No acknowledgments.

This protocol involves research on human subjects and is in alliance with institutional and ethical guidelines of local ethical committees and the Declaration of Helsinki. Informed consent was obtained from subjects for using their data in the study.
1. Pre-experimental procedures
<ol>
	<li>Screening of the subject. Screen the subject for intracranial implants, epilepsy, history of seizures, and pregnancy. Use questionnaire guidelines to ensure compliance with up-to-date safety precautions32.
	<ol>
		<li>The delivery of electromagnetic pulses with TMS is contraindicated for individuals with intracranial implants of ferromagnetic material, such as shrapnel, aneurysm clips, or fragments from welding. Take precautions with individuals at increased likelihood of seizures.</li>
		<li>TMS assessment poses no fetal risk for pregnant women who are advised to have a conservative stance when dealing with this population. It is safe to apply TMS in pediatric populations, proceed cautiously in certain developmental stages (i.e., closure of the fontanelle, maturation of cortical excitability, and growth of the external auditory canal)33.</li>
	</ol>
	</li>
	<li>Preparation of materials. For this procedure, other than the TMS and EMG devices, have at your disposal a swim cap, alcohol pads (with the preparation of 70% isopropyl alcohol), conductive gel, and a computer turned on with the EMG software setup and a dynamometer appropriate for the investigated muscle (see Table of materials). 
	&#8203;NOTE: Swim caps have the advantage of being the cheapest and most accessible option that still allows for reliable and reproducible TMS assessments without causing the discomfort of marking the subjects&#39; head.</li>
</ol>
2. Appropriate instructions to the patients
<ol>
	<li>Explain the basic steps of the procedure and how much time it will take.</li>
	<li>Instruct the participant to remain awake but not to perform cognitive activities that require extra attention and/or focus (e.g., mathematical calculations, meditation, etc.) and anticipate that they might experience hand/jaw twitching or plausible side effects. Such events might seem unexpected for an inexperienced subject and thus jeopardize the procedure. 
	&#8203;NOTE: Single- and paired-pulse TMS have only been associated with mild, transient, adverse events, including headache, local pain, neck pain, toothache, and paresthesia. Seizures are rare, and no other serious adverse events have been associated33. For extra safety, it is recommended to offer earplugs, due to the possibility of harmful sounds, and bite-blocks for possible masseter contraction34.</li>
</ol>
3. Experimental procedures (Figure 1)
<ol>
	<li>Select the muscle for positioning the electrodes.
	<ol>
		<li>Ask the subject to put their hand over the table, in a prone position. Select the FDI muscle, localized between the first and second metacarpal osseous. To identify the FDI, ask the subject to abduct their index finger against resistance, keeping the rest of the hand still and laying on the table, while you are palpating the area.</li>
		<li>Expose the selected area. Use a disposable razor to shave the area to improve electrode contact with the skin, if necessary, and clean the area with alcohol pads to remove skin oils and other factors that could increase impedance. Certify that there is free skin to ensure contact with the electrode. 
		NOTE: If evaluating lower limb activity, use the TA muscle for electrode placement. It is localized on the lateral side of the tibia and lies near the superficies of the skin. It can be identified by ankle dorsiflexion.</li>
	</ol>
	</li>
	<li>Place the surface EMG electrodes
	<ol>
		<li>With the area exposed and cleaned, apply the conductive gel to each electrode of the channel to ensure good impedance.</li>
		<li>Place the negative electrode on the belly of the FDI muscle (the center or the most prominent bulge of the muscle belly) and the positive on the distal interphalangeal joint, with an inter-electrode distance of at least 1.5 cm. Place the reference electrode (neutral) on the wrist, over the ulnar styloid process. 
		NOTE: The presence of motor endpoints, muscle tendons, or other active muscles can impact the stability of the recordings, so it is important to avoid these locations35. For the TA muscle, the electrodes should be placed at one-third on the line that connects the tip of the fibula and the tip of the medial malleolus. Provide a 20 mm distance between each electrode&#39;s pole and place the reference electrode in the ankle.</li>
	</ol>
	</li>
	<li>Determine the required muscle contraction force
	<ol>
		<li>Use a digital pinch dynamometer and a quadrangular pyramid support to minimize mechanical distortions and elevate the sensitivity for minimal contractions.</li>
		<li>Place the dynamometer between the first and second fingers with the help of the pyramidal support. Ensure that the third, fourth, and fifth fingers lay still on the table, while the 1st and 2nd generate the forces of the pinching movement.</li>
