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Neurochemical Mechanisms of the Awake vs. Anesthetized Brain

Early Phase 1
Conditions
Anesthesia
Healthy
Interventions
Registration Number
NCT05435560
Lead Sponsor
Massachusetts General Hospital
Brief Summary

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

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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
30
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
SalineSalineA 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.
DexmedetomidineDexmedetomidineDuring 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).
Primary Outcome Measures
NameTimeMethod
Functional magnetic resonance imaging (fMRI) signals.2 hours

fMRI measures of hemodynamic responses.

Differences in electroencephalography (EEG) measures between arousal and anesthesia.2 hours

Arousal states will be characterized from changes in the EEG power spectrum.

Brain positron emission tomography (PET) imaging signals.2 hours

Changes in dopamine receptor availability will be quantified from brain PET images.

Secondary Outcome Measures
NameTimeMethod
Respiratory physiology2 hours

Breathing rate (breaths per minute).

Heart rate2 hours

Heart rate variability.

Pulse oximetry2 hours

Amplitude of pulse oximetry signal.

Trial Locations

Locations (1)

Athinoula A. Martinos Center for Biomedical Imaging

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Charlestown, Massachusetts, United States

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