Neural Mechanisms of Interpersonal Expectations on Negative Affect

NCT06980090 | Recruiting

• 1 other identifier: 467251
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn whether non-invasive brain stimulation, called transcranial temporal interference stimulation (tTIS), can reduce negative affect, and how expectations shaped by care providers influence these effects. The main questions this study aims to answer are: (1)Does active tTIS reduce negative affect more effectively than sham (inactive) tTIS? (2)Do positive treatment expectations enhance the effects compared to negative expectations? Participants will: (1) Receive either active or sham tTIS. (2) Be provided with positive or negative messaging regarding treatment effectiveness. (3) Interact with care providers and complete assessments measuring negative affect and physiological responses.

Conditions

Negative Affectivity; Non-invasive Brain Stimulation; Placebo Effect; Expectations

Keywords

Transcranial temporal interference stimulation; Pain; Fear; Cognitive effort

Outcome Measures

Primary Outcomes (3)

• Cognitive effort ratings

  Participants report cognitive effort after each trial on a Generalized Linear Magnitude scale (GLMS) with anchors of "No effort" and "Most effort imaginable". Raw units are on a 0-180 scale.

  3-10 sec post-stimulus throughout testing sessions, with all sessions complete within 1 month

• Subjective fear ratings

  Participants report subjective fear experience after each trial on a well-validated Generalized Linear Magnitude scale (GLMS) with anchors of "No fear" and "Most intense fear imaginable". Raw units are on a 0-180 scale.

  3-10 sec post-stimulus throughout testing sessions, with all sessions complete within 1 month

• Pain ratings

  Participants report subjective pain experience after each trial on a well-validated Generalized Linear Magnitude scale (GLMS) with anchors of "No pain" and "Most intense pain imaginable". Raw units are on a 0-180 scale.

  3-10 sec post-stimulus throughout testing sessions, with all sessions complete within 1 month

Secondary Outcomes (1)

• Electrodermal autonomic responses to painful heat, fear-related images and cognitive effort

  Peri-stimulus throughout testing sessions, with all sessions complete within 1 month

Study Arms (6)

Experiment 1 - Crossover Order: Session A-B-C-D

EXPERIMENTAL

Participants complete all four experimental sessions in the following sequence: 1. Session A; 2. Session B; 3. Session C; 4.Session D

Behavioral: Session A: Positive Placebo + Active tTIS; Behavioral: Session B: Positive Placebo + Sham tTIS; Behavioral: Session C: Negative Placebo + Active tTIS; Behavioral: Session D: Negative Placebo + Sham tTIS

Experiment 1- Crossover Order: Session B-C-D-A

EXPERIMENTAL

Participants complete all four experimental sessions in the following sequence: 1. Session B; 2. Session C; 3. Session D; 4. Session A

Behavioral: Session A: Positive Placebo + Active tTIS; Behavioral: Session B: Positive Placebo + Sham tTIS; Behavioral: Session C: Negative Placebo + Active tTIS; Behavioral: Session D: Negative Placebo + Sham tTIS

Experiment 1- Crossover Order: Session C-D-A-B

EXPERIMENTAL

Participants complete all four experimental sessions in the following sequence: 1. Session C; 2.Session D; 3. Session A; 4. Session B

Behavioral: Session A: Positive Placebo + Active tTIS; Behavioral: Session B: Positive Placebo + Sham tTIS; Behavioral: Session C: Negative Placebo + Active tTIS; Behavioral: Session D: Negative Placebo + Sham tTIS

Experiment 1- Crossover Order: Session D-A-B-C

EXPERIMENTAL

Participants complete all four experimental sessions in the following sequence: 1. Session D; 2. Session A; 3. Session B; 4. Session C

Behavioral: Session A: Positive Placebo + Active tTIS; Behavioral: Session B: Positive Placebo + Sham tTIS; Behavioral: Session C: Negative Placebo + Active tTIS; Behavioral: Session D: Negative Placebo + Sham tTIS

Experiment 2 - Crossover Order : Session E-F

EXPERIMENTAL

Participants complete all two experimental sessions in the following sequence: 1. Session E; 2. Session F

Behavioral: Session E: On-Placebo + Sham tTIS; Behavioral: Session F: Off-Placebo + Sham tTIS

Experiment 2 - Crossover Order : Session F-E

EXPERIMENTAL

Participants complete all two experimental sessions in the following sequence: 1. Session F; 2. Session E

Behavioral: Session E: On-Placebo + Sham tTIS; Behavioral: Session F: Off-Placebo + Sham tTIS

Interventions

Session A: Positive Placebo + Active tTIS BEHAVIORAL

Participants receive active tTIS, with two signals set at 2000 Hz and 2080 Hz, creating an 80 Hz interference beat targeting the anterior/mid-cingulate cortex (aMCC). Stimulation is delivered at 2 mA for 20 minutes. The stimulation is combined with a positive social placebo intervention delivered by the care provider. Participants complete three multimodal negative affect tasks (MNAT) before and after the stimulation.

