The authors wish to thank Aisha Dar, Vanathy Niranjan, and Dr. Umar Dar for technical assistance with rTMS delivery and data collection. The authors also wish to acknowledge the generous support of the Toronto General and Western Hospital Foundation, the Buchan Family Foundation, and the Ontario Brain Institute in funding this work.

This study was approved by the Research Ethics Board at the University Health Network.
1. Subject Selection
<ol>
	<li>Conduct an initial assessment on a prospective patient. The inclusion criteria included the presence of a current depressive episode that is resistant to at least 1 adequate trial of medication, and a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (DSM-5) diagnosis of MDD as established by the assessing psychiatrist. Confirm the diagnosis with a standardized Mini Mental State Examination (MINI).</li>
	<li>Ensure that patients are on a stable medication or are washed out of their medication routine for at least 4 weeks prior to their first rTMS treatment session. Do not alter this medication regiment throughout rTMS treatment to help disambiguate the cause of any observed clinical improvement or deterioration.</li>
	<li>Exclude patients who may have a potential contraindication to rTMS or MRI, including seizure history, cardiac arrhythmia, implanted or foreign devices/metal particulates, unstable medical conditions, or pregnancy. Patients with comorbid post-traumatic stress disorder, obsessive-compulsive disorder, other anxiety disorders, attention deficit hyperactivity disorder, bulimia nervosa or binge eating disorder, or moderate Cluster B personality features are also suitable for this treatment and need not be excluded. Patients with bipolar disorder rather than MDD may also be suitable for this treatment. Patients with psychotic disorders, active substance use, a primary diagnosis of borderline or antisocial personality disorder, or persistent depressive disorder (dysthymia) may be less suitable for treatment and may require exclusion.</li>
</ol>
2. Acquiring Magnetic Resonance Images
<ol>
	<li>Acquire patients&#8217; MRIs at any time prior to treatment. Here, use a 3 Tesla scanner with an 8-channel phased-array head coil (refer to Table of Materials), or any scanner capable of created a 3D representation of a patient&#8217;s brain.</li>
	<li>Adhering to local site protocol, acquire a T1-weighted fast spoiled gradient-echo anatomical scan. Use the following parameters: TE = 12 msec, TI = 300 msec, flip angle = 20&#176;, 116 sagittal slices, thickness = 1.5 mm, no gap, 256 x 256 matrix, FOV 240 mm. This scan will be used for real-time rTMS neuronavigation during motor thresholding and treatment sessions.</li>
</ol>
3. Preprocessing Anatomical Scans for Real-time Neuronavigation
<ol>
	<li>Prepare for MRI guidance using a neuronavigation system. 
	Note: The following steps employ the Visor 2.0 neuronavigation system (refer to Table of Materials), but other navigation systems such as the Brainsight TMS Navigation, StealthStation, Aimnav, and NBS System 4 use similar procedures.</li>
	<li>Segment anatomical MRIs into its scalp and brain components. Register the two segments into standard stereotactic space, such as Talairach and Tournoux space19.</li>
	<li>Place target markers by selecting the following points on the MRI: Nasion; Left and right ear, targeting the tragus; Anterior commissure; Posterior commissure; Interhemispheric point (point between the two hemispheres); the anterior most point of the brain; the posterior most point of the brain; the superior most point of the brain; and the left and right most point of the brain.</li>
	<li>Reconstruct the surfaces of the patient&#8217;s scalp and brain in standard space to create a three-dimensional surface-based head model &#8211; this image will be used to identify stereotactic scalp coordinates overlying the dmPFC (Talairach and Tournoux coordinate X0, Y+60, Z+60) for optimal coil vertex placement during treatment. 
	Note: This method uses population coordinates to identify the stimulation target. Other methods to identify a stimulation target, outlined in the Discussion, include single-subject anatomy or fMRI activation maps.</li>
	<li>Register brain and scalp coordinates from stereotactic space to patient space for individualized coil placement.</li>
</ol>
4. Motor Threshold Assessment
<ol>
