Negative AffectivityNCT06980090
Neural Mechanisms of Interpersonal Expectations on Negative Affect
A study of Negative Affectivity and Non-invasive Brain Stimulation, run by Trustees of Dartmouth College at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Negative Affectivity, Non-invasive Brain Stimulation, Placebo Effect
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 196 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2025to 3 Mar 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 'Doctors' are recruited from medical students at the Geisel School of Medicine and resident physicians at Dartmouth Hitchcock Medical Center (DHMC).
Who cannot join
- 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
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- 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)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Dartmouth College, Department of Psychological and Brain Sciences
Hanover, New Hampshire, 03755
Tor D. Wager, Ph.D., 603-646-2196, tor.d.wager@dartmouth.edu
Zhaoxing Wei, Ph.D.
About this study
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.
Read the detailed description
The study employs a within-subject, crossover factorial design, consisting of two experiments.
Experiment 1
In Experiment 1, 36 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 2010 Hz, generating an 10 Hz interference beat targeted at the anterior/mid-cingulate cortex (aMCC) at 2 mA for 20 minutes. Sham tTIS uses same frequencies (2000 Hz and 2010 Hz), targeting the same region for only 80 seconds.
Sessions are administered in a counterbalanced order based on a Williams 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.
- Being tested
- Session A: Positive Placebo + Active tTIS, Session B: Positive Placebo + Sham tTIS, Session C: Negative Placebo + Active tTIS, Session D: Negative Placebo + Sham tTIS, Session E: On-Placebo + Sham tTIS
- Keywords
- Transcranial temporal interference stimulation, Pain, Fear, Cognitive effort
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Session A: Positive Placebo + Active tTISBehavioural
Participants receive active tTIS with two channels set at 2000 Hz and 2010 Hz, creating a 10 Hz interference beat targeting the anterior/mid-cingulate cortex (aMCC). Stimulation is delivered at 2 mA per channel 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.
Session B: Positive Placebo + Sham tTISBehavioural
Participants receive sham tTIS (brief 80-second stimulation followed by no current) paired with a positive social placebo intervention. The device mimics active parameters (2 mA per channel, 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.
Session C: Negative Placebo + Active tTISBehavioural
Participants receive active tTIS (2000 Hz and 2010 Hz signals, 2 mA per channel, 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.
Session D: Negative Placebo + Sham tTISBehavioural
Participants receive sham tTIS (brief 80-second stimulation followed by no current) combined with a negative social placebo intervention. Participants complete three MNAT tasks before and after the session.
Session E: On-Placebo + Sham tTISBehavioural
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.
Session F: Off-Placebo + Sham tTISBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| Experiment 1 - Crossover Order: Session A-B-D-C | Experimental | Participants complete all four experimental sessions in the following sequence: 1. Session A; 2. Session B; 3. Session D; 4. Session C Receives: 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-A-D | Experimental | Participants complete all four experimental sessions in the following sequence: 1. Session B; 2. Session C; 3. Session A; 4. Session D Receives: 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-B-A | Experimental | Participants complete all four experimental sessions in the following sequence: 1. Session C; 2.Session D; 3. Session B; 4. Session A Receives: 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-C-B | Experimental | Participants complete all four experimental sessions in the following sequence: 1. Session D; 2. Session A; 3. Session C; 4. Session B Receives: 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 Receives: 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 Receives: Behavioral: Session E: On-Placebo + Sham tTIS; Behavioral: Session F: Off-Placebo + Sham tTIS |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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
Skin conductance (EDA) is recorded continuously throughout test sessions and per-stimulus amplitude of canonical stimulus-locked EDA responses is reported in microsiemens (uS). Higher values indicate a higher EDA response.
Measured: Peri-stimulus throughout testing sessions, with all sessions complete within 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2025
- Study start1 Sep 2025
- Primary completion31 Aug 2027 (estimated)
- Study completion3 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Negative AffectivityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- 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 Williams 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.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 196 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Trustees of Dartmouth College
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tor Wager, Trustees of Dartmouth College
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06980090
- Sponsor's protocol ID
- 467251
- Status last verified
- Jun 2026
- First submitted
- 9 May 2025
- Last updated
- 11 Jun 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 36061593Wessel 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.
PubMed 37857774von 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.
PubMed 35839572Violante 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.
PubMed 37857775Vassiliadis 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.
PubMed 38811696Sandra 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.
PubMed 37405829Grossman 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.
PubMed 28575667
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neural Mechanisms of Interpersonal Expectations on Negative Affect
- ClinicalTrials.gov ID
- NCT06980090
- Acronym / sponsor ID
- 467251
- Keywords
- Transcranial temporal interference stimulation, Pain, Fear, Cognitive effort
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 196 participants (estimated)
- Lead sponsor
- Trustees of Dartmouth CollegeUniversity, hospital or other
- Study start
- 1 Sep 2025 (actual)
- Primary completion
- 31 Aug 2027 (estimated)
- Study completion
- 3 Mar 2028 (estimated)
- First posted
- 20 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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, 36 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 2010 Hz, generating an 10 Hz interference beat targeted at the anterior/mid-cingulate cortex (aMCC) at 2 mA for 20 minutes. Sham tTIS uses same frequencies (2000 Hz and 2010 Hz), targeting the same region for only 80 seconds.
