The authors wish to thank Elyssa Sisko and Bella Tendler for manuscript review and editing.

NOTE: Before beginning any TMS protocols, there are three precautionary statements. First, patients and operators should use earplugs with a 30 dB rating. Second, patients with ferromagnetic material in the skull cannot receive TMS. Finally, patients with epilepsy must have protocol modifications. In addition, the individual&#39;s motor threshold (MT) must be determined (see below for the specific procedure). The MT is defined as the lowest machine intensity necessary to activate a muscle in five out of ten attempts (50%), typically the abductor pollicis brevis, by visual inspection. MT is used to adjust the stimulator output for the specific individual receiving the treatment. Each protocol includes specific parameters, such as the stimulation frequency, the number of trains, the inter-train interval (ITI), or the number of pulses in each train. Each disorder has a minimum number of daily or thrice-weekly treatments that should be attempted before someone can be considered a treatment failure, and responders generally need a prolonged course of twice-weekly treatments to get maximal sustained benefit. Additionally, patients in recovery may benefit from weekly maintenance treatments. Continuation and maintenance protocols for the different disorders are still being studied, but all of the parameters that were used in the preliminary investigations are provided in Table 1 and should be referred to for each specific disorder. Patients undergoing dTMS should have a baseline assessment with clinician and patient rating scales, as well as follow-up scales. The definition of disease states and the rating scale options to define improvement and remission are beyond the scope of this paper. An example of a patient rating scale for depression would be the quick inventory of depressive symptoms or the Beck depression inventory. An example of a clinician rating scale is the clinician&#39;s global impression or the Hamilton depression rating scale. These scales have defined cutoffs for remission, while a 50% drop in the score is defined as response.
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Disorder</td>
			<td>Anatomical Target/ H1 Position</td>
			<td>Stimulation Protocols</td>
			<td>Treatment Frequency</td>
			<td>Treatment Changes</td>
		</tr>
		<tr>
			<td>MDD6,7,8</td>
			<td>Left PFC 
			Coil tilted</td>
			<td>120 MT, 18 HZ, 2 sec train, 20 sec interval, 55 trains, 1,980 total pulses</td>
			<td>5d a week until remission or sustained improvement. If unimproved after 44 treatments choose an alternative treatment approach.</td>
			<td>After sustained improvement for two weeks or remission decrease frequency to 2x week for three months.</td>
		</tr>
		<tr>
			<td>Bipolar Depression9,10</td>
			<td>Left PFC 
			Coil tilted</td>
			<td>120 MT, 20 HZ, 2 sec train, 20 sec interval, 42 trains, 1,680 total pulses</td>
			<td>5d a week until remission or sustained improvement. If unimproved after 20 treatments choose an alternative treatment.</td>
			<td>If the patient is in remission or sustained improvement, continue treatments twice a week for a period of three months.</td>
		</tr>
		<tr>
			<td>Schizophrenia - Negative Symptoms11,12</td>
			<td>Left PFC 
			Coil tilted</td>
			<td>120 MT, 20 HZ, 2 sec train, 20 sec interval, 42 trains, 1,680 total pulses</td>
			<td>5d a week until remission or sustained improvement If the patient is unimproved after 20 treatments &#160;choose an alternative treatment.</td>
			<td>If the patient is in remission or sustained improvement, continue treatments twice a week for a period of three months.</td>
		</tr>
		<tr>
			<td>Migraine13</td>
			<td>Left PFC 
			Coil tilted</td>
			<td>100 MT, 10 HZ, 2 sec train, 20 sec interval, 18 trains, 360 total pulses</td>
			<td>3d a week for four weeks. &#160;If the patient does not respond after 12 sessions, choose an alternative treatment.</td>
			<td>If the patient is in remission or sustained improvement, continue treatments twice a week for a period of three months.</td>
		</tr>
		<tr>
			<td>PTSD14</td>
			<td>Medial PFC 
			Coil symmetrical</td>
			<td>After listening to a personalized&#160; traumatic script, 120 MT, 20 HZ, 2 sec train, 20 sec interval, 42 trains, 1680 total pulses</td>
			<td>3d a week for 5 weeks. If the patient does not respond after 15 treatments, choose an alternative treatment.</td>
			<td>If the patient goes into remission or has a sustained improvement, continue treatments twice a week for a period of three months. For complex PTSD with multiple traumatic events, change the traumatic script and start again</td>
		</tr>
		<tr>
			<td>Alcohol Addiction15,16,17,18,19</td>
			<td>Medial PFC 
			Coil symmetrical</td>
			<td>After 90 sec personalized provocation of alcohol cravings, 120 MT, 20 HZ, 2.5 sec train, 30 sec interval, 30 trains, 1,500 total pulses</td>
			<td>5d a week until remission or sustained improvement. If the patient is does not respond after 20 treatments &#160;choose an alternative treatment.</td>
			<td>If the patient goes into remission, continue treatments twice a week for a period of three months.</td>
		</tr>
		<tr>
			<td>Schizophrenia - Auditory hallucinations20,21</td>
			<td>Left TPJ 
			Coil tilted</td>
			<td>110 MT, 1 HZ, 600 Pulses</td>
			<td>5d a week for 4 weeks. &#160;If the patient does not respond after 20 sessions, choose an alternative treatment.</td>
			<td>If the patient goes into remission or has a sustained improvement, continue treatments twice a week for a period of three months.</td>
		</tr>
		<tr>
			<td>Chronic Tinnitus22</td>
			<td>Left TPJ 
			Coil tilted</td>
			<td>110 MT, 18 HZ, 2 sec train, 20 sec interval, 55 trains, 1,980 total pulses</td>
			<td>5d a week for 2 weeks. &#160;If the patient does not respond after 10 sessions, choose an alternative treatment.</td>
			<td>If the patient goes into remission or has a sustained improvement, continue treatments twice a week for a period of three months.</td>
		</tr>
		<tr>
			<td>Anxiety23</td>
			<td>Right PFC 
			Coil tilted</td>
			<td>120 MT 1 HZ 600-2,000 Pulses</td>
			<td>5d a week for 6 weeks. &#160;If the patient does not respond after 30 sessions, choose an alternative treatment.</td>
			<td>If the patient goes into remission or has a sustained improvement, continue treatments twice a week for a period of three months.</td>
		</tr>
		<tr>
			<td>Parkinson&#8217;s Disease24</td>
			<td>Motor Cortex and PFC 
			Coil symmetrical</td>
			<td>Motor Cortex: 110 MT, 1 HZ, 1,000 Pulses 
			PFC: 120 MT, 20 HZ, 2 sec train, 20 sec interval 50 trains, 2,000 pulses</td>
			<td>5d a week for 4 weeks. &#160;If the patient does not respond after 20 sessions, choose an alternative treatment. Responders may lower levodopa dosage.</td>
			<td>After sustained response continue treatments twice a week to achieve maximum benefit. Patients will regress after three months without maintenance.</td>
		</tr>
		<tr>
			<td>MS Fatigue25</td>
			<td>Motor Cortex and PFC 
			Coil symmetrical</td>
			<td>Motor Cortex: 80 MT, 10 HZ, 2 sec train, 1 sec interval, 70 trains, 1,400 total pulses 
			PFC: 120 MT, 18 HZ, 2 sec train, 20 sec interval, 39 trains, 1,404 total pulses</td>
			<td>5d a week for 4 weeks. &#160;If the patient does not respond after 20 sessions, choose an alternative treatment.</td>
			<td>Patients should receive booster treatments on an as needed basis.</td>
		</tr>
	</tbody>
</table>
NOTE: H1 Protocol: The focus of this paper is to demonstrate the positioning of the coil over the MC, lPFC, mPFC, rPFC, and left TPJ (see steps 2-7 below). It will not focus on programing the stimulator. That information is more readily available in the instructions for use that comes with the device. These protocols were designed in accordance with the principles outlined in the declaration of Helsinki.
1. Measure the Motor Threshold
<ol>
	<li>Place the blue cap with the two intercepting rulers on the subject.</li>
	<li>Place the 0-cm mark of the white sagittal ruler on the nasion and the 25 cm mark of the clear coronal ruler at 40% of the nasion-inion distance, with the 0 on the left side of the patient&#39;s head.</li>
	<li>Use the helmet to find the resting MT of the right hand, starting with the front of the helmet 7 cm from the nasion and the left side of the coil tilted 2 cm to the right.</li>
	<li>Using the &#34;Single Pulse&#34; mode on the stimulator touch screen, administer single pulses at 50% of the stimulator output while observing the patient&#39;s resting right hand. Increase the stimulator intensity if no visible movement is observed or if a visible movement is observed less than 50% of the time. Initially, use 5% intervals.</li>
	<li>Decrease the stimulator intensity if a visible movement is observed more than 50% of the time. Start with 5% intervals and then fine-tune it.</li>
	<li>Repeat steps 1.4 and 1.5 to identify the minimal MT. This location is called the &#34;hot spot.&#34;</li>
</ol>
2. Setting Up Parameters Within the Device User Interface
<ol>
	<li>Press &#34;Repetitive Mode&#34; on the stimulator touchscreen.</li>
	<li>Enter parameters by touching the boxes on the screen and adjusting them using the side wheel. Enter the parameters from Table 1 and press &#34;Run Session.&#34;</li>
	<li>Arm the machine by pressing the green button. Warn the patient that the stimulation is starting, and start the stimulation with the yellow button or the pedal.</li>
</ol>
3. Stimulate the MC for Parkinson&#39;s or MS Fatigue
<ol>
	<li>After finding the MT, straighten the helmet in a symmetrical fashion over the MC, with the 0 on the front of the helmet over the sagittal ruler.</li>
</ol>
4. Stimulate the Left PFC for Depression, Bipolar Depression, Negative Symptoms of Schizophrenia, and Migraine
<ol>
	<li>Advance the tilted helmet from the MT location over the MC to the left PFC by moving it 6 cm forward along the sagittal ruler.</li>
</ol>
5. Stimulate the mPFC for Alcohol Dependence or PTSD
<ol>
	<li>Place the helmet over the mPFC, symmetrically with respect to right-left, with the 0 mark on the helmet&#39;s front edge aligned with the 3 cm mark on the sagittal ruler of the cap (i.e., 3 cm from the nasion).</li>
</ol>
6. Stimulate the Right PFC for Generalized Anxiety or Panic Disorder
<ol>
	<li>Find the left-hand MT with the helmet (following the mirror image of steps 1.3-1.4 by tilting the helmet 2 cm to the left and watching the resting left hand).</li>
	<li>Move the tilted helmet 6 cm forward along the sagittal ruler to the right PFC.</li>
</ol>
7. Stimulate the Left TPJ for Tinnitus or Auditory Hallucinations
<ol>
	<li>Place the helmet over the left TPJ by moving the coil 4.5 cm posteriorly and 6.5 cm laterally (to the left shoulder) from the right-hand MC &#34;hot spot.&#34;</li>
</ol>
8. Electrical Field Measurements
<ol>
	<li>Attach the coil to an inverted saline-filled head over the left DLPFC. Set the stimulator intensity to 50%. Using a dipole probe connected to an oscilloscope, move it cm by cm so that, when single pulses are delivered through the coil, the oscilloscope measures the induced electric field at each point in the saline-filled head26. 
	NOTE: The process of producing field maps based on the head model measurements is beyond the scope of this paper. In short, the field values at any point are normalized according to the relevant protocol. For instance, for depression, the accepted protocol is 120% of MT. Hence, the field values are scaled so that the value at the hand MC is 120 V/m, while the threshold for neural stimulation is defined as 100 V/m. Then, a color map of the electric field distribution in the brain is produced, where pixels with a field of 100 V/m or above are indicated in red so that one can see which brain regions are stimulated above the threshold for neural stimulation. The colored field maps are superimposed on MRI scans of the brain26,27.</li>
</ol>

