The Brain Metabolism of Unpredictable Signals

Quantifying the Brain Metabolism Underlying Task-Based BOLD Imaging

The investigators will be studying brain glucose and oxygen metabolism using hybrid PET/fMRI imaging to better understand how decoupling between brain glucose and oxygen metabolism relates to the processing of unpredictable sensory signals.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy
• Intervention / Treatment: Behavioral: (Un)predictable and (un)attended stimuli

Detailed Description

The proposed research consists of one experiment, combining positron emission tomography (PET) and magnetic resonance imaging (MRI) techniques to simultaneously estimate the cerebral metabolic rates of glucose (CMRglc) and oxygen (CMRO2), and their ratio (oxygen:glucose index; OGI). These outcome measures will be collected in the context of a behavioral intervention presenting subjects with predictable and unpredictable stimuli, and attended and unattended stimuli. Functional PET uses a slow infusion of 2-[18F]-fluro-deoxyglucose (FDG) to estimate regional CMRglc, measuring relative changes in radiotracer uptake between blocks of task and rest. Dual-calibrated fMRI uses a sequence of hyperoxic (increased O2) and hypercapnic (increased CO2) challenges, along with a specialized sequence of MRI scans (estimating cerebral blood flow and blood-oxygen level-dependent signal) to estimate absolute CMRO2.

All subjects will be scanned, and each will complete the same behavioral intervention. First, the investigators will aim to assess the reliability of this hybrid imaging technique by having subjects complete two identical scan sessions. Second, the investigators will deliver a behavioral intervention to test the relationship between stimuli predictability, CMRglc, CMRO2, and OGI.

This experimental design is capable of producing effects observable in single subjects, and prior studies using fPET and dual-calibrated fMRI have produced effect sizes that our sample size is more than adequate to detect.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Irena Bass; Phone Number: 6177269034; Email: ibass@mgh.harvard.edu
• Study Contact Backup: Name: Christin Y Sander, PhD; Phone Number: 6177269034; Email: csander@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Charlestown, Massachusetts, United States, 02129
      • Athinoula A. Martinos Center for Biomedical Imaging
      • Contact: Irena Bass; Phone Number: 617-726-9034; Email: ibass@mgh.harvard.edu
      • Principal Investigator: Christin Y Sander, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults aged 21-35.
• No contraindications to MRI or PET scanning.
• Right-handed.
• Fluent to speak, read, and understand English.

Exclusion Criteria:

• Adults unable to consent
• Contraindications to fMRI scanning and PET scanning (including the 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)
• Inability to lie motionless in the scanner
• Pregnancy, seeking or suspecting pregnancy, or breastfeeding
• History of major head trauma
• Intracranial lesion
• Cardiovascular disorders, including heart disorders or high blood pressure [>155/95]
• Breathing problems such as severe asthma, emphysema, or pulmonary disease
• Bleeding disorder, or use of anticoagulants
• Bladder obstruction, urinary problems, or history of impaired elimination
• Known kidney or liver problems
• Past severe COVID-19 infection
• Intestinal blockage
• Raynaud syndrome
• Anemia
• Peripheral nerve injury
• Diabetes
• Glaucoma
• Current or recent use of medications (neurological or psychiatric) affecting brain function
• Current or past history of major medical, neurological, or psychiatric condition
• Current or past history of chronic pain (assessed at the discretion of PI)
• Current smoker
• Body mass index above 35
• Research-related radiation exposure exceeds current Radiology Department guidelines
• Lack of current health insurance coverage
• Employed under the direct supervision of the investigators conducting the research
• Unwilling or unable to cooperate with breathing maneuvers required during the gas challenge
• Respiratory or cardiac limitations to breathing at 20 L/min

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Behavioral intervention; Subjects are presented with a simultaneous sequence of faces and spoken words. Face stimuli include a representative sample of realistic faces across a range of ages. Spoken word stimuli are simple nouns spoken by a single female speaker.

Behavioral: (Un)predictable and (un)attended stimuli; Subjects will complete four task conditions in each scan session: (1) Visual Unpredictable, (2) Visual Predictable, (3) Auditory Unpredictable, and (4) Auditory Predictable. In visual and auditory conditions subjects attend to visual or auditory stimuli and ignore the other domain, pressing a button when they detect an infrequently occurring stimulus inversion in the target domain. In unpredictable and predictable conditions, the attended domain either presents random (unpredictable) stimuli, or the same face or word stimuli repeated (predictable).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain positron emission tomography (PET) imaging signals	Changes in glucose metabolism will be quantified from brain PET images	after PET image analysis and with study completion, an average of 1 year
Functional magnetic resonance imaging (fMRI) signals	Changes in oxygen metabolism will be quantified from dual-calibrated fMRI	after fMRI image analysis and with study completion, an average of 1 year
Oxygen-glucose index	Ratio of cerebral metabolic rates of glucose and oxygen from PET and fMRI signals	after PET/fMRI image analysis and with study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Christin Y Sander, PhD, Athinoula A. Martinos Center for Biomedical Imaging

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2023
• Primary Completion (Anticipated): February 28, 2024
• Study Completion (Anticipated): February 28, 2025

Study Registration Dates

• First Submitted: February 15, 2023
• First Submitted That Met QC Criteria: February 23, 2023
• First Posted (Estimate): March 6, 2023

Study Record Updates

• Last Update Posted (Estimate): March 6, 2023
• Last Update Submitted That Met QC Criteria: February 23, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Positron Emission Tomography; Magnetic Resonance Imaging; Brain metabolism
• Other Study ID Numbers: 2022P002851

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No