Clinical trial NCT02677740: Mechanisms of Non-Invasive Neuromodulation Interventions: Influence on Human Neurochemistry and Functional Connectivity
Official title: Mechanisms of Non-Invasive Neuromodulation Interventions: Influence on Human Neurochemistry and Functional Connectivity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Non-invasive Neuromodulation in Healthy Subjects
Keywords: MRI
MRS
rTMS
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2016-02-09
Enrollment: 8
Sex: MALE
Minimum age (years): 21
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: Inclusion Criteria:

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

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

Primary outcomes:
measure: Percent Change of GABA Concentration in a Voxel Encompassing the Left Motor Cortex, Measured at 30 Min After rTMS
timeFrame: Baseline/Pre-rTMS and 30 min after rTMS
measure: Percent Change of GABA Concentration in a Voxel Encompassing the Right Motor Cortex, Measured at 60 Min After rTMS
timeFrame: Baseline/Pre-rTMS and 60 min after rTMS
measure: 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
timeFrame: Baseline/Pre-rTMS and 80 min after rTMS
measure: 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
timeFrame: Baseline/Pre-rTMS and 80 min after rTMS
Secondary outcomes:
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Center for Magnetic Resonance Research, Dept. of Radiology, University of Minnesota
state: Minnesota
Study officials:
affiliation: Dept. of Radiology, University of Minnesota
name: Silvia Mangia, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Emara TH, Moustafa RR, ElNahas NM, ElGanzoury AM, Abdo TA, Mohamed SA, ElEtribi MA. Repetitive transcranial magnetic stimulation at 1Hz and 5Hz produces sustained improvement in motor function and disability after ischaemic stroke. Eur J Neurol. 2010 Sep;17(9):1203-1209. doi: 10.1111/j.1468-1331.2010.03000.x. Epub 2010 Apr 8.
citation: Machado S, Bittencourt J, Minc D, Portella CE, Velasques B, Cunha M, Budde H, Basile LF, Chadi G, Cagy M, Piedade R, Riberio P. Therapeutic applications of repetitive transcranial magnetic stimulation in clinical neurorehabilitation. Funct Neurol. 2008 Jul-Sep;23(3):113-22.
citation: Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-2039. doi: 10.1016/j.clinph.2009.08.016. Epub 2009 Oct 14.
citation: Bednarik P, Tkac I, Giove F, DiNuzzo M, Deelchand DK, Emir UE, Eberly LE, Mangia S. Neurochemical and BOLD responses during neuronal activation measured in the human visual cortex at 7 Tesla. J Cereb Blood Flow Metab. 2015 Mar 31;35(4):601-10. doi: 10.1038/jcbfm.2014.233.
citation: Smith SM, Beckmann CF, Andersson J, Auerbach EJ, Bijsterbosch J, Douaud G, Duff E, Feinberg DA, Griffanti L, Harms MP, Kelly M, Laumann T, Miller KL, Moeller S, Petersen S, Power J, Salimi-Khorshidi G, Snyder AZ, Vu AT, Woolrich MW, Xu J, Yacoub E, Ugurbil K, Van Essen DC, Glasser MF; WU-Minn HCP Consortium. Resting-state fMRI in the Human Connectome Project. Neuroimage. 2013 Oct 15;80:144-68. doi: 10.1016/j.neuroimage.2013.05.039. Epub 2013 May 20.