Identifying Decision Making Parameters and Their Neural Correlates, Using Human Neuroimaging, in Healthy Volunteers (HV) and Anxiety Patients (AD).

Sponsor
National Institute of Mental Health (NIMH) (NIH)
Overall Status
Recruiting
CT.gov ID
NCT05092971
Collaborator
(none)
140
Enrollment
1
Location
2
Arms
7.2
Anticipated Duration (Months)
19.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Study Description:

This study has two goals: (1) to identify parameters of interest in decision making in the context of anxiety disorders, using theoretical models (2) and to identify neural correlates of these parameters, using human neuroimaging in healthy volunteers (HV) and anxiety patients (AD). Participants are asked to complete a decision-making task, namely the Multi-armed Bandit Task. The study includes 2 arms: Clinic, Scanner.

  1. Clinic: Participants (HV and AD) are asked to fill out questionnaires and complete the Multi-armed Bandit Task. An electric shock is used as the aversive stimulus. Monetary reward is used as the reward stimulus. Additionally, physiological signals (Heart rate, skin conductance activity, startle) are collected during the course of the task.

In addition, in a pilot study, participants startle responses for varying shock parameters are recorded and analyzed.

  1. Scanner: Participants (HV) are asked to fill out questionnaires and complete the Multi-armed Bandit Task. An electric shock is used as the aversive stimulus. Monetary reward is used as the reward stimulus. Additionally, physiological signals (Heart rate, breathing rate) are collected during the course of the task.
Objectives:

The primary objective of this study is to use theoretical models in healthy volunteers (HV) and patients with an anxiety disorder (AD) to better understand how changes in anxiety are associated with changes in decision making. The neural correlates of these decision-making parameters will be identified using functional imaging. In addition, this study will ascertain whether decision making parameters correlate with certain behavioral measures such as trait and state anxiety using (i) questionnaires, (ii) physiological measures.

Endpoints:

The primary endpoint of this study is a significant difference in model derived parameters between experimental manipulations (conditions) and/or population groups. The parameters of interest include: 1) Learning Rate, 2) Exploration parameter, 3) Discount rate, 4) Loss aversion, 5) Inverse Temperature.

The neural correlates of these decision-making parameters will be identified using functional imaging parametric modulation.

The secondary endpoints are a significant correlation between functions of model derived parameters and behavioral and/or physiological measures of anxiety including:

  1. Questionnaire scores

  2. Startle

  3. Skin conductance

Study Population:

Participants will be males and females, 18 years and older. They must be English-speaking.

The study population will include patient and volunteer participants. Number of participants:
  1. Clinic:

Multi-arm Bandit task: 80 (40 HV, 40 AD)

Pilot: 20 HV

TOTAL for clinic study: 100

  1. Scanner:

Multi-arm Bandit task: 40 HV

TOTAL for fMRI: 40 HV

TOTAL ACCRUAL CEILING: 140 volunteers

Description of Sites/Facilities Enrolling Participants:

Single-site study at National Institutes of Health

Description of Study Intervention:

Multi-arm Bandit task.

Electric shocks: Electric shocks are used as aversive stimuli. Electric shocks are one of the most efficient ways to induce anxiety in the laboratory. The shocks will be delivered through two disk electrodes located on the forearm or on two fingers

Auditory startle: The startle reflex will be elicited with a 102 dB white noise (40-ms duration) delivered binaurally via headphones.

fMRI: A high-resolution T1-weighted anatomical scan of the whole brain using a magnetization prepared gradient echo sequence (MPRAGE) and the functional scans will be acquired. Participants will be scanned in the 7-Tesla fMRI scanner.

Study Duration:

12 months

Participant Duration:

One outpatient visit

Condition or DiseaseIntervention/TreatmentPhase
  • Behavioral: Multi-arm bandit task
  • Device: Multi-arm bandit task
N/A

Detailed Description

Study Description:

This study has two goals: (1) to identify parameters of interest in decision making in the context of anxiety disorders, using theoretical models (2) and to identify neural correlates of these parameters, using human neuroimaging in healthy volunteers (HV) and anxiety patients (AD). Participants are asked to complete a decision-making task, namely the Multi-armed Bandit Task. The study includes 2 arms: Clinic, Scanner.

