no significant difference in post-MI exercise EF improvement, the magnitude of difference in the EF between preexercise and 30-min postexercise recovery period was moderately larger in MI40, but not in MI10 and MI20, indicating that the EF improvement during postexercise recovery could be sustained after MI40. Conclusion: The present findings showed that postexercise EF improvement could be prolonged after MI exercise with a moderate duration compared with volume-matched LI exercise with a longer duration. In addition, MI exercise with a relatively long duration may slightly prolong the postexercise EF improvement.

Arterial baroreflex function is important for blood pressure control during exercise, but its contribution to cardiovascular adjustments at the onset of cycling exercise remains unclear. Fifteen healthy male subjects (24 +/- 1 yr) performed 45-s trials of low- and moderate-intensity cycling, with carotid baroreceptor stimulation by neck suction at -60 Torr applied 0-5, 10-15, and 30-35 s after the onset of exercise. Cardiovascular responses to neck suction during cycling were compared with those obtained at rest. An attenuated reflex decrease in heart rate following neck suction was detected during moderate-intensity exercise, compared with the response at rest (P &lt; 0.05). Furthermore, compared with the reflex decrease in blood pressure elicited at rest, neck suction elicited an augmented decrease in blood pressure at 0-5 and 10-15 s during low- intensity exercise and in all periods during moderate-intensity exercise (P &lt; 0.05). The reflex depressor response at the onset of cycling was primarily mediated by an increase in the total vascular conductance. These findings evidence altered carotid baroreflex function during the first 35 s of cycling compared with rest, with attenuated bradycardic response, and augmented depressor response to carotid baroreceptor stimulation.

A single bout of aerobic exercise improves executive function (EF), but only for a short period. Compared with a single bout of aerobic exercise, we recently found that high-intensity interval exercise (HIIE) could maintain a longer improvement in EF. However, the mechanism underlying the effect of different exercise modes on the modifications of EF remains unclear. The purpose of the current investigation was to test our hypothesis that the amount of exercise-induced lactate production and its accumulation affects human brain function during and after exercise, thereby affecting post-exercise EF: Ten healthy male subjects performed cycle ergometer exercise. The HIIE protocol consisted of four 4-min bouts at 90% peak VO2 with a 3-min active recovery period at 60% peak VO2. The amount of lactate produced during exercise was manipulated by repeating the HIIE twice with a resting period of 60 min between the 1st HIIE and 2nd HIIE. To evaluate EF, a color-word Stroop task was performed, and reverse-Stroop interference scores were obtained. EF immediately after the 1st HIIE was significantly improved compared to that before exercise, and the improved EF was sustained during 40 min of the post-exercise recovery. However, for the 2nd HIIE, the improved EF was sustained for only 10 min of the post-exercise recovery period, despite the performance of the same exercise. In addition, during and following HIIE, the glucose and lactate accumulation induced by the 2nd HIIE was significantly lower than that induced by the 1st HIIE. Furthermore, there was an inverse relationship between lactate and EF by plotting the changes in lactate levels against changes in EF from pre-exercise during the late phase of post-exercise recovery. These findings suggested the possibility that repeated bouts of HIIE, which decreases lactate accumulation, may dampen the positive effect of exercise on EF during the post-exercise recovery. (C) 2016 The Authors. Published by Elsevier Inc.

Aerobic moderate-intensity continuous exercise (MCE) can improve executive function (EF) acutely, potentially through the activation of both physiological and psychological factors. Recently, high-intensity interval exercise (HIIE) has been reported to be more beneficial for physical adaptation than MCE. Factors for EF improvement can potentially be more enhanced by HIIE than by MCE; but the effects of HIIE on EF remain unknown. Therefore, we aimed to examine to what extent HIIE impacts post-exercise EF immediately after exercise and during post-exercise recovery, compared with traditional MCE. Twelve healthy male subjects performed cycle ergometer exercise based on either HIIE or MCE protocols in a randomized and counterbalanced order. The HIIE protocol consisted of four 4-min bouts at 90% of peak VO2 with 3-min active recovery at 60% of peak VO2. A volume matched MCE protocol was applied at 60% of peak VO2. To evaluate EF, a color-words Stroop task was performed pre- and post-exercise. Improvement in EF immediately after exercise was the same for the HIIE and MG protocols. However, the improvement of EF by HIIE was sustained during 30 min of post-exercise recovery, during which MCE returned to the pre-exercise level. The EF response in the post-exercise recovery was associated with changes in physiological and psychological responses. The present findings showed that HIIE and MCE were capable of improving EF. Moreover, HIIE could prolong improvement in EF during post-exercise recovery. For the first time, we suggest that HIIE may be more effective strategy than MCE for improving EF. (C) 2015 Elsevier Inc. All rights reserved.

