The study was funded by China Postdoctoral Science Foundation funded project (2019M652854) and Natural Science Foundation of Guangdong, China (Grant No. 2020A1515010077).

Inform all participants about the study and ask them to sign the informed consent form prior to the start of the study. The present protocol was approved by the Research Ethics Committee of the Affiliated Brain Hospital of Guangzhou Medical University.
NOTE: In this double-blind study, patients with depression were randomly divided into two groups. In the experimental group, stimulation targets are located by the DLPFC-sgACC-based individualized location method (Please see 3.3 for detailed description). The targets of the control group are obtained by the average 5-cm method (i.e. (-41, 16, 54))22.
1. Participants&#39; selection
<ol>
	<li>Recruit patients with a diagnosis of MDD as confirmed by an expert psychiatrist. 
	NOTE: Confirm the diagnosis with the standardized MINI-International Neuropsychiatric Interview (M.I.N.I.)23 . The total score of Montgomery-Asberg Depression Rating Scale (MADRS)24 should be no less than 22.</li>
	<li>Exclude patients who meet the exclusion criteria: (1) serious physical diseases such as malignant tumor, acute heart failure, multiple organ failure, or severe neurological conditions including but not limited to epilepsy, stroke, encephalitis, brain trauma; (2) comorbidity of other mental illness, or a history of substance use disorder; (3) having metallic implants, especially in brain or heart; (4) women during pregnancy or lactation; (5) had suicidal behaviors or attempted suicide in the past six months; and (6) a diagnosis of bipolar depression or psychotic depression. 
	&#8203;NOTE: Recruit at least 36 subjects for each group to ensure statistical power. A balanced demographic profile between the two groups is recommended.</li>
</ol>
2. Preparation of Magnetic Resonance Imaging (MRI) and TMS
<ol>
	<li>Obtain fMRI images by a 3T MRI scanner before performing TMS.
	<ol>
		<li>Reconfirm that the patient has no contraindications before an MRI scanning. Instruct the patient to try to lie still and think of nothing during the scan.</li>
		<li>Conduct a resting-state fMRI (rs-fMRI) scan using the FFE-EPI sequence with the following parameters: TR/TE = 2000/30 ms, FA = 90&#176;, field-of-view = 220 x 220 x 256 mm3, matrix = 64 x 64, voxel size = 3.44 x 3.44 x 4 mm3, gap = 0.6 mm, number of signal averages = 1, volumes = 240, number of slices = 33.</li>
		<li>Conduct a structural MRI scan using the sagittal T1 weighted 3D turbo field echo (T1W 3D TFE) sequence with the following parameters: field of view = 256 x 256 mm2, TR/TE = 8.2/3.8 ms, view matrix= 256 x 256, slice thickness= 1 mm.</li>
	</ol>
	</li>
	<li>Set TMS parameters. 
	NOTE: The protocol of TMS in our study is the intermittent theta-burst stimulation (iTBS). A daily treatment session includes 60 cycles of 10 bursts of 3 pulses at 50 Hz delivered at 100% RMT in 2-s trains, with an interval of 8 s. The whole treatment consists of 10 sessions carried out on weekdays of two consecutive weeks.</li>
</ol>
3. Treatment (Figure 1)
<ol>
	<li>Conduct MRI scans and clinical assessments of symptoms and cognitive performance one day before the treatment.</li>
	<li>Assign the patient randomly to one of the two groups, after scanning.</li>
	<li>For the experimental group, identify the subregion of DLPFC that shows strongest functional anti-connectivity with sgACC. For the control group, simply locate the target in the standard-space using the average 5-cm method, then convert it to the individual space coordinates.
	<ol>
		<li>rs-fMRI data preprocessing
		<ol>
			<li>Preprocess the rs-fMRI data using an MRI analysis software: (a) remove the first 10 volumes; (b) conduct&#160; the slice timing correction; (c) correct the head motion; (d) co-register EPI images to T1 images; (e) perform segmentation; (f) perform normalization using T1 images; (g) smooth the normalized images with a 6-mm Gaussian kernel of full-width half maximum (FWHM); (h) band-pass filter (0.01 - 0.08 Hz); and (i) perform nuisance regression (head motion effects, linear trends, white matter, cerebrospinal fluid, and global mean time course).</li>
		</ol>
		</li>
		<li>Functional connectivity (FC) of the sgACC
		<ol>
			<li>Select the sgACC (MNI coordinate: 6, 16, &#8722;10; Fox et al.) as the region of interest (ROI)25 with a 10-mm radius.</li>
			<li>Remove the white matter and cerebrospinal fluid in the ROI based on the Harvard-Oxford cortical atlas (http://www.cma.mgh.harvard.edu/),&#160;using a gray matter probability threshold of 0.25.</li>
			<li>Extract the average time course of the ROI.</li>
			<li>To generate FC map, compute Pearson&#39;s correlation coefficients between the ROI (sgACC) and DLPFC in a voxel-wise manner. Normalize each correlation coefficient using the Fisher&#39;s r-to-z Transformation. 
			NOTE: The DLPFC mask is a combination of 20mm radius spheres centered along the left hemisphere at BA9 (x=-36, y=39, z=43), BA46 (x=-44, y=40, z=29), the 5-cm approach site (x=-41, y=16, z=54), and the F3 Beam group-average stimulation site (x=-39, y=26, z=49)26.</li>