		<li>With the fixed position, ask the participant to press the dynamometer with the first finger and the side of the pyramid with the index finger, squeezing the dynamometer-pyramid system with their maximum force and creating a strong contraction of the FDI muscle.</li>
		<li>Using that value as reference, determine the 20% of maximum force. The participant must practice maintaining the target at 20% of sustained contraction. Allow for variations from 15%-25% of MVC. 
		NOTE: Alternatively, in case of unavailability of a dynamometer that can catch the isolated muscle activity being investigated, use EMG feedback to standardize force. The recording software will measure the maximum peak-to-peak amplitude that corresponds to the subject&#39;s maximum force, and using that value as reference, will determine the 20% MVC. Subjects can receive visual and/or auditory clues of when 20% is achieved.</li>
	</ol>
	</li>
	<li>Identification of the initial location for hotspot searching
	<ol>
		<li>Put a swim cap on the subject&#39;s head. All the reference points will be marked on it.</li>
		<li>Measure the sagittal circumference of the head from the nasion (the point between the forehead and the nose) to the inion (the most prominent point in the occipital region). Divide that value by two and mark that middle spot on the head.</li>
		<li>Mark the location of the patient&#39;s nasion, inion, the helix of both right and left external ears, and right and left supraorbital ridge. This is to certify that the cap has not slipped during the procedure, and/or that in future experiments it will be equally positioned on the patient&#39;s head.</li>
		<li>As described above, measure the tragus-to-tragus distance and add a mark halfway. Mark the intersection between them, a point identified as the vertex (Cz).</li>
		<li>From the vertex, move 5 cm laterally in parallel to the midsagittal line, on the contralateral side to the selected muscle. This mark approximately identifies the (M1), on the same coronal level as the hand motor cortex. Use this as the first spot to initiate the search for the hotspot.</li>
		<li>The hotspot is the area of the motor cortex where the lowest motor threshold is detectable. Set up a low intensity (e.g., 30% of maximum stimulator output [MSO]) and initiate the search by delivering multiple pulses to the first spot.</li>
		<li>Pursue with small intensity increments until identifying the lowest stimulus that detects an EMG-indexed response (i.e., MEP). For the delivery of the stimuli, angle the figure-of-eight coil at 45&#176; in relation to the midsagittal line with the handle pointed toward the posterior of the patient.</li>
		<li>To ensure that the best spot was identified, move around the first spot and test the subsequent ~3 MEPs at 1 cm anterior, 1 cm lateral, 1 cm medial, and 1 cm posterior to it. Repeat this procedure as many times as needed for a consistent response; stick to the spot that elicits the largest MEP36.</li>
		<li>Once the hotspot is found, mark that spot in the patient&#39;s head (swim cap). Use this location during this experiment and the potential follow-up visits. Be cautious as not to cause discomfort to the subject due to extra pressure. Use both hands to support the coil on the subject&#39;s head.</li>
	</ol>
	</li>
	<li>Determine resting motor threshold (RMT)
	<ol>
		<li>Estimate the motor threshold as the minimum intensity required to promote an MEP of a minimal detectable amplitude (usually at least 50-100 &#181;V).</li>
		<li>To determine the motor threshold, apply ten consecutive stimuli at the hotspot and select the lowest intensity that produced an MEP with a peak-to-peak amplitude of at least 50 &#181;V on the target muscle, in 50% of the trials. 
		NOTE: This protocol can be done with the target muscle at rest (resting motor threshold [RMT]) or during active contraction (active motor threshold [AMT]). Both can further be used as references for the suprathreshold TMS pulses. The acquisition of the AMT is more prone to variability because it relies on the standardization of MVC, which can be an issue for longitudinal studies with multiple assessments.</li>
	</ol>
	</li>
	<li>CSP protocol
	<ol>
		<li>Deliver suprathreshold stimuli to elicit MEPs during tonic voluntary contraction of the target muscle.</li>
		<li>Deliver 10 stimuli with the stimulation intensity (SI) of 120% of the RMT with 10 s period in between them. During the application of the stimuli, ask the patient to maintain 20% of the maximum motor contraction of the target muscle, as practiced with the dynamometer.</li>
		<li>To ensure capturing the whole SP, certify that the EMG time window is long enough to capture up to 400 ms of EMG activity. Not infrequently - depending on the disease being studied - subjects might require higher SIs for a successful cSP to be obtained.</li>
	</ol>
	</li>
</ol>

Abhishek Datta is CEO, Co-founder and CTO of Soterix Medical Inc., and Kamran Nazin is Chief Product Officer of the same company. Soterix Medical Inc. provided the material used in the making of this video publication. The remaining authors declare having no competing financial interests.

