Hypoxia alters posterior cingulate cortex metabolism during a memory task: A 1H fMRS study.

Environmental hypoxia (fraction of inspired oxygen (FIO2) ∼ 0.120) is known to trigger a global increase in cerebral blood flow (CBF). However, regionally, a heterogeneous response is reported, particularly within the posterior cingulate cortex (PCC) where decreased CBF is found after two hours of hypoxic exposure. Furthermore, hypoxia reverses task-evoked BOLD signals within the PCC, and other regions of the default mode network, suggesting a reversal of neurovascular coupling. An alternative explanation is that the neural architecture supporting cognitive tasks is reorganised. Therefore, to confirm if this previous result is neural or vascular in origin, a measure of neural activity that is not haemodynamic-dependant is required. To achieve this, we utilised functional magnetic resonance spectroscopy to probe the glutamate response to memory recall in the PCC during normoxia (FIO2 = 0.209) and after two hours of poikilocapnic hypoxia (FIO2 = 0.120). We also acquired ASL-based measures of CBF to confirm previous findings of reduced CBF within the PCC in hypoxia. Consistent with previous findings, hypoxia induced a reduction in CBF within the PCC and other regions of the default mode network. Under normoxic conditions, memory recall was associated with an 8% increase in PCC glutamate compared to rest (P = 0.019); a change which was not observed during hypoxia. However, exploratory analysis of other neurometabolites showed that PCC glucose was reduced during hypoxia compared to normoxia both at rest (P = 0.039) and during the task (P = 0.046). We conclude that hypoxia alters the activity-induced increase in glutamate, which may reflect a reduction in oxidative metabolism within the PCC. The reduction in glucose in hypoxia reflects continued metabolism, presumably by non-oxidative means, without replacement of glucose due to reduced CBF.

The influence of short-term high-altitude acclimatization on cerebral and leg tissue oxygenation post-orthostasis.

PURPOSE: Orthostasis at sea level decreases brain tissue oxygenation and increases risk of syncope. High altitude reduces brain and peripheral muscle tissue oxygenation. This study determined the effect of short-term altitude acclimatization on cerebral and peripheral leg tissue oxygenation index (TOI) post-orthostasis. METHOD: Seven lowlanders completed a supine-to-stand maneuver at sea level (450 m) and for 3 consecutive days at high altitude (3776 m). Cardiorespiratory measurements and near-infrared spectroscopy-derived oxygenation of the frontal lobe (cerebral TOI) and vastus lateralis (leg TOI) were measured at supine and 5-min post-orthostasis. RESULTS: After orthostasis at sea level, cerebral TOI decreased [mean Δ% (95% confidential interval): - 4.5%, (- 7.5, - 1.5), P < 0.001], whilst leg TOI was unchanged [- 4.6%, (- 10.9, 1.7), P = 0.42]. High altitude had no effect on cerebral TOI following orthostasis [days 1-3: - 2.3%, (- 5.3, 0.7); - 2.4%, (- 5.4, 0.6); - 2.1%, (- 5.1, 0.9), respectively, all P > 0.05], whereas leg TOI decreased [days 1-3: - 12.0%, (- 18.3, - 5.7); - 12.1%, (- 18.4, - 5.8); - 10.2%, (- 16.5, - 3.9), respectively, all P < 0.001]. This response did not differ with days spent at high altitude, despite evidence of cardiorespiratory acclimatization [increased peripheral oxygen saturation (supine: P = 0.01; stand: P = 0.02) and decreased end-tidal carbon dioxide (supine: P = 0.003; stand: P = 0.01)]. CONCLUSION: Cerebral oxygenation is preferentially maintained over leg oxygenation post-orthostasis at high altitude, suggesting different vascular regulation between cerebral and peripheral circulations. Short-term acclimatization to high altitude did not alter cerebral and leg oxygenation responses to orthostasis.

Bilateral regional extracranial blood flow regulation to hypoxia and unilateral duplex ultrasound measurement error.

