Clinical trial NCT06980090: Neural Mechanisms of Interpersonal Expectations on Negative Affect
Official title: Neural Mechanisms of Interpersonal Expectations on Negative Affect
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Negative Affectivity
Non-invasive Brain Stimulation
Placebo Effect
Expectations
Keywords: Transcranial temporal interference stimulation
Pain
Fear
Cognitive effort
Lead sponsor: Trustees of Dartmouth College
Sponsor class: OTHER
First posted: 2025-05-20
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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.
Primary purpose: BASIC_SCIENCE

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.

Detailed description: The study employs a within-subject, crossover factorial design, consisting of two experiments.

Experiment 1

In Experiment 1, 30 participants ('patients') will complete all combinations of two independent variables-stimulation type (active vs. sham tTIS) and placebo manipulation (positive vs. negative placebo messaging)-resulting in four sessions:

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

Participants complete three multimodal negative affect tasks (MNAT) before and after each stimulation session. Active tTIS delivers two signals at 2000 Hz and 2080 Hz, generating an 80 Hz interference beat targeted at the anterior/mid-cingulate cortex (aMCC) at 2 mA for 20 minutes. Sham tTIS uses identical frequencies (2000 Hz and 2000 Hz) with no effective interference.

Sessions are administered in a counterbalanced order based on a Balanced Latin Square to minimize order effects, with at least 48 hours between sessions. Participants thus serve as their own controls.

Experiment 2

Experiment 2 includes 160 participants divided into two groups: 120 'patients' and 40 'doctors'.

A within-subject crossover design is employed, focusing specifically on placebo manipulation effects. Patients complete two experimental sessions involving sham tTIS only:

* Session E: On-Placebo + Sham tTIS (with social placebo intervention)
* Session F: Off-Placebo + Sham tTIS (without placebo intervention)

In both sessions, patients complete the same MNAT tasks before and after stimulation. Sham tTIS involves a brief 15-second stimulation followed by no current for the remainder of the session, preserving the illusion of active stimulation.

'Doctors' are trained to administer the sham stimulation and deliver the placebo manipulation. During placebo induction sessions, providers simulate a "personalization" procedure, adjusting sham parameters while covertly reducing pain stimulus intensity to enhance placebo effects. Providers also monitor patients' nonverbal behavior and reported affect, offering feedback to enhance engagement and perceived treatment quality.

Participants undergo MRI scanning, physiological monitoring, and behavioral assessments during Experiment 2. Multimodal physiological data-including ECG, respiration, skin conductance, photoplethysmography (PPG), and trans-radial electrical bioimpedance velocimetry (TRVE)-are collected using the BIOPAC 160 system.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* 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)

Primary outcomes:
measure: Cognitive effort ratings
timeFrame: 3-10 sec post-stimulus throughout testing sessions, with all sessions complete within 1 month
measure: Subjective fear ratings
timeFrame: 3-10 sec post-stimulus throughout testing sessions, with all sessions complete within 1 month
measure: Pain ratings
timeFrame: 3-10 sec post-stimulus throughout testing sessions, with all sessions complete within 1 month
Secondary outcomes:
measure: Electrodermal autonomic responses to painful heat, fear-related images and cognitive effort
timeFrame: Peri-stimulus throughout testing sessions, with all sessions complete within 1 month
Other outcomes:
Locations:
city: Hanover
country: United States
facility: Dartmouth College
state: New Hampshire
Study officials:
References:
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