<ol>
	<li>Johnson, K. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prefrontal+rTMS+for+treating+depression:+location+and+intensity+results+from+the+OPT-TMS+multi-site+clinical+trial.">Prefrontal rTMS for treating depression: location and intensity results from the OPT-TMS multi-site clinical trial.</a> Brain Stimul. 6 (2), 108-117 (2013).</li><li>Fox, M. D., Buckner, R. L., White, M. P., Greicius, M. D., Pascual-Leone, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Efficacy+of+transcranial+magnetic+stimulation+targets+for+depression+is+related+to+intrinsic+functional+connectivity+with+the+subgenual+cingulate.">Efficacy of transcranial magnetic stimulation targets for depression is related to intrinsic functional connectivity with the subgenual cingulate.</a> Biol Psychiatry. 72 (7), 595-603 (2012).</li><li>Fox, M. D., Liu, H., Pascual-Leone, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Identification+of+reproducible+individualized+targets+for+treatment+of+depression+with+TMS+based+on+intrinsic+connectivity.">Identification of reproducible individualized targets for treatment of depression with TMS based on intrinsic connectivity.</a> Neuroimage. 66, 151-160 (2013).</li><li>Zangen, A., Roth, Y., Voller, B., Hallett, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transcranial+magnetic+stimulation+of+deep+brain+regions:+evidence+for+efficacy+of+the+H-coil.">Transcranial magnetic stimulation of deep brain regions: evidence for efficacy of the H-coil.</a> Clin Neurophysiol. 116 (4), 775-779 (2005).</li><li>Marcolin, M. A., Padberg, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Transcranial Brain Stimul for treatment of psychiatric disorders. Vol. 23. , (2007).</li><li>Levkovitz, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Efficacy+and+safety+of+deep+transcranial+magnetic+stimulation+for+major+depression:+A+prospective+multicenter+randomized+controlled+trial.">Efficacy and safety of deep transcranial magnetic stimulation for major depression: A prospective multicenter randomized controlled trial.</a> World Psychiatry. 14 (1), 64-73 (2015).</li><li>Rosenberg, O., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Long-term+Follow-up+of+MDD+Patients+Who+Respond+to+Deep+rTMS:+A+Brief+Report.">Long-term Follow-up of MDD Patients Who Respond to Deep rTMS: A Brief Report.</a> Isr J Psychiatry Relat Sci. 52 (1), 17-23 (2015).</li><li>Harel, E. V., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=H-coil+repetitive+transcranial+magnetic+stimulation+for+treatment+resistant+major+depressive+disorder:+An+18-week+continuation+safety+and+feasibility+study.">H-coil repetitive transcranial magnetic stimulation for treatment resistant major depressive disorder: An 18-week continuation safety and feasibility study.</a> World J Biol Psychiatry. 15 (4), 298-306 (2014).</li><li>Harel, E. V., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=H-coil+repetitive+transcranial+magnetic+stimulation+for+the+treatment+of+bipolar+depression:+an+add-on,+safety+and+feasibility+study.">H-coil repetitive transcranial magnetic stimulation for the treatment of bipolar depression: an add-on, safety and feasibility study.</a> World J Biol Psychiatry. 12 (2), 119-126 (2011).</li><li>Bersani, F. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Deep+transcranial+magnetic+stimulation+for+treatment-resistant+bipolar+depression:+a+case+report+of+acute+and+maintenance+efficacy.">Deep transcranial magnetic stimulation for treatment-resistant bipolar depression: a case report of acute and maintenance efficacy.</a> Neurocase. 19 (5), 451-457 (2013).</li><li>Rabany, L., Deutsch, L., Levkovitz, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Double-blind,+randomized+sham+controlled+study+of+deep-TMS+add-on+treatment+for+negative+symptoms+and+cognitive+deficits+in+schizophrenia.">Double-blind, randomized sham controlled study of deep-TMS add-on treatment for negative symptoms and cognitive deficits in schizophrenia.</a> J Psychopharmacol. 28 (7), 686-690 (2014).</li><li>Levkovitz, Y., Rabany, L., Harel, E. V., Zangen, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Deep+transcranial+magnetic+stimulation+add-on+for+treatment+of+negative+symptoms+and+cognitive+deficits+of+schizophrenia:+a+feasibility+study.">Deep transcranial magnetic stimulation add-on for treatment of negative symptoms and cognitive deficits of schizophrenia: a feasibility study.</a> Int J Neuropsychopharmacol. 14 (7), 991-996 (2011).</li><li>Rapinesi, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Add-on+deep+Transcranial+Magnetic+Stimulation+(dTMS)+for+the+treatment+of+chronic+migraine:+A+preliminary+study.">Add-on deep Transcranial Magnetic Stimulation (dTMS) for the treatment of chronic migraine: A preliminary study.</a> Neurosci Lett. 623, 7-12 (2016).</li><li>Isserles, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effectiveness+of+deep+transcranial+magnetic+stimulation+combined+with+a+brief+exposure+procedure+in+post-traumatic+stress+disorder--a+pilot+study.">Effectiveness of deep transcranial magnetic stimulation combined with a brief exposure procedure in post-traumatic stress disorder--a pilot study.</a> Brain Stimul. 6 (3), 377-383 (2013).</li><li>Ceccanti, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Deep+TMS+on+alcoholics:+effects+on+cortisolemia+and+dopamine+pathway+modulation.+A+pilot+study.">Deep TMS on alcoholics: effects on cortisolemia and dopamine pathway modulation. A pilot study.</a> Can J Physiol Pharmacol. 93 (4), 283-290 (2015).</li><li>Girardi, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Add-on+deep+transcranial+magnetic+stimulation+(dTMS)+in+patients+with+dysthymic+disorder+comorbid+with+alcohol+use+disorder:+a+comparison+with+standard+treatment.">Add-on deep transcranial magnetic stimulation (dTMS) in patients with dysthymic disorder comorbid with alcohol use disorder: a comparison with standard treatment.</a> World J Biol Psychiatry. 16 (1), 66-73 (2015).</li><li>Rapinesi, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Alcohol+and+suicidality:+could+deep+transcranial+magnetic+stimulation+(dTMS)+be+a+possible+treatment.">Alcohol and suicidality: could deep transcranial magnetic stimulation (dTMS) be a possible treatment.</a> Psychiatr Danub. 26 (3), 281-284 (2014).</li><li>Rapinesi, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Antidepressant+effectiveness+of+deep+Transcranial+Magnetic+Stimulation+(dTMS)+in+patients+with+Major+Depressive+Disorder+(MDD)+with+or+without+Alcohol+Use+Disorders+(AUDs):+a+6-month,+open+label,+follow-up+study.">Antidepressant effectiveness of deep Transcranial Magnetic Stimulation (dTMS) in patients with Major Depressive Disorder (MDD) with or without Alcohol Use Disorders (AUDs): a 6-month, open label, follow-up study.</a> J Affect Disord. 174, 57-63 (2015).</li><li>Rapinesi, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Efficacy+of+add-on+deep+transcranial+magnetic+stimulation+in+comorbid+alcohol+dependence+and+dysthymic+disorder:+three+case+reports.">Efficacy of add-on deep transcranial magnetic stimulation in comorbid alcohol dependence and dysthymic disorder: three case reports.