The default SI to elicit MEP and SPs can vary according to the population. Intensities as low as 80% RMT have been shown to elicit cSP in healthy individuals39, still studies on both healthy and diseased populations have used intensities as high as 150% RMT49,50,51. Although this source of heterogeneity can be inherent to the nature of the target population, it should not be neglected as different SIs hav...

The silent period (SP) is a period of electromyographic (EMG) silence that follows a motor-evoked potential (MEP) induced by transcranial magnetic stimulation (TMS) applied during sustained muscle contraction. The suprathreshold TMS pulse can either be applied to the contralateral or ipsilateral primary motor cortex (M1) of the target muscle from which the EMG activity is being recorded yielding two phenomena: contralateral silent period (cSP) and ipsilateral silent period (iSP).
Even though iSP and cSP share similar features, they may reflect slightly different components. The first is thought to reflect transcallosal inhibition and thus be entirely of cortical origin1,2. Conversely, cSP is investigated as a possible surrogate of corticospinal inhibition, most likely mediated by gamma-aminobutyric acid (GABA) B receptors within M13,4,5.
Supporting the role of cSP in GABA-mediated pathways, previous works have found an increase in cSP duration after oral administration of GABA-enhancing components5,6,7,8. Still, spinal processes are also involved in altering its duration. The earlier phase (&#60;50 ms) of the cSP is associated with decreased H-reflex values3-a reflex that is a product of peripheral neurocircuitry and that quantifies the excitability of spinal neurons9. Spinal processing is thought to be mediated through the activation of Renshaw cells, motoneuron after-hyperpolarization, and postsynaptic inhibition by spinal interneurons10,11,12,13,14.
Despite spinal contribution, cSP results mainly from the activation of cortical inhibitory neurons, which are responsible for generating the later part of the cSP (50-200 ms)3,10,13,15,16. In that respect, the early part of cSP duration has been associated with spinal inhibition mechanisms, whereas long cSPs request larger cortical inhibitory mechanisms3,13,17,18.
Therefore, cSP is a promising biomarker candidate for corticospinal maladaptation due to neurological disorders, whereas more significant cSP durations potentially reflect an increase in corticospinal inhibition and vice versa5,11. Accordingly, previous works have found an association between cSP duration and pathologies such as dystonia, Parkinson&#39;s Disease, chronic pain, stroke, and other neurodegenerative and psychiatric conditions19,20,21,22. To illustrate, in a knee osteoarthritis cohort, a higher intracortical inhibition (as indexed by cSP) was associated with younger age, greater cartilage degeneration, and less cognitive performance in the Montreal cognitive assessment scale23. Moreover, cSP changes could also longitudinally index treatment response and motor recovery24,25,26,27,28,29,30.
As promising as the role of cSP in the neuropsychiatry field is, a challenging aspect of its assessment is that it can be too sensitive to protocol variations. For instance, the cSP duration (~100-300 ms)11&#160;is distinguishable between upper and lower limbs. Salerno et al. found an average cSP duration of 121.2 ms (&#177; 32.5) for the first dorsal interosseous muscle (FDI) and 75.5 ms (&#177; 21) for the tibialis anterior muscle (TA), in a sample of fibromyalgia patients31. Thus, the literature conveys a myriad of divergences in the parameters used to elicit cSPs, which in turn jeopardizes comparability across studies and delays the translation to clinical practice. Within a similar population, protocols have been heterogeneous regarding the suprathreshold TMS pulse setting used to stimulate M1 and the target muscle, for example. On top of that, researchers have failed to properly report the parameters used in their protocols.
Therefore, the goal is to provide a visual guideline on how to apply a feasible, reliable, and easily reproducible cSP protocol for evaluating M1 corticospinal excitability of upper and lower limbs and to discuss the practical methodological challenges of that procedure. Also, to help illustrate the reasoning for the choice of parameters, we conducted a non-exhaustive literature review on Pubmed/MEDLINE to identify published papers on cSP in chronic pain and rehabilitation populations, using the search term: Rehabilitation (Mesh) or rehabilitation or chronic pain&#160;or stroke and terms such as transcranial magnetic stimulation and single pulse or cortical silent period. No inclusion criteria were defined for the extraction, and pooled results are displayed in Table 1 for illustrative purposes only.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Alcohol pads</td>
			<td>Medline</td>
			<td></td>
			<td>Preparation with 70% isopropyl alcohol</td>
		</tr>
		<tr>
			<td>Conductive gel</td>
			<td>Weaver and Company</td>
			<td></td>
			<td>Used on the electrode</td>
		</tr>
		<tr>
			<td>Echo Pinch</td>
			<td>JTECH medical</td>
			<td>0902A302</td>
			<td>Digital dynamometer.</td>
		</tr>
		<tr>
			<td>Mega-EMG</td>
			<td>Soterix Medical</td>
			<td>NS006201</td>
			<td>Digital multiple channel EMG with built in software.</td>
		</tr>
		<tr>
			<td>MEGA-TMS coil</td>
			<td>Soterix Medical</td>
			<td>NS063201</td>
			<td>8 shaped TMS coil</td>
		</tr>
		<tr>
			<td>Mega-TMS stimulator</td>
			<td>Soterix Medical</td>
			<td>6990061</td>
			<td>Single Pulse TMS</td>
		</tr>
		<tr>
			<td>Neuro-MEP.NET</td>
			<td>Soterix Medical</td>
			<td></td>
			<td>EMG software used to analyse the muscles eletrical activity.</td>
		</tr>
		<tr>
			<td>Swim cap</td>
			<td>Kiefer</td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

