Corticospinal excitability is associated with hypocapnia but not changes in cerebral blood flow.

KEY POINTS: Reductions in cerebral blood flow (CBF) may be implicated in the development of neuromuscular fatigue; however, the contribution from hypocapnic-induced reductions (i.e. P ETC O2) in CBF versus reductions in CBF per se has yet to be isolated. We assessed neuromuscular function while using indomethacin to selectively reduce CBF without changes in P ETC O2 and controlled hyperventilation-induced hypocapnia to reduce both CBF and P ETC O2. Increased corticospinal excitability appears to be exclusive to reductions in P ETC O2 but not reductions in CBF, whereas sub-optimal voluntary output from the motor cortex is moderately associated with decreased CBF independent of changes in P ETC O2. These findings suggest that changes in CBF and P ETC O2 have distinct roles in modulating neuromuscular function. ABSTRACT: Although reductions in cerebral blood flow (CBF) may be involved in central fatigue, the contribution from hypocapnia-induced reductions in CBF versus reductions in CBF per se has not been isolated. This study examined whether reduced arterial PCO2 (P aC O2), independent of concomitant reductions in CBF, impairs neuromuscular function. Neuromuscular function, as indicated by motor-evoked potentials (MEPs), maximal M-wave (Mmax ) and cortical voluntary activation (cVA) of the flexor carpi radialis muscle during isometric wrist flexion, was assessed in ten males (29 ± 10 years) during three separate conditions: (1) cyclooxygenase inhibition using indomethacin (Indomethacin, 1.2 mg kg(-1) ) to selectively reduce CBF by 28.8 ± 10.3% (estimated using transcranial Doppler ultrasound) without changes in end-tidal PCO2 (P ETC O2); (2) controlled iso-oxic hyperventilation-induced reductions in P aC O2 (Hypocapnia), P ETC O2  = 30.1 ± 4.5 mmHg with related reductions in CBF (21.7 ± 6.3%); and (3) isocapnic hyperventilation (Isocapnia) to examine the potential direct influence of hyperventilation-mediated activation of respiratory control centres on CBF and changes in neuromuscular function. Change in MEP amplitude (%Mmax ) from baseline was greater in Hypocapnia tha in Isocapnia (11.7 ± 9.8%, 95% confidence interval (CI) [2.6, 20.7], P = 0.01) and Indomethacin (13.3 ± 11.3%, 95% CI [2.8, 23.7], P = 0.01) with a large Cohen's effect size (d ≥ 1.17). Although not statistically significant, cVA was reduced with a moderate effect size in Indomethacin (d = 0.7) and Hypocapnia (d = 0.9) compared to Isocapnia. In summary, increased corticospinal excitability - as reflected by larger MEP amplitude - appears to be exclusive to reduced P aC O2, but not reductions in CBF per se. Sub-optimal voluntary output from the motor cortex is moderately associated with decreased CBF, independent of reduced P aC O2.

Neither short-term sprint nor endurance training enhances thermal response to exercise in a hot environment.

Improvements in fitness from a brief period of physical training may elicit sufficient physiological adaptations to decrease thermal strain during exercise in the heat. This study tested heat adaptation from short-term endurance (ET) and sprint-interval (SIT) training in moderately fit individuals. The ET group (n = 8) cycled at 65% [Formula: see text] for 8 sessions (4 sessions each at 60 and 90 min, respectively) over two weeks, while the SIT group (n = 8) performed repeated 30-s Wingate sprints (resistance 7.5% body mass; 4 sessions each of 4 and 5 sprints, respectively). [Formula: see text] and heat stress testing (HST; 60 min cycling at 65% [Formula: see text] at 35ºC, 40% relative humidity) were performed pre- and post-training. [Formula: see text]increased by 11% (p = 0.025) and 14% (p = 0.020) for the ET and SIT groups post-training, respectively. Thermal stress was similar pre- and post-training, with no significant difference in the rate of whole-body metabolic heat production (p = 0.106) for either group post-training. Cardiovascular improvement was evident with both ET and SIT, with a significant mean decrease (p = 0.014) in HR for both groups (ET: 146 ± 15 beats·min(-1)pre vs. 142 ± 12 beats·min(-1)post; SIT: 149 ± 15 beats·min(-1)pre vs. 146 ± 12 beats·min(-1)post) during the HST post-training. However, mean sweat loss (p = 0.248) and the rise in core temperature (p = 0. 260) did not change significantly comparing pre- and post-training HST. While short-term ET and SIT both induced significant improvements in aerobic fitness and decreased cardiovascular strain, neither elicited improved thermal responses during exercise in the heat and do not replace heat acclimatization.

