MC and JR are supported by the German Research Foundation (DFG RE 2740/3-1).

Ethics statement: Human studies require written informed consent of participants before study entry. Obtain approval by the relevant ethics committee before recruitment of participants. Make sure studies are in accordance with the Declaration of Helsinki. The representative findings reported here (Figure 4) are based on a study performed in accordance with the Declaration of Helsinki amended by the 59th WMA General Assembly, Seoul, October 2008 and approved by the local Ethics Committee of the University of Freiburg. All subjects gave written informed consent before study entry6.
1. Safety Screening
<ol>
	<li>Screen the participant for potential contraindications for noninvasive brain stimulation3, e.g., by using questionnaires25.</li>
</ol>
2. Motor Cortex Localization
<ol>
	<li>Locate the participant&#39;s hand motor cortex by one of two distinct approaches, by locating the brain representation of the muscle of interest by transcranial magnetic stimulation (TMS)-induced MEP, or by locating the standard M1 position (C3/C4) based on the EEG 10/20 international system with a measuring tape26.</li>
	<li>For TMS-induced MEP recording ask the participant to remove any object that may be influenced by TMS magnetic field, including credit cards, mobile phones and metal objects in general.</li>
	<li>Ask the participant to sit comfortably.</li>
	<li>Verify connections between EMG amplifier and the computer used for signal configuration and acquisition when using a software interface.</li>
	<li>Turn on the EMG amplifier and connect EMG electrode cables.</li>
	<li>Clean participant&#39;s skin by softly rubbing with skin preparation paste in the regions of the hand where the electrodes will be placed. Remove excess with clean gauze pad.</li>
	<li>Attach EMG surface electrodes in a belly-tendon montage on the hand muscle of interest (e.g., M. abductor pollicis brevis of the right hand) and connect a ground electrode (e.g., on forearm). The purpose of the study determines which hand muscle to use. 
	Note: For reusable electrodes it is necessary to apply a small amount of conductive paste on the electrode surface before attaching it to the participant&#39;s skin.</li>
	<li>(optional step) Start the recording software for MEP acquisition if MEP data storage is desired.</li>
	<li>Check the EMG impedance values. Ensure that the impedance is &#60; 20 kOhm.</li>
	<li>Turn on the magnetic stimulator and charge the capacitor by pressing the corresponding &#34;charge&#34; button.</li>
	<li>Place a figure-of-eight TMS coil on the participant scalp on the interhemispheric fissure and move it to the motor cortex area (around positions C3/C4 of the EEG 10/20 international system). Hold the TMS coil at a 45o-50o angle referenced to the interhemispheric fissure27,28, with the handle oriented backwards, producing a cortical current flow from posterior to anterior29. 
	Note: Two distinct TMS coils are used for motor cortex localization: figure-of-eight or circular coils. If possible, use a figure-of-eight coil as it provides more focal brain stimulation30 and greater reliability of measurements of cortical excitability31.</li>
	<li>When the magnetic stimulator is charged (visible on the display), discharge the stimulator either by pressing the trigger button or by stepping on the foot switch or automatically by a software program. This will subsequently deliver a single TMS pulse through the connected TMS coil placed over the participant&#39;s scalp. Default TMS pulse settings (e.g., 100 &#181;s rise time of the induced current and 800 &#181;s decay time for monophasic stimuli; shorter decay times for biphasic stimuli) are specific to the device (firmware).</li>
	<li>Start with low stimulation intensity (e.g., set the intensity to 45% output using the stimulation intensity controller knob on the stimulator) and watch for MEPs visible on the EMG amplifier.
	<ol>
		<li>If no MEP is visible increase the stimulation intensity in 2-5% steps until an MEP is clearly present (e.g., 0.5-1 mV amplitude). Repeat stimulation by pressing the trigger button or activating the foot switch if pulse delivery is not automated. Inform the participant that stimulation will be slightly stronger and that limb movements, facial twitch and eye-blinks are expected. 