measuring contralateral silent period induced by single-pulse transcranial magnetic stimulation to investigate m1 corticospinal inhibition

Contralateral silent period (cSP) is a period of suppression in the background electrical muscle activity captured by electromyography (EMG) after a motor evoked potential (MEP). To obtain this, an MEP is elicited by a suprathreshold transcranial magnetic stimulation (TMS) pulse delivered to the primary motor cortex (M1) of the target muscle selected, while the participant provides a standardized voluntary target muscle contraction. The cSP is a result of inhibitory mechanisms that occur after the MEP; it provides a broad temporal assessment of spinal inhibition in its initial ~50 ms, and cortical inhibition after. Researchers have tried to better understand the neurobiological mechanism behind the cSP to validate it as a potential diagnostic, surrogate, and predictive biomarker for different neuropsychiatric diseases. Therefore, this article describes a method to measure M1 cSP of lower and upper limbs, including a selection of target muscle, electrode placement, coil positioning, method of measuring voluntary contraction stimulation, intensity setup, and data analysis to obtain a representative result. It has the educational objective of giving a visual guideline in performing a feasible, reliable, and reproducible cSP protocol for lower and upper limbs and discussing practical challenges of this technique.

After following the step-by-step procedure, the delivery of a suprathreshold TMS pulse (120% of the RMT) will elicit an observable MEP in the EMG recording of the target muscle, and a subsequent period of background EMG activity suppression of approximately 150 ms to 300 ms (Figure 2). From that EMG pattern, it&#39;s possible to calculate the cSP metrics. The most reported outcomes are the duration (in the range of ms) of the relative and absolute SP. The relative SP is measured from the MEP...

Watch this Scientific Journal Video about Measuring Contralateral Silent Period Induced by Single-Pulse Transcranial Magnetic Stimulation to Investigate M1 Corticospinal Inhibition at JoVE.com

Measuring Contralateral Silent Period Induced by Single-Pulse Transcranial Magnetic Stimulation to Investigate M1 Corticospinal Inhibition

Contralateral silent period (cSP) assessment is a promising biomarker to index cortical excitability and treatment response. We demonstrate a protocol to assess cSP intended for studying M1 corticospinal inhibition of upper and lower limbs.

Contralateral silent period (cSP) is a period of suppression in the background electrical muscle activity captured by electromyography (EMG) after a motor ...

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2.4K Views.  Harvard Medical School. Contralateral silent period (cSP) assessment is a promising biomarker to index cortical excitability and treatment response. We demonstrate a protocol to assess cSP intended for studying M1 corticospinal inhibition of upper and lower limbs.