NEW FINDINGS: What is the central question of this study? Is blood flow regulation to hypoxia different between the internal carotid arteries (ICAs) and vertebral arteries (VAs), and what is the measurement error in unilateral extracranial artery assessments compared to bilateral? What is the main finding and its importance? ICA and VA blood flow regulation to hypoxia is comparable when factoring for vessel type and vessel side. Compared to bilateral assessment, vessels assessed unilaterally had individual measurement errors of up to 37%. Assessing the vessel with the larger resting blood flow, not the left or right vessel, reduces unilateral measurement error. ABSTRACT: Whether blood flow regulation to hypoxia is similar between left and right internal carotid arteries (ICAs) and vertebral arteries (VAs) is unclear. Extracranial blood flow is regularly calculated by doubling a unilateral assessment; however, lateral artery differences may lead to measurement error. This study aimed to determine extracranial blood flow regulation to hypoxia when factoring for vessel type (ICAs or VAs) and vessel side (left or right) effects, and to investigate unilateral assessment measurement error compared to bilateral assessment. In a repeated-measures crossover design, extracranial arteries of 44 participants were assessed bilaterally by duplex ultrasound during 90 min of normoxic and poikilocapnic hypoxic (12.0% fraction of inspired oxygen) conditions. Linear mixed model analyses revealed no Condition × Vessel Type × Vessel Side interaction for blood flow, vessel diameter and flow velocity (all P > 0.05) indicating left and right ICA and VA blood flow regulation to hypoxia was similar. Bilateral hypoxic reactivity was comparable (ICAs, 1.4 (1.0) vs. VAs, 1.7 (1.1) Δ%·Δ SpO2-1 ; P = 0.12). Compared to bilateral assessment, unilateral mean measurement error of the relative blood flow response to hypoxia was up to 5%, but individual errors reached 37% and were greatest in ICAs and VAs with the smaller resting blood flow due to a ratio-scaling problem. In conclusion, left and right ICA and VA regulation to hypoxia is comparable when factoring for vessel type and vessel side. Assessing the ICA and VA vessels with the larger resting blood flow, not the left or right vessel, reduces unilateral measurement error.

Isolating the independent effects of hypoxia and hyperventilation-induced hypocapnia on cerebral haemodynamics and cognitive function.

NEW FINDINGS: What is the central question of this study? What are the independent effects of hypoxia and hypocapnia on cerebral haemodynamics and cognitive function? What is the main finding and its importance? Exposure to hyperventilation-induced hypocapnia causes cognitive impairment in both normoxia and hypoxia. In addition, supplementation of carbon dioxide during hypoxia alleviates the cognitive impairment and reverses hypocapnia-induced vasoconstriction of the cerebrovasculature. These data provide new evidence for the independent effect of hypocapnia on the cognitive impairment associated with hypoxia. ABSTRACT: Hypoxia, which is accompanied by hypocapnia at altitude, is associated with cognitive impairment. This study examined the independent effects of hypoxia and hypocapnia on cognitive function and assessed how changes in cerebral haemodynamics may underpin cognitive performance outcomes. Single reaction time (SRT), five-choice reaction time (CRT) and spatial working memory (SWM) tasks were completed in 20 participants at rest and after 1 h of isocapnic hypoxia (IH, end-tidal oxygen partial pressure ( PETO2 ) = 45 mmHg, end-tidal carbon dioxide partial pressure ( PETCO2 ) clamped at normal) and poikilocapnic hypoxia (PH, PETO2  = 45 mmHg, PETCO2 not clamped). A subgroup of 10 participants were also exposed to euoxic hypocapnia (EH, PETO2  = 100 mmHg, PETCO2 clamped 8 mmHg below normal). Middle cerebral artery velocity (MCAv) and prefrontal cerebral haemodynamics were measured with transcranial Doppler and near infrared spectroscopy, respectively. IH did not affect SRT and CRT performance from rest (566 ± 50 and 594 ± 70 ms), whereas PH (721 ± 51 and 765 ± 48 ms) and EH (718 ± 55 and 755 ± 34 ms) slowed response times (P < 0.001 vs. IH). Performance on the SWM task was not altered by condition. MCAv increased during IH compared to PH (P < 0.05), which was unchanged from rest. EH caused a significant fall in MCAv and prefrontal cerebral oxygenation (P < 0.05 vs. baseline). MCAv was moderately correlated to cognitive performance (R2  = 0.266-0.289), whereas prefrontal cerebral tissue perfusion and saturation were not (P > 0.05). These findings reveal a role of hyperventilation-induced hypocapnia per se on the development of cognitive impairment during normoxic and hypoxic exposures.