NCT06219681

Modulating Repetitive Negative Thinking Related Brain Networks in Young Adults With Depression

• Status: Terminated
• Phase: N/A
• Study type: Interventional
• Enrollment: 54 (actual)
• Sponsor: Laureate Institute for Brain Research, Inc. · Academic / Other
• Sex: All
• Age: 18 Years – 35 Years
• Healthy volunteers: Not accepted

Summary

In this project, the investigators use real-time fMRI neurofeedback (rtfMRI-nf) to causally relate dysfunction of right anterior insula (rAI) and right superior temporal sulcus (rSTS) connectivity with the intensity of repetitive negative thinking (RNT). The investigators hypothesize that rtfMRI-nf reducing rAI-rSTS connectivity would reduce RNT. The investigators propose a randomized double-blind, sham-controlled trial of rtfMRI-nf with 110 young adults (n=55/arm) with major depressive disorder (MDD) and high trait-RNT levels.

Detailed description

Young adult mental health is crucial, as 1 in 10 young adults (ages 18-25) suffer from major depressive disorder (MDD), impacting long-term outcomes such as comorbid mental disorders, unemployment and suicide . With increasing rates of MDD among young adults, new explanatory disease models focusing on targetable disease-modifying processes (DMPs) are needed. Repetitive negative thinking (RNT) is a key DMP in MDD, involving difficulty controlling distressing thoughts and past events , and predicting depression severity and suicidal ideation/attempts in early adulthood. Current treatments, such as medication and psychotherapy including cognitive-behavioral therapy (CBT), often have limited effectiveness for MDD, with higher levels of RNT associated with slower and poorer response rates. In theory, novel treatments designed to modify the neurobiological mechanisms underlying RNT could facilitate recovery in MDD. Real-time functional Magnetic Resonance Imaging neurofeedback (rtfMRI-nf) is a non-invasive method, providing individuals with feedback concerning their brain activity in order to facilitate one's self-control. Our preliminary studies identified a circuit with stronger connectivity between the right anterior insular (rAI, emotional salience processing hub) and the right superior temporal sulcus (rSTS, episodic memory/language processing area), correlating with the severity of RNT apart from depression. This finding aligns with the framework that views RNT as heightened evaluative and dialogic inner speech, resulting from an inability to disengage from self-critical and threatening interpretations of episodic memories. The investigators propose that excessive functional connectivity between the rAI and STS may contribute to RNT in young adults with MDD. This project is a research project at the Laureate Institute for Brain Research (LIBR). In this project, the investigators use rtfMRI-nf to causally relate dysfunction of rAI-rSTS connectivity with the intensity of RNT. The investigators hypothesize that rtfMRI-nf reducing rAI-rSTS connectivity would reduce RNT. The investigators propose a randomized double-blind, sham-controlled trial of rtfMRI-nf with 110 young adults (n=55/arm) with MDD and high trait-RNT levels. Primary outcome will be active vs. sham rtfMRI-nf's effect on rAI-rSTS connectivity. Secondary outcomes will be active vs. sham rtfMRI-nf's effect on state-RNT (Brief State Rumination Inventory, BSRI) and depression severity (Montgomery-Asberg Depression Rating Scale, MADRS). Exploratory outcomes will be the relationship between reducing rAI-rSTS connectivity and BSRI scores. Participants will perform a self-regulation task involving neurofeedback, receiving either real-time feedback on rAI-rSTS connectivity (active group) or artificial feedback unrelated to rAI-rSTS connectivity (sham group). The investigators will collect data across two visits, one week apart. The first visit will include five runs of the self-regulation task, the middle three containing the neurofeedback condition (Visit 1). The second visit will include one run of the self-regulation task without the neurofeedback condition 1-week later (Visit 2).

Conditions

• Depressive Disorder, Major

Interventions

Type	Name	Description
BEHAVIORAL	Active neurofeedback	The session will be done on an individual basis. The active group will receive neurofeedback training from the repetitive negative thinking (RNT) related brain functional connectivity.
BEHAVIORAL	Sham neurofeedback	The session will be done on an individual basis. The sham group will receive neurofeedback training from an artificially generated random feedback signal.

Timeline

• Start date: 2024-01-12
• Primary completion: 2025-04-04
• Completion: 2025-04-04
• First posted: 2024-01-23
• Last updated: 2025-04-11

Locations

1 site across 1 country: United States