RECOVERS - Realigning Emotion and COgnition Via prEcision Regulation networkS

RECOVERS - Realigning Emotion and COgnition Via prEcision Regulation networkS - Phase I Study: Multimodal Computational Modeling of Cognitive Flexibility and Emotion Regulation Networks

In this research study, the investigators are examining how brain activity (electrical and blood flow) changes during tests of emotional processing, attention and memory in the magnetic resonance imaging (MRI) scanner and outside the MRI using functional near-infrared spectroscopy (fNIRS). Investigators are also using non-invasive brain stimulation to probe different parts of the brain and measuring brain activity (electrical and blood flow).

Study 1

This study includes healthy participants and researchers hope this will help us develop improved brain-based treatments for emotional difficulties like depression.

Study 2

This study includes participants with depression and researchers hope this will help us develop improved brain-based treatments for emotional difficulties like depression.

Study Overview

• Status: Recruiting
• Conditions: Healthy; Depression - Major Depressive Disorder
• Intervention / Treatment: Device: fMRI-EEG-TMS; Device: fNIRS-EEG-TMS; Device: fNIRS-EEG-rTMS Interleaved with CBT

Detailed Description

Investigators hypothesize that targeted neuroplastic changes induced by individually-tailored rTMS will substantially reduce clinical symptoms underlying depression, anxiety and suicidality, and in general, revolutionize non-invasive treatments of mental health disorders. Investigators hypothesize that functional coupling in cognitive flexibility (CF) and emotion regulation (ER) networks is indexed by the phase of the brain's alpha oscillations. Using a novel integrated instrument that enables simultaneous functional magnetic resonance imaging (fMRI), electroencephalography (EEG) and transcranial magnetic stimulation (TMS), investigators propose to identify individualized stimulation parameters that reflect the strongest coupling of the CF/ER networks. Investigators will also use an instrument that enables simultaneous functional near-infrared spectroscopy (fNIRS), EEG, and TMS in attempt to identify the same parameters outside the scanner. The neuromechanistic model further posits that by applying repetitive TMS (rTMS) with these individualized parameters, one can induce entrainment in brain networks that drive neuroplastic changes in CF and ER.

Study 1

This study is a proof-of-principle study in healthy control participants.

Study 2

This study is a proof-of-principle study in participants with depression.

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Lisa McTeague, PhD; Phone Number: 843-792-8274; Email: mcteague@musc.edu
• Study Contact Backup: Name: Jacob Eade, MS; Email: recovers@musc.edu

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical Univeristy of South Carolina
      • Contact: Lisa M McTeague, PhD; Phone Number: 843-792-8274; Email: mcteague@musc.edu
      • Contact: Jacob Eade; Email: eadej@musc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Participants are healthy and depressed volunteers from the community.

Description

Study 1

Inclusion Criteria

• Male or female
• Age 18-65
• Endorse good health with no history of mental or physical illness or implanted metal
• English as a primary language
• Capacity to consent
• Negative urine pregnancy test if female of childbearing potential
• Willingness to adhere to the study schedule and assessments

Exclusion Criteria

• Any current psychiatric diagnosis or current Clinical Global Impression ratings of psychiatric illness > 1
• Neurodevelopmental disorders, history of CNS disease, concussion, overnight hospitalization, or other neurologic sequela, tumors, seizures, meningitis, encephalitis, or abnormal CT or MRI of the brain
• Any head trauma resulting in loss of consciousness
• Visual impairment (except the use of glasses)
• Inability to complete cognitive testing
• Active participation or plan for enrollment in clinical trial affecting the psychosocial function
• Repeated abuse or dependence upon drugs (excluding nicotine and caffeine) or taking medications including stimulants, modafinil, thyroid medication, or steroids
• Implanted devices/ferrous metal of any kind
• History of seizure or epilepsy, currently taking medications that lower seizure thresholds
• Claustrophobia or other conditions that would prevent the MRI assessment.

• Pregnancy (or suspected/possible pregnancy or plan to become pregnant in the short term).

  o Urine Pregnancy Test: If the subject is a woman of childbearing potential and /or a man capable of fathering a child before, during, and/or after participation precautions should be taken. Examples of acceptable methods of birth control for participants involved in the study include birth control pills, patches, IUDs, condoms, sponges, diaphragm with spermicide, or avoiding sexual activity that could cause the subject to become pregnant.