Endurance capacity impairment in cold air ranging from skin cooling to mild hypothermia.

We tested the effects of cold air (0°C) exposure on endurance capacity to different levels of cold strain ranging from skin cooling to core cooling of Δ-1.0°C. Ten males completed a randomized, crossover, control study consisting of a cycling time to exhaustion (TTE) at 70% of their peak power output following: 1) 30-min of exposure to 22°C thermoneutral air (TN), 2) 30-min exposure to 0°C air leading to a cold shell (CS), 3) 0°C air exposure causing mild hypothermia of -0.5°C from baseline rectal temperature (HYPO-0.5°C), and 4) 0°C air exposure causing mild hypothermia of -1.0°C from baseline rectal temperature (HYPO-1.0°C). The latter three conditions tested TTE in 0°C air. Core temperature and seven-site mean skin temperature at the start of the TTE were: TN (37.0 ± 0.2°C, 31.2 ± 0.8°C), CS (37.1 ± 0.3°C, 25.5 ± 1.4°C), HYPO-0.5°C (36.6 ± 0.4°C, 22.3 ± 2.2°C), HYPO-1.0°C (36.4 ± 0.5°C, 21.4 ± 2.7°C). There was a significant condition effect (P ≤ 0.001) for TTE, which from TN (23.75 ± 13.75 min) to CS (16.22 ± 10.30 min, Δ-30.9 ± 21.5%, P = 0.055), HYPO-0.5°C (8.50 ± 5.23 min, Δ-61.4 ± 19.7%, P ≤ 0.001), and HYPO-1.0°C (6.50 ± 5.60 min, Δ-71.6 ± 16.4%, P ≤ 0.001). Furthermore, participants had a greater endurance capacity in CS compared with HYPO-0.5°C (P = 0.046), and HYPO-1.0°C (P = 0.007), with no differences between HYPO-0.5°C and HYPO-1.0°C (P = 1.00). Endurance capacity impairment at 70% peak power output occurs early in cold exposure with skin cooling, with significantly larger impairments with mild hypothermia up to Δ-1.0°C.NEW & NOTEWORTHY We developed a novel protocol that cooled skin temperature, or skin plus core temperature (Δ-0.5°C or Δ-1.0 °C), to determine a dose-response of cold exposure on endurance capacity at 70% peak power output. Skin cooling significantly impaired exercise tolerance time by ∼31%, whereas core cooling led to a further reduction of 30%-40% with no difference between Δ-0.5°C and Δ-1.0°C. Overall, simply cooling the skin impaired endurance capacity, but this impairment is further magnified by core cooling.

Effects of skin and mild core cooling on cognitive function in cold air in men.

This study tested the effects of skin and core cooling on cognitive function in 0°C cold air. Ten males completed a randomized, repeated measures study consisting of four environmental conditions: (i) 30 min of exposure to 22°C thermoneutral air (TN), (ii) 15 min to 0°C cold air which cooled skin temperature to ~27°C (CS), (iii) 0°C cold air exposure causing mild core cooling of ∆-0.3°C from baseline (C-0.3°C) and (iv) 0°C cold air exposure causing mild core cooling of ∆-0.8°C from baseline (C-0.8°C). Cognitive function (reaction time [ms] and errors made [#]) were tested using a simple reaction test, a two-six item working memory capacity task, and vertical flanker task to assess executive function. There were no condition effects (all p > 0.05) for number of errors made on any task. There were no significant differences in reaction time relative to TN for the vertical flanker and item working memory capacity task. However, simple reaction time was slower in C-0.3°C (297 ± 33 ms) and C-0.8°C (296 ± 41 ms) compared to CS (267 ± 26 ms) but not TN (274 ± 38). Despite small changes in simple reaction time (~30 ms), executive function and working memory was maintained in 0°C cold air with up to ∆-0.8°C reduction in core temperature.