			<li>According to the FC map, identify the peak coordinate in DLPFC that has the largest Pearson&#39;s anti-correlation coefficient with sgACC. This is the subregion of DLPFC with the strongest negative FC with sgACC, which will be later targeted in the TMS treatment for the experimental group.</li>
		</ol>
		</li>
	</ol>
	</li>
	<li>Determine the resting motor threshold (RMT) for each subject and record the hotspot.
	<ol>
		<li>Instruct the patient to sit back and relax, then put two recording electrodes on the thenar of the right hand and a reference electrode on the bony part of the wrist.</li>
		<li>Stimulate the motor hotspot with 10 consecutive stimulations with different intensities; in the meanwhile, record the times of thenar muscle contraction.</li>
		<li>Identify the minimum TMS intensity at which a motor evoked potential (MEP) &#8805; 50 &#181;V is recorded at least 5 times. Define it as the patient&#39;s RMT.</li>
	</ol>
	</li>
	<li>Assess the severity of depression using clinical scales as described in Clinical Data Collection.</li>
	<li>Perform TMS treatment twice a day for 10 days. 
	NOTE: For a subject who did not receive treatments as planned, perform additional stimulations after the end of treatment course as needed. However, any subject who misses the treatment for more than four consecutive days should be excluded.
	<ol>
		<li>Create a new patient entry.
		<ol>
			<li>Select the option Create New Patient. Input the patient&#39;s ID number or name in the textbox.</li>
		</ol>
		</li>
		<li>Overlay the structural MRI images onto the navigation system.
		<ol>
			<li>Select Import patient MRI, and then import the structural image of the patient and select the image type.</li>
		</ol>
		</li>
		<li>Create individual head model and define the stimulation target.
		<ol>
			<li>Press the button Specify MRI Fiducials.</li>
			<li>Place the crosshair on these spots in the MRI image: (1) Fiducial Markers: nasion, both left and right tragi; (2) AC-PC Markers for Talairach: anterior commissure, posterior commissure, inter-hemispheric point; (3) Talairach Markers: anterior point, posterior point, superior point, inferior point, left point, and right point. 
			NOTE: The &#34;Talairach Markers&#34; mark the borders of the brain.</li>
			<li>Press Create Head Model. Select Manual Brain Segmentation and adjust the threshold of the scalp, the lower brain, and the upper brain.</li>
			<li>Click Define Target to proceed.</li>
			<li>Select Target Marker page. Click &#8230; to input the coordinate of the treatment target as identified in step 3.3, and then press Go to. Press Add Marker to name the point. 
			NOTE: The coordinates of the control group will be (-41, 16, 54).</li>
		</ol>
		</li>
		<li>Coil calibration
		<ol>
			<li>Click Proceed to Neuronavigation. In the textbox, select the right type of tools to be used in the treatment. Ensure all the tools of reference are in the view of the infrared camera.</li>
			<li>Press Validate Coil. Put the tip of pointer on the marked coil point. Press Validate (or the green button on the remote control) when the indicator of each tool turns green.</li>
		</ol>
		</li>
		<li>Select patient and target.
		<ol>
			<li>Select patient&#39;s name or ID on the Select Patient page. Click Select Targets on the next page.</li>
			<li>Choose Read target markers to browse the file of targets. Import the file and select the target as in step 3.6.3.5.</li>
		</ol>
		</li>
		<li>Define the coordinate system.
		<ol>
			<li>Click Define Coordinate System. Put a headband with a reference tool on the patient. Make sure the coil tracker and the reference tool are in the vision of the navigation system.</li>
			<li>Place pointer&#39;s tip on the nasion and both tragi in turn. Press the green button on the remote control each time when the indicator of a marker turns green.</li>
		</ol>
		</li>
		<li>Head shape generation
		<ol>
			<li>Continuously move the pointer&#39;s tip on the top of the head. Press the button on the remote control (or Fit) to continue. 
			NOTE: One can press Pause to stop the process, and resume by pressing the Start button again, once the pointer has been placed correctly.</li>
		</ol>
		</li>
		<li>Neuronavigation and stimulation
		<ol>
			<li>Press Neuronavigation. On the Active Coil page, set the stimulation intensity to 100% RMT. Choose Stimulate at targets to see the target on the head model online.</li>
			<li>When the coil matches the target crosshair, that is, when the indicator text turns green, stimulate.</li>
		</ol>
		</li>
		<li>Prepare and start the treatment from step 3.6.4 directly if the patient&#39;s entry had been created before.</li>
	</ol>
	</li>
	<li>Conduct follow-up assessments on Day 1, Day 28, and Day 56 after the whole treatment course.</li>
</ol>
4. Clinic data collection (Figure 1b)
<ol>
	<li>Perform clinical assessments using MADRS24, Hamilton Depression Rating Scale (HAMD)27, Beck Depression Inventory-II (BDI-II)28, Hamilton Anxiety Scale (HAMA)29, Clinical Global Impression (CGI)30 and MATRICS Consensus Cognitive Battery (MCCB)31,32. 
	NOTE: MINI and MADRS are used for the screening. All the above scales are applied for pre- and post-treatment clinical assessment.</li>
</ol>