Video: Measuring Contralateral Silent Period Induced by Single-Pulse Transcranial Magnetic Stimulation to Investigate M1 Corticospinal Inhibition

A Novel Approach for Documenting Phosphenes Induced by Transcranial Magnetic Stimulation

Stimulation of the human visual cortex produces a transient perception of light, known as a phosphene. Phosphenes are induced by invasive electrical stimulation of the occipital cortex, but also by non-invasive Transcranial Magnetic Stimulation (TMS)1 of the same cortical regions. The intensity at which a phosphene is induced (phosphene threshold) is a well established measure of visual cortical excitability and is used to study cortico-cortical interactions, functional organization 2, susceptibility to pathology 3,4 and visual processing 5-7. Phosphenes are typically defined by three characteristics: they are observed in the visual hemifield contralateral to stimulation; they are induced when the subject s eyes are open or closed, and their spatial location changes with the direction of gaze 2. Various methods have been used to document phosphenes, but a standardized methodology is lacking. We demonstrate a reliable procedure to obtain phosphene threshold values and introduce a novel system for the documentation and analysis of phosphenes. We developed the Laser Tracking and Painting system (LTaP), a low cost, easily built and operated system that records the location and size of perceived phosphenes in real-time. The LTaP system provides a stable and customizable environment for quantification and analysis of phosphenes.

Phosphenes are transient percepts of light that can be induced by applying Transcranial Magnetic Stimulation (TMS) to visually sensitive regions of cortex. We demonstrate a standard protocol for determining the phosphene threshold value and introduce a novel method for quantifying and analyzing perceived phosphenes.

Stimulation of the human visual cortex produces a transient perception of light, known as a phosphene. Phosphenes are induced by invasive electrical ...

Combining Transcranial Magnetic Stimulation and fMRI to Examine the Default Mode Network

The default mode network is a group of brain regions that are active when an individual is not focused on the outside world and the brain is at "wakeful rest."1,2,3 It is thought the default mode network corresponds to self-referential or "internal mentation".2,3
It has been hypothesized that, in humans, activity within the default mode network is correlated with certain pathologies (for instance, hyper-activation has been linked to schizophrenia 4,5,6 and autism spectrum disorders 7 whilst hypo-activation of the network has been linked to Alzheimer's and other neurodegenerative diseases 8). As such, noninvasive modulation of this network may represent a potential therapeutic intervention for a number of neurological and psychiatric pathologies linked to abnormal network activation. One possible tool to effect this modulation is Transcranial Magnetic Stimulation: a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate cortical excitability (either increasing or decreasing it) via the application of localized magnetic field pulses.9
In order to explore the default mode network's propensity towards and tolerance of modulation, we will be combining TMS (to the left inferior parietal lobe) with functional magnetic resonance imaging (fMRI). Through this article, we will examine the protocol and considerations necessary to successfully combine these two neuroscientific tools.

In this article, we examine the methodology and considerations relevant to the combination of TMS and fMRI to examine the effects of brain stimulation on the default network.

The default mode network is a group of brain regions that are active when an individual is not focused on the outside world and the brain is at "wakeful ...

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 ...

Effects of Transcranial Alternating Current Stimulation on the Primary Motor Cortex by Online Combined Approach with Transcranial Magnetic Stimulation

Transcranial Alternating Current Stimulation (tACS) is a neuromodulatory technique able to act through sinusoidal electrical waveforms in a specific frequency and in turn modulate ongoing cortical oscillatory activity. This neurotool allows the establishment of a causal link between endogenous oscillatory activity and behavior. Most of the tACS studies have shown online effects of tACS. However, little is known about the underlying action mechanisms of this technique because of the AC-induced artifacts on Electroencephalography (EEG) signals. Here we show a unique approach to investigate online physiological frequency-specific effects of tACS of the primary motor cortex (M1) by using single pulse Transcranial Magnetic Stimulation (TMS) to probe cortical excitability changes. In our setup, the TMS coil is placed over the tACS electrode while Motor Evoked Potentials (MEPs) are collected to test the effects of the ongoing M1-tACS. So far, this approach has mainly been used to study the visual and motor systems. However, the current tACS-TMS setup can pave the way for future investigations of cognitive functions. Therefore, we provide a step-by-step manual and video guidelines for the procedure.

Transcranial Alternating Current Stimulation (tACS) allows the modulation of cortical excitability in a frequency-specific fashion. Here we show a unique approach which combines online tACS with single pulse Transcranial Magnetic Stimulation (TMS) in order to "probe" cortical excitability by means of Motor Evoked Potentials.

