Mechanisms of Non-Invasive Neuromodulation Interventions: Influence on Human Neurochemistry and Functional Connectivity

Not Applicable

Completed

• Conditions: Non-invasive Neuromodulation in Healthy Subjects
• Interventions: Device: Inhibitory rTMS (1 Hz); Device: Excitatory rTMS (5 Hz)

• Registration Number: NCT02677740
• Lead Sponsor: University of Minnesota

Brief Summary

The aim of this project is to increase our understanding of how two different protocols of repetitive transcranial magnetic stimulation (rTMS), inhibitory (1 Hz) and excitatory (5 Hz), applied over the primary motor cortex of the presumed dominant hemisphere, affect functional connectivity and neurochemistry in the brain.

Detailed Description

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation method which is effective for treating both psychiatric and non-psychiatric disorders, such as posttraumatic stress disorder, obsessive compulsive disorder, pain syndromes and for improving motor function in neurodegenerative diseases or following stroke. rTMS uses series of brief pulses of magnetic field applied to the surface of the head for a period of time (e.g. 20 minutes). The effects of rTMS are transient, and critically dependent upon the location, frequency and intensity of stimulation. Several studies have provided evidence that rTMS can influence the excitability and function of neurons (neuromodulation) for up to one hour, both near to, and distant from, the site of stimulation. However it is still unclear how these transient local and distant changes in function induced by specific rTMS protocols are mediated. In this project we will combine expertise in Magnetic Resonance Imaging (MRI), Magnetic Resonance Spectroscopy (MRS) and rTMS neuromodulation to develop and test protocols for examining the changes produced by non-invasive brain stimulation on healthy subjects. rTMS will be applied outside the scanner using standard TMS coils and MRI/S at 7 Tesla will be acquired before and immediately after rTMS. Our aim is to increase the understanding of how the two different rTMS protocols, inhibitory (1 Hz) and excitatory (5 Hz), applied over the primary motor cortex of the presumed dominant hemisphere, affect functional connectivity and neurochemistry in the brain.

Study Timeline

• Study First Submitted: 2016-02-02
• Study First Submitted QC: 2016-02-04
• Study First Posted: 2016-02-09
• Study Start: 2016-08-29
• Primary Completion: 2017-03-19
• Study Completion: 2017-03-19
• Results First Submitted: 2019-06-12
• Results First Submitted QC: 2019-07-17
• Results First Posted: 2019-08-06
• Status Verified: 2019-11
• Last Update Submitted: 2019-11-04
• Last Update Posted: 2019-11-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 8

Inclusion Criteria

Those volunteers who are evaluated as normal and not met exclusion criteria will be potential candidates for this study.

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Exclusion Criteria

The following participants will be excluded from this study, including but not limited to:

• Females
• Left handed males
• Participants who never underwent MRI at 7 Tesla

Participants with:

• any type of bio-implant activated by mechanical, electronic, or magnetic means (e.g. cochlear implants, pacemakers, neurostimulators, bio stimulators, electronic infusion pumps.)
• any type of ferromagnetic bio-implant that could potentially be displaced or damaged, such as aneurysm clips, metallic skull plates, etc.
• non-removable piercing or permanent eyeliner
• retained metal in their body, either from a medical procedure or an injury

Participants who:

• have been diagnosed by a physician as having a psychiatric disorder, substance abuse, neurological and/or cardiovascular disease
• have cardiac or known circulatory impairment, and/or the inability to perspire (poor thermoregulatory function)
• have hyper- or hypotension or arrhythmias
• have known conditions which can lead to emergency medical care
• had a head injury that caused them to lose consciousness for more than 30 minutes or have amnesia for more than 24 hours
• had a brain tumor or stroke
• had one or more seizures, or been given a diagnosis of epilepsy
• have a history of sleep apnea or head trauma that may have caused Traumatic Brain Injury (TBI)
• have a history of anxiety, syncope, panic attacks and/or claustrophobia
• cannot adhere to the experimental protocol for any reason
• started taking chemotherapy or immunomodulatory agents, or had any radiation treatment that could affect the brain
• are currently on any medication

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Inhibitory rTMS (1 Hz)	Inhibitory rTMS (1 Hz)	Subjects are exposed to a 20-min inhibitory rTMS intervention that transiently suppresses the excitability of cortical structures beneath the site of stimulation. Subjects undergo MRI and MRS both before and right after the rTMS intervention.
Excitatory rTMS (5 Hz)	Excitatory rTMS (5 Hz)	Subjects are exposed to a 20-min excitatory rTMS intervention that transiently increases the net excitability of cortical structures beneath the site of stimulation. Subjects undergo MRI and MRS both before and right after the rTMS intervention.

Primary Outcome Measures

Name	Time	Method
Percent Change of GABA Concentration in a Voxel Encompassing the Right Motor Cortex, Measured at 60 Min After rTMS	Baseline/Pre-rTMS and 60 min after rTMS	GABA concentration is quantified with MRS at 7 Tesla. Percent change of GABA concentration is calculated from baseline (i.e., pre-rTMS).
Percent Change of GABA Concentration in a Voxel Encompassing the Left Motor Cortex, Measured at 30 Min After rTMS	Baseline/Pre-rTMS and 30 min after rTMS	GABA concentration is quantified with MRS at 7 Tesla. Percent change of GABA concentration is calculated from baseline (i.e., pre-rTMS).
Percent Change of Functional Connectivity in Left Motor Cortex, Where Functional Connectivity is Measured as a Dimensionless Fractional Amplitude of Low-frequency Fluctuations (fALFF), at 80 Min After rTMS	Baseline/Pre-rTMS and 80 min after rTMS	Functional connectivity is measured with MRI at 7 Tesla as a dimensionless fractional amplitude of low-frequency fluctuations (fALFF). This is an index which reflects the intensity of spontaneous regional brain activity. It is calculated as the ratio of power spectra of low frequency (0.01-0.08 Hz) to that of the entire frequency range. Percent change of functional connectivity is calculated from baseline (i.e., pre-rTMS).
Percent Change of Functional Connectivity in Right Motor Cortex, Where Functional Connectivity is Measured as a Dimensionless Fractional Amplitude of Low-frequency Fluctuations (fALFF), at 80 Min After rTMS	Baseline/Pre-rTMS and 80 min after rTMS	Functional connectivity is measured with MRI at 7 Tesla as a dimensionless fractional amplitude of low-frequency fluctuations (fALFF). This is an index which reflects the intensity of spontaneous regional brain activity. It is calculated as the ratio of power spectra of low frequency (0.01-0.08 Hz) to that of the entire frequency range. Percent change of functional connectivity is calculated from baseline (i.e., pre-rTMS).

Trial Locations

Locations (1)

Center for Magnetic Resonance Research, Dept. of Radiology, University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States