	<li>Seat patient in the treatment chair, adjusting the camera for an unobstructed view of the patient.</li>
	<li>Place the headband with the marker clip attached to it around the patient&#8217;s head. The marker clip should sit above bridge of nose.</li>
	<li>Preprocess the anatomical scan for the patient as described above in Step 3.</li>
	<li>Load the preprocessed anatomical scans to the neuronavigation program and turn on the camera.</li>
	<li>Using a neuronavigation pen, highlight each scalp target point on the patient. The movements made with the neuronavigation pen will be projected on the television screen in the form of red lines.</li>
	<li>Assess patients&#8217; motor thresholds, the minimum intensity needed to globally excite the motor pathway, prior to rTMS treatment. For this step, begin by having the patient&#8217;s lower limbs extended and supported from below, using a stool or a chair equipped with an extensible leg rest.</li>
	<li>For motor threshold determination, under neuronavigation, target the medial primary motor cortex. Place the coil vertex over the sagittal fissure, 0.5-1.0 cm anterior to the central sulcus. Use an angled or double-cone coil for deeper pulse penetration into medial areas. Use stimulator equipped with a fluid-cooled coil, whose windings are angled at 120&#176; to allow deeper penetration of the pulses (refer to Table of Materials).</li>
	<li>Perform motor thresholding separately for the left and right hemispheres. Orient the coil laterally to direct rTMS-evoked current flow to the desired hemisphere20. For example, to stimulate the left hemisphere, orient the coil with the handle pointing rightwards and the direction of current flow toward the left hemisphere. Observe the contralateral (right) lower limb for movements during this procedure.</li>
	<li>Determine threshold and elicited motor movement visually by the halluces longus muscle of the big toe. 
	Note: Unlike conventional motor threshold testing that targets the hand muscle, stimulating the medial wall of the motor cortex will target the toe muscle. Motor evoked potentials (MEPs) may also be used as a more accurate determination of motor threshold, however it is a much lengthier approach.
	<ol>
		<li>Begin by stimulating at 55% of maximum machine intensity, then adjust upwards or downwards in increments of ~5% depending on whether a response is observed. Reduce the increment size steadily to ~1% as the motor threshold is approached, as previously described21. Stimulate no more frequently than 0.2 Hz (once per 5 sec) to avoid inhibitory or excitatory effects over time.</li>
		<li>Once a motor threshold is established, move the vertex 1-2 cm anteriorly and posteriorly, in exploratory increments of 2-3 mm, to determine whether any alternative site offers a lower motor threshold. Use the lowest threshold achieved along this arc for each side.</li>
	</ol>
	</li>
</ol>
5. rTMS Treatment &#38; Adaptive Titration
<ol>
	<li>Perform a course of neuronavigated dmPFC-rTMS, using a total of 20-30 daily sessions over 4-6 weeks. For treatments, use the 120&#176; angled, fluid-cooled coil and the parameters listed below for dmPFC stimulation in each treatment session (refer to Table of Materials).</li>
	<li>Seat the patient in the treatment chair, adjusting the camera for an unobstructed view of the patient.</li>
	<li>Place a headband with a marker clip attached to it around the patient&#8217;s head (placed laterally so as not to block the rTMS coil placement over the medial target site) as described above. Using a camera, the neuronavigation system, will detect the marker clip and will allow for preprocessing and neuronavigation.</li>
	<li>Load the preprocessed anatomical scans to the neuronavigation program and turn on the camera.</li>
	<li>Using a neuronavigation pen, highlight each scalp target point on the patient. The movements made with the neuronavigation pen will be projected on the television screen in the form of red lines.</li>
	<li>Place the coil over the dmPFC target under MRI guidance using the neuronavigation system. For verification purposes, this point should lie close to 25% of the distance from nasion to inion. Laterally. Orient the coil laterally, with the handle pointing away from the hemisphere to be stimulated. Stimulate the left hemisphere, then re-orient the coil by 180&#176; to stimulate the right hemisphere, maintaining the vertex in the same location over the dmPFC scalp site.</li>
