Article Figures & Data
Figures
- Figure 1.
Experimental workflow and procedures. Fifteen healthy participants were recruited to participate in the study. A familiarization session was conducted to collect the baseline neuropsychological assessment (Cognitive Tests) and introduce the participant to the hypoxia intervention (Hypoxia). Participants were then randomized into an initial supplementation regime (CrM or PLA), and supplementation was conducted for 7 d, with a 5 week washout period. Experimental sessions were conducted 24 h after supplementation, involving the collection of neuroimaging, neurophysiological, and neuropsychological data. Structural MRI was used to position an MRS volume of interest (voxel) over the hand knob of the primary motor cortex. The location was verified with functional MRI. The red–yellow contrast shows areas of increased activation during a functional finger-tapping task (Z > 2.3, p < 0.05). Spectroscopy data were acquired and corrected for the proportion of tissue types using neural tissue segmentation and transformed to absolute quantities using a brain-mimicking phantom containing a range of known physiological Cr concentrations. Neurophysiological data, as assessed via TMS and PNS, were recorded using surface EMG at baseline and during the hypoxia intervention to measure central and peripheral excitability levels, respectively. The hypoxia intervention was conducted for 90 min using a gas mixture with a fraction of inspired oxygen (FiO2) of 0.1 and delivered via a one-way valve face-mask system. Cardiovascular measures [arterial oxygen saturation (SpO2), heart rate (HR), and blood pressure (BP)] were monitored throughout to assess autonomic system regulation to the hypoxic intervention.
- Figure 2.
Neural creatine concentration after supplementation. a, Mean Cr concentration detected in the sensorimotor cortex increased after 1 week of dietary CrM supplementation (black bars) compared to PLA (white bars). Data were recorded using 1H MRS, transformed to an absolute quantity (in millimoles per liter) and corrected for the proportion of gray and white matter present in the volume of interest. Bars show the mean ± SEM. *p < 0.05. b, Amplitude of the Cr + PCr peaks from 1H MRS. An example spectra acquired at 3 T from the sensorimotor cortex of one participant is shown. Resonances at 3.069 and 3.960 ppm represent the primary and secondary Cr + PCr peaks, respectively.
- Figure 3.
Autonomic regulation during hypoxia. Arterial oxygen saturation (SpO2) was reduced by 19% during hypoxia. A compensatory 12% increase, on average, in heart rate (HR) occurred, with no changes in blood pressure (BP) detected. Gray shading represents wash-in stabilization period followed by 80 min of hypoxia for CrM (black circles) and PLA (white circles) treatments. Data are mean ± SD; n = 12 (n = 11 for BP). **p < 0.01 for 0 min versus subsequent observations.
- Figure 4.
Changes in cognitive domain scores with hypoxia. Hypoxia degraded performance significantly in four neurocognitive domains with PLA (white bars), but these decrements were lessened or prevented with CrM (black bars). Standard scores are raw scores relative to an age-matched normative data set of healthy individuals. Bars show the mean ± SEM. *p < 0.05; †p ≥ 0.05 and <0.1.
- Figure 5.
Corticomotor excitability and correlations with cognition during hypoxia. a, Stimulus–response curves for CrM and PLA treatments during normoxic (circles) and hypoxic (triangles) conditions. Data are mean ± SD; n = 13. b, Compared to normoxia, corticomotor excitability increased during hypoxia with CrM (black fill), but not PLA (white fill). Bars show the mean ± SEM; n = 13. *p < 0.05; ** p < 0.01. c, Correlations between the change in corticomotor excitability and the change in cognitive performance from baseline. Decreases in cognitive performance were prevalent in most variables with PLA. Bold type highlights statistically significant correlations.
Tables
Baseline, raw scores Creatine, raw scores Placebo, raw scores Effect of hypoxiaa Effect of supplementationb t p t p Alertness rating scale 4.1 ± 0.8 2.7 ± 0.9 2.6 ± 1.0 −4.1 < 0.001* 0.1 0.464 Complex attention 93.7 ± 16.8 86.4 ± 22.7 70.7 ± 51.5 −2.0 0.031* 1.8 0.049* ST, incongruent CE 1.9 ± 1.8 2.1 ± 1.8 2.0 ± 1.5 1.5 0.079† 0.9 0.195 SAT, errors 5.4 ± 3.8 6.4 ± 4.4 8.3 ± 6.9 2.4 0.017* −0.8 0.230 CPT, CE 0.7 ± 1.2 1.1 ± 1.7 3.0 ± 5.6 2.5 0.013* −2.2 0.020* CPT, omission errors 0.1 ± 0.3 0.9 ± 1.9 1.8 ± 4.6 1.4 0.087† −1.1 0.140 Executive function 100.5 ± 17.9 100.9 ± 17.9 91.9 ± 28.9 −1.2 0.118 1.5 0.082† SAT, correct 55.5 ± 9.0 56.6 ± 8.4 52.9 ± 12.4 −0.8 0.226 1.3 0.110 SAT, errors 5.4 ± 3.8 6.4 ± 4.4 8.3 ± 6.9 2.4 0.017* −0.8 0.230 Cognitive flexibility 98.8 ± 18.2 98.9 ± 19.3 88.9 ± 31.7 −1.4 0.092† 1.6 0.072† SAT, correct 55.5 ± 9.0 56.6 ± 8.4 52.9 ± 12.4 −0.8 0.226 1.3 0.110 SAT, errors 5.4 ± 3.8 6.4 ± 4.4 8.3 ± 6.9 2.4 0.017* −0.8 0.230 ST, incongruent CE 1.9 ± 1.8 2.1 ± 1.8 2.0 ± 1.5 1.5 0.079† 0.9 0.195 Neurocognitive index 104.2 ± 10.6 99.7 ± 14.3 92.2 ± 23.0 −2.2 0.022* 1.6 0.071† Composite memory 106.0 ± 13.1 97.8 ± 21.2 96.1 ± 16.7 −2.1 0.029* 0.3 0.400 Psychomotor speed 118.8 ± 18.5 114.5 ± 23.0 112.0 ± 22.9 −2.0 0.033* 0.6 0.279 Reaction time 103.2 ± 10.6 100.7 ± 12.6 98.9 ± 13.8 −0.7 0.259 0.4 0.332 Complex attention 93.7 ± 16.8 86.4 ± 22.7 70.7 ± 51.5 −2.0 0.031* 1.8 0.049* Cognitive flexibility 98.8 ± 18.2 98.9 ± 19.3 88.9 ± 31.7 −1.4 0.092† 1.6 0.072† A range of composite domain (italic type) and standard neurophysiological scores were reduced by hypoxia during PLA (effect of hypoxia). CrM standard scores tended to be higher during hypoxia than PLA (effect of supplementation), suggesting that these processes were robust to the effects of hypoxia. Note that for standard neurophysiological scores, higher error scores indicate worse performance, and higher correct response scores indicate better performance. For composite domain scores, higher scores indicate better performance. The alertness rating was measured using a six-point rating scale and was reduced with hypoxia and not corrected by CrM. ST, Stroop test; SAT, shifting attention test; CPT, continuous performance test; CE, commission errors. Descriptive data are mean ± SD.
↵aComparisons with baseline used one-sample t tests of normalized PLA scores compared to baseline (0) to assess the effects of hypoxia.
↵bBetween-treatment comparisons used paired t tests of normalized scores for CrM compared to PLA to assess the effects of supplementation.
↵*p < 0.05;
↵†p ≥ 0.05 and <0.1. Bold type highlights statistically significant comparisons.
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