</a> Prim Care Companion CNS Disord. 15 (1), (2013).</li><li>Rosenberg, O., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Deep+transcranial+magnetic+stimulation+add-on+for+the+treatment+of+auditory+hallucinations:+a+double-blind+study.">Deep transcranial magnetic stimulation add-on for the treatment of auditory hallucinations: a double-blind study.</a> Ann Gen Psychiatry. 11, 13 (2012).</li><li>Rosenberg, O., Roth, Y., Kotler, M., Zangen, A., Dannon, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Deep+transcranial+magnetic+stimulation+for+the+treatment+of+auditory+hallucinations:+a+preliminary+open-label+study.">Deep transcranial magnetic stimulation for the treatment of auditory hallucinations: a preliminary open-label study.</a> Ann Gen Psychiatry. 10 (1), 3 (2011).</li><li>Salviati, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Deep+transcranial+magnetic+stimulation+in+a+woman+with+chronic+tinnitus:+clinical+and+FMRI+findings.+Seeking+relief+from+a+symptom+and+finding+vivid+memories+by+serendipity.">Deep transcranial magnetic stimulation in a woman with chronic tinnitus: clinical and FMRI findings. Seeking relief from a symptom and finding vivid memories by serendipity.</a> Brain Stimul. 7 (3), 492-494 (2014).</li><li>Hovav, S., Kinback, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Deep+TMS+for+comorbid+Major+Depressive+Disorder+and+Anxiety+-+A+Brief+Report+of+Patients+in+a+Real-World+Practice.">Deep TMS for comorbid Major Depressive Disorder and Anxiety - A Brief Report of Patients in a Real-World Practice.</a> Brain Stimul. 7 (5), 20 (2014).</li><li>Tendler, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reversal+of+Motor+Symptoms+in+Parkinson's+Disease+using+Deep+TMS+with+the+H1+Coil:+Longitudinal+Case+Series.">Reversal of Motor Symptoms in Parkinson's Disease using Deep TMS with the H1 Coil: Longitudinal Case Series.</a> Brain Stimul. 7 (5), 25 (2014).</li><li>Tendler, A., Sisko, E., Allsup, H., DeLuca, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Deep+Repetitive+Transcranial+Magnetic+Stimulation+({dTMS})+for+Multiple+Sclerosis+({MS})+Fatigue,+Irritability+and+Parasthesias:+Case+Report.">Deep Repetitive Transcranial Magnetic Stimulation ({dTMS}) for Multiple Sclerosis ({MS}) Fatigue, Irritability and Parasthesias: Case Report.</a> Brain Stimul. 7 (5), 24-25 (2014).</li><li>Roth, Y., Amir, A., Levkovitz, Y., Zangen, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Three-dimensional+distribution+of+the+electric+field+induced+in+the+brain+by+transcranial+magnetic+stimulation+using+figure-8+and+deep+H-coils.">Three-dimensional distribution of the electric field induced in the brain by transcranial magnetic stimulation using figure-8 and deep H-coils.</a> J Clin Neurophysiol. 24 (1), 31-38 (2007).</li><li>Roth, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Motor+cortex+activation+by+H-coil+and+figure-8+coil+at+different+depths.+Combined+motor+threshold+and+electric+field+distribution+study.">Motor cortex activation by H-coil and figure-8 coil at different depths. Combined motor threshold and electric field distribution study.</a> Clin Neurophysiol. 125 (2), 336-343 (2014).</li><li>Rosenberg, O., Roth, Y., Kotler, M., Zangen, A., Dannon, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Deep+transcranial+magnetic+stimulation+for+the+treatment+of+auditory+hallucinations:+a+preliminary+open-label+study.">Deep transcranial magnetic stimulation for the treatment of auditory hallucinations: a preliminary open-label study.</a> Ann Gen Psychiatry. 10 (1), 3 (2011).</li><li>George, M. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Daily+left+prefrontal+transcranial+magnetic+stimulation+therapy+for+major+depressive+disorder:+a+sham-controlled+randomized+trial.">Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial.</a> Arch Gen Psychiatry. 67 (5), 507-516 (2010).</li><li>Fox, M. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Resting-state+networks+link+invasive+and+noninvasive+Brain+Stimul+across+diverse+psychiatric+and+neurological+diseases.">Resting-state networks link invasive and noninvasive Brain Stimul across diverse psychiatric and neurological diseases.</a> Proc Natl Acad Sci U S A. 111 (41), 4367-4375 (2014).</li><li>Deng, Z. -. D., Lisanby, S. H., Peterchev, A. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electric+field+depth-focality+tradeoff+in+transcranial+magnetic+stimulation:+simulation+comparison+of+50+coil+designs.">Electric field depth-focality tradeoff in transcranial magnetic stimulation: simulation comparison of 50 coil designs.</a> Brain Stimul. 6 (1), 1-13 (2013).</li><li>Deng, Z. -. D., Lisanby, S. H., Peterchev, A. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Coil+design+considerations+for+deep+transcranial+magnetic+stimulation.">Coil design considerations for deep transcranial magnetic stimulation.</a> Clin Neurophysiol. 125 (6), 1202-1212 (2014).</li><li>Deng, Z. -. D., Peterchev, A. V., Lisanby, S. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Coil+design+considerations+for+deep-brain+transcranial+magnetic+stimulation+(dTMS).">Coil design considerations for deep-brain transcranial magnetic stimulation (dTMS).</a> Conf Proc IEEE Eng Med Biol Soc. 2008, 5675-5679 (2008).</li><li>Lee, W. H., Lisanby, S. H., Laine, A. F., Peterchev, A. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+electric+field+strength+and+spatial+distribution+of+electroconvulsive+therapy+and+magnetic+seizure+therapy+in+a+realistic+human+head+model.">Comparison of electric field strength and spatial distribution of electroconvulsive therapy and magnetic seizure therapy in a realistic human head model.</a> Eur Psychiatry. 36, 55-64 (2016).</li><li>Roth, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Motor+cortex+activation+by+H-coil+and+figure-8+coil+at+different+depths.+Combined+motor+threshold+and+electric+field+distribution+study.">Motor cortex activation by H-coil and figure-8 coil at different depths. Combined motor threshold and electric field distribution study.</a> Clin Neurophysiol. 125 (2), 336-343 (2014).</li><li>Guadagnin, V., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electric+field+estimation+in+deep+transcranial+magnetic+stimulation.">Electric field estimation in deep transcranial magnetic stimulation.</a> Brain Stimul. 8 (2), 327 (2015).</li><li>Fiocchi, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Modelling+of+the+Electric+Field+Distribution+in+Deep+Transcranial+Magnetic+Stimulation+in+the+Adolescence,+in+the+Adulthood,+and+in+the+Old+Age.">Modelling of the Electric Field Distribution in Deep Transcranial Magnetic Stimulation in the Adolescence, in the Adulthood, and in the Old Age.</a> Comput Math Methods Med. 2016, 9039613 (2016).</li><li>Guadagnin, V., Parazzini, M., Fiocchi, S., Liorni, I., Ravazzani, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Deep+Transcranial+Magnetic+Stimulation:+Modeling+of+Different+Coil+Configurations.">Deep Transcranial Magnetic Stimulation: Modeling of Different Coil Configurations.</a> IEEE Trans Biomed Eng. 63 (7), 1543-1550 (2016).</li></ol>

