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

Environmental hypoxia (fraction of inspired oxygen (FIO2) similar to 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.

Automated summary

This study found that hypoxia alters cerebral blood flow and neural activity in the posterior cingulate cortex (PCC), resulting in reduced glucose metabolism and glutamate response.