Individualized Temporal Interference Stimulation for Reward Processing in Late-Life Depression

November 3, 2026 updated by: Xiang Yang Zhang, Beijing HuiLongGuan Hospital

Neural Mechanisms Underlying the Modulation of Reward Processing by Individualized Temporal Interference Stimulation Targeting the Nucleus Accumbens in Late-Life Depression

This study aims to investigate the effects and neural mechanisms of individualized temporal interference stimulation (TI) targeting the left nucleus accumbens in older adults with depression. A total of 70 participants aged 60-80 years will be randomly assigned to receive active TI or sham stimulation. Clinical and cognitive assessments, a probabilistic reversal learning (PRL) task, MRI, and TMS-EEG will be used to evaluate changes in depressive symptoms, reward processing, and brain activity. Clinical and cognitive follow-up assessments will be conducted at 1 and 4 weeks after the intervention.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a randomized, double-blind, sham-controlled, parallel-group study involving 70 adults aged 60-80 years who meet DSM-5 criteria for a current episode of major depressive disorder and have at least moderate depressive symptoms.

Participants will be randomly assigned in a 1:1 ratio to an active TI group (n=35) or a sham stimulation group (n=35). Individualized TI will target the left nucleus accumbens, with stimulation administered for approximately 20 minutes per session, twice daily for five consecutive days (10 sessions in total).

Clinical and neuropsychological assessments will evaluate depressive symptoms, anxiety, anhedonia, sleep, and cognitive function. A probabilistic reversal learning (PRL) task will assess reward learning and cognitive flexibility. Structural MRI will support individualized stimulation planning, while resting-state functional MRI (rs-fMRI) and TMS-EEG will be used to investigate changes in brain networks and neurophysiological activity.

Assessments will be conducted at baseline and after the intervention, with additional follow-ups at 1 and 4 weeks. The study will compare changes between groups and explore associations among clinical outcomes, reward processing, and neural measures.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
70

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

60 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Aged 60-80 years.
  • Meet the DSM-5 diagnostic criteria for a current episode of major depressive disorder (MDD).
  • Have at least moderate depressive symptoms.
  • Able to understand and comply with study procedures, provide written informed consent, and voluntarily participate in the study.

Exclusion Criteria:

  • History of severe neurological disorders or epilepsy.
  • Severe or unstable medical conditions.
  • Contraindications to MRI, transcranial magnetic stimulation (TMS), or transcranial electrical stimulation.
  • Comorbid severe psychiatric disorders, such as bipolar disorder or schizophrenia.
  • Significant cognitive impairment that interferes with informed consent or completion of study procedures.
  • High suicide risk.
  • Any other medical or safety condition that, in the investigator's judgment, makes participation inappropriate.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Active Temporal Interference Stimulation

Participants will receive individualized active temporal interference stimulation (TI) targeting the left nucleus accumbens, for 20 minutes per session, twice daily for five consecutive days (10 sessions in total).
Device: Active Temporal Interference Stimulation

Individualized active temporal interference stimulation (TI) targeting the left nucleus accumbens, delivered for 20 minutes per session, twice daily for five consecutive days (10 sessions in total).
Sham Comparator: Sham Temporal Interference Stimulation

Participants will receive sham temporal interference stimulation (TI) with similar electrode placement and procedures, following the same schedule as the active group (10 sessions over five days).
Device: Sham Temporal Interference Stimulation

Sham temporal interference stimulation (TI) with similar electrode placement and procedures, without sustained effective stimulation, following the same schedule as the active group (10 sessions over five days).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Hamilton Depression Rating Scale (HAMD-24)
Time Frame: Baseline, immediately after the intervention, and at 1-week and 4-week follow-ups

The 24-item Hamilton Depression Rating Scale (HAMD-24) assesses depressive symptom severity. Total scores range from 0 to 76, with higher scores indicating more severe depressive symptoms.
Baseline, immediately after the intervention, and at 1-week and 4-week follow-ups
Snaith-Hamilton Pleasure Scale (SHAPS)
Time Frame: Baseline, immediately after the intervention, and at 1-week and 4-week follow-ups

Anhedonia will be assessed using the 14-item Snaith-Hamilton Pleasure Scale (SHAPS). Total scores range from 14 to 56, with higher scores indicating more severe anhedonia. Changes from baseline will be compared between groups.
Baseline, immediately after the intervention, and at 1-week and 4-week follow-ups
Probabilistic Reversal Learning (PRL) Task
Time Frame: Baseline, immediately after the intervention, and at 1-week and 4-week follow-ups

The PRL task assesses reward-based learning and cognitive flexibility. Participants learn from probabilistic feedback and adjust their choices when reward contingencies change. Task performance will be evaluated using behavioral measures of reward learning and reversal learning.
Baseline, immediately after the intervention, and at 1-week and 4-week follow-ups

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Hamilton Anxiety Rating Scale (HAMA)
Time Frame: Baseline, immediately after the intervention, and at 1-week and 4-week follow-ups

Anxiety severity will be assessed using the 14-item HAMA. Total scores range from 0 to 56, with higher scores indicating more severe anxiety.
Baseline, immediately after the intervention, and at 1-week and 4-week follow-ups
Pittsburgh Sleep Quality Index (PSQI)
Time Frame: Baseline, immediately after the intervention, and at 1-week and 4-week follow-ups