Aron Tendler, Yiftach Roth, and Abraham Zangen own stock and receive income from Brainsway, the manufacturer of the H1 coil.

Critical Steps Within the Protocol 
The most important component of any dTMS protocol is the correct measurement of the MT. The MT determines the individualized dosage or stimulator intensity necessary and safe to treat the patient. If a patient&#39;s MT is incorrectly measured at higher than their actual MT, they will end up getting a higher intensity treatment, increasing the patient&#39;s seizure risk. Similarly, if the patient receives too low of a dose (e.g., 110% of the MT instead of 120% during treatment for depression), they will not go into remission. It is also imperative that the component of the coil that is being used is positioned on the head over the region one is trying to stimulate. When stimulating the left PFC, the wires from the left front half of the helmet should be touching the skull overlying the left PFC; there may be several centimeters of space between the right side of the helmet and the skull. When stimulating the right PFC, the right front half of the helmet should be touching the skull overlying the right PFC, and there will probably be a space between the left side of the helmet and the skull. When stimulating the mPFC, the front of the helmet should be pushed down onto the top of the forehead. The sides of the coil can be brought closer together by tightening a drawstring in the back of the coil.
Modifications and troubleshooting 
The most common modifications in clinical practice are adjustments to the tilt of the coil while it is over the PFC, due to comfort, and differences in the distance of the coil from the MC, caused by variations in head size. If a patient feels too much right temporal stimulation during the left PFC protocol for depression, the helmet can be tilted towards the symmetrical position. Additionally, if advancing the coil 6 cm from the MC puts the front of the helmet below the patient&#39;s eyebrows, the helmet should be adjusted posteriorly. If there is difficulty in finding the resting MT, the first step should be to find the active MT, which is always lower.
Limitations of the technique 
The stimulation protocols listed in Table 1, with the exception of major depression, are far from final. Even the depression protocol may not be optimal. These are potential protocols that were conceived according to knowledge available at the time of the specific experiment, and when they were utilized over those anatomical regions, they were successful. As time goes by, protocols can be improved due to accumulation of knowledge with regard to the brain network that is involved in the specific neuropathology, dTMS field distribution, mechanism of action, optimal parameters, safety data, device durability data, and publication of more and larger case series. In addition, if one wanted to stimulate a very focal, specific target, this would not be an appropriate coil. For such a goal, the figure-8 coil, which stimulates very focal and superficial regions on the cortex surface, would be better suited. However, since stimulation by the figure-8 coil is so focal, it can easily miss important DLPFC structures relevant for mood disorders. Indeed, with the simple 5-cm rule, the figure-8 may even be located outside the PFC1,29. Moreover, recent studies suggest that stimulation of prefrontal cortical regions with extensive connections to the subgenual cingulate may be crucial for the antidepressant action of standard rTMS2,3,30. Since the exact location of these cortex regions varies greatly between individuals3, optimal stimulation targets may be easily missed with a figure-8 coil. In order to remedy this problem, the physician must send the patient to have an fMRI and must use neuro-navigation. All these problems do not arise with the H1, since its broad field stimulates all the relevant PFC targets.
Significance of the technique with respect to existing/alternative methods 
The H1 dTMS coil is the newest coil to enter the rTMS arena. It has been widely adopted by psychiatrists due to its high efficacy and tolerability for patients with treatment-resistant depression, its short treatment time, and its ease in determining the MT. All of these are functions of the ability of the H1 to stimulate a much deeper and larger volume of neuronal tissue than figure-8 coils. However, the fact the coil is in a helmet and is not visible to the eye makes the idea of moving the coil from its intended target almost heretical. Additionally, the hard external helmet causes clinicians to forget that a key aspect of the H-coils is their design with soft, bendable copper wires. The base of the coil is meant to be adjacent to the skull near the neuronal fibers that one wants to stimulate. It is conceptually difficult for clinicians who have not taken math and physics in many years to comprehend the design of the dTMS coils.
Figure-8 coils are easier to understand, completely visible, and their effects are very focal. Clinicians are much more comfortable moving them from location to location. Additionally, they have been in use for many more years, and there are more publications describing their use for off-label conditions. However, this should not discourage the application of the H1 coil to targets outside the DLPFC in accordance with the protocols that were reviewed here or in a novel fashion.
Regarding the electric field diagrams as a measurement of the potential effects of the device, electric field diagrams measured from a saline solution-filled head model have advantages over alternative methods. Some investigators have calculated or modeled the induced fields using a spherical head model, which is less accurate31,32,33,34. Measuring the induced field of the real coil in a realistically-shaped head model filled with saline is more representative than any mathematical model, but it is not completely accurate35. Recently, investigators have modeled the electric fields in anatomically-correct virtual tissue34,36,37,38. More accurate electric field diagrams could be obtained from cadavers implanted with multiple recording electrodes, but this experiment has not yet been done.
Future applications or directions after mastering this technique 
After understanding the concept of reviewing the coil diagram and the electric field diagram to apply the coil to different anatomical targets, use the same procedure for different H-coils and disorders based on what is already known in the literature with regard to possible targets and stimulation parameters. For example, the H7 coil is designed to be placed over the mPFC and anterior cingulate cortex (ACC) for the treatment of OCD. The H7 coil can be placed over the medial MC for the treatment of diabetic neuropathy of the feet and over the posterior parietal cortex (PPC) for stimulation of the precuneus in mild cognitive impairment.