	<li>Ensure that the scalp site for dmFPC remains in close contact with the coil itself throughout treatment. Ensure that the patient and operator wear earplugs or other hearing protection during treatment.</li>
	<li>For 10 Hz stimulation, use a duty cycle of 5 sec on, 10 seconds off for a total of 60 trains (3,000 pulses) per hemisphere per session. Perform this protocol of the left then right hemisphere by orienting the coil laterally, as previously described20. 
	Note: The described protocol for 10 Hz rTMS is outside international safety guidelines (Rossi&#160;et al., 2009). There is evidence for its safety18,22.</li>
	<li>For TBS stimulation, use a duty cycle of 2 sec on, 8 sec off for a total of 600 pulses per hemisphere per session. Perform this protocol of the left then right hemisphere by orienting the coil laterally, as previously described20.</li>
	<li>Adaptively titrate the rTMS stimulus intensity upwards from an initial value of 20% maximum stimulator intensity, to allow the patient to habituate to the pain and scalp discomfort associated with rTMS during the initial sessions23. Increment the stimulation intensity by 2-5% on each train of stimulation, as tolerated.
	<ol>
		<li>To assess tolerability, have the patient rate pain on a verbal analogue scale (VAS) from 0 to 10 (0 = no pain, 10 = limit of tolerability without emotional distress) after each train of stimulation is delivered.</li>
	</ol>
	</li>
	<li>Begin with a higher stimulation intensity on each session, using a level associated with moderate tolerability (VAS 5-6) from the previous session, until the patient is starting at the target intensity of 120% of resting motor threshold on each hemisphere. Maintain a verbal analogue scale of less than 9 throughout treatments during this titration process. Titration is typically completed in 2-5 days.</li>
	<li>Monitor the patient for other adverse effects during treatment. 
	Note: The most common treatment-interrupting adverse effect is a syncopal episode, arising during the first or second session of treatment in ~1% of patients. The patient may recount feeling dizzy, faint, or disoriented, and may transiently (~10 sec) lose consciousness. Regular, repeated convulsive movements or post-episode confusion lasting more than a few seconds should be absent, however. In the event of a syncopal episode, lower the headrest on the chair if possible and encourage the patient to remain still until recovered. The session may proceed if the patient is recovered and willing to go on after a few min.</li>
	<li>Monitor the patient for a generalized tonic-clonic seizure during treatment. 
	Note: These events are rare, and we have not observed a seizure in ~8,000 sessions of dmPFC-rTMS across &#62;200 individual patients to date. Regular, rhythmical, vigorous convulsive movements lasting 10-40 sec, initially around 3 Hz and becoming progressively less rapid, accompanied by unresponsiveness, are suggestive of seizure rather than syncope. However, the two may be difficult to distinguish for an untrained observer.
	<ol>
		<li>Use video monitoring during all treatments so that the episode can be reviewed by a neurologist at subsequent assessment, if necessary. In the event of such an episode, apply standard seizure first aid steps, including clearing the area of objects with the potential to cause injury, placing the patient on the ground if possible or lowering the treatment chair to the horizontal position if not, laying the patient on the left side if possible, ensuring a clear airway, and ensuring that someone remains with the patient until the seizure terminates and the person regains full alertness.</li>
		<li>Call emergency services if the seizure does not self-terminate after ~60 sec.</li>
	</ol>
	</li>
</ol>
6. Clinical Data Collection
<ol>
	<li>Collect standardized self-reported questionnaires at baseline, weekly throughout treatment and at follow-up (e.g., 2, 4, 6, 12, and 26 weeks post-treatment). Collect the following self-report data: Beck Depression Inventory (BDI-II)24, and Beck Anxiety Inventory25 on a daily basis throughout treatment.</li>
	<li>Collect depression severity scores via the clinician-rated 17-item Hamilton Rating Scale for Depression score26 (HamD17) at baseline, weekly during treatment, and at 2, 4, 6, 12 and 26 weeks post-treatment in follow-up.</li>
</ol>

