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.

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.