• Inability to adhere to the treatment schedule

Study 2

Inclusion Criteria

• Male or female
• Age 18-65
• Endorse current depression, identified via the Hamilton Depression Rating Scale (HAM-D scores ≥ 17), but no history of psychosis or mania, determined via the Quick Structured Clinical Interview for DSM-5 Disorders (SCID).
• English as a primary language
• Capacity to consent
• Negative urine pregnancy test if female of childbearing potential
• Willingness to adhere to the study schedule and assessments

Exclusion Criteria

• Neurodevelopmental disorders, history of CNS disease, concussion, overnight hospitalization, or other neurologic sequela, tumors, seizures, meningitis, encephalitis, or abnormal CT or MRI of the brain
• Any head trauma resulting in loss of consciousness
• Visual impairment (except the use of glasses)
• Inability to complete cognitive testing
• Active participation or plan for enrollment in clinical trial affecting the psychosocial function
• Repeated abuse or dependence upon drugs (excluding nicotine and caffeine) or taking medications including stimulants, modafinil, thyroid medication, or steroids
• Implanted devices/ferrous metal of any kind
• History of seizure or epilepsy, currently taking medications that lower seizure thresholds

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy Participants; Endorse good health with no history of mental or physical illness or implanted metal	Device: fMRI-EEG-TMS; Participants will undergo a magnetic resonance imaging (MRI) scan with combined electroencephalography (EEG), and single-pulse transcranial magnetic stimulation (TMS) while completing cognitive flexibility (CF) and emotion recognition (CR) tasks.; Device: fNIRS-EEG-TMS; Participants brain activity will be measured using functional near-infrared spectroscopy (fNIRS) with combined electroencephalography (EEG), and single-pulse transcranial magnetic stimulation (TMS) while completing cognitive flexibility (CF) and emotion recognition (CR) tasks.
Depressed Participants; Endorse current depression, identified via the Hamilton Depression Rating Scale (HAM-D scores ≥ 17), but no history of psychosis or mania, determined via the Quick Structured Clinical Interview for DSM-5 Disorders (SCID).	Device: fMRI-EEG-TMS; Participants will undergo a magnetic resonance imaging (MRI) scan with combined electroencephalography (EEG), and single-pulse transcranial magnetic stimulation (TMS) while completing cognitive flexibility (CF) and emotion recognition (CR) tasks.; Device: fNIRS-EEG-TMS; Participants brain activity will be measured using functional near-infrared spectroscopy (fNIRS) with combined electroencephalography (EEG), and single-pulse transcranial magnetic stimulation (TMS) while completing cognitive flexibility (CF) and emotion recognition (CR) tasks.; Device: fNIRS-EEG-rTMS Interleaved with CBT; Participants brain activity will be measured using functional near-infrared spectroscopy (fNIRS) with combined electroencephalography (EEG), and repetitive transcranial magnetic stimulation (rTMS). rTMS will be delivered via a MagVenture MagPro100 and Cool-B65 coil. The investigators will use a standard resting motor threshold (rMT) determination to determine the TMS dose. Treatment will be delivered at 120% of the motor threshold. The accelerated paradigm will consist 6 session a day for 5-6 days. Each rTMS session will be separated by 30 minutes of Cognitive Behavioral Therapy (CBT). rTMS treatment will be delivered at an individualized left DLPFC target based on each participant's individualized scans from prior neuroimaging sessions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in reaction time (RT) tasks - Incongruent Stimuli	Tasks will be used to see differences between incongruent emotional stimuli.	Day 1, Day 2, Day 3
Change in reaction time (RT) tasks - Congruent Stimuli	Tasks will be used to see differences between congruent emotional stimuli.	Day 1, Day 2, Day 3
Change in reaction time (RT) tasks and accuracy - Incongruent Stimuli	Tasks will be used to see differences between incongruent emotional stimuli.	Day 1, Day 2, Day 3
Change in reaction time (RT) tasks and accuracy - Congruent Stimuli	Tasks will be used to see differences between congruent emotional stimuli.	Day 1, Day 2, Day 3
Clinical Improvement	25% reduction in Hamilton Score (HAMD) as a meaningful treatment response.	Day 13, Day 18
Clinical Improvement	25% reduction in Passive and Active Suicidal Ideation Scale (PASIS) as a meaningful treatment response.	Day 13, Day 18
Clinical Improvement	25% reduction in Patient Health Questionnaire (PHQ-9) as a meaningful treatment response.	Day 13, Day 18
Clinical Improvement	25% reduction in Generalized Anxiety Disorder -7 Questionnaire (GAD7) as a meaningful treatment response.	Day 13, Day 18

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: Columbia University; University of Wisconsin, Madison; University of Oklahoma; Defense Advanced Research Projects Agency
• Investigators: Principal Investigator: Lisa McTeague, PhD, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2024
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: June 29, 2023
• First Submitted That Met QC Criteria: July 26, 2023
• First Posted (Actual): August 4, 2023

Study Record Updates

• Last Update Posted (Estimated): September 2, 2025
• Last Update Submitted That Met QC Criteria: August 25, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: healthy volunteer; magnetic resonance imaging (MRI); electroencephalography (EEG); transcranial magnetic stimulation (TMS); cognitive behavioral therapy (CBT); functional near-infrared spectroscopy (fNIRS)
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: 00129566

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: Yes
• product manufactured in and exported from the U.S.: No