This study uses magnetic resonance imaging to determine whether 3 weeks of repeated exposure to Acute Intermittent Hypoxia can improve brain blood flow or blood flow regulation in healthy adults.

This study aims to identify an intervention to improve the function of blood vessels in the human brain, in order to mitigate damage to overall brain function and improve health outcomes across the lifespan. Hypoxia is a potent driver of angiogenesis and vascular plasticity, and acute intermittent hypoxia (AIH) protocols, in which an individual alternates between breathing mildly hypoxic air and normal air, are being rigorously examined for their potential in improving human physiology. This study tests whether AIH evokes beneficial vascular plasticity in the human brain, using a randomized crossover design to determine the impact of different daily AIH or sham interventions on MRI measures of cerebrovascular physiology.

Healthy, able-bodied participants between 21 and 50 years old will be invited to participate in this study. The daily AIH intervention consists of repeated visits to the PI laboratory over a three-week period to have an AIH or sham protocol administered via a hypoxia generator and face mask (Hyp-123, Hypoxico). Blood pressure readings will be taken before and after all intervention visits, and SpO2 levels continuously recorded for safety monitoring.

The effectiveness of the different interventions at improving cerebrovascular function will be assessed using MRI. In the week prior to each intervention period the participant will undergo MRI scanning. In addition to structural and diffusion weighted scans, multiple perfusion metrics will be extracted. Whole-brain cerebral blood flow will be measured using phase-contrast MRI, and quantitative CBF maps of regional perfusion will be measured using arterial spin labeling MRI. These perfusion metrics will be acquired three times: during normoxic (baseline), hypoxic, and hypercapnic conditions. Changes in perfusion values during gas challenges will measure whole-brain and regional cerebrovascular reactivity. The MRI protocol will be repeated one day after the last intervention visit.

Inclusion Criteria:

• Healthy volunteers between ages of 21 and 50 years
• No known neurological, respiratory or vascular conditions
• Safe to be scanned using MRI
• Able to communicate in English

Exclusion Criteria:

• MRI contraindications as indicated on MRI safety screening form
• Subjects with pacemakers, cochlear (in the ear) implants, or aneurysm clips or subjects who have worked with metal
• Pregnant women
• Individuals with known neurological or vascular conditions
• Individuals with sleep apnea, emphysema, or other respiratory conditions
• Individuals with severe claustrophobia
• Subjects unwilling or unable to give written informed consent in English
• Prisoners
• Frequent smoker
• Allergy to Tegaderm
• Blood pressure greater than 140/90 or less than 90/55.
• Individuals who report headaches, feeling dizzy or light-headed, or have heart palpitations on the day of the study.
• Individuals prescribed Aripiprazole and/or Lamotrigine*

Note, mild (well-controlled) asthma is not immediate grounds for exclusion.

*Other prescription medications may be grounds for exclusion; prescription medication information will be acquired during initial screening and at subsequent follow-up visits

MR imaging data and the associated physiologic data collected during MRI scanning will be shared in an anonymized format, along with the extracted quantitative perfusion maps and cerebrovascular reactivity maps. These data will be made available to public through the Open Science Framework (osf.io) or similar public repository. Code will be made available through the PI's laboratory Github account. A link to these resources will be included with publications resulting from this study to facilitate access.

At time of publication (or within one year of project completion, whichever occurs first).

Data will be anonymized and made publicly available, and at that time no approval is needed and therefore there are no access criteria.

Participants will not know whether they are receiving active or sham hypoxia during individual AIH sessions.