The Pittsburgh Sleep Quality Index (PSQI) assesses sleep quality and disturbances. The global score, calculated from seven components, ranges from 0 to 21, with higher scores indicating poorer sleep quality.
Baseline, immediately after the intervention, and at 1-week and 4-week follow-ups
Mini-Mental State Examination (MMSE)
Time Frame: Baseline, immediately after the intervention, and at 1-week and 4-week follow-ups

Global cognitive function will be assessed using the MMSE. Total scores range from 0 to 30, with higher scores indicating better cognitive function.
Baseline, immediately after the intervention, and at 1-week and 4-week follow-ups
Auditory Verbal Learning Test (AVLT) Performance
Time Frame: Baseline, immediately after the intervention, and at 1-week and 4-week follow-ups

Verbal learning and memory will be evaluated using the numbers of correctly recalled words during immediate recall, delayed recall, category-cued recall, and recognition testing.
Baseline, immediately after the intervention, and at 1-week and 4-week follow-ups
Verbal Fluency Test (VF) Performance
Time Frame: Baseline, immediately after the intervention, and at 1-week and 4-week follow-ups

Verbal fluency will be assessed using the numbers of valid responses generated during animal naming, phonemic word generation, and action fluency tasks, each lasting one minute.
Baseline, immediately after the intervention, and at 1-week and 4-week follow-ups
3D Confusion Assessment Method (3D-CAM)
Time Frame: Baseline, immediately after the intervention, and at 1-week and 4-week follow-ups

Delirium will be assessed using the 3-Minute Diagnostic Interview for CAM-Defined Delirium (3D-CAM). The outcome will be recorded as the presence or absence of delirium.
Baseline, immediately after the intervention, and at 1-week and 4-week follow-ups
Clock Drawing Test (CDT)
Time Frame: Baseline, immediately after the intervention, and at 1-week and 4-week follow-ups

Visuospatial and executive functioning will be assessed using a four-point Clock Drawing Test. Scores range from 0 to 4, with higher scores indicating better performance.
Baseline, immediately after the intervention, and at 1-week and 4-week follow-ups
Digit Span Test (DST) Performance
Time Frame: Baseline, immediately after the intervention, and at 1-week and 4-week follow-ups

Attention and working memory will be assessed using forward and backward digit span, including maximum correctly recalled span length and the number of correct sequences.
Baseline, immediately after the intervention, and at 1-week and 4-week follow-ups
Trail Making Test (TMT)
Time Frame: Baseline, immediately after the intervention, and at 1-week and 4-week follow-ups

Processing speed, attention, and executive functioning will be evaluated using completion time in seconds across the four TMT conditions in the study protocol. Errors will also be recorded.
Baseline, immediately after the intervention, and at 1-week and 4-week follow-ups
Neuropsychiatric Inventory (NPI)
Time Frame: Baseline, immediately after the intervention, and at 1-week and 4-week follow-ups

The 12-domain Neuropsychiatric Inventory (NPI) assesses neuropsychiatric symptoms. The total score is calculated by summing frequency × severity scores across 12 domains and ranges from 0 to 144, with higher scores indicating more severe symptoms.
Baseline, immediately after the intervention, and at 1-week and 4-week follow-ups
Activities of Daily Living (ADL)
Time Frame: Baseline, immediately after the intervention, and at 1-week and 4-week follow-ups

Daily functioning will be assessed using the 20-item ADL scale. Scores range from 20 to 80, with higher scores indicating greater functional impairment.
Baseline, immediately after the intervention, and at 1-week and 4-week follow-ups
Resting-State fMRI Brain Network Measures
Time Frame: Baseline, immediately after the intervention

Resting-state fMRI will be used to evaluate changes in nucleus accumbens-related functional connectivity and brain network characteristics following the intervention.
Baseline, immediately after the intervention
TMS-Evoked Global Mean Field Amplitude (GMFA)
Time Frame: Baseline, immediately after the intervention

Global mean field amplitude (GMFA) will be calculated from TMS-evoked EEG recordings to quantify the overall cortical response to stimulation. Changes in GMFA amplitude will be assessed.
Baseline, immediately after the intervention
TMS-EEG Time-Frequency Power
Time Frame: Baseline, immediately after the intervention

Time-frequency analysis of TMS-EEG recordings will be used to assess changes in oscillatory power across frequency bands following stimulation.
Baseline, immediately after the intervention
TMS-EEG Functional Connectivity
Time Frame: Baseline, immediately after the intervention

Functional connectivity will be assessed using TMS-EEG recordings to evaluate changes in the synchronization and interaction of cortical brain regions.
Baseline, immediately after the intervention
TMS-EEG Source-Localized Cortical Activity
Time Frame: Baseline, immediately after the intervention

EEG source reconstruction will be used to estimate changes in TMS-evoked cortical activity at the source level.
Baseline, immediately after the intervention
TMS-Evoked Potential (TEP) Amplitude
Time Frame: Baseline, immediately after the intervention

TMS-evoked potentials (TEPs) will be analyzed to assess changes in cortical responses, including the amplitude of TMS-evoked EEG components.
Baseline, immediately after the intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Beijing HuiLongGuan Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Xiangyang Zhang, Ph.D, Tsinghua University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 10, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 31, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 24, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 3, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 9, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 9, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 3, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CASPsy13

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The datasets generated and/or analyzed during the current study are not publicly available due to ethical restrictions (as they contain information that could compromise participant privacy), but will be available from the corresponding author upon reasonable request after completion of the study and approval by the ethics committee.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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