Individualized Temporal Interference Stimulation for Reward Processing in Late-Life Depression
Major Depressive Disorder (MDD
What this study involves
The registry does not currently label this study as recruiting. Ask about its status before planning a screening visit.
- Study type
- Interventional
- Phase
- Not applicable
- Age range
- 60 years - 80 years
- Sex eligible
- All sexes
- Healthy volunteers
- Not accepted
- Participants
- 70 Estimated
These are starting points, not an eligibility decision. The research team must review the full requirements.
About the research
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.
Read the full 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.
Who may be able to participate?
The list below is the sponsor’s full registry wording. It can include conditions, prior treatment, test results and other requirements. A match in search does not mean you qualify.
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.
Treatment, groups and participation
The registry may describe treatments and study duration without a complete visit calendar. Ask the study team for the exact schedule, procedures, risks, costs and alternatives. Keep your usual care plan unless your treating clinician tells you otherwise.
- Assignment
- Random assignment
- Masking
- Double masked
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
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
Active Temporal Interference Stimulation DEVICE
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 Temporal Interference Stimulation DEVICE
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 researchers are measuring
Outcome measures describe what is being studied. They are not proof that a treatment works.
Primary measures
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.
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.
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.
Secondary measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Review the complete result tables and limitations in the official record.
Open official results ↗Research locations (1)
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1 locations
Hefei Fourth People's HospitalHefei, Anhui, ChinaStatus unknown
Study team and timeline
- Lead sponsor
- Beijing HuiLongGuan Hospital
- Study start
- Nov 10, 2026 Estimated
- Primary completion
- Oct 31, 2027 Estimated
- Study completion
- Dec 30, 2027 Estimated
- First posted
- Nov 9, 2026 Actual
- Last updated
- Nov 9, 2026 Actual
Official study contacts
Official study title
Neural Mechanisms Underlying the Modulation of Reward Processing by Individualized Temporal Interference Stimulation Targeting the Nucleus Accumbens in Late-Life Depression
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Source: ClinicalTrials.gov API v2. Information is submitted by sponsors and investigators. NLM does not approve the safety or science of all listed studies. Registry disclaimer.
Retrieved: Nov 12, 2026 · Last registry update: Nov 9, 2026