The Clamping of End-Tidal Carbon Dioxide Does Not Influence Cognitive Function Performance During Moderate Hyperthermia With or Without Skin Temperature Manipulation.

Increases in body temperature from heat stress (i.e., hyperthermia) generally impairs cognitive function across a range of domains and complexities, but the relative contribution from skin versus core temperature changes remains unclear. Hyperthermia also elicits a hyperventilatory response that decreases the partial pressure of end-tidal carbon dioxide (PetCO2) and subsequently cerebral blood flow that may influence cognitive function. We studied the role of skin and core temperature along with PetCO2 on cognitive function across a range of domains. Eleven males completed a randomized, single-blinded protocol consisting of poikilocapnia (POIKI, no PetCO2 control) or isocapnia (ISO, PetCO2 maintained at baseline levels) during passive heating using a water-perfused suit (water temperature ~ 49°C) while middle cerebral artery velocity (MCAv) was measured continuously as an index of cerebral blood flow. Cognitive testing was completed at baseline, neutral core-hot skin (37.0 ± 0.2°C-37.4 ± 0.3°C), hot core-hot skin (38.6 ± 0.3°C-38.7 ± 0.2°C), and hot core-cooled skin (38.5 ± 0.3°C-34.7 ± 0.6°C). The cognitive test battery consisted of a detection task (psychomotor processing), 2-back task (working memory), set-shifting and Groton Maze Learning Task (executive function). At hot core-hot skin, poikilocapnia led to significant (both p < 0.05) decreases in PetCO2 (∆-21%) and MCAv (∆-26%) from baseline, while isocapnia clamped PetCO2 (∆ + 4% from baseline) leading to a significantly (p = 0.023) higher MCAv (∆-18% from baseline) compared to poikilocapnia. There were no significant differences in errors made on any task (all p > 0.05) irrespective of skin temperature or PetCO2 manipulation. We conclude that neither skin temperature nor PetCO2 maintenance significantly alter cognitive function during passive hyperthermia.

Cognitive Performance during a 24-Hour Cold Exposure Survival Simulation.

Survivor of a ship ground in polar regions may have to wait more than five days before being rescued. Therefore, the purpose of this study was to explore cognitive performance during prolonged cold exposure. Core temperature (T c) and cognitive test battery (CTB) performance data were collected from eight participants during 24 hours of cold exposure (7.5°C ambient air temperature). Participants (recruited from those who have regular occupational exposure to cold) were instructed that they could freely engage in minimal exercise that was perceived to maintaining a tolerable level of thermal comfort. Despite the active engagement, test conditions were sufficient to significantly decrease T c after exposure and to eliminate the typical 0.5-1.0°C circadian rise and drop in core temperature throughout a 24 h cycle. Results showed minimal changes in CTB performance regardless of exposure time. Based on the results, it is recommended that survivors who are waiting for rescue should be encouraged to engage in mild physical activity, which could have the benefit of maintaining metabolic heat production, improve motivation, and act as a distractor from cold discomfort. This recommendation should be taken into consideration during future research and when considering guidelines for mandatory survival equipment regarding cognitive performance.

Oxidative fuel selection and shivering thermogenesis during a 12- and 24-h cold-survival simulation.