We examined whether a mixed lactate and caffeine compound (LC) could effectively elicit proliferation and differentiation of satellite cells or activate anabolic signals in skeletal muscles. We cultured C2C12 cells with either lactate or LC for 6 h. We found that lactate significantly increased myogenin and follistatin protein levels and phosphorylation of P70S6K while decreasing the levels of myostatin relative to the control. LC significantly increased protein levels of Pax7, MyoD, and Ki67 in addition to myogenin, relative to control. LC also significantly increased follistatin expression relative to control and stimulated phosphorylation of mTOR and P70S6K. In an in vivo study, male F344/DuCrlCrlj rats were assigned to control (Sed, n = 10), exercise (Ex, n = 12), and LC supplementation (LCEx, n = 13) groups. LC was orally administered daily. The LCEx and Ex groups were exercised on a treadmill, running for 30 min at low intensity every other day for 4 wk. The LCEx group experienced a significant increase in the mass of the gastrocnemius (GA) and tibialis anterior (TA) relative to both the Sed and Ex groups. Furthermore, the LCEx group showed a significant increase in the total DNA content of TA compared with the Sed group. The LCEx group experienced a significant increase in myogenin and follistatin expression of GA relative to the Ex group. These results suggest that administration of LC can effectively increase muscle mass concomitant with elevated numbers of myonuclei, even with low-intensity exercise training, via activated satellite cells and anabolic signals.

No studies have identified the direct effect of changes in cerebral blood flow (CBF) on cognitive function at rest and during exercise. In this study, we manipulated CBF using hypercapnic gas to examine whether an increase in CBF improves cognitive function during prolonged exercise. The speed and the accuracy of cognitive function were assessed using the Stroop color-word test. After the Stroop test at rest, the subjects began exercising on a cycling ergometer in which the workload was increased by 0.5 kilopond every minute until a target heart rate of 140 beats/min was achieved. Then, the subjects continued to cycle at a constant rate for 50 min. At four time points during the exercise (0, 10, 20, 50 min), the subjects performed a Stroop test with and without hypercapnic respiratory gas (2.0% CO2), with a random order of the exposures in the two tests. Despite a decrease in the mean blood flow velocity in the middle cerebral artery (MCA Vmean), the reaction time for the Stroop test gradually decreased during the prolonged exercise without any loss of performance accuracy. In addition, the hypercapnia-induced increase in MCA Vmean produced neither changes in the reaction time nor error in the Stroop test during exercise. These findings suggest that the changes in CBF are unlikely to affect cognitive function during prolonged exercise. Thus, we conclude that improved cognitive function may be due to cerebral neural activation associated with exercise rather than global cerebral circulatory condition.

Relevance of decreased cerebral blood flow (CBF) and impaired cognitive function has been pointed out, however, the direct relationship between changes in CBF and cognitive function has not been sufficiently elucidated. The purpose of this study was to determine whether cognitive function would be affected by the acute reductions in CBF in 14 male healthy students. Middle cerebral artery mean blood velocity (MCA V_<mean>) and cognitive function were measured at three conditions; rest (pre), reduced CBF condition (during), and CBF recovery condition (post). The reduction in MCA V_<mean> was elicited by voluntary hyperventilation induced-hypocapnia. Cognitive function was impaired with the reduction in MCA V_<mean>; i.e. reaction time at during hyperventilation condition was significantly longer than those of pre and post conditions (in conflict task; P<0.01). These results suggest that cognitive function may be affected by acute change in MCA V_<mean> by hyperventilation.