Until recently, only superficial, repetitive transcranial magnetic stimulation (rTMS) coils, such as the circular, figure-8, or double-cone coils, were available. Although those coils could easily be moved anywhere over the skull to target altered brain activity in different disorders, the decay of their electrical fields was quite rapid. This fast decay limited their efficacy and made them impractical for use in cases where deeper stimulation is necessary, since the high stimulator output that is required can be dangerous and painful to the patient. Moreover, the focality of figure-8 and double-cone coils truly requires neuro-navigation, especially if one wants to be certain that they are affecting the correct anatomical target1,2,3.
In recent years, the clinical use of rTMS has progressed because of two factors. The first is advances in functional neuroimaging, clarifying meaningful and specific neuroanatomical targets for psychiatric and neurological symptoms and disorders. The second is advances in bioengineering that enabled the delivery of non-invasive, tolerable, high-frequency stimulation to deep brain regions with specifically-designed dTMS H-coils4,5 and improved cooling technologies (long cooling time between trains results in very long treatment sessions). Together, these developments allow long-term normalization of pathological brain activity in a variety of targets that were identified for a specific symptom or condition. The combination of these advances greatly expands the physician&#39;s toolbox, changing the practice of psychiatry and neurology, as it provides a safe and effective way to treat even drug-resistant patients.
There are fourteen different H-coils designed to target specific brain regions, and they are available for research or for clinical use in different countries. However, only the H1 coil is FDA-cleared for commercial use, and therefore, among the different H-coils, it is the most accessible coil for patients. Because of this, it is important for clinicians to be familiar with the alternative protocols that can be administered using the H1 coil and how each can be used to benefit their refractory patients. It is important to qualify that there are better-designed H-coils for symptoms that cannot be alleviated by targeting the left DLPFC. However, since the H1 coil is currently the most readily-available H-coil, this paper is intended to explain how to position it appropriately in an off-label fashion.

<table><tbody><tr><td>dTMS System</td><td>Brainsway</td><td></td><td>Includes H1 coil, positioning arm, cart,stimulator, cooling system</td></tr><tr><td>Patient Caps</td><td>Brainsway</td><td></td><td>Includes blue caps with rulers</td></tr><tr><td>Ear plugs</td><td></td><td></td><td>Rated to 30 dB</td></tr></tbody></table>

how to use the h1 deep transcranial magnetic stimulation coil for conditions other than depression

Deep transcranial magnetic stimulation (dTMS) is a relatively new technique that uses different coils for the treatment of different neuropathologies. The coils are made of soft copper windings in multiple planes that lie adjacent to the skull. They are located within a special helmet so that their magnetic fields combine and improve depth penetration. The H1 dTMS coil is designed to stimulate bilateral prefrontal cortices with greater effective stimulation over the left than the right. By positioning the left side of the coil close to the left dorsolateral prefrontal cortex (DLPFC), the H1 coil was used in a multisite study, leading to FDA approval for treatment-resistant depression. In this same position, the H1 coil was also explored as a possible treatment for negative symptoms of schizophrenia, bipolar depression, and migraine. When moved to different positions over the subject's skull, the H1 coil was also explored as a possible treatment for other conditions. Such manipulation of the H1 coil was demonstrated for PTSD and alcohol dependence by positioning it over the medial prefrontal cortex (mPFC), for anxiety by positioning it over the right prefrontal cortex (rPFC), for auditory hallucinations and tinnitus by positioning it over the temporoparietal junction (TPJ), and for Parkinson's and fatigue from multiple sclerosis (MS) by positioning it over the motor cortex (MC) and PFC. Corresponding electrical field diagrams measured with an oscilloscope through a saline-filled head are included.

