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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Inhibitory rTMS (1 Hz) | Experimental | 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. |
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| Excitatory rTMS (5 Hz) | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Inhibitory rTMS (1 Hz) | Device | Participants receive rTMS at a rate of 1 Hz, applied with a 70-mm figure-eight TMS coil connected to a stimulator, over the motor cortex hotspot contralateral to the dominant arm for 20 minutes at an intensity of 90% resting motor threshold (RMT) for a total of 600 TMS pulses. The total number of stimuli applied is well within the published safety guidelines for use of rTMS. rTMS is applied outside the scanner, whereas functional connectivity and neurochemistry are measured with MRI and MRS, respectively, at 7 Tesla. The MRI/MRS data are collected right before and immediately after the inhibitory rTMS intervention. |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change of GABA Concentration in a Voxel Encompassing the Left Motor Cortex, Measured at 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). | Baseline/Pre-rTMS and 30 min after rTMS |
| Percent Change of GABA Concentration in a Voxel Encompassing the Right Motor Cortex, Measured at 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). | Baseline/Pre-rTMS and 60 min after 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 | 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). | Baseline/Pre-rTMS and 80 min after 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 | 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). | Baseline/Pre-rTMS and 80 min after rTMS |
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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:
Participants with:
Participants who:
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| Name | Affiliation | Role |
|---|---|---|
| Silvia Mangia, PhD | Dept. of Radiology, University of Minnesota | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Center for Magnetic Resonance Research, Dept. of Radiology, University of Minnesota | Minneapolis | Minnesota | 55455 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20402755 | Background | 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. | |
| 19152730 |
| Label | URL |
|---|---|
| Profile of Principal Investigator | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. One week before the MRI/MRS acquisitions, neurophysiological parameters are also measured before and right after the rTMS intervention. Inhibitory rTMS (1 Hz): Participants receive rTMS at a rate of 1 Hz, applied with a 70-mm figure-eight TMS coil connected to a stimulator, over the motor cortex hotspot contralateral to the dominant arm for 20 minutes at an intensity of 90% resting motor threshold (RMT) for a total of 600 TMS pulses. The total number of stimuli applied is well within the published safety guidelines for use of rTMS. rTMS is applied outside the scanner, whereas functional connectivity and neurochemistry are measured with MRI and MRS, respectively, at 7 Tesla. The MRI/MRS data are collected right before and immediately after the |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 1, 2019 |
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| Excitatory rTMS (5 Hz) | Device | Participants receive rTMS at a rate of 5 Hz, applied with a 70-mm figure-eight TMS coil connected to a stimulator, over the motor cortex hotspot contralateral to the dominant arm for 20 minutes at an intensity of 90% RMT for a total of 600 TMS pulses. The total number of stimuli applied is well within the published safety guidelines for use of rTMS. rTMS is applied outside the scanner, whereas functional connectivity and neurochemistry are measured with MRI and MRS, respectively, at 7 Tesla. The MRI/MRS data are collected right before and immediately after the excitatory rTMS intervention. |
|
| 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. |
| 19833552 | Background | 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. |
| 25564236 | Background | 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. |
| 23702415 | Background | 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. |
| FG001 | 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. One week before the MRI/MRS acquisitions, neurophysiological parameters are also measured before and right after the rTMS intervention. Excitatory rTMS (5 Hz): Participants receive rTMS at a rate of 5 Hz, applied with a 70-mm figure-eight TMS coil connected to a stimulator, over the motor cortex hotspot contralateral to the dominant arm for 20 minutes at an intensity of 90% RMT for a total of 600 TMS pulses. The total number of stimuli applied is well within the published safety guidelines for use of rTMS. rTMS is applied outside the scanner, whereas functional connectivity and neurochemistry are measured with MRI and MRS, respectively, at 7 Tesla. The MRI/MRS data are collected right before and immediately after the excitatory rTMS interv |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. One week before the MRI/MRS acquisitions, neurophysiological parameters are also measured before and right after the rTMS intervention. Inhibitory rTMS (1 Hz): Participants receive rTMS at a rate of 1 Hz, applied with a 70-mm figure-eight TMS coil connected to a stimulator, over the motor cortex hotspot contralateral to the dominant arm for 20 minutes at an intensity of 90% resting motor threshold (RMT) for a total of 600 TMS pulses. The total number of stimuli applied is well within the published safety guidelines for use of rTMS. rTMS is applied outside the scanner, whereas functional connectivity and neurochemistry are measured with MRI and MRS, respectively, at 7 Tesla. The MRI/MRS data are collected right before and immediately after the |
