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| Name | Class |
|---|---|
| Columbia University | OTHER |
| University of Oklahoma | OTHER |
| Defense Advanced Research Projects Agency | FED |
| University of Wisconsin, Madison |
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In this research study, investigators examine how brain activity changes during tests of emotional processing, attention, and memory using multimodal neuroimaging methods including electroencephalography (EEG), functional magnetic resonance imaging (fMRI), and functional near-infrared spectroscopy (fNIRS). Transcranial magnetic stimulation (TMS) is used to probe and modulate brain networks related to cognitive flexibility and emotion regulation.
The study includes multiple related sub-studies involving healthy participants and participants with depression. Some study components focus on mechanistic modeling using non-therapeutic neurostimulation in healthy participants, while other components include interventional approaches such as individualized EEG-synchronized repetitive TMS (rTMS), cognitive tasks, and brief cognitive behavioral therapy (CBT) in participants with depression. Certain study components also evaluate CBT alone without TMS to assess behavioral intervention effects.
Investigators aim to characterize and modulate brain networks underlying cognitive flexibility (CF) and emotion regulation (ER) using a multimodal, precision neuroscience approach. The central hypothesis is that functional coupling within CF and ER networks is indexed by the phase of the brain's alpha oscillations, and that targeted modulation of these networks through individualized neurostimulation can induce neuroplastic changes associated with improved clinical outcomes in depression and suicidality.
To test this hypothesis, investigators utilize a novel integrated system that enables simultaneous functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and transcranial magnetic stimulation (TMS) to identify individualized stimulation parameters associated with optimal network coupling. A complementary system using functional near-infrared spectroscopy (fNIRS), EEG, and TMS is also used to extend these findings in a more scalable and accessible format.
This protocol includes multiple related sub-studies (Studies 1-4) conducted under a single IRB approval. These sub-studies are parallel investigations with differing populations and interventions and are not randomized arms of a single trial.
Study 1 is a proof-of-principle mechanistic study conducted in healthy adult participants. In this study, single-pulse TMS is delivered during EEG and neuroimaging sessions as a non-therapeutic probe to assess cortical excitability and functional connectivity during cognitive flexibility and emotion regulation tasks.
Study 2 is a proof-of-principle interventional study in participants with depression. It incorporates individualized, EEG-synchronized repetitive transcranial magnetic stimulation (rTMS) designed to entrain neural oscillatory dynamics within CF and ER networks. Participants may receive rTMS alone or in combination with cognitive tasks and brief cognitive behavioral therapy (CBT), with the goal of enhancing neuroplasticity and improving clinical symptoms.
Study 3 builds upon Study 2 and includes similar EEG-synchronized rTMS and CBT-based interventions in participants with depression, with ongoing refinements to stimulation parameters, task paradigms, and treatment delivery. This study further evaluates the reproducibility and effectiveness of individualized neurostimulation approaches.
Study 4 includes participants with depression who receive a course of cognitive behavioral therapy (CBT) along with MRI and behavioral assessments, without the use of TMS or EEG-based neurostimulation. This study allows for evaluation of behavioral intervention effects independent of neurostimulation.
Across interventional studies, rTMS may be delivered alone or in combination with cognitive flexibility and emotion regulation tasks or paired with CBT to promote synergistic effects on network engagement and neuroplasticity. These approaches are designed to test whether targeted modulation of CF and ER networks produces measurable changes in behavior, brain function, and clinical outcomes.
Participants in interventional studies may also complete ecological momentary assessment (EMA) surveys via mobile devices to monitor mood, stress, and safety in real time. These data may be used to capture dynamic changes in symptoms and may trigger predefined safety protocols and clinical follow-up when indicated.
Outcome measures across studies include changes in clinical symptoms (e.g., depression, anxiety, and suicidal ideation), behavioral performance on cognitive tasks, and neuroimaging-based measures of network connectivity and synchronization.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy Participants (Study 1) | Other | Healthy adult participants with no history of psychiatric or neurological illness who undergo mechanistic and modeling procedures, including multimodal neuroimaging, behavioral cognitive tasks, and non-therapeutic neurostimulation, to characterize brain networks underlying cognitive flexibility and emotion regulation. |
|
| Depressed Participants - EEG-Synchronized rTMS (Studies 2 and 3) | Experimental | Participants with major depressive disorder who receive individualized, EEG-synchronized repetitive transcranial magnetic stimulation (rTMS), delivered alone or in combination with cognitive tasks and/or brief cognitive behavioral therapy (CBT), to modulate neural networks underlying cognitive flexibility and emotion regulation. |
|
| Depressed Participants - Non-Synchronized rTMS Comparator | Active Comparator | Participants with major depressive disorder who receive repetitive transcranial magnetic stimulation delivered using standard stimulation parameters without EEG phase synchronization, serving as a comparator condition. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Single-Pulse Transcranial Magnetic Stimulation | Device | Single-pulse transcranial magnetic stimulation delivered during EEG or neuroimaging sessions for non-therapeutic mapping of cortical excitability and functional connectivity. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Hamilton Depression Rating Scale (HAM-D) Score | Change in clinician-rated depression severity measured using the Hamilton Depression Rating Scale (HAM-D). Scores range from 0 to 52; higher scores indicate more severe depression. | Baseline to Day 7 |
| Change in Patient Health Questionnaire-9 (PHQ-9) Score | Change in self-reported depression severity measured using the Patient Health Questionnaire-9 (PHQ-9). Scores range from 0 to 27; higher scores indicate more severe depression. | Baseline to Day 7 |
| Change in Suicidal Ideation Severity (Passive and Active Suicidal Ideation Scale [PASIS]) | Change in suicidal ideation severity measured using the Passive and Active Suicidal Ideation Scale (PASIS). Higher scores indicate greater severity of suicidal ideation. | Baseline to Day 7 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Reaction Time During Cognitive Flexibility Tasks | Change in reaction time (milliseconds) during cognitive flexibility and emotion regulation tasks under congruent and incongruent conditions. | Baseline to Day 7 |
| Change in Accuracy on Cognitive Flexibility Tasks |
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Study 1 (Healthy Participants)
Inclusion Criteria:
Exclusion Criteria:
Studies 2, 3, and 4 (Participants with Depression)
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Lisa McTeague, PhD | Contact | 843-792-8274 | MCTEAGUE@MUSC.EDU | |
| Christina Marsicano | Contact | recovers@musc.edu |
| Name | Affiliation | Role |
|---|---|---|
| Lisa McTeague, PhD | Medical University of South Carolina | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical Univeristy of South Carolina | Recruiting | Charleston | South Carolina | 29425 | United States |
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| OTHER |
Groups described in this record correspond to cohorts within multiple related sub-studies and are not randomized arms of a single trial.