See the references in Table 1 for preliminary results of the various protocols. Figures 2-5 are representative electric field diagrams of the H1 coil in different anatomical positions. One example of H1 manipulation to a different position was with PTSD patients that failed to benefit from antidepressants or psychotherapy14. In this study, the H1 coil was positioned over the mPFC. As seen in Figure 3, positioning the coil in this fashion clearly stimulates the mPFC; this is not the same pattern of neuronal activation that is seen when the H1 coil is placed over the left PFC, in Figure 2. Thirty PTSD patients were randomly assigned to receive dTMS after brief exposure to a recorded script of their traumatic event, dTMS after brief exposure to a non-traumatic script, or sham stimulation after brief exposure to their traumatic script. The stimulation administration consisted of 12 sessions (3 per week for 4 weeks) of 20-Hz stimulation at 120% of MT, with forty-two 2 sec trains and a 20 sec inter-train interval for a total of 1,680 pulses. The primary outcome measure was the CAPS score at four weeks. A graphical representation of the selected results can be seen in Figure 614. Analysis of the results revealed a significant improvement only in the group that received active dTMS after brief exposure to the traumatic event, with a group x time interaction for the intrusion component of the CAPS. Following completion of this study, a multi-center study of dTMS to the mPFC for PTSD was initiated.
<img alt="Figure 1" src="/files/ftp_upload/55100/55100fig1.jpg" /> 
Figure 1: Deep TMS Device. Wire diagram of the H1 coil (a) and photograph of the dTMS system with the H1 helmet, positioning arm, stimulator, cooling system, and cart (b). <a href="http://cloudflare.jove.com/files/ftp_upload/55100/55100fig1large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 2" src="/files/ftp_upload/55100/55100fig2.jpg" /> 
Figure 2: Electric Field Diagram of the H1 Over the Left PFC. Colored field maps indicate the absolute magnitude of the electrical field in each pixel at 120% MT of the hand for 10 coronal slices 1 cm apart. Red pixels indicate regions with a field intensity above the threshold for neuronal activation, which is 100 V/m. <a href="http://cloudflare.jove.com/files/ftp_upload/55100/55100fig2large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 3" src="/files/ftp_upload/55100/55100fig3.jpg" /> 
Figure 3: Electric Field Diagram of the H1 Over the Medial PFC. Colored field maps indicate the absolute magnitude of the electrical field in each pixel at 120% of the hand MT for 10 coronal slices 1 cm apart. Red pixels indicate regions with a field intensity above the threshold for neuronal activation, which is 100 V/m. <a href="http://cloudflare.jove.com/files/ftp_upload/55100/55100fig3large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 4" src="/files/ftp_upload/55100/55100fig4.jpg" /> 
Figure 4: Electric Field Diagram of the H1 Over the Right PFC. Colored field maps indicate the absolute magnitude of the electrical field in each pixel at 120% MT of the hand for 10 coronal slices 1 cm apart. Red pixels indicate regions with a field intensity above the threshold for neuronal activation, which is 100 V/m. <a href="http://cloudflare.jove.com/files/ftp_upload/55100/55100fig4large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 5" src="/files/ftp_upload/55100/55100fig5.jpg" /> 
Figure 5: Electric Field Diagram of the H1 Over the Left TPJ. Colored field maps indicate the absolute magnitude of the electrical field in each pixel at 110% MT of the hand for coronal slices 1 cm apart. Red pixels indicate regions with a field intensity above the threshold for neuronal activation, which is 100 V/m. This figure is modified from Reference 28. <a href="http://cloudflare.jove.com/files/ftp_upload/55100/55100fig5large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 6" src="/files/ftp_upload/55100/55100fig6.jpg" /> 
Figure 6: Clinician-administerd PTSD Scale (CAPS) Severity Score at Baseline and Post-treatment in the First (blinded) Phase. Panel A depicts the total CAPS score, while Panels B, C, and D show the intrusion, avoidance/numbing, and hyper-arousal components, respectively. Values are presented as the mean &#177; the standard errors. *P &#60;0.05 relative to baseline. Reused with permission from reference14. <a href="http://cloudflare.jove.com/files/ftp_upload/55100/55100fig6large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>

Watch this Scientific Journal Video about How to Use the H1 Deep Transcranial Magnetic Stimulation Coil for Conditions Other than Depression at JoVE.com

How to Use the H1 Deep Transcranial Magnetic Stimulation Coil for Conditions Other than Depression

The H1 deep transcranial magnetic stimulation coil is FDA-cleared for the treatment of depression. We demonstrate how to utilize the H1 for other conditions, such as auditory hallucinations and PTSD, by moving the helmet to different locations over the subject's skull.

Deep transcranial magnetic stimulation (dTMS) is a relatively new technique that uses different coils for the treatment of different neuropathologies. The ...

how-to-use-h1-deep-transcranial-magnetic-stimulation-coil-for

Research

JoVE Journal

Behavior

24.0K Views.  Brainsway LTD. The H1 deep transcranial magnetic stimulation coil is FDA-cleared for the treatment of depression. We demonstrate how to utilize the H1 for other conditions, such as auditory hallucinations and PTSD, by moving the helmet to different locations over the subject's skull.

Video: How to Use the H1 Deep Transcranial Magnetic Stimulation Coil for Conditions Other than Depression

Transcranial Magnetic Stimulation for Investigating Causal Brain-behavioral Relationships and their Time Course

Transcranial magnetic stimulation (TMS) is a safe, non-invasive brain stimulation technique that uses a strong electromagnet in order to temporarily disrupt information processing in a brain region, generating a short-lived &#8220;virtual lesion.&#8221; Stimulation that interferes with task performance indicates that the affected brain region is necessary to perform the task normally. In other words, unlike neuroimaging methods such as functional magnetic resonance imaging (fMRI) that indicate correlations between brain and behavior, TMS can be used to demonstrate causal brain-behavior relations. Furthermore, by varying the duration and onset of the virtual lesion, TMS can also reveal the time course of normal processing. As a result, TMS has become an important tool in cognitive neuroscience. Advantages of the technique over lesion-deficit studies include better spatial-temporal precision of the disruption effect, the ability to use participants as their own control subjects, and the accessibility of participants. Limitations include concurrent auditory and somatosensory stimulation that may influence task performance, limited access to structures more than a few centimeters from the surface of the scalp, and the relatively large space of free parameters that need to be optimized in order for the experiment to work. Experimental designs that give careful consideration to appropriate control conditions help to address these concerns. This article illustrates these issues with TMS results that investigate the spatial and temporal contributions of the left supramarginal gyrus (SMG) to reading.

Transcranial magnetic stimulation (TMS) is a technique for non-invasively disrupting neural information processing and measuring its effect on behavior. When TMS interferes with a task, it indicates that the stimulated brain region is necessary for normal task performance, allowing one to systematically relate brain regions to cognitive functions.

Transcranial magnetic stimulation (TMS) is a safe, non-invasive brain stimulation technique that uses a strong electromagnet in order to temporarily ...