Authors Ms. Dunlop and Ms. Gapriellian have no disclosures to report.

Here, MRI-guided dmPFC-rTMS was applied for treatment-resistant MDD. In general, rTMS at this site was well tolerated, with mild scalp discomfort and pain at the site of stimulation that was adequately managed using adaptive titration. In open-label trials and a chart review, both 10 Hz and theta burst stimulation resulted in significant improvements in depressive severity as measured by the HamD17 and BDI-II.
There are two critical steps worth noting in the rTMS treatment procedure...

Repetitive transcranial magnetic stimulation (rTMS) is a form of indirect focal cortical stimulation. rTMS employs brief, focal electromagnetic field pulses that penetrate the skull to stimulate target brain regions. rTMS is thought to engage the mechanisms of synaptic long-term potentiation and long-term depression, thereby increasing or decreasing the cortical excitability of the region stimulated1. Generally, the rTMS pulse frequency determines its effects: higher frequency stimulation tends to be excitatory, while lower frequency is inhibitory. Non-invasive stimulatory procedures are also widely used as a causal probe to induce temporary &#8216;cortical lesions&#8217;, and establish neural-behavior relationships or functional regions by temporarily disabling the function of a desired cortical region2&#8211;4.
Therapeutic rTMS involves multiple stimulation sessions, usually applied once daily over several weeks, to treat a variety of disorders, including major depressive disorder (MDD)5, eating disorders6, and obsessive-compulsive disorder7. rTMS for MDD is a potential option for medically refractory patients, and allows the clinician to noninvasively target and alter the excitability of a cortical region directly involved with depressive etiology or pathophysiology. The conventional cortical target for MDD-rTMS is the dorsolateral prefrontal cortex (DLPFC)8. However, convergent evidence from neuroimaging, lesion, and stimulation studies identifies the dorsomedial prefrontal cortex (dmPFC) as a potentially important therapeutic target for MDD9 and a variety of other psychiatric disorders characterized by deficits in self-regulation of thoughts, behaviors, and emotional states10. The dmPFC is a region of consistent activation in emotional regulation11, behavioral regulation12,13. The dmPFC is also associated with neurochemical14, structural15, and functional16 abnormalities in MDD
Described here is the procedure for 20 sessions (4 weeks) of magnetic resonance imaging (MRI) guided rTMS to the dmPFC bilaterally, as a treatment for major depressive disorder. In addition to a conventional 10 Hz protocol applied over 30 min, an intermittent theta burst stimulation protocol (TBS) is discussed, which applies 50 Hz triplet bursts at 5 Hz over a 6 min session17. Both protocols are thought to be excitatory, with the TBS protocol having the potential to achieve comparable effects using a much shorter session18. In both protocols, anatomical MRIs as well as clinical assessments are acquired prior to rTMS. Neuronavigation uses the anatomical scans to account for anatomical variability of dmPFC and optimize the location of rTMS. A relatively new 120&#176;-angled fluid-cooled rTMS coil was also used in order to stimulate deeper midline cortical structures. Finally, rTMS intensity titration was used over the first week of rTMS sessions to ensure that patients could habituate to the higher pain levels associated with dmPFC stimulation as compared to conventional DLPFC stimulation.

<table><tbody><tr><td>3T GE Signa HDx Scanner</td><td>GE</td><td>n/a</td><td></td></tr><tr><td>Visor 2.0 Neuronavigation System</td><td>ANT Neuro</td><td>n/a</td><td></td></tr><tr><td>MagPro R30 Stimulator</td><td>MagVenture</td><td>n/a</td><td></td></tr><tr><td>Cool-DB80 Coil</td><td>MagVenture</td><td>n/a</td><td></td></tr></tbody></table>

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.

In previous work, HamD17 was used as a measure of treatment response for 10 Hz dmPFC-rTMS. Table 1 displays the pre- and post-treatment HamD17 scores in a previously published case series27. Among all subjects, pre-treatment HamD17 score was 21.66.9 that significantly decreased by 4,331% to 12.58.2 post-rTMS (t22 = 6.54, p &#60;0.0001)27. Using a remission criterion of HamD17 &#8804;7, 8 of 23 subjects remitted following treatme...

Watch this Scientific Journal Video about MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder at JoVE.com

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

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 ...