Experiment 1 - Crossover Order: Session A-B-C-D; Experiment 1- Crossover Order: Session B-C-D-A; Experiment 1- Crossover Order: Session C-D-A-B; Experiment 1- Crossover Order: Session D-A-B-C

Session B: Positive Placebo + Sham tTIS BEHAVIORAL

Participants receive sham tTIS, using two identical 2000 Hz signals that produce no low-frequency interference. The device mimics active parameters (2 mA, 20 minutes) without delivering effective stimulation. The sham stimulation is paired with a positive social placebo intervention. Participants complete three MNAT tasks before and after the session.

Experiment 1 - Crossover Order: Session A-B-C-D; Experiment 1- Crossover Order: Session B-C-D-A; Experiment 1- Crossover Order: Session C-D-A-B; Experiment 1- Crossover Order: Session D-A-B-C

Session C: Negative Placebo + Active tTIS BEHAVIORAL

Participants receive active tTIS (2000 Hz and 2080 Hz signals, 2 mA, 20 minutes) combined with a negative social placebo intervention (neutral or skeptical messaging about treatment efficacy). Participants complete three MNAT tasks before and after the stimulation.

Experiment 1 - Crossover Order: Session A-B-C-D; Experiment 1- Crossover Order: Session B-C-D-A; Experiment 1- Crossover Order: Session C-D-A-B; Experiment 1- Crossover Order: Session D-A-B-C

Session D: Negative Placebo + Sham tTIS BEHAVIORAL

Participants receive sham tTIS (identical 2000 Hz signals, mimicking active stimulation) combined with a negative social placebo intervention. Participants complete three MNAT tasks before and after the session.

Experiment 1 - Crossover Order: Session A-B-C-D; Experiment 1- Crossover Order: Session B-C-D-A; Experiment 1- Crossover Order: Session C-D-A-B; Experiment 1- Crossover Order: Session D-A-B-C

Session E: On-Placebo + Sham tTIS BEHAVIORAL

Participants receive sham tTIS (brief 15-second stimulation followed by no current) paired with a positive social placebo intervention. Participants complete three MNAT tasks before and after the session.

Experiment 2 - Crossover Order : Session E-F; Experiment 2 - Crossover Order : Session F-E

Session F: Off-Placebo + Sham tTIS BEHAVIORAL

Participants receive sham tTIS (brief 15-second stimulation, then no current) without any placebo intervention. Participants complete three MNAT tasks before and after the session.

Experiment 2 - Crossover Order : Session E-F; Experiment 2 - Crossover Order : Session F-E

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 'Doctors' are recruited from medical students at the Geisel School of Medicine and resident physicians at Dartmouth Hitchcock Medical Center (DHMC).

You may not qualify if:

• No self-reported current or history of depression, bipolar disorder, or other psychiatric diagnosis
• No self-reported current seizure disorder (i.e., seizure within past 10 years), or history of stroke or other major neurological diagnosis that can cause cognitive impairment
• No self-reported current chronic pain, or acute pain within three months of the study period
• No current migraine disorder (i.e., 15 headache days or more in 1 month)
• No use of central nervous system-effective medication or other medication for neurological/psychiatric treatment
• No self-reported substance abuse within the last six months
• No contraindication to MRI or tTIS (e.g., pregnancy, claustrophobia, pacemakers, ear/cochlear implants, shrapnel injuries, clips, or other ferromagnetic/electrical objects/devices, diagnosed brain abnormality such as tumor, or skin lesions on the scalp.)
• No contraindications for induced pain (e.g., no heart disease, high blood pressure, heart surgery, heart problems of any kind, severe asthma, respiratory problems of any kind, fibromyalgia, Raynaud's Syndrome or Disease, chronic pain, diabetes)
• Participants must be capable of performing experimental tasks (e.g., are able to read), are fluent or native speakers of English
• Participants must be able to tolerate the maximum level of thermal pain stimuli (for thermal stimuli)