Because the majority of cold exposure studies are constrained to short-term durations of several hours, the long-term metabolic demands of cold exposure, such as during survival situations, remain largely unknown. The present study provides the first estimates of thermogenic rate, oxidative fuel selection, and muscle recruitment during a 24-h cold-survival simulation. Using combined indirect calorimetry and electrophysiological and isotopic methods, changes in muscle glycogen, total carbohydrate, lipid, protein oxidation, muscle recruitment, and whole body thermogenic rate were determined in underfed and noncold-acclimatized men during a simulated accidental exposure to 7.5 °C for 12 to 24 h. In noncold-acclimatized healthy men, cold exposure induced a decrease of ∼0.8 °C in core temperature and a decrease of ∼6.1 °C in mean skin temperature (range, 5.4-6.9 °C). Results showed that total heat production increased by approximately 1.3- to 1.5-fold in the cold and remained constant throughout cold exposure. Interestingly, this constant rise in Hprod and shivering intensity was accompanied by a large modification in fuel selection that occurred between 6 and 12 h; total carbohydrate oxidation decreased by 2.4-fold, and lipid oxidation doubled progressively from baseline to 24 h. Clearly, such changes in fuel selection dramatically reduces the utilization of limited muscle glycogen reserves, thus extending the predicted time to muscle glycogen depletion to as much as 15 days rather than the previous estimates of approximately 30-40 h. Further research is needed to determine whether this would also be the case under different nutritional and/or colder conditions.

Effect of segmental, localized lower limb cooling on dynamic balance.

PURPOSE: This study aimed to determine the effect of cooling progressively greater portions of the lower extremities on dynamic balance and neuromuscular activation. METHODS: Ten healthy males (22.8 ± 3.4 yr, 76.5 ± 9.1 kg) performed one room air temperature control (22.4°C ± 0.8°C) and three trials of cold water immersion at 12°C (lateral malleolus, ankle; lateral femoral epicondyle, knee; anterior superior iliac spine, hip) for 10 min before performing a unipedal balance test (Star Excursion Balance Test (SEBT)) with their dominant limb. Muscle activation of the vastus lateralis, biceps femoris, tibialis anterior, and lateral gastrocnemius was measured with surface EMG during the SEBT. RESULTS: Core temperature remained euthermic throughout all trials. Gastrocnemius temperature decreased from control (30.4°C ± 0.5°C) with knee (23.7°C ± 1.7°C) and hip immersion (22.4°C ± 1.0°C), whereas vastus lateralis temperature decreased from control (33.7°C ± 1.7°C) with hip immersion (27.3°C ± 2.0°C) (P < 0.01 for all comparisons). Cold water immersion influenced mean anterior and posterior reach distance on the SEBT in a dose-dependent fashion. Compared with those in control, mean anterior and posterior SEBT reach distances were not decreased with ankle (-1.38% and -0.74%, respectively) and knee immersion (-2.48% and -2.74%), whereas hip immersion significantly reduced SEBT by 4.73% and 4.05% (P < 0.05, d = 0.52-0.58). Muscle activation was largely unaffected as the lower extremities were cooled, with only the lateral gastrocnemius during the anterior SEBT approaching a decrease (P = 0.059). CONCLUSIONS: Cooling larger portions of the lower extremities progressively affect dynamic balance, and thermal protection strategies should focus on maintaining temperature in the large muscle mass of the thigh.

Freely chosen cadence during a covert manipulation of ambient temperature.

The present study investigated relationships between changes in power output (PO) to torque (TOR) or freely chosen cadence (FCC) during thermal loading. Twenty participants cycled at a constant rating of perceived exertion while ambient temperature (Ta) was covertly manipulated at 20-min intervals of 20 °C, 35 °C, and 20 °C. The magnitude responses of PO, FCC and TOR were analyzed using repeated-measures ANOVA, while the temporal correlations were analyzed using Auto-Regressive Integrated Moving Averages (ARIMA). Increases in Ta caused significant thermal strain (p < .01), and subsequently, a decrease in PO and TOR magnitude (p < .01), whereas FCC remained unchanged (p = .51). ARIMA indicates that changes in PO were highly correlated to TOR (stationary r2 = .954, p = .04), while FCC was moderately correlated (stationary r2 = .717, p = .01) to PO. In conclusion, changes in PO are caused by a modulation in TOR, whereas FCC remains unchanged and therefore, unaffected by thermal stressors.

