Neurochemical Mechanisms of the Awake vs. Anesthetized Brain

Study Overview
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Brief Summary
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The investigators will be studying the sedative drug dexmedetomidine using hybrid PET/fMRI/EEG imaging to better understand the neuropharmacology of anesthesia/artificially induced sleep.

Detailed Description
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A group of healthy volunteers will undergo simultaneous PET/fMRI/EEG imaging under two different conditions: while being administered a sedative (dexmedetomidine), and while being administered a normal saline infusion, as a control. The order of these two scans will be randomized, and the study design is open label (ie subjects and investigators know which session will be the control scan and which one will be the sedative scan). Investigators hope that by comparing the results of the sedative and control scans, the different neuromodulatory states involved in the transition from wakefulness to medically induced vs naturally occurring sleep can be better understood.

Official Title
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Characterizing the Neuropharmacology of Dexmedetomidine Through Trimodal Imaging

Conditions
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Anesthesia, Healthy

Intervention / Treatment
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* Drug: Dexmedetomidine
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults aged 18-45. No contraindications to MRI or PET scanning. Exclusion Criteria: Contraindications to fMRI scanning and PET scanning (including presence of a cardiac pacemaker or pacemaker wires, metallic particles in the body, vascular clips in the head or previous neurosurgery, prosthetic heart valves, claustrophobia); Pregnancy or breast feeding; Current or past history of major medical, neurological, or psychiatric condition; History of major head trauma; Any cardiovascular disorders, including heart disorders or high blood pressure [>155/95]; Breathing problems such as severe asthma; Bleeding disorder, or use of anticoagulants; Bladder obstruction, urinary problems, or history of impaired elimination; Known kidney or liver problems; Intestinal blockage; Raynaud syndrome Peripheral nerve injury; Diabetes; Glaucoma; Sleep disorder, such as sleep apnea, insomnia, or narcolepsy Current use of any drugs that affect sleep Current or recent use of medications (neurological or psychiatric) affecting brain function Current or past history of chronic pain (assessed at discretion of PI); History of allergic reactions History of chronic obstructive pulmonary diseases Ulcerative skin conditions or other dermatologic conditions which could interfere with blood pressure cuff placement Body mass index above 30 Current smoker Lack of current health insurance coverage Employed under the direct supervision of the investigators conducting the research Hair in dreadlocks, twists, or braids that cannot be removed Eczema on the scalp or face

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

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
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dexmedetomidine<br>During the imaging scan subjects will receive an initial 1µg/kg bolus of dexmedetomidine up to a maximum dose of 80 µg, infused through IV over 10 minutes. After the bolus has been administered, a constant infusion of up to 0.6 µg/kg/hr (0.01 µg/kg/min) of dexmedetomidine will be maintained for the remainder of the scan (about 60 minutes). | Drug: Dexmedetomidine<br>* During the imaging scan subjects will receive an initial bolus of dexmedetomidine over 10 minutes. After the bolus has been administered, a constant infusion of dexmedetomidine will be maintained for the remainder of the scan (about 60 minutes).<br>* Other names: Precedex;|
| Placebo Comparator: Saline<br>A saline infusion will be used as a placebo comparator for the dexmedetomidine infusion. It will be administered in the same manner and dosages as the dexmedetomidine. | Drug: Saline<br>* During the imaging scan subjects will receive an initial bolus of saline over 10 minutes. After the bolus has been administered, a constant infusion of saline will be maintained for the remainder of the scan (about 60 minutes).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain positron emission tomography (PET) imaging signals. | Changes in dopamine receptor availability will be quantified from brain PET images. | 2 hours | 
| Functional magnetic resonance imaging (fMRI) signals. | fMRI measures of hemodynamic responses. | 2 hours | 
| Differences in electroencephalography (EEG) measures between arousal and anesthesia. | Arousal states will be characterized from changes in the EEG power spectrum. | 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart rate | Heart rate variability. | 2 hours | 
| Pulse oximetry | Amplitude of pulse oximetry signal. | 2 hours | 
| Respiratory physiology | Breathing rate (breaths per minute). | 2 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dopamine, Anesthesia, Positron Emission Tomography, Magnetic Resonance Imaging, Electroencephalograpy, Sleep