Sponsors & Collaborators

• Trustees of Dartmouth College: lead

Study Sites (1)

Dartmouth College, Department of Psychological and Brain Sciences

Hanover, New Hampshire, 03755, United States

RECRUITING

Related Publications (7)

• Acerbo E, Jegou A, Luff C, Dzialecka P, Botzanowski B, Missey F, Ngom I, Lagarde S, Bartolomei F, Cassara A, Neufeld E, Jirsa V, Carron R, Grossman N, Williamson A. Focal non-invasive deep-brain stimulation with temporal interference for the suppression of epileptic biomarkers. Front Neurosci. 2022 Aug 17;16:945221. doi: 10.3389/fnins.2022.945221. eCollection 2022.

  PMID: 36061593 BACKGROUND

• Wessel MJ, Beanato E, Popa T, Windel F, Vassiliadis P, Menoud P, Beliaeva V, Violante IR, Abderrahmane H, Dzialecka P, Park CH, Maceira-Elvira P, Morishita T, Cassara AM, Steiner M, Grossman N, Neufeld E, Hummel FC. Noninvasive theta-burst stimulation of the human striatum enhances striatal activity and motor skill learning. Nat Neurosci. 2023 Nov;26(11):2005-2016. doi: 10.1038/s41593-023-01457-7. Epub 2023 Oct 19.

  PMID: 37857774 BACKGROUND

• von Conta J, Kasten FH, Schellhorn K, Curcic-Blake B, Aleman A, Herrmann CS. Benchmarking the effects of transcranial temporal interference stimulation (tTIS) in humans. Cortex. 2022 Sep;154:299-310. doi: 10.1016/j.cortex.2022.05.017. Epub 2022 Jun 16.

  PMID: 35839572 BACKGROUND

• Violante IR, Alania K, Cassara AM, Neufeld E, Acerbo E, Carron R, Williamson A, Kurtin DL, Rhodes E, Hampshire A, Kuster N, Boyden ES, Pascual-Leone A, Grossman N. Non-invasive temporal interference electrical stimulation of the human hippocampus. Nat Neurosci. 2023 Nov;26(11):1994-2004. doi: 10.1038/s41593-023-01456-8. Epub 2023 Oct 19.

  PMID: 37857775 BACKGROUND

• Vassiliadis P, Beanato E, Popa T, Windel F, Morishita T, Neufeld E, Duque J, Derosiere G, Wessel MJ, Hummel FC. Non-invasive stimulation of the human striatum disrupts reinforcement learning of motor skills. Nat Hum Behav. 2024 Aug;8(8):1581-1598. doi: 10.1038/s41562-024-01901-z. Epub 2024 May 29.

  PMID: 38811696 BACKGROUND

• Sandra DA, Olson JA, Langer EJ, Roy M. Presenting a sham treatment as personalised increases the placebo effect in a randomised controlled trial. Elife. 2023 Jul 5;12:e84691. doi: 10.7554/eLife.84691.

  PMID: 37405829 BACKGROUND

• Grossman N, Bono D, Dedic N, Kodandaramaiah SB, Rudenko A, Suk HJ, Cassara AM, Neufeld E, Kuster N, Tsai LH, Pascual-Leone A, Boyden ES. Noninvasive Deep Brain Stimulation via Temporally Interfering Electric Fields. Cell. 2017 Jun 1;169(6):1029-1041.e16. doi: 10.1016/j.cell.2017.05.024.

  PMID: 28575667 BACKGROUND

MeSH Terms

Conditions

Pain

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Zhaoxing Wei, Ph.D.

CONTACT

6033220577; zhaoxing.wei@dartmouth.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Diana L. Taylor Distinguished Professor

Model Details: Experiment 1 involves participants completing all conditions formed by combinations of active vs. sham transcranial temporal interference stimulation (tTIS) and positive vs. negative placebo manipulations. The order of sessions is counterbalanced using a Balanced Latin Square approach to minimize order effects, with each participant serving as their own control. Experiment 2 specifically focuses on placebo manipulation effects. Participants complete two experimental sessions-one with placebo intervention (On-Placebo) and one without (Off-Placebo)-both sessions utilizing sham tTIS. Session order is counterbalanced, enabling each participant to act as their own control to isolate and assess the effects of the placebo manipulation.

Study Record Dates

• First Submitted: May 9, 2025
• First Posted: May 20, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): March 3, 2028
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

US (1)