Utilizing Transcranial Magnetic Stimulation to Study the Human Neuromuscular System

Transcranial magnetic stimulation (TMS) has been in use for more than 20 years 1, and has grown exponentially in popularity over the past decade. While the use of TMS has expanded to the study of many systems and processes during this time, the original application and perhaps one of the most common uses of TMS involves studying the physiology, plasticity and function of the human neuromuscular system. Single pulse TMS applied to the motor cortex excites pyramidal neurons transsynaptically 2 (Figure 1) and results in a measurable electromyographic response that can be used to study and evaluate the integrity and excitability of the corticospinal tract in humans 3. Additionally, recent advances in magnetic stimulation now allows for partitioning of cortical versus spinal excitability 4,5. For example, paired-pulse TMS can be used to assess intracortical facilitatory and inhibitory properties by combining a conditioning stimulus and a test stimulus at different interstimulus intervals 3,4,6-8. In this video article we will demonstrate the methodological and technical aspects of these techniques. Specifically, we will demonstrate single-pulse and paired-pulse TMS techniques as applied to the flexor carpi radialis (FCR) muscle as well as the erector spinae (ES) musculature. Our laboratory studies the FCR muscle as it is of interest to our research on the effects of wrist-hand cast immobilization on reduced muscle performance6,9, and we study the ES muscles due to these muscles clinical relevance as it relates to low back pain8. With this stated, we should note that TMS has been used to study many muscles of the hand, arm and legs, and should iterate that our demonstrations in the FCR and ES muscle groups are only selected examples of TMS being used to study the human neuromuscular system.

Transcranial magnetic stimulation (TMS) is a non-invasive tool to gain insight on the physiology and function of the human nervous system. Here, we present our TMS techniques to study cortical excitability of the upper limb and lumbar musculature.

Transcranial magnetic stimulation (TMS) has been in use for more than 20 years 1, and has grown exponentially in popularity over the past decade.  While ...

Medicine

Non-Invasive Electrical Brain Stimulation Montages for Modulation of Human Motor Function

Non-invasive electrical brain stimulation (NEBS) is used to modulate brain function and behavior, both for research and clinical purposes. In particular, NEBS can be applied transcranially either as direct current stimulation (tDCS) or alternating current stimulation (tACS). These stimulation types exert time-, dose- and in the case of tDCS polarity-specific effects on motor function and skill learning in healthy subjects. Lately, tDCS has been used to augment the therapy of motor disabilities in patients with stroke or movement disorders. This article provides a step-by-step protocol for targeting the primary motor cortex with tDCS and transcranial random noise stimulation (tRNS), a specific form of tACS using an electrical current applied randomly within a pre-defined frequency range. The setup of two different stimulation montages is explained. In both montages the emitting electrode (the anode for tDCS) is placed on the primary motor cortex of interest. For unilateral motor cortex stimulation the receiving electrode is placed on the contralateral forehead while for bilateral motor cortex stimulation the receiving electrode is placed on the opposite primary motor cortex. The advantages and disadvantages of each montage for the modulation of cortical excitability and motor function including learning are discussed, as well as safety, tolerability and blinding aspects.

Non-invasive electrical brain stimulation can modulate cortical function and behavior, both for research and clinical purposes. This protocol describes different brain stimulation approaches for modulation of the human motor system.

Non-invasive electrical brain stimulation (NEBS) is used to modulate brain function and behavior, both for research and clinical purposes. In particular, ...

Treating Clinical Depression with Repetitive Deep Transcranial Magnetic Stimulation Using the Brainsway H1-coil

Repetitive transcranial magnetic stimulation (rTMS) is an emerging non-pharmacological approach to treating many brain-based disorders. rTMS uses electromagnetic coils to stimulate areas of the brain non-invasively. Deep transcranial magnetic stimulation (dTMS) with the Brainsway H1-coil system specifically is a type of rTMS indicated for treating patients with major depressive disorder (MDD) who are resistant to medication. The unique H1-coil design of this device is able to stimulate neuronal pathways that lie deeper in the targeted brain areas than those reached by conventional rTMS coils. dTMS is considered to be low-risk and well tolerated, making it a viable treatment option for people who have not responded to medication or psychotherapy trials for their depression.
Randomized, sham-control studies have demonstrated that dTMS produces significantly greater improvement in depressive symptoms than sham dTMS treatment in patients with major depression that has not responded to antidepressant medication. In this paper, we will review the methodology for treating major depression with dTMS using an H1-coil.

Here we present a protocol outlining the methodology for treatment of Major Depressive Disorder using the deep Transcranial Magnetic Stimulation (dTMS) system.

Repetitive transcranial magnetic stimulation (rTMS) is an emerging non-pharmacological approach to treating many brain-based disorders. rTMS uses ...

Repetitive Transcranial Magnetic Stimulation to the Unilateral Hemisphere of Rat Brain

Previous rodent models of repetitive transcranial magnetic stimulation (rTMS) adopted whole-brain stimulation instead of unilateral hemispheric rTMS, which is unlike the protocols used for human subjects. We report a successful application of rTMS to the unilateral hemisphere of rat brain. The rTMS was delivered with a low-frequency (1 Hz), high-frequency (20 Hz), or sham stimulation protocol to one side of the brain by using a small 25-mm figure-8 coil. We placed the center of the coil 1 cm lateral to the vertex on the biauricular line and angulated the coil 45&#176; to the ground to minimize a potential direct effect of rTMS on the contralateral cortex. We also used an in-house water cooling system to enable repetitive magnetic stimulation for more than 20 min, even at a 20-Hz stimulation frequency. Increases in the transcriptions of immediate early genes (Arc, Junb, and Egr2) were greater after rTMS than after sham stimulation. After 5 consecutive days of 20-min 1-Hz rTMS, bdnf mRNA expression was significantly higher in stimulated cortex than in contralateral side. The model presented herein will elucidate the molecular mechanisms of rTMS by allowing analysis of the inter-hemispheric difference in its effect.

We applied repetitive transcranial magnetic stimulation (rTMS) to the unilateral hemisphere of rat brain, by placing a 25-mm figure-8 coil 1 cm lateral to the vertex on the biauricular line and angulating the coil by 45&#176;. An in-house water cooling system was used for rTMS for more than 20 min.

Previous rodent models of repetitive transcranial magnetic stimulation (rTMS) adopted whole-brain stimulation instead of unilateral hemispheric rTMS, ...

The Use of Magnetic Resonance Spectroscopy as a Tool for the Measurement of Bi-hemispheric Transcranial Electric Stimulation Effects on Primary Motor Cortex Metabolism

Transcranial direct current stimulation (tDCS) is a neuromodulation technique that has been increasingly used over the past decade in the treatment of neurological and psychiatric disorders such as stroke and depression. Yet, the mechanisms underlying its ability to modulate brain excitability to improve clinical symptoms remains poorly understood 33. To help improve this understanding, proton magnetic resonance spectroscopy (1H-MRS) can be used as it allows the in vivo quantification of brain metabolites such as &#947;-aminobutyric acid (GABA) and glutamate in a region-specific manner 41. In fact, a recent study demonstrated that 1H-MRS is indeed a powerful means to better understand the effects of tDCS on neurotransmitter concentration 34. This article aims to describe the complete protocol for combining tDCS (NeuroConn MR compatible stimulator) with 1H-MRS at 3 T using a MEGA-PRESS sequence. We will describe the impact of a protocol that has shown great promise for the treatment of motor dysfunctions after stroke, which consists of bilateral stimulation of primary motor cortices 27,30,31. Methodological factors to consider and possible modifications to the protocol are also discussed.