Sessions are administered in a counterbalanced order based on a Williams 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 6
- 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 Williams 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.
| Arm | Type | Receives |
|---|---|---|
| Experiment 1 - Crossover Order: Session A-B-D-C | Experimental | 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 tTISParticipants complete all four experimental sessions in the following sequence: 1. Session A; 2. Session B; 3. Session D; 4. Session C |
| Experiment 1- Crossover Order: Session B-C-A-D | Experimental | 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 tTISParticipants complete all four experimental sessions in the following sequence: 1. Session B; 2. Session C; 3. Session A; 4. Session D |
| Experiment 1- Crossover Order: Session C-D-B-A | Experimental | 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 tTISParticipants complete all four experimental sessions in the following sequence: 1. Session C; 2.Session D; 3. Session B; 4. Session A |
| Experiment 1- Crossover Order: Session D-A-C-B | Experimental | 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 tTISParticipants complete all four experimental sessions in the following sequence: 1. Session D; 2. Session A; 3. Session C; 4. Session B |
| Experiment 2 - Crossover Order : Session E-F | Experimental | Behavioral: Session E: On-Placebo + Sham tTIS, Behavioral: Session F: Off-Placebo + Sham tTISParticipants complete all two experimental sessions in the following sequence: 1. Session E; 2. Session F |
| Experiment 2 - Crossover Order : Session F-E | Experimental | Behavioral: Session E: On-Placebo + Sham tTIS, Behavioral: Session F: Off-Placebo + Sham tTISParticipants complete all two experimental sessions in the following sequence: 1. Session F; 2. Session E |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- 'Doctors' are recruited from medical students at the Geisel School of Medicine and resident physicians at Dartmouth Hitchcock Medical Center (DHMC).
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Session A: Positive Placebo + Active tTISParticipants receive active tTIS with two channels set at 2000 Hz and 2010 Hz, creating a 10 Hz interference beat targeting the anterior/mid-cingulate cortex (aMCC). Stimulation is delivered at 2 mA per channel 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. | Behavioural | Experiment 1 - Crossover Order: Session A-B-D-C, Experiment 1- Crossover Order: Session B-C-A-D, Experiment 1- Crossover Order: Session C-D-B-A, Experiment 1- Crossover Order: Session D-A-C-B |
| Session B: Positive Placebo + Sham tTISParticipants receive sham tTIS (brief 80-second stimulation followed by no current) paired with a positive social placebo intervention. The device mimics active parameters (2 mA per channel, 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. | Behavioural | Experiment 1 - Crossover Order: Session A-B-D-C, Experiment 1- Crossover Order: Session B-C-A-D, Experiment 1- Crossover Order: Session C-D-B-A, Experiment 1- Crossover Order: Session D-A-C-B |
| Session C: Negative Placebo + Active tTISParticipants receive active tTIS (2000 Hz and 2010 Hz signals, 2 mA per channel, 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. | Behavioural | Experiment 1 - Crossover Order: Session A-B-D-C, Experiment 1- Crossover Order: Session B-C-A-D, Experiment 1- Crossover Order: Session C-D-B-A, Experiment 1- Crossover Order: Session D-A-C-B |
| Session D: Negative Placebo + Sham tTISParticipants receive sham tTIS (brief 80-second stimulation followed by no current) combined with a negative social placebo intervention. Participants complete three MNAT tasks before and after the session. | Behavioural | Experiment 1 - Crossover Order: Session A-B-D-C, Experiment 1- Crossover Order: Session B-C-A-D, Experiment 1- Crossover Order: Session C-D-B-A, Experiment 1- Crossover Order: Session D-A-C-B |
| Session E: On-Placebo + Sham tTISParticipants 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. | Behavioural | Experiment 2 - Crossover Order : Session E-F, Experiment 2 - Crossover Order : Session F-E |
| Session F: Off-Placebo + Sham tTISParticipants receive sham tTIS (brief 15-second stimulation, then no current) without any placebo intervention. Participants complete three MNAT tasks before and after the session. | Behavioural | Experiment 2 - Crossover Order : Session E-F, Experiment 2 - Crossover Order : Session F-E |
Primary outcome
Cognitive effort ratings
Time frame: 3-10 sec post-stimulus throughout testing sessions, with all sessions complete within 1 month
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.
Subjective fear ratings
Time frame: 3-10 sec post-stimulus throughout testing sessions, with all sessions complete within 1 month
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.
Pain ratings
Time frame: 3-10 sec post-stimulus throughout testing sessions, with all sessions complete within 1 month
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.
1 secondary outcome
Electrodermal autonomic responses to painful heat, fear-related images and cognitive effort
Time frame: Peri-stimulus throughout testing sessions, with all sessions complete within 1 month
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2026.
- Background: PubMed 36061593Acerbo 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.
- Background: PubMed 37857774Wessel 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.
- Background: PubMed 35839572von 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.
- Background: PubMed 37857775Violante 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.
- Background: PubMed 38811696Vassiliadis 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.
- Background: PubMed 37405829Sandra 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study of Negative Affectivity and Non-invasive Brain Stimulation, run by Trustees of Dartmouth College at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zhaoxing Wei, Ph.D. (6033220577, zhaoxing.wei@dartmouth.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cognitive effort ratings (time frame: 3-10 sec post-stimulus throughout testing sessions, with all sessions complete within 1 month). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06980090, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2026.