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13.8K Views.  University of Toronto. 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.

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

The NeuroStar TMS Device: Conducting the FDA Approved Protocol for Treatment of Depression

The Neuronetics NeuroStar Transcranial Magnetic Stimulation (TMS) System is a class II medical device that produces brief duration, pulsed magnetic fields. These rapidly alternating fields induce electrical currents within localized, targeted regions of the cortex which are associated with various physiological and functional brain changes.1,2,3
In 2007, O'Reardon et al., utilizing the NeuroStar device, published the results of an industry-sponsored, multisite, randomized, sham-stimulation controlled clinical trial in which 301 patients with major depression, who had previously failed to respond to at least one adequate antidepressant treatment trial, underwent either active or sham TMS over the left dorsolateral prefrontal cortex (DLPFC). The patients, who were medication-free at the time of the study, received TMS five times per week over 4-6 weeks.4
The results demonstrated that a sub-population of patients (those who were relatively less resistant to medication, having failed not more than two good pharmacologic trials) showed a statistically significant improvement on the Montgomery-Asberg Depression Scale (MADRS), the Hamilton Depression Rating Scale (HAMD), and various other outcome measures. In October 2008, supported by these and other similar results5,6,7, Neuronetics obtained the first and only Food and Drug Administration (FDA) approval for the clinical treatment of a specific form of medication-refractory depression using a TMS Therapy device (FDA approval K061053).
In this paper, we will explore the specified FDA approved NeuroStar depression treatment protocol (to be administered only under prescription and by a licensed medical profession in either an in- or outpatient setting).

In this article, we examine the methodology and considerations relevant to the FDA approved depression treatment protocol using the Neuronetics NeuroStar TMS device.

The Neuronetics NeuroStar Transcranial Magnetic Stimulation (TMS) System is a class II medical device that produces brief duration, pulsed magnetic ...

Neuroscience

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 ...

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 ...

Behavior

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, ...

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.

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 ...

Utilizing Repetitive Transcranial Magnetic Stimulation to Improve Language Function in Stroke Patients with Chronic Non-fluent Aphasia

Transcranial magnetic stimulation (TMS) has been shown to significantly improve language function in patients with non-fluent aphasia1. In this experiment, we demonstrate the administration of low-frequency repetitive TMS (rTMS) to an optimal stimulation site in the right hemisphere in patients with chronic non-fluent aphasia. A battery of standardized language measures is administered in order to assess baseline performance. Patients are subsequently randomized to either receive real rTMS or initial sham stimulation. Patients in the real stimulation undergo a site-finding phase, comprised of a series of six rTMS sessions administered over five days; stimulation is delivered to a different site in the right frontal lobe during each of these sessions. Each site-finding session consists of 600 pulses of 1 Hz rTMS, preceded and followed by a picture-naming task. By comparing the degree of transient change in naming ability elicited by stimulation of candidate sites, we are able to locate the area of optimal response for each individual patient. We then administer rTMS to this site during the treatment phase. During treatment, patients undergo a total of ten days of stimulation over the span of two weeks; each session is comprised of 20 min of 1 Hz rTMS delivered at 90% resting motor threshold. Stimulation is paired with an fMRI-naming task on the first and last days of treatment. After the treatment phase is complete, the language battery obtained at baseline is repeated two and six months following stimulation in order to identify rTMS-induced changes in performance. The fMRI-naming task is also repeated two and six months following treatment. Patients who are randomized to the sham arm of the study undergo sham site-finding, sham treatment, fMRI-naming studies, and repeat language testing two months after completing sham treatment. Sham patients then cross over into the real stimulation arm, completing real site-finding, real treatment, fMRI, and two- and six-month post-stimulation language testing.

We explore the use of repetitive transcranial magnetic stimulation (rTMS) to improve language abilities in patients with chronic stroke and non-fluent aphasia. After identifying a site in the right frontal gyrus for each patient that responds optimally to stimulation, we target this site during ten days of rTMS treatment.

Transcranial magnetic stimulation (TMS) has been shown to significantly improve language function in patients with non-fluent aphasia1. In this ...