Regional changes in brain blood flow during severe passive hyperthermia: effects of PaCO2 and extracranial blood flow.

We investigated 1) the regional distribution of cerebral blood flow (CBF), 2) the influence of end-tidal Pco2 (PetCO2) on CBF, and 3) the potential for an extracranial blood "steal" from the anterior brain region during passive hyperthermia. Nineteen (13 male) volunteers underwent supine passive heating until a steady-state esophageal temperature of 2°C above resting was established. Measurements were obtained 1) during normothermia (Normo), 2) during poikilocapnic hyperthermia (Hyper), and 3) during hyperthermia with PetCO2 and end-tidal Po2 clamped to Normo levels (Hyper-clamp). Blood flow in the internal carotid (Qica), vertebral (QVA), and external carotid (Qeca) arteries (Duplex ultrasound), blood velocity of the middle cerebral (MCAv) and posterior cerebral (PCAv) arteries (transcranial Doppler), and cutaneous vascular conductance on the cheek (cheek CVC; Doppler velocimetry) were measured at each stage. During Hyper, PetCO2 was lowered by 7.0 ± 5.2 mmHg, resulting in a reduction in Qica (-18 ± 17%), Qva (-31 ± 21%), MCAv (-22 ± 13%), and PCAv (-18 ± 10%) compared with Normo (P < 0.05). The reduction in QVA was greater than that in QICA (P = 0.017), MCAv (P = 0.047), and PCAv (P = 0.034). Blood flow/velocity was completely restored in each intracranial vessel (ICA, VA, MCA, and PCA) during Hyper-clamp. Despite a ∼250% increase in QECA and a subsequent increase in cheek CVC during Hyper compared with Normo, reductions in QICA were unrelated to changes in QECA. These data provide three novel findings: 1) hyperthermia attenuates QVA to a greater extent than QICA, 2) reductions in CBF during hyperthermia are governed primarily by reductions in arterial Pco2, and 3) increased QECA is unlikely to compromise QICA during hyperthermia.

The effect of a covert manipulation of ambient temperature on heat storage and voluntary exercise intensity.

The modulation of sub-maximal voluntary exercise intensity during heat stress has been suggested as a behavioral response to maintain homeostasis; however, the relationship between thermophysiological cues and the associated response remains unclear. Awareness of an environmental manipulation may influence anticipatory planning before the start of exercise, making it difficult to isolate the dynamic integration of thermophysiological afferents during exercise itself. The purpose of the present study was to examine the direct real-time relationship between thermophysiological afferents and the behavioral response of voluntary exercise intensity. Participants were tasked with cycling at a constant rating of perceived exertion while ambient temperature (T(a)) was covertly changed from 20 °C to 35 °C and then back to 20 °C at 20-minute intervals. Overall, power output (PO) and heat storage, quantified using repeated measures ANOVA, changed significantly over 20-minute intervals (135 ± 39 W, 133 ± 46 W, 120 ± 45 W; 52.35 ± 36.15 W·m(-2), 66.34 ± 22.02 W·m(-2), -66.53 ± 56.01 W·m(-2)). The synchronicity of PO fluctuations with changes in thermophysiological status was quantified using Auto-Regressive Integrated Moving Average (ARIMA) time series analysis. Fluctuations in PO were not synchronized in real time with changes in T(a); heat storage; rectal, skin, or mean body temperature; or sweat rate (stationary-r(2) ≤ 0.10 and Ljung-Box statistic > 0.05 for all variables). We conclude that, while the thermal environment affects physiological responses and voluntary power output while cycling at a constant perceived effort, the behavioral response of voluntary exercise intensity did not depend on a direct response to real-time integration of thermal afferent inputs.