Neuromodulation of Brain and Emotional Responses to Psychological Stress

NCT06603064 | Recruiting

• 2 other identifiers: STUDY24020114K01MH137517
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

Investigators are conducting this study to test if temporarily and non-invasively stimulating the brain will affect the emotional response to stress in healthy participants. Participants will perform a series of tasks while completing an MRI scan. After this, participants will be randomized to undergo transcranial magnetic stimulation (TMS) at two visits, undergoing active stimulation at one visit and undergoing 'sham' stimulation at another visit. Immediately following both stimulation sessions, participants will repeat the tasks during MRI scanning.

Conditions

Healthy; Anxiety

Keywords

stress; emotion; transcranial magnetic stimulation; TMS; functional Magnetic Resonance Imaging; fMRI; neuromodulation; cardiovascular

Outcome Measures

Primary Outcomes (7)

• Dorsal anterior cingulate cortex activation to stress

  Blood-oxygen-level-dependent (BOLD) signal in a dorsal anterior cingulate cortex (dACC) region of interest mask extracted from the incongruent (stress) vs congruent (control) contrast.

  30-60 mins post-stimulation

• Dorsal anterior cingulate cortex connectivity to stress

  Generalized psychophysiological interaction (gPPI) estimate reflecting stressor-evoked dorsal anterior cingulate cortex (dACC) functional connectivity to the anterior insula, amygdala, and periaqueductal gray.

  30-60 mins post-stimulation

• Change in arousal during stress

  Rating on a modified self-assessment manikin scale (SAM) measuring subjective ratings of arousal ("To what extent do you feel calm?" 1 - very calm, 9 - very aroused) following the psychological stressor task compared to a pre-stressor baseline.

  30-60 mins post-stimulation

• Change in valence during stress

  Rating on a modified self-assessment manikin scale (SAM) measuring subjective ratings of valence ("To what extent do you feel happy vs unhappy?" 1 - very unhappy, 9 - very unhappy) following the psychological stressor task compared to a pre-stressor baseline.

  30-60 mins post-stimulation

• Change in perceived control during stress

  Rating on a modified self-assessment manikin scale (SAM) measuring subjective ratings of perceived control ("To what extent do you feel in control?" 1 - very little control, 9 - very much control) following the psychological stressor task compared to a pre-stressor baseline.

  30-60 mins post-stimulation

• Systolic blood pressure response to stress

  The difference in systolic blood pressure (in mmHg) obtained during the psychological stress task compared to a resting pre-stressor period.

  30-60 mins post-stimulation

• Heart rate response to stress

  The difference in heart rate (in beats per minute) obtained during the psychological stress task compared to a resting pre-stressor period.

  30-60 mins post-stimulation

Secondary Outcomes (2)

• Dorsal anterior cingulate cortex (dACC) resting cerebral blood flow (rCBF)

  30-60 mins post-stimulation

• Positive and Negative Affect Schedule - Expanded Form (PANAS-X)

  30-60 mins post-stimulation

Study Arms (2)

Active then Sham

EXPERIMENTAL

In this arm, participants will first undergo active theta burst stimulation (cTBS) at the first visit and then undergo sham cTBS in the second visit.

Device: Active continuous theta burst stimulation; Device: Sham continuous theta burst stimulation

Sham then Active

EXPERIMENTAL

In this arm, participants will first undergo sham theta burst stimulation (cTBS) at the first visit and then undergo active cTBS in the second visit.

Device: Active continuous theta burst stimulation; Device: Sham continuous theta burst stimulation

Interventions

Active continuous theta burst stimulation DEVICE

This intervention involves an active form of continuous theta burst stimulation (cTBS) that will be targeted to the dorsal anterior cingulate cortex based on neural navigation software. cTBS will be delivered in one session, lasting a few minutes, before participants complete additional testing.

Active then Sham; Sham then Active

Sham continuous theta burst stimulation DEVICE

This intervention involves an sham form of continuous theta burst stimulation (cTBS) that will be targeted to the dorsal anterior cingulate cortex based on neural navigation software. cTBS will be delivered in one session, lasting a few minutes, before participants complete additional testing.

Active then Sham; Sham then Active

Eligibility Criteria

• Age: 30 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• e. A person who reports that he or she was once on a disallowed medication but has discontinued this medication for at least a month or longer and is otherwise eligible, is allowed to participate in the study.
• Anyone reporting 35 or more alcoholic drinks in the last 7 days is excluded.
• Anyone reporting consumption of 6 or more alcoholic drinks on 3 or more occasions in the past 7 days is excluded.
• Anyone reporting use of illicit drugs on 7 or more days in the past 2 weeks is excluded.
• Medical conditions:
• Epilepsy or a history of seizures.
• Self-reported prior heart attack, stroke, bypass surgery, angioplasty, congestive heart failure, arrhythmia (cardiac rhythm problems).
• Severe hypertension (SBP/DBP \> 160/and/or \>100 mmHg)
• Cancer (treatment in last 12 months, allowances for non-melanoma skin cancer)
• Liver disease
• Kidney disease
• Type I diabetes
• Self-reported history of a major neurological disorder or brain injury resulting in ongoing symptoms or cognitive impairment (e.g., multiple sclerosis, cerebral palsy, major head injury)
• Self-reported chronic psychotic illness (schizophrenia, bipolar disorder)
• Pregnant participants, or participants actively planning to become pregnant in the next 3 months, are excluded.

Sponsors & Collaborators

• University of Pittsburgh: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

MeSH Terms

Conditions

Anxiety Disorders

Condition Hierarchy (Ancestors)

Mental Disorders

Study Officials

• Thomas E Kraynak, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Thomas E Kraynak, PhD

CONTACT

412-246-6361; tekraynak@pitt.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Participants, study staff, and the principal investigator will be blinded (masked) to participant assignment. The TMS coil to be used for this study is specifically designed to ensure participant and study staff blinding to condition.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This study will use a within-subject crossover design involving an \'active\' TMS arm and a \'sham\' (placebo) TMS arm. Each arm involves one visit (approx 2 hours each). Participants will complete both arms of the design.

Study Record Dates

• First Submitted: September 16, 2024
• First Posted: September 19, 2024
• Study Start: April 9, 2025
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2029
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1)