		Note: Establish a minimum interval of 5 sec&#160;between pulses to avoid low-frequency stimulation effects on brain excitability.</li>
	</ol>
	</li>
	<li>Move the coil radially in 1 cm steps around the initially stimulated site to find the spot with the largest MEP response following the application of single TMS pulses. From there, start again moving the coil to secure the &#34;hotspot&#34; (cortical area with maximal MEP amplitude). 
	Note: The use of a head cap (e.g., used for grid markings) for the localization procedure is not recommended since the cap needs to be removed for NEBS electrode placement and the hotspot position may be lost.</li>
	<li>Reduce the stimulation intensity in approximately 2%-steps using the stimulation intensity controller knob on the stimulator (MEP must still be present). This will avoid inaccuracy due to supramaximal stimulation. Reconfirm the hotspot by moving the coil radially in 1 cm steps around the hotspot and checking for MEP size. The hotspot should still correspond to the largest and most consistent MEP amplitude. 
	Note: Ask the participant to voluntarily contract the muscle of interest if the hotspot is difficult to find (e.g., no MEP present at high stimulation intensities). By doing so, the stimulation intensity needed to elicit MEP is decreased and it may be easier to identify relevant cortical stimulation sites. If this method is used, ask the participant to relax the muscle after finding a relevant stimulation site and adjust stimulation intensity so that reliable MEPs can be found when the muscle is at rest. Proceed to find the hotspot.</li>
	<li>Mark the hotspot position and coil orientation with non-permanent skin marker.</li>
	<li>For bilateral M1 stimulation, repeat steps 2.11 to 2.16 for the contralateral limb.</li>
</ol>
3. NEBS Electrode Preparation
<ol>
	<li>Connect cables to rubber electrodes, and place the electrodes inside the sponge bags. Make sure electrode size and sponge bag size do match. Materials are commercially available in standard sizes (e.g., 5x5 cm2, 5x7 cm2).</li>
	<li>Soak sponge bags on both sides with isotonic NaCl solution, but avoid excessive soaking to prevent salt bridges or dripping onto the volunteer.
	<ol>
		<li>This step is optional: To prevent leakage of NaCl solution when using bandages instead of rubber bands, place the electrodes and sponge bags inside non-conductive rubber sponge covers. 
		Note: Alternatively, cover the rubber electrode with conductive paste and place them directly on the participant&#39;s head, i.e., not using sponge bags or rubber sponge covers.</li>
	</ol>
	</li>
</ol>
4. NEBS Electrode Placement (Figure 1)
<ol>
	<li>Find the head marking(s) indicating the motor cortical hotspot and separate the hair around the area.</li>
	<li>To improve conductance clean the skin before electrode placement by gently rubbing the skin area around the head markings with a swab soaked with 40-50% alcohol or skin preparation paste. Do not scratch the skin! Remove excess with a swab and clean area again with isotonic NaCl solution. Dry the area afterwards. 
	Note: Make sure the head marking(s) remain visible; remark if needed.</li>
	<li>Place one electrode following the head marking for the M1 of interest (contralateral to the hand of interest). Bring the sponge as much as possible in direct contact with the skin. Place the electrode cable towards the participant&#39;s back to avoid disturbance during stimulation and/or task execution and to ease connection to the NEBS device. 
	Note: The hair below the electrode should get damp. In case of excessive hair moistening, use paper or hand towels to absorb the excess. 
	Note: For anodal tDCS, the electrode placed on the motor cortical hotspot of interest (increase of excitability is desired) corresponds to the anode, usually connected to the red cable. The cathode (usually connected to a black or blue cable) is placed on the opposite supraorbital area or M1 (see below). Conventionally, electrode placement is the same for tRNS, although in the classical protocol there is no polarity specificity due to the alternating current flow. Specific placement may be important if the stimulation settings include a stimulation offset.</