  1. Clinic: Participants (HV and AD) are asked to fill out questionnaires and complete the Multi-armed Bandit Task. An electric shock is used as the aversive stimulus. Monetary reward is used as the reward stimulus. Additionally, physiological signals (Heart rate, skin conductance activity, startle) are collected during the course of the task.

In addition, in a pilot study, participants startle responses for varying shock parameters are recorded and analyzed.

  1. Scanner: Participants (HV) are asked to fill out questionnaires and complete the Multi-armed Bandit Task. An electric shock is used as the aversive stimulus. Monetary reward is used as the reward stimulus. Additionally, physiological signals (Heart rate, breathing rate) are collected during the course of the task.
Objectives:

The primary objective of this study is to use theoretical models in healthy volunteers (HV) and patients with an anxiety disorder (AD) to better understand how changes in anxiety are associated with changes in decision making. The neural correlates of these decision-making parameters will be identified using functional imaging. In addition, this study will ascertain whether decision making parameters correlate with certain behavioral measures such as trait and state anxiety using (i) questionnaires, (ii) physiological measures.

Endpoints:

The primary endpoint of this study is a significant difference in model derived parameters between experimental manipulations (conditions) and/or population groups. The parameters of interest include: 1) Learning Rate, 2) Exploration parameter, 3) Discount rate, 4) Loss aversion, 5) Inverse Temperature.

The neural correlates of these decision-making parameters will be identified using functional imaging parametric modulation.

The secondary endpoints are a significant correlation between functions of model derived parameters and behavioral and/or physiological measures of anxiety including:

  1. Questionnaire scores

  2. Startle

  3. Skin conductance

Study Population:

Participants will be males and females, 18 years and older. They must be English-speaking.

The study population will include patient and volunteer participants. Number of participants:
  1. Clinic:

Multi-arm Bandit task: 80 (40 HV, 40 AD)

Pilot: 20 HV

TOTAL for clinic study: 100

  1. Scanner:

Multi-arm Bandit task: 40 HV

TOTAL for fMRI: 40 HV

TOTAL ACCRUAL CEILING: 140 volunteers

Description of Sites/Facilities Enrolling Participants:

Single-site study at National Institutes of Health

Description of Study Intervention:

Multi-arm Bandit task.

Electric shocks: Electric shocks are used as aversive stimuli. Electric shocks are one of the most efficient ways to induce anxiety in the laboratory. The shocks will be delivered through two disk electrodes located on the forearm or on two fingers

Auditory startle: The startle reflex will be elicited with a 102 dB white noise (40-ms duration) delivered binaurally via headphones.

fMRI: A high-resolution T1-weighted anatomical scan of the whole brain using a magnetization prepared gradient echo sequence (MPRAGE) and the functional scans will be acquired. Participants will be scanned in the 7-Tesla fMRI scanner.

Study Duration:

12 months

Participant Duration:

One outpatient visit

Study Design

Study Type:
Interventional
Anticipated Enrollment :
140 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
Identifying Decision Making Parameters and Their Neural Correlates, Using Human Neuroimaging, in Healthy Volunteers (HV) and Anxiety Patients (AD).
Anticipated Study Start Date :
Nov 24, 2021
Anticipated Primary Completion Date :
Jun 1, 2022
Anticipated Study Completion Date :
Jul 1, 2022

Arms and Interventions

ArmIntervention/Treatment
Other: Clinic

Tasks to be completed in OP4 clinic

Behavioral: Multi-arm bandit task
Part 1 to be completed in the clinic. Subject participation is for one part and is pseudo-randomly.

Other: fMRI

Tasks to be completed in fMRI

Device: Multi-arm bandit task
Part 2 to be completed in the scanner. Subject participation is for one part and is pseudo-randomly.

Outcome Measures

Primary Outcome Measures

  1. Learning rate [End of study]

    The primary endpoint of this study is a significant difference in model derived parameters between experimental manipulations (conditions) and/or population groups.

  2. Risk-taking (vs. risk aversion) [End of study]

    The primary endpoint of this study is a significant difference in model derived parameters between experimental manipulations (conditions) and/or population groups.

  3. Discount rate [End of study]

    The primary endpoint of this study is a significant difference in model derived parameters between experimental manipulations (conditions) and/or population groups.

