The proposed study is designed to determine whether small changes in the positioning of a transcranial magnetic stimulation coil over the frontal parts of the brain cause different patterns of brain activation measured by electroencephalography (EEG) and quantitative EEG (QEEG).
A previously recorded MRI will be loaded into Brainsight, a stereotactic neuronavigation system specifically designed to be used with rTMS, and the scalp surface site overlying the centre of Brodmann area 46 in the dorsolateral prefrontal cortex (DLPFC) of both the left and right hemisphere will be identified and marked on a spandex swim cap placed on the subjects head over 31 EEG electrodes (notched to prevent eddy currents) placed at international 10-20 locations . Three trains of true 10 Hz (110% motor threshold (MT)\] rTMS (one train each with duration=2,4, and 8 seconds) and 6 similar trains of sham rTMS (3 of active sham and 3 of inactive sham) will be delivered to the left hemisphere in Brodmann area 46 in random order. Eyes-closed QEEG power will be recorded across all leads over 10 second "blocks" for 1 minute after each 10 Hz stimulus to determine the distribution and time course of any changes in electrical potential and QEEG spectrum. The subjects will be asked to rate their mood and anxiety by placing a mark along 100 mm long Visual Analogue Scales for depression and anxiety after each stimulus train. We will also measure ERPs after 1 Hz stimulation to the right DLPFC (centre of Brodmann area 46). We will administer three 60-second trains of true 1 Hz rTMS (at 90%, 100% and 110% motor threshold), and six 60-second trains of sham rTMS (3 of "active" sham and 3 of "inactive" sham) with device intensity setting of 10 %, 30% and 50% motor threshold and coil tilted at 90 degrees away form the head. Part 2 (location testing): Twenty four to 48 hours later, the swim hat will be placed on the subject's head and the neuroanatomical landmarks reconfirmed using Brainsight. One true train and 1 inactive sham train of 10 Hz rTMS (10 Hz, 110% MT) will be delivered in random order to Brodmann area 46 and two other sites (in Brodmann areas 9 and 10). The rTMS train duration will be 8 seconds. The subjects will be asked to rate their mood and anxiety by placing a mark along 100 mm long Visual Analogue Scales for depression and anxiety after each stimulus train. The same procedure will be done over the right hemisphere using 1 Hz stimulation set at 110% motor threshold. True rTMS pulses at 1 Hz, or inactive sham rTMS pulses will be delivered in 60 second trains to the 3 sites as described above, but marked over the right DLPFC. QEEG activity will be recorded for 1 minute after each stimulus train. The subjects will be asked to rate their mood and anxiety by placing a mark along 100 mm long Visual Analogue Scales for depression and anxiety after each stimulus train. Diffusion Tensor Imaging: The 15 healthy subjects (18-65 years old) will also undergo diffusion tensor imaging (DTI) along with the MRI, which will add approximately 10 minutes to the MRI procedure. Following a routine brain imaging protocol whole brain DTI measurements will be conducted in each subject using a single shot spin echo EPI diffusion tensor imaging sequence.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
17
10 Hz stimulation will be given at 110% motor threshold for 8 seconds to Brodmann areas 46, 9 and 10 in the left hemisphere. The coil will be held flat over the skull surface with the coil handle held at approximately 45 degrees to the floor
10 Hz stimulation will be given at 110% motor threshold for 8 seconds to Brodmann areas 46, 9 and 10 in the left hemisphere. The passive (inactive) coil will be held flat over the skull surface with the coil handle held at approximately 45 degrees to the floor. An active coil will be held vertically in a mechanical holder 50 cm behind the subject head and run at 10 Hz with an intensity set to 150% of motor threshold.
St. Joseph's Healthcare, Centre for Mountain Health Services
Hamilton, Ontario, Canada
The primary outcome measure will be global mean field amplitude (GMFA) before and after treatment with true or sham rTMS using a range of stimulus train durations and several stimulation sites.
Time frame: The GMFA will be measured for 1 minutes after each rTMS train is delivered.
Secondary outcome measures will include magnetically evoked response potentials in the multi-channel recorded EEG signals.
The magnetically evoked response potentials will be measured over the first 500 milliseconds after each TMS pulse. We will also determine weather rTMS can produce measurable changes in left/right alpha power ratio (L/R APR). The L/R APR will be measured for 1 minute after each TMS train is delivered.
Time frame: The L/R APR will be measured for 1 minute after each TMS train is delivered.
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