Metabolic Changes in the Activated Human Visual Cortex During Mild Hypoxia

Study Overview
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Brief Summary
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The primary objective of this research is to measure changes in neurochemical concentrations during stimulation of the primary visual cortex, in both conditions of normoxia (normal oxygen availability) and induced mild hypoxia (reduced oxygen availability).

Detailed Description
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The goal is to determine the effect of mild hypoxia on human brain energy metabolism of healthy young adult subjects. For this purpose, the Investigator will utilize non-invasive imaging modalities based on functional magnetic resonance spectroscopy (fMRS) to estimate metabolic changes during a visual stimulus, while subjects are exposed to well-controlled gas mixtures that resembles conditions of either normoxia or mild hypoxia. Identifying the impact of mild hypoxia on functional brain energy metabolism in the healthy human brain is a crucial step for generating hypotheses in multiple patient populations that experience mild hypoxia as consequence of their pathological condition, such as in sleep apnea and traumatic brain injury. The Investigator hypothesize that the energetic demands of neuronal activation as revealed by fMRS will not be affected by mild hypoxia.

Official Title
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Metabolic Changes in the Activated Human Visual Cortex During Mild Hypoxia

Conditions
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Brain Hypoxia

Intervention / Treatment
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* Device: Mild Hypoxia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Those volunteers who are evaluated as normal and not met exclusion criteria will be potential candidates for this study. Exclusion Criteria: Subjects with any type of bio-implant activated by mechanical, electronic, or magnetic means (e.g. cochlear implants, pacemakers, neurostimulators, biostimulators, electronic infusion pumps, etc.). Subjects with any type of ferromagnetic bio-implant that could potentially be displaced or damaged, such as aneurysm clips, metallic skull plates, etc. Females. Subjects that exhibit noticeable anxiety and/or claustrophobia. Subjects who cannot adhere to the experimental protocol for any reason. Subjects who have cardiac or known circulatory impairment, and/or the inability to perspire (poor thermoregulatory function). Subjects who have known conditions which can lead to emergency medical care. Been diagnosed by a physician as having a psychiatric disorder, substance abuse, neurological, cardiovascular. Been diagnosed by a physician as having respiratory diseases. Had a brain tumor or stroke. Started taking chemotherapy or immunomodulatory agents, or had any radiation treatment that could affect the brain. Had two or more seizures, or been given a diagnosis of epilepsy. Gotten a non-removable piercing or permanent eyeliner. Had a head injury that caused you to lose consciousness for more than 30 minutes or have amnesia for more than 24 hours. Anyone with a history of sleep apnea or head trauma that may have caused Traumatic Brain Injury (TBI). Gotten some type of metal in your body, either from a medical procedure or an injury. Male subjects with long beard which wouldn't allow a complete seal between the mask and the face. Anyone who is not able to see long distance without glasses or contacts.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mild Hypoxia<br>Subjects are exposed to an intervention that controls the composition of breathed air by using a gas blender (RespirAct). Subjects undergo MRI and MRS while breathing air with both normal oxygen concentration (normoxia) and reduced oxygen concentration (mild hypoxia). | Device: Mild Hypoxia<br>* During normoxia, the computer-controlled gas blender provides a gas mixture that generates pressures of expired O2 and CO2 similar to the resting values measured for each subject (32-35mmHg and 100-110 mmHg, respectively). During mild hypoxia, we will target the same expired CO2 of normoxia and a 60 mmHg reduction of expired O2 from the resting value (to a minimum limit of 50 mmHg), which is expected to reduce arterial oxygen saturation to 82-85%. In mild hypoxia, the fraction of inspired oxygen is reduced from  21% (room air) to  12% (equivalent to an altitude of 4000 meters). During both conditions of normoxia and mild hypoxia, the brain activity of subjects is monitored with functional magnetic resonance spectroscopy (fMRS) while they are presented with visual stimuli.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glutamate Concentration During a Visual Stimulus Measured by fMRS at Normoxia | Relative change in glutamate concentration from rest to visual stimulation as measured by fMRS (with water suppression) in the primary visual cortex during conditions of normoxia. | Baseline and Visual Stimulation at 4 minutes | 
| Change in Glutamate Concentration During a Visual Stimulus Measured by Functional MRS at Hypoxia | Relative change in glutamate concentration from rest to visual stimulation as measured by fMRS (with water suppression) in the primary visual cortex during conditions of hypoxia. | Baseline and Visual Stimulation at 4 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain Activity Measured by Blood Oxygenation Level Dependent (BOLD) Signal at Normoxia | Relative change in water signal intensity from rest to visual stimulation as measured by fMRS (without water suppression) in the primary visual cortex during conditions of normoxia. | Baseline and Visual Stimulation at 30 seconds | 
| Brain Activity Measured by Blood Oxygenation Level Dependent (BOLD) Signal at Hypoxia | Relative change in water signal intensity from rest to visual stimulation as measured by fMRS (without water suppression) in the primary visual cortex during conditions of hypoxia. | Baseline and Visual Stimulation at 30 seconds | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Functional MRS, Glutamate