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| Depressed Participants - Cognitive Behavioral Therapy Only (Study 4) |
| Experimental |
Participants with major depressive disorder who receive a course of cognitive behavioral therapy (CBT) along with MRI and behavioral assessments, without transcranial magnetic stimulation or EEG-based neurostimulation. This group allows evaluation of behavioral intervention effects independent of neurostimulation. |
|
| EEG-Synchronized Repetitive Transcranial Magnetic Stimulation (rTMS) | Device | Repetitive transcranial magnetic stimulation delivered using individualized, EEG-derived stimulation parameters designed to synchronize stimulation timing with participants' alpha oscillatory phase. This closed-loop approach is intended to modulate neural networks underlying cognitive flexibility and emotion regulation. Stimulation may be delivered in accelerated sessions across multiple days. |
|
| Cognitive Behavioral Therapy (CBT) | Behavioral | A structured, brief cognitive behavioral therapy program targeting depression and related symptoms, including cognitive restructuring, emotion regulation, and coping skill development, delivered in an accelerated format during the study period. |
|
| Cognitive Flexibility and Emotion Regulation Tasks | Behavioral | Behavioral tasks designed to engage and assess cognitive flexibility and emotion regulation processes, performed during or adjacent to neurostimulation sessions or as part of study assessments. |
|
| Non-Synchronized Repetitive Transcranial Magnetic Stimulation | Device | Repetitive transcranial magnetic stimulation delivered using standard stimulation parameters without EEG phase synchronization, serving as a comparator condition. |
|
Change in task accuracy (percentage correct responses) during cognitive flexibility and emotion regulation tasks. |
| Baseline to Day 7 |
| Change in Generalized Anxiety Disorder-7 (GAD-7) Score | Change in anxiety severity measured using the Generalized Anxiety Disorder 7-item scale (GAD-7). Scores range from 0 to 21; higher scores indicate more severe anxiety. | Baseline to Day 7 |
| Change in EEG Alpha Phase Synchronization | Change in EEG alpha phase synchronization measured as phase-locking value (PLV) during cognitive task performance and neurostimulation sessions. | Baseline to Day 7 |
| Change in Functional Connectivity Strength (fMRI) | Change in functional connectivity within cognitive flexibility and emotion regulation networks measured using resting-state functional magnetic resonance imaging (fMRI), quantified as correlation coefficients between predefined brain regions. | Baseline to Day 7 |
| Change in Functional Connectivity Strength (fNIRS) | Change in functional connectivity measured using functional near-infrared spectroscopy (fNIRS), quantified as coherence between cortical regions during task performance. | Baseline to Day 7 |
| Proportion of Participants With ≥50% Reduction in HAM-D Score | Clinical response defined as a ≥50% reduction from baseline in Hamilton Depression Rating Scale (HAM-D) score. | Day 28 |
| Proportion of Participants With ≥50% Reduction in PASIS Score | Clinical response defined as a ≥50% reduction from baseline in Passive and Active Suicidal Ideation Scale (PASIS) score. | Day 28 |
| ID | Term |
|---|---|
| D003863 | Depression |
| D003865 | Depressive Disorder, Major |
| D059020 | Suicidal Ideation |
| D000092864 | Suicide Prevention |
| ID | Term |
|---|---|
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
| D013405 | Suicide |
| D016728 | Self-Injurious Behavior |
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| ID | Term |
|---|---|
| D050781 | Transcranial Magnetic Stimulation |
| D015928 | Cognitive Behavioral Therapy |
| ID | Term |
|---|---|
| D055909 | Magnetic Field Therapy |
| D013812 | Therapeutics |
| D001521 | Behavior Therapy |
| D011613 | Psychotherapy |
| D004191 | Behavioral Disciplines and Activities |
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