Authors have no disclosures to report.

The sgACC is responsible for emotional processing and plays an important role in stress regulation16,17,18. A study suggests that targeting on a subregion of DLPFC that shows strongest functional anti-connectivity with sgACC (6, 16, -10) may enhance the antidepressant effect25. Therefore, precisely locating this target is the critical step of this protocol. Before the stimulation, the borders of the brain...

Major depressive disorder (MDD) is characterized by significant and persistent depression, and in more severe cases, patients can encounter hallucinations and/or delusions1,2. Compared with the general population, the risk of suicide among MDD patients is approximately 20 times higher3. While medication is currently the most used treatment for MDD, 30% - 50% of the patients lack adequate response to antidepressants4. For the responders, the symptom improvement tends to appear after a relatively long latent period and is accompanied by side effects. Psychotherapy, although effective for some patients, is costly and time-consuming. A safer and more effective treatment for MDD is therefore urgently required.
Repetitive transcranial magnetic stimulation (rTMS)is a non-invasive and safe technique and has been approved for the treatment of various mental disorders5,6,7. Although its therapeutic mechanism remains unclear, rTMS was speculated to work by regulating the activity of the stimulated brain regions and the neural plasticity8,9,10, thus normalizing specific functional networks10,11,12. rTMS also causes network effect, which evokes changes in remote brain areas through connection pathways, leading to an amplified therapeutic effect13. Although rTMS changes brain activity immediately and robustly, its response rate in the treatment of MDD is only about 18%14. The main reason may be the inaccurate location of stimulation targets15.
The subgenual anterior cingulate cortex (sgACC) is mainly responsible for emotional processing and plays a role in regulating the response to stressful events, emotional response to internal and external stimuli, and emotional expression16,17,18. This subregion of ACC shares substantial structural and functional connectivity with the cerebral cortex and the limbic system19,20. Interestingly, studies have shown that the post-stimulation activity of this area is closely related to the clinical efficacy of TMS. For instance, the blood flow of sgACC decreased after a course of TMS targeted on the right dorsolateral prefrontal cortex (DLPFC), which was associated with the alleviation of depressive symptoms21. Vink et al.8 found that stimulation targeted on DLPFC was propagated to sgACC, and suggested that sgACC activity can be a biomarker of the treatment response of TMS. According to previous researches, Fox and colleagues22&#160;proposed that targeting on a subregion of DLPFC that shows strongest functional anti-connectivity with sgACC (MNI coordinate: 6, 16, -10) enhances the antidepressant effect. Here, we demonstrate a study protocol aimed to examine this hypothesis.

