RecruitingNot ApplicableNCT06748274

The Brain-Heart-Gut Connection

The Brain-heart-gut Connection (BHG-CONNECT): Targeting the Frontal-vagal Pathway to Personalize Noninvasive Brain Stimulation

Sponsor

University of Bern

Enrollment

98 participants

Start Date

Jun 1, 2025

Study Type

INTERVENTIONAL

Conditions

Major Depression Functional Dyspepsia Autonomous Dysfunction

Summary

Major Depressive Disorder (MDD) often co-occurs with cardiovascular and gastrointestinal symptoms, highlighting the importance of the brain-heart-gut connection in developing comprehensive treatments. Previous research suggests that key hubs in the depression network, such as the dorsolateral prefrontal cortex (DLPFC) and the subgenual anterior cingulate cortex (sgACC), overlap with structures that are involved in autonomic control, particularly the vagus nerve. Repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC is an established treatment for MDD; however, antidepressant efficacy varies greatly across individuals, and optimal DLPFC targeting remains a significant challenge. Personalized rTMS based on DLPFC-sgACC connectivity improves outcomes but is limited by practical and financial constraints. Recently, rTMS-induced heart-brain coupling (HBC) has emerged as a promising method to utilize heart rate responses to guide treatment. The primary goal of this project is to personalize HBC to improve DLPFC-based targeting for the treatment of MDD while also probing additional readouts of the frontal-vagal system. In Study Arm 1, we will implement an innovative frontal mapping technique to identify the personalized "Grid-Spot" that elicits the strongest HBC in healthy participants. In subsequent visits, we will compare heart rate responses during the 10Hz "Dash" protocol between the "Grid-Spot", conventional DLPFC targeting using "Beam-F3" and an active control region (Cz). Additionally, we will integrate various autonomic nervous system (ANS) measures, including gut motility, pupil dilation and electrodermal activity (EDA), to explore the brain-heart-gut axis and assess their utility in improving target engagement. Furthermore, we will extend our methodology to the personalized application of high-definition transcranial direct current stimulation (HD-tDCS). Specifically, we will explore the effects of anodal versus sham HD-tDCS over the HBC-guided "Grid-Spot" on ANS readouts and compare these outcomes to those observed with rTMS. In Study Arm 2, we will repeat experimental rTMS visits from Study Arm 1 with participants exhibiting elevated symptom scores in depression, autonomic dysfunction and functional dyspepsia. In Study Arm 2 we will also validate our optimal "Grid-Spot" identification through neuroimaging of DLPFC-sgACC connectivity. This project will deepen our understanding of the brain-heart-gut connection and contribute to more accessible, personalized brain stimulation treatments for MDD.

Eligibility

Min Age: 18 YearsMax Age: 65 Years

Plain Language Summary

Simplified for easier understanding

This study is exploring the connection between the brain, heart, and gut — specifically how the automatic (autonomic) nervous system, mood symptoms like depression, and digestive symptoms are all linked. Researchers are recruiting both healthy volunteers and people with a combination of these symptoms. **You may be eligible if...** - You are between 18 and 65 years old - For the general arm: You are a healthy adult with no significant health conditions - For the symptom arm: You have a combination of autonomic symptoms (e.g., heart rate irregularities, dizziness), depressive symptoms, and stomach or intestinal complaints **You may NOT be eligible if...** - You do not fall within the 18–65 age range - You are unable to provide written informed consent - You do not meet the specific symptom score thresholds required for the symptom arm of the study Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DEVICETranscranial Magnetic Stimulation (TMS)

Transcranial Magnetic Stimulation (TMS) is a sophisticated neuromodulation technique that involves the use of a magnetic coil placed against the scalp to generate brief magnetic pulses. These pulses induce electric currents in the cortical neurons, leading to depolarization or hyperpolarization depending on the parameters of the stimulation.

DEVICEHigh-definition transcranial direct current stimulation (HD-tDCS)

Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain stimulation technique that involves applying a low-intensity electrical current to specific areas of the scalp. The electric current induces alterations in the membrane potentials of underlying neuronal networks. The application of tDCS with concentric ring electrodes is a more targeted form of tDCS, allowing for more precise modulation of cortical activity compared to traditional tDCS methods.