| BG001 | 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. One week before the MRI/MRS acquisitions, neurophysiological parameters are also measured before and right after the rTMS intervention. Excitatory rTMS (5 Hz): Participants receive rTMS at a rate of 5 Hz, applied with a 70-mm figure-eight TMS coil connected to a stimulator, over the motor cortex hotspot contralateral to the dominant arm for 20 minutes at an intensity of 90% RMT for a total of 600 TMS pulses. The total number of stimuli applied is well within the published safety guidelines for use of rTMS. rTMS is applied outside the scanner, whereas functional connectivity and neurochemistry are measured with MRI and MRS, respectively, at 7 Tesla. The MRI/MRS data are collected right before and immediately after the excitatory rTMS interv |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent Change of GABA Concentration in a Voxel Encompassing the Left Motor Cortex, Measured at 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). | Posted | Mean | Standard Deviation | percent change | Baseline/Pre-rTMS and 30 min after rTMS |
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| Primary | Percent Change of GABA Concentration in a Voxel Encompassing the Right Motor Cortex, Measured at 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). | Posted | Mean | Standard Deviation | percent change | Baseline/Pre-rTMS and 60 min after rTMS |
| |||||||||||||||||||||||||||||||
| Primary | 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 | 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). | Posted | Mean | Standard Deviation | percent change | Baseline/Pre-rTMS and 80 min after rTMS |
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| Primary | 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 | 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). | Posted | Mean | Standard Deviation | percent change | Baseline/Pre-rTMS and 80 min after rTMS |
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approximately 4 hours
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. One week before the MRI/MRS acquisitions, neurophysiological parameters are also measured before and right after the rTMS intervention. Inhibitory rTMS (1 Hz): Participants receive rTMS at a rate of 1 Hz, applied with a 70-mm figure-eight TMS coil connected to a stimulator, over the motor cortex hotspot contralateral to the dominant arm for 20 minutes at an intensity of 90% resting motor threshold (RMT) for a total of 600 TMS pulses. The total number of stimuli applied is well within the published safety guidelines for use of rTMS. rTMS is applied outside the scanner, whereas functional connectivity and neurochemistry are measured with MRI and MRS, respectively, at 7 Tesla. The MRI/MRS data are collected right before and immediately after the | 0 | 7 | 0 | 7 | 7 | 7 |
| EG001 | 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. One week before the MRI/MRS acquisitions, neurophysiological parameters are also measured before and right after the rTMS intervention. Excitatory rTMS (5 Hz): Participants receive rTMS at a rate of 5 Hz, applied with a 70-mm figure-eight TMS coil connected to a stimulator, over the motor cortex hotspot contralateral to the dominant arm for 20 minutes at an intensity of 90% RMT for a total of 600 TMS pulses. The total number of stimuli applied is well within the published safety guidelines for use of rTMS. rTMS is applied outside the scanner, whereas functional connectivity and neurochemistry are measured with MRI and MRS, respectively, at 7 Tesla. The MRI/MRS data are collected right before and immediately after the excitatory rTMS interv | 0 | 1 | 0 | 1 | 1 | 1 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sleepiness | General disorders | Systematic Assessment |
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| Warmth | General disorders | Non-systematic Assessment |
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| Metallic Taste | General disorders | Non-systematic Assessment |
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| Anxiety/Worry/Nervousness | Psychiatric disorders | Non-systematic Assessment |
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| Headache | General disorders | Non-systematic Assessment |
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| Tooth Pain | General disorders | Non-systematic Assessment |
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| Shoulder Pain | General disorders | Non-systematic Assessment |
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The study was initially registered with a larger number of subjects (30) than what the pilot funds allowed (8) to allow more studies in the future. However, we decided to close the protocol after 8 studies reported here to avoid prolonged inactivity.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Silvia Mangia, Associate Professor | University of Minnesota | 6126254920 | mangia@umn.edu |
| Jul 17, 2019 |
| Prot_SAP_000.pdf |
| >=65 years |
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| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| OG001 | 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. One week before the MRI/MRS acquisitions, neurophysiological parameters are also measured before and right after the rTMS intervention. Excitatory rTMS (5 Hz): Participants receive rTMS at a rate of 5 Hz, applied with a 70-mm figure-eight TMS coil connected to a stimulator, over the motor cortex hotspot contralateral to the dominant arm for 20 minutes at an intensity of 90% RMT for a total of 600 TMS pulses. The total number of stimuli applied is well within the published safety guidelines for use of rTMS. rTMS is applied outside the scanner, whereas functional connectivity and neurochemistry are measured with MRI and MRS, respectively, at 7 Tesla. The MRI/MRS data are collected right before and immediately after the excitatory rTMS interv |
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| OG001 | 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. One week before the MRI/MRS acquisitions, neurophysiological parameters are also measured before and right after the rTMS intervention. Excitatory rTMS (5 Hz): Participants receive rTMS at a rate of 5 Hz, applied with a 70-mm figure-eight TMS coil connected to a stimulator, over the motor cortex hotspot contralateral to the dominant arm for 20 minutes at an intensity of 90% RMT for a total of 600 TMS pulses. The total number of stimuli applied is well within the published safety guidelines for use of rTMS. rTMS is applied outside the scanner, whereas functional connectivity and neurochemistry are measured with MRI and MRS, respectively, at 7 Tesla. The MRI/MRS data are collected right before and immediately after the excitatory rTMS interv |
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