Individualized rTMS Treatment for Depression using an fMRI-Based Targeting Method

To achieve greater clinical efficacy, a revolution in treatment for major depressive disorder (MDD) is highly anticipated. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive and safe neuromodulation technique that immediately changes brain activity. Despite its wide application in the treatment for MDD, the treatment response remains different among individuals, which may be attributable to the inaccurate positioning of the stimulation target. Our study aims to examine whether the functional magnetic resonance imaging (fMRI)-assisted positioning improves the efficacy of rTMS in treating depression. We intend to identify and stimulate the subregion of dorsolateral prefrontal cortex (DLPFC) in MDD with strongest anti-correlation with the subgenual anterior cingulate cortex (sgACC), and to conduct a comparative investigation of this novel method and the traditional 5-cm rule. To achieve more precise stimulation, both methods were applied under the guidance of neuronavigation system. We expected that the TMS treatment with individualized positioning based on resting state functional connectivity may show better clinical efficacy than the 5-cm method.

The present protocol describes the application of repetitive transcranial magnetic stimulation (rTMS), where a subregion of the dorsolateral prefrontal cortex (DLPFC) with the strongest functional anticorrelation with the subgenual anterior cingulate cortex (sgACC) was located as the stimulation target under the assistance of a fMRI-based neuronavigation system.

To achieve greater clinical efficacy, a revolution in treatment for major depressive disorder (MDD) is highly anticipated. Repetitive transcranial ...

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 ...

Vagus Nerve Stimulation As an Adjunctive Neurostimulation Tool in Treatment-resistant Depression

Vagus nerve stimulation (VNS) is an approved neurostimulation therapy. The purpose of the method is to treat patients with therapy-resistant depression (TRD). VNS exhibits antidepressive and stabilizing effects. This method is particularly useful as a long-term treatment, in which up to two-thirds of patients respond. The vagus nerve stimulator is positioned on the left vagus nerve during a surgical procedure and is activated telemetrically by a wand connected to a handheld computerized device. The treating physician can perform various adjustments of the vagus nerve stimulator during in-office visits (e.g., by modifying stimulation intensity or stimulation frequency) to achieve maximum therapeutic effects with low side effects. Set-up of the device usually takes several months. Typical side effects include wound infection, temporary salivation, coughing, paralysis of the vocal cords, bradycardia, or even asystole. The patient can stop the VNS by placing a magnet over the generator. The current protocol describes delivery of the specific stimulation tool and methods for adjusting the tuning parameters to achieve the best remission rates in patients with TRD.

Vagus nerve stimulation (VNS) has been shown to be effective as an adjunct treatment for treatment-resistant depression (TRD). VNS leads to antidepressive and antisuicidal effects and quality of life improvements. This protocol offers a step-by-step guide to managing and adjusting a vagus nerve stimulator for efficient treatment of TRD.

Vagus nerve stimulation (VNS) is an approved neurostimulation therapy. The purpose of the method is to treat patients with therapy-resistant depression ...

Employing Transcranial Magnetic Stimulation in a Resource Limited Environment to Establish Brain-Behavior Relationships

Neuroimaging is typically perceived as a resource demanding discipline. While this is the case in certain circumstances, institutions with limited resources have historically contributed significantly to the field of neuroscience, including neuroimaging. In the study of self-deception, we have successfully employed single-pulse TMS to determine the brain correlates of abilities including overclaiming and self-enhancement. Even without the use of neuro-navigation, methods provided here lead to successful outcomes. For example, it was discovered that decreases in self-deceptive responding lead to a decrease in affect. These methods provide data that are reliable and valid, and such methods provide research opportunities otherwise unavailable.&#160;Through the use of these methods, the overall knowledge base in the field of neuroscience is expanded, providing research opportunities to students such as those at our institution&#160;(Montclair State University is a Hispanic-Serving Institute) who are often denied such research experiences.

Transcranial Magnetic Stimulation (TMS) and low-frequency TMS (lfTMS) have&#160;been demonstrated to be major contributors to brain literature. Here we highlight the methods for investigating the cortical correlates of self-deception using TMS.

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

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