<table><tbody><tr><td>3T Philips Achieva MRI scanner</td><td>Philips</td><td></td><td></td></tr><tr><td>Harvard/Oxford cortical template</td><td>http://www.cma.mgh.harva rd.edu/</td><td></td><td></td></tr><tr><td>MATLAB</td><td>MathWorks</td><td></td><td></td></tr><tr><td>SPM12</td><td>http://www.fil.ion.ucl.ac.uk/spm</td><td></td><td></td></tr><tr><td>The Visor2 system</td><td>ANT Neuro</td><td></td><td>The Visor2 software, the optical tracking system, tracking tools and calibration board are part of the visor2 system.</td></tr><tr><td>TMS device</td><td>Magstim, Carmarthenshire, UK</td><td></td><td></td></tr></tbody></table>

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.

ROI-wise FC analysis should show that sgACC is significantly anti-correlated with DLPFC, in which the strongest negative correlation is the stimulus target to be chosen. Significant anti-correlation between the sgACC-DLPFC functional connectivity and the treatment response should be found in the correlation analysis33.
The current protocol is based on an innovative TMS targeting method that no previous studies have applied. Here we present results from an fMRI-guided TM...

Watch this Scientific Journal Video about Individualized rTMS Treatment for Depression using an fMRI-Based Targeting Method at JoVE.com

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

individualized-rtms-treatment-for-depression-using-an-fmri-based

Universidad San Sebastian

Research

JoVE Journal

Behavior

3.4K Views.  Affiliated Brain Hospital of Guangzhou Medical University. 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.

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

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

Neuronavigation-guided Repetitive Transcranial Magnetic Stimulation for Aphasia

Repetitive transcranial magnetic stimulation (rTMS) is widely used for several neurological conditions, as it has gained acknowledgement for its potential therapeutic effects. Brain excitability is non-invasively modulated by rTMS, and rTMS to the language areas has proved its potential effects on treatment of aphasia. In our protocol, we aim to artificially induce virtual aphasia in healthy subjects by inhibiting Brodmann area 44 and 45 using neuronavigational TMS (nTMS), and F3 of the International 10-20 EEG system for conventional TMS (cTMS). To measure the degree of aphasia, changes in reaction time to a picture naming task pre- and post-stimulation are measured and compare the delay in reaction time between nTMS and cTMS. Accuracy of the two TMS stimulation methods is compared by averaging the Talairach coordinates of the target and the actual stimulation. Consistency of stimulation is demonstrated by the error range from the target. The purpose of this study is to demonstrate use of nTMS and to describe the benefits and limitations of the nTMS compared to those of cTMS.

This study is designed to test the hypothesis that neuronavigational system-guided transcranial magnetic stimulation has higher accuracy for targeting the intended target as demonstrated by eliciting a greater degree of virtual aphasia in healthy subjects, measured by delay in reaction time to picture naming.

Repetitive transcranial magnetic stimulation (rTMS) is widely used for several neurological conditions, as it has gained acknowledgement for its potential ...

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, ...

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 ...

Medicine

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 ...

A Multimodal Imaging- and Stimulation-based Method of Evaluating Connectivity-related Brain Excitability in Patients with Epilepsy

Resting-state functional connectivity MRI (rs-fcMRI) is a technique that identifies connectivity between different brain regions based on correlations over time in the blood-oxygenation level dependent signal. rs-fcMRI has been applied extensively to identify abnormalities in brain connectivity in different neurologic and psychiatric diseases. However, the relationship among rs-fcMRI connectivity abnormalities, brain electrophysiology and disease state is unknown, in part because the causal significance of alterations in functional connectivity in disease pathophysiology has not been established. Transcranial Magnetic Stimulation (TMS) is a technique that uses electromagnetic induction to noninvasively produce focal changes in cortical activity. When combined with electroencephalography (EEG), TMS can be used to assess the brain's response to external perturbations. Here we provide a protocol for combining rs-fcMRI, TMS and EEG to assess the physiologic significance of alterations in functional connectivity in patients with neuropsychiatric disease. We provide representative results from a previously published study in which rs-fcMRI was used to identify regions with abnormal connectivity in patients with epilepsy due to a malformation of cortical development, periventricular nodular heterotopia (PNH). Stimulation in patients with epilepsy resulted in abnormal TMS-evoked EEG activity relative to stimulation of the same sites in matched healthy control patients, with an abnormal increase in the late component of the TMS-evoked potential, consistent with cortical hyperexcitability. This abnormality was specific to regions with abnormal resting-state functional connectivity. Electrical source analysis in a subject with previously recorded seizures demonstrated that the origin of the abnormal TMS-evoked activity co-localized with the seizure-onset zone, suggesting the presence of an epileptogenic circuit. These results demonstrate how rs-fcMRI, TMS and EEG can be utilized together to identify and understand the physiological significance of abnormal brain connectivity in human diseases.

