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The Brain-Heart-Gut Connection
Sponsor: University of Bern
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.
Official title: The Brain-heart-gut Connection (BHG-CONNECT): Targeting the Frontal-vagal Pathway to Personalize Noninvasive Brain Stimulation
Key Details
Gender
All
Age Range
18 Years - 65 Years
Study Type
INTERVENTIONAL
Enrollment
34
Start Date
2025-06-01
Completion Date
2025-12-31
Last Updated
2026-04-08
Healthy Volunteers
Yes
Interventions
Transcranial 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.
High-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.
Locations (1)
University Hospital of Old Age Psychiatry and Psychotherapy Bern
Bern, Canton of Bern, Switzerland