Neuro-Cardiac-Guided Transcranial Magnetic Stimulation: Replication and Dose-response.

Study Overview
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Brief Summary
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Autonomic regulation is disturbed in patients with major depressive disorder (MDD), indicated by a higher heart rate (HR) and lower heart rate variability (HRV). Moreover, the heart seems to be functionally connected via the vagus nerve (VN) to other brain structures that are dysregulated in depression, such as the subgenual anterior cingulate cortex (sgACC), and the dorsolateral prefrontal cortex (DLPFC), suggesting dysregulated network function in MDD. In line with this network dysregulation hypothesis of MDD, optimal transcranial magnetic stimulation (TMS) sites are currently thought to be those that show functional connectivity to the sgACC such as the DLPFC and multiple studies have shown that stimulation of the DLPFC, sgACC and nervus vagus decreased heart rate, suggestive of parasymphatetic action. It is hypothesized that this influence on parasympathetic activity can be used as a functional outcome measure reflecting adequate targeting of the DLPFC-sgACC network, similar to the motor evoked potential (MEP) as functional key measure for primary motor cortex stimulation. Recently, a pilot study was conducted, proposing a new functional neuronavigation method for localizing the frontal area representation of DLPFC-sgACC connectivity using HR, called: Neuro-Cardiac-Guided TMS (NCG-TMS), which is being replicated in the current study. .

Official Title
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Neuro-Cardiac-Guided Transcranial Magnetic Stimulation: a Method to Probe the Depression Network. Replication and Dose-response

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Device: Transcranial magnetic stimulation (TMS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Between ages 18-60 Exclusion Criteria: No prior experience with epilepsy No pregnancy No metal in the head No cochlear implants

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Left<br>Subjects are ascribed to left hemispheric stimulation | Device: Transcranial magnetic stimulation (TMS)<br>* Subjects receive TMS on several cortical brain locations, while recording the heart rate.<br>|
| Active Comparator: Right<br>Subjects are ascribed to right hemispheric stimulation | Device: Transcranial magnetic stimulation (TMS)<br>* Subjects receive TMS on several cortical brain locations, while recording the heart rate.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart rate during stimulation, converted to RR intervals |  | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Target engagement, TMS, Heart-brain pathway, Depression, Neuromodulation, DLPFC, Heart rate