Resting-state functional-connectivity MRI has identified abnormalities in patients with a wide range of neuropsychiatric disorders, including epilepsy due to malformations of cortical development. Transcranial Magnetic Stimulation in combination with EEG can demonstrate that patients with epilepsy have cortical hyperexcitability in regions with abnormal connectivity.

Resting-state functional connectivity MRI (rs-fcMRI) is a technique that identifies connectivity between different brain regions based on correlations ...

Use of Real-Time Functional Magnetic Resonance Imaging-Based Neurofeedback to Downregulate Insular Cortex in Nicotine-Addicted Smokers

It has been more than a decade since the first functional magnetic resonance imaging (fMRI)-based neurofeedback approach was successfully implemented. Since then, various studies have demonstrated that participants can learn to voluntarily control a circumscribed brain region. Consequently, real-time fMRI (rtfMRI) provided a novel opportunity to study modifications of behavior due to manipulation of brain activity. Hence, reports of rtfMRI applications to train self-regulation of brain activity and the concomitant modifications in behavioral and clinical conditions such as neurological and psychiatric disorders [e.g., schizophrenia, obsessive compulsive Disorder (OCD), stroke] have rapidly increased.
Neuroimaging studies in addiction research have shown that the anterior cingulate cortex, orbitofrontal cortex, and insular cortex are activated during the presentation of drug-associated cues. Also, activity in both left and right insular cortices have been shown to be highly correlated with drug urges when participants are exposed to craving-eliciting cues. Hence, the bilateral insula is of particular importance in researching drug urges and addiction due to its role in the representation of bodily (interoceptive) states. This study explores the use of rtfMRI neurofeedback for the reduction in blood oxygen-level dependent (BOLD) activity in bilateral insular cortices of nicotine-addicted participants. The study also tests if there are neurofeedback training-associated modifications in the implicit attitudes of participants towards nicotine-craving cues and explicit-craving behavior.

In real-time functional magnetic resonance imaging (rtfMRI), brain activity is experimentally manipulated as an independent variable, and behavior is measured as a dependent variable. The protocol presented here focuses on the practical use of rtfMRI as a therapeutic tool for psychiatric disorders such as nicotine addiction.

It has been more than a decade since the first functional magnetic resonance imaging (fMRI)-based neurofeedback approach was successfully implemented. ...

Neuronavigated tDCS for Enhanced Electrode Placement Accuracy in fMRI Studies

Neuronavigated Focalized Transcranial Direct Current Stimulation Administered During Functional Magnetic Resonance Imaging

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that allows the modulation of the excitability and plasticity of the human brain. Focalized tDCS setups use specific electrode arrangements to constrain the current flow to circumscribed brain regions. However, the effectiveness of focalized tDCS can be compromised by electrode positioning errors on the scalp, resulting in significant reductions of the current dose reaching the target brain regions for tDCS. Electrode placement guided by neuronavigation based on the individual&#39;s head and brain anatomy derived from structural magnetic resonance imaging (MRI) data may be suited to improve positioning accuracy.
This protocol describes the method of neuronavigated electrode placement for a focalized tDCS setup, which is suitable for concurrent administration during functional MRI (fMRI). We also quantify the accuracy of electrode placement and investigate electrode drift in a concurrent tDCS-fMRI experiment. Critical steps involve the optimization of electrode positions based on current modeling that considers the individual&#39;s head and brain anatomy, the implementation of neuronavigated electrode placement on the scalp, and the administration of optimized and focal tDCS during fMRI.
The regional precision of electrode placement is quantified using the Euclidean norm (L2&#160;Norm) to determine deviations of the actual from the intended electrode positions during a concurrent tDCS-fMRI study. Any potential displacement of electrodes (drift) during the experiment is investigated by comparing actual electrode positions before and after the fMRI acquisition. In addition, we directly compare the placement accuracy of neuronavigated tDCS to that achieved by a scalp-based targeting approach (a 10-20 Electroencephalography (EEG) system). These analyses demonstrate superior placement accuracy for neuronavigation compared to scalp-based electrode placement and negligible electrode drift across a 20 min scanning period.

This protocol describes the method of neuronavigated electrode placement for focal, transcranial direct current stimulation (tDCS) administered during functional magnetic resonance imaging (fMRI).

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that allows the modulation of the excitability and plasticity ...