This article aims to describe a basic protocol for combining transcranial direct current stimulation (tDCS) with proton magnetic resonance spectroscopy (1H-MRS) measurements to investigate the effects of bilateral stimulation on primary motor cortex metabolism.

Transcranial direct current stimulation (tDCS) is a neuromodulation technique that has been increasingly used over the past decade in the treatment of ...

Neuroscience

MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder

Here we outline the protocol for magnetic resonance imaging (MRI) guided repetitive transcranial magnetic stimulation (rTMS) to the dorsal medial prefrontal cortex (dmPFC) in patients with major depressive disorder (MDD). Technicians used a neuronavigation system to process patient MRIs to generate a 3-dimensional head model. The head model was subsequently used to identify patient-specific stimulatory targets. The dmPFC was stimulated daily for 20 sessions. Stimulation intensity was titrated to address scalp pain associated with rTMS. Weekly assessments were conducted on the patients using the Hamilton Rating Scale for Depression (HamD17) and Beck Depression Index II (BDI-II). Treatment-resistant MDD patients achieved significant improvements on both HAMD and BDI-II. Of note, angled, double-cone coil rTMS at 120% resting motor threshold allows for optimal stimulation of deeper midline prefrontal regions, which results in a possible therapeutic application for MDD. One major limitation of the rTMS field is the heterogeneity of treatment parameters across studies, including duty cycle, number of pulses per session and intensity. Further work should be done to clarify the effect of stimulation parameters on outcome. Future dmPFC-rTMS work should include sham-controlled studies to confirm its clinical efficacy in MDD.

Here we outline the procedure for MRI-guided repetitive transcranial magnetic stimulation to the dorsomedial prefrontal cortex as an experimental treatment for major depressive disorder.

Here we outline the protocol for magnetic resonance imaging (MRI) guided repetitive transcranial magnetic stimulation (rTMS) to the dorsal medial ...

Combined Transcranial Magnetic Stimulation and Electroencephalography of the Dorsolateral Prefrontal Cortex

Transcranial magnetic stimulation (TMS) is a non-invasive method that produces neural excitation in the cortex by means of brief, time-varying magnetic field pulses. The initiation of cortical activation or its modulation depends on the background activation of the neurons of the cortical region activated, the characteristics of the coil, its position and its orientation with respect to the head. TMS combined with simultaneous electrocephalography (EEG) and neuronavigation (nTMS-EEG) allows for the assessment of cortico-cortical excitability and connectivity in almost all cortical areas in a reproducible manner. This advance makes nTMS-EEG a powerful tool that can accurately assess brain dynamics and neurophysiology in test-retest paradigms that are required for clinical trials. Limitations of this method include artifacts that cover the initial brain reactivity to stimulation. Thus, the process of removing artifacts may also extract valuable information. Moreover, the optimal parameters for dorsolateral prefrontal (DLPFC) stimulation are not fully known and current protocols utilize variations from the motor cortex (M1) stimulation paradigms. However, evolving nTMS-EEG designs hope to address these issues. The protocol presented here introduces some standard practices for assessing neurophysiological functioning from stimulation to the DLPFC that can be applied in patients with treatment resistant psychiatric disorders that receive treatment such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), magnetic seizure therapy (MST) or electroconvulsive therapy (ECT).

The protocol presented here is for TMS-EEG studies utilizing intracortical excitability test-retest design paradigms. The intent of the protocol is to produce reliable and reproducible cortical excitability measures for assessing neurophysiological functioning related to therapeutic interventions in the treatment of neuropsychiatric diseases such as major depression.

Transcranial magnetic stimulation (TMS) is a non-invasive method that produces neural excitation in the cortex by means of brief, time-varying magnetic ...

Measuring and Manipulating Functionally Specific Neural Pathways in the Human Motor System with Transcranial Magnetic Stimulation

Understanding interactions between brain areas is important for the study of goal-directed behavior. Functional neuroimaging of brain connectivity has provided important insights into fundamental processes of the brain like cognition, learning, and motor control. However, this approach cannot provide causal evidence for the involvement of brain areas of interest. Transcranial magnetic stimulation (TMS) is a powerful, noninvasive tool for studying the human brain that can overcome this limitation by transiently modifying brain activity. Here, we highlight recent advances using a paired-pulse, dual-site TMS method with two coils that causally probes cortico-cortical interactions in the human motor system during different task contexts. Additionally, we describe a dual-site TMS protocol based on cortical paired associative stimulation (cPAS) that transiently enhances synaptic efficiency in two interconnected brain areas by applying repeated pairs of cortical stimuli with two coils. These methods can provide a better understanding of the mechanisms underlying cognitive-motor function as well as a new perspective on manipulating specific neural pathways in a targeted fashion to modulate brain circuits and improve behavior. This approach may prove to be an effective tool to develop more sophisticated models of brain-behavior relations and improve diagnosis and treatment of many neurological and psychiatric disorders.

This article describes new approaches to measure and strengthen functionally specific neural pathways with transcranial magnetic stimulation. These advanced noninvasive brain stimulation methodologies can provide new opportunities for the understanding of brain-behavior relations and development of new therapies to treat brain disorders.

Understanding interactions between brain areas is important for the study of goal-directed behavior. Functional neuroimaging of brain connectivity has ...

Conventional and Threshold-Tracking Transcranial Magnetic Stimulation Tests for Single-handed Operation

Most single-pulse transcranial magnetic stimulation (TMS) parameters (e.g., motor threshold, stimulus-response function, cortical silent period) are used to examine corticospinal excitability. Paired-pulse TMS paradigms (e.g., short- and long-interval intracortical inhibition (SICI/LICI), short-interval intracortical facilitation (SICF), and short- and long-latency afferent inhibition (SAI/LAI)) provide information about intracortical inhibitory and facilitatory networks. This has long been done by the conventional TMS method of measuring changes in the size of the motor-evoked potentials (MEPs) in response to stimuli of constant intensity. An alternative threshold-tracking approach has recently been introduced whereby the stimulus intensity for a target amplitude is tracked. The diagnostic utility of threshold-tracking SICI in amyotrophic lateral sclerosis (ALS) has been shown in previous studies. However, threshold-tracking TMS has only been used in a few centers, in part due to the lack of readily available software but also perhaps due to uncertainty over its relationship to conventional single- and paired-pulse TMS measurements.
A menu-driven suite of semi-automatic programs has been developed to facilitate the broader use of threshold-tracking TMS techniques and to enable direct comparisons with conventional amplitude measurements. These have been designed to control three types of magnetic stimulators and allow recording by a single operator of the common single- and paired-pulse TMS protocols.
This paper shows how to record a number of single- and paired-pulse TMS protocols on healthy subjects and analyze the recordings. These TMS protocols are fast and easy to perform and can provide useful biomarkers in different neurological disorders, particularly neurodegenerative diseases such as ALS.

We present a suite of standardized single- and paired-pulse transcranial magnetic stimulation (TMS) recording protocols, with options for conventional amplitude measurements and threshold-tracking. This program can control three different types of magnetic stimulators and is designed to enable all tests to be performed conveniently by a single operator.

Most single-pulse transcranial magnetic stimulation (TMS) parameters (e.g., motor threshold, stimulus-response function, cortical silent period) are used ...