Transcranial Alternating Current Stimulation (tACS) is a neuromodulatory technique able to act through sinusoidal electrical waveforms in a specific ...

Online Transcranial Magnetic Stimulation Protocol for Measuring Cortical Physiology Associated with Response Inhibition

We describe the development of a reproducible, child-friendly motor response inhibition task suitable for online Transcranial Magnetic Stimulation (TMS) characterization of primary motor cortex (M1) excitability and inhibition. Motor response inhibition prevents unwanted actions and is abnormal in several neuropsychiatric conditions. TMS is a non-invasive technology that can quantify M1 excitability and inhibition using single- and paired-pulse protocols and can be precisely timed to study cortical physiology with high temporal resolution. We modified the original Slater-Hammel (S-H) stop signal task to create a &#34;racecar&#34; version with TMS pulses time-locked to intra-trial events. This task is self-paced, with each trial initiating after a button push to move the racecar towards the 800 ms target. GO trials require a finger-lift to stop the racecar just before this target. Interspersed randomly are STOP trials (25%) during which the dynamically adjusted stop signal prompts subjects to prevent finger-lift. For GO trials, TMS pulses were delivered at 650 ms after trial onset; whereas, for STOP trials, the TMS pulses occurred 150 ms after the stop signal. The timings of the TMS pulses were decided based on electroencephalography (EEG) studies showing event-related changes in these time ranges during stop signal tasks. This task was studied in 3 blocks at two study sites (n=38) and we recorded behavioral performance and event-related motor-evoked potentials (MEP). Regression modelling was used to analyze MEP amplitudes using age as a covariate with multiple independent variables (sex, study site, block, TMS pulse condition [single- vs. paired-pulse], trial condition [GO, successful STOP, failed STOP]). The analysis showed that TMS pulse condition (p&#60;0.0001) and its interaction with trial condition (p=0.009) were significant. Future applications for this online S-H/TMS paradigm include the addition of simultaneous EEG acquisition to measure TMS-evoked EEG potentials. A potential limitation is that in children, the TMS pulse sound could&#160;affect behavioral task performance.

We describe an experimental procedure to quantify excitability and inhibition of primary motor cortex during a motor response inhibition task by using Transcranial Magnetic Stimulation throughout the course of a Stop Signal Task.

We describe the development of a reproducible, child-friendly motor response inhibition task suitable for online Transcranial Magnetic Stimulation (TMS) ...

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 ...

Bilateral Assessment of the Corticospinal Pathways of the Ankle Muscles Using Navigated Transcranial Magnetic Stimulation

Distal leg muscles receive neural input from motor cortical areas via the corticospinal tract, which is one of the main motor descending pathway in humans and can be assessed using transcranial magnetic stimulation (TMS). Given the role of distal leg muscles in upright postural and dynamic tasks, such as walking, a growing research interest in the assessment and modulation of the corticospinal tracts relative to the function of these muscles has emerged in the last decade. However, methodological parameters used in previous work have varied across studies making the interpretation of results from cross-sectional and longitudinal studies less robust. Therefore, use of a standardized TMS protocol specific to the assessment of leg muscles&#39; corticomotor response (CMR) will allow for direct comparison of results across studies and cohorts. The objective of this paper is to present a protocol that provides the flexibility to simultaneously assess the bilateral CMR of two main ankle antagonistic muscles, the tibialis anterior and soleus, using single pulse TMS with a neuronavigation system. The present protocol is applicable while the examined muscle is either fully relaxed or isometrically contracted at a defined percentage of maximum isometric voluntary contraction. Using each subject&#39;s structural MRI with the neuronavigation system ensures accurate and precise positioning of the coil over the leg cortical representations during assessment. Given the inconsistency in CMR derived measures, this protocol also describes a standardized calculation of these measures using automated algorithms. Though this protocol is not conducted during upright postural or dynamic tasks, it&#160;can be used to assess bilaterally any pair of leg muscles, either antagonistic or synergistic, in both neurologically intact and impaired subjects.

The present protocol describes the simultaneous, bilateral assessment of the corticomotor response of the tibialis anterior and soleus during rest and tonic voluntary activation using a single pulse transcranial magnetic stimulation and neuronavigation system.

Distal leg muscles receive neural input from motor cortical areas via the corticospinal tract, which is one of the main motor descending pathway in humans ...

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 ...

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.

Neuroimaging is typically perceived as a resource demanding discipline. While this is the case in certain circumstances, institutions with limited ...

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 ...