Depression, Major Depressive Disorder
Conditions
Keywords
theta burst stimulation, reinforcement learning, neuroimaging
Brief summary
The goal of this clinical trial is to learn how different types of non-invasive brain stimulation affect mood and brain function in adults with major depressive disorder (MDD). It will also study how brain stimulation may work together with antidepressant treatments. The main questions this study aims to answer are: How do different patterns of brain stimulation affect mood in people with depression? Do brain networks involved in emotion and self-reflection respond differently depending on the type of stimulation? What are the combined effects of brain stimulation and antidepressant treatments on mood and brain activity? Researchers will compare different brain stimulation patterns and target areas to understand their individual and combined effects. Participants will: Receive three types of brain stimulation (intermittent, continuous, and sham) in different sessions Undergo MRI scans during the administration of either a fast-acting or conventional antidepressant Complete mood assessments during the scan and for one week after each session This study may help identify brain-based strategies to improve treatment for depression.
Detailed description
This mechanistic clinical trial will investigate the role of large-scale brain networks in modulating mood responses in adults with major depressive disorder (MDD) using non-invasive neuromodulation and neuroimaging. The study will focus on the salience network (SN), default mode network (DMN), and functional connectivity (FC) between them, given prior evidence linking these systems to mood regulation and antidepressant response. Using a 2x3 factorial design, 200 participants with MDD will be randomized to receive theta burst stimulation (TBS) targeting either the SN or the DMN (between-subject factor). Each participant will complete three within-subject TBS sessions one week apart: intermittent TBS (iTBS), continuous TBS (cTBS), and sham stimulation. TBS will be delivered over individualized fMRI-based targets derived from prior resting-state connectivity maps. Following each stimulation session, participants will complete an MRI protocol that includes administration of either a fast-acting or conventional antidepressant, as well as resting-state functional imaging. Primary neural outcomes include changes in activation and connectivity within and between SN and DMN regions, measured using task-based and resting-state fMRI. Behavioral outcomes include mood ratings acquired repeatedly during the scanning session and via daily remote assessments for one week post-stimulation. This design allows for within-subject comparison of the acute and sub-acute effects of different TBS patterns, and between-subject comparison of SN- vs. DMN-targeted stimulation. The study aims to identify brain circuits that can be engaged or modulated to enhance treatment response in depression, with the longer-term goal of informing precision neuromodulation strategies. Note: Certain information is withheld to protect the scientific integrity of the study design.
Interventions
DEVICEIntermittent theta burst stimulation
Aimed at potentiating the stimulation target.
No effect is expected on stimulation target
Aimed at depotentiating the stimulation target
Sponsors
Marta Peciña, MD PhD
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Intervention model description
This is a mechanistic trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Adults ages 18-55 (\ 60% female). 2. Diagnosis of Major Depressive Disorder (MDD) with or without comorbid anxiety disorders (e.g., panic disorder) or Axis II disorders. 3. Psychotropic-free at enrollment.
Exclusion criteria
1. being pregnant or breastfeeding; 2. diagnosis of psychotic depression, schizophrenia, bipolar disorder, or other Axis I disorders, except for anxiety disorders; 3. severe substance use (excluding nicotine) in the last 2 months as determined by using the MINI, a structured interview that uses the Diagnostic and Statistical Manual of Mental Disorders; 4. requiring immediate hospitalization; 5. epilepsy or conditions requiring an anticonvulsant; 6. receiving vagus nerve stimulation, electroconvulsive therapy (ECT), or TMS in the last 2 months; 7. currently taking or have taken within the last 21 days psychiatric medication or augmenting agents; 8. receiving depression-specific psychotherapy; 9. actively suicidal or considered a high suicide risk; 10. enrolled in another study; or 11. MRI/TMS contraindication as determined by the fMRI and TMS screening questionnaires
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bold Signal Change in the Salience Network During the fMRI Experiment | Assessed at approximately day 7, day 14, and day 21 following baseline. | Change in blood oxygenation level-dependent (BOLD) signal within the salience network (SN), measured during the fMRI experiment. Comparisons is made across transcranial magnetic stimulation conditions: intermittent theta burst stimulation (iTBS) vs. sham TBS (sTBS), and continuous TBS (cTBS) vs. sTBS. SN activation is assessed using fMRI contrasts sensitive to expectancy-induced neural modulation. |
| BOLD Signal Change in the Default Mode Network During the fMRI Experiment | Assessed at approximately day 7, day 14, and day 21 following baseline. | Change in blood oxygenation level-dependent (BOLD) signal within the default mode network (DMN), measured during the fMRI experiment. Comparisons is made across transcranial magnetic stimulation conditions: intermittent theta burst stimulation (iTBS) vs. sham TBS (sTBS), and continuous TBS (cTBS) vs. sTBS. DMN activation is assessed using fMRI contrasts sensitive to expectancy-induced neural modulation. |
| Changes in Mood Ratings Following TBS and the fMRI Experiment | Baseline | Change in self-reported mood, coded as a binary indicator of perceived mood improvement (yes/no), is assessed after each TBS session (iTBS, cTBS, sTBS) during the fMRI task. Participants are considered to show mood improvement if their post-stimulation average mood rating across trials increased relative to baseline. Between-condition comparisons (iTBS vs. sTBS; cTBS vs. sTBS) are conducted to evaluate the acute effects of TBS on mood reactivity. |
| Subcute Mood Change Following TBS and the fMRI experiment | Approximately at day 7, 14, and 21 | Change in depressive symptoms is assessed using the 16-item Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR16; range: 0-27), where higher scores indicate greater depressive symptom severity. The QIDS-SR16 evaluates core domains of depression, including mood, interest, sleep, appetite, and concentration, over the past 7 days. Between-session changes (baseline to days 7, 14, and 21) are analyzed to assess subacute mood effects of intermittent TBS (iTBS), continuous TBS (cTBS), and sham TBS (sTBS) and the fMRI experimental manipulation. |
Countries
United States
Contacts
Primary ContactEli Strohecker, BS
Backup ContactGaurav Badhan, BS
Outcome results
None listed