The brain encounters input varying with many different time courses. Given such temporal variability, it would seem practical for adaptation to operate at multiple timescales. Indeed, to account for peculiar effects such as spacing, savings, and spontaneous recovery, many recent models of learning and adaptation have postulated multiple mechanisms operating at different timescales. However, despite this assumption, and compelling modelling results, different timescales of cortical adaptation and learning are rarely isolated in behaving animals. Here we demonstrate in a series of experiments that early visual cortex adapts at two distinct and separable timescales: fast (saturating with a time constant of roughly 30 seconds) and infinite (a perfect integrator: exhibiting no signs of decay or diminishing returns within the range of intervals tested). We further demonstrate that these two timescales sum linearly and appear to be operating independently and in parallel.

Acute mountain sickness (AMS) is a common condition occurring within hours of rapid exposure to high altitude. Despite its frequent occurrence, the pathophysiological mechanisms that underlie the condition remain poorly understood. We investigated the role of cerebral oxygen metabolism (CMR(O(2))) in AMS. The purpose of this study was to test 1) if CMR(O(2)) changes in response to hypoxia, and 2) if there is a difference in how individuals adapt to oxygen metabolic changes that may determine who develops AMS and who does not. Twenty-six normal human subjects were recruited into two groups based on Lake Louise AMS score (LLS): those with no AMS (LLS ≤ 2), and those with unambiguous AMS (LLS ≥ 5). [Subjects with intermediate scores (LLS 3-4) were not included.] CMR(O(2)) was calculated from cerebral blood flow and arterial-venous difference in O(2) content. Cerebral blood flow was measured using arterial spin labeling MRI; venous O(2) saturation was calculated from the MRI of transverse relaxation in the superior sagittal sinus. Arterial O(2) saturation was measured via pulse oximeter. Measurements were made during normoxia and after 2-day high-altitude exposure at 3,800 m. In all subjects, CMR(O(2)) increased with sustained high-altitude hypoxia [1.54 (0.37) to 1.82 (0.49) μmol·g(-1)·min(-1), n = 26, P = 0.045]. There was no significant difference in CMR(O(2)) between AMS and no-AMS groups. End-tidal Pco(2) was significantly reduced during hypoxia. Low arterial Pco(2) is known to increase neural excitability, and we hypothesize that the low arterial Pco(2) resulting from ventilatory acclimatization causes the observed increase in CMR(O(2)).

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Ventilation and cerebral blood flow (CBF) are both sensitive to hypoxia and hypercapnia. To compare chemosensitivity in these two systems, we made simultaneous measurements of ventilatory and cerebrovascular responses to hypoxia and hypercapnia in 35 normal human subjects before and after acclimatization to hypoxia. Ventilation and CBF were measured during stepwise changes in isocapnic hypoxia and iso-oxic hypercapnia. We used MRI to quantify actual cerebral perfusion. Measurements were repeated after 2 days of acclimatization to hypoxia at 3,800 m altitude (partial pressure of inspired O = 90 Torr) to compare plasticity in the chemosensitivity of these two systems. Potential effects of hypoxic and hypercapnic responses on acute mountain sickness (AMS) were assessed also. The pattern of CBF and ventilatory responses to hypercapnia were almost identical. CO responses were augmented to a similar degree in both systems by concomitant acute hypoxia or acclimatization to sustained hypoxia. Conversely, the pattern of CBF and ventilatory responses to hypoxia were markedly different. Ventilation showed the well-known increase with acute hypoxia and a progressive decline in absolute value over 25 min of sustained hypoxia. With acclimatization to hypoxia for 2 days, the absolute values of ventilation and O sensitivity increased. By contrast, O sensitivity of CBF or its absolute value did not change during sustained hypoxia for up to 2 days. The results suggest a common or integrated control mechanism for CBF and ventilation by CO but different mechanisms of O sensitivity and plasticity between the systems. Ventilatory and cerebrovascular responses were the same for all subjects irrespective of AMS symptoms. NEW & NOTEWORTHY Ventilatory and cerebrovascular hypercapnic response patterns show similar plasticity in CO sensitivity following hypoxic acclimatization, suggesting an integrated control mechanism. Conversely, ventilatory and cerebrovascular hypoxic responses differ. Ventilation initially increases but adapts with prolonged hypoxia (hypoxic ventilatory decline), and ventilatory sensitivity increases following acclimatization. In contrast, cerebral blood flow hypoxic sensitivity remains constant over a range of hypoxic stimuli, with no cerebrovascular acclimatization to sustained hypoxia, suggesting different mechanisms for O sensitivity in the two systems.