  4. Inverse temperature [End of study]

    The primary endpoint of this study is a significant difference in model derived parameters between experimental manipulations (conditions) and/or population groups.

  5. Loss aversion [End of study]

    The primary endpoint of this study is a significant difference in model derived parameters between experimental manipulations (conditions) and/or population groups.

  6. Exploration parameter [End of study]

    The primary endpoint of this study is a significant difference in model derived parameters between experimental manipulations (conditions) and/or population groups.

Secondary Outcome Measures

  1. Startle [End of study]

    The secondary endpoints are a significant correlation between functions of model derived parameters and behavioral and/or physiological measures of anxiety including:

  2. STAI questionnaire [End of study]

    The secondary endpoints are a significant correlation between functions of model derived parameters and behavioral and/or physiological measures of anxiety including:

  3. Skin conductance [End of study]

    The secondary endpoints are a significant correlation between functions of model derived parameters and behavioral and/or physiological measures of anxiety including:

  4. MASQ [End of study]

    The secondary endpoints are a significant correlation between functions of model derived parameters and behavioral and/or physiological measures of anxiety including:

  5. BIS/BAS [End of study]

    The secondary endpoints are a significant correlation between functions of model derived parameters and behavioral and/or physiological measures of anxiety including:

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 50 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
  • INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

Clinic and fMRI:
  1. Provision of signed and dated informed consent form

  2. Male or female, aged 18-50, inclusive

  3. Patients only: Primary DSM5 diagnoses of an anxiety disorder (GAD, SAD, panic disorder)

EXCLUSION CRITERIA:
Clinic and fMRI:

An individual who meets any of the following criteria will be excluded from participation in this

study:

  1. Non-English speaking individual

  2. Pregnancy or positive pregnancy test

  3. Any significant medical or neurological problems as determined by investigators (e.g. cardiovascular illness, respiratory illness, neurological illness, seizure, etc.)

  4. Current use of medications that pass the blood brain barrier and act on histamine (i.e. diphenhydramine), dopamine (methylphenidate), norepinephrine (buproprion), serotonin (sertraline), or acetylcholine (amitryptiline) receptors. Subjects will be excluded if they take these medications on a chronic basis. Subjects will be included if they have not taken the medication for five half-lives prior to a study visit.

  5. Current or past serious mental disorders (e.g., bipolar or psychotic disorders) (except for anxiety and depressive disorders in patients)

  6. Current alcohol or substance use disorder

  7. History of moderate or severe alcohol or substance use disorder within one year prior to screening

  8. Current psychotropic medication use. Anxiolytic medications are allowed if they are taken on an as needed basis and the subject has not taken the medication for five halflives prior to a study visit.

  9. Current or past significant organic central nervous system disorders as determined by investigators, including but not limited to seizure disorder or neurological symptoms of the wrist and arm (e.g., carpal tunnel syndrome) for shocks to be delivered on affected arm.

  10. Positive urine toxicology screen at screening visit under 01-M-0254

  11. Employees of NIMH or an immediate family member of a NIMH employee.

  12. fMRI study only: Any medical condition that increases risk for fMRI:

  13. Any metal implants (clips, screws, plates, pins, etc) that are not deemed to be MRI safe

  14. Any sort of medical implants that are determined to be not safe for MRI (aneurysm clips, pacemaker, insulin pump, Hickman line, etc.) Certain types of IUD and other implants are allowable if they are determined to be safe for MRI.

  15. Permanent makeup and tattoos above the neck

  16. Patients who have difficulty lying flat on their back for up to 120 min in the scanner

  17. Healthy volunteers only: Current DSM-5 disorders.

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1National Institutes of Health Clinical CenterBethesdaMarylandUnited States20892

Sponsors and Collaborators

  • National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: Monique Ernst, M.D., National Institute of Mental Health (NIMH)

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier:
NCT05092971
Other Study ID Numbers:
  • 10000378
  • 000378-M
First Posted:
Oct 26, 2021
Last Update Posted:
Nov 19, 2021
Last Verified:
Nov 10, 2021
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by National Institute of Mental Health (NIMH)
Additional relevant MeSH terms:

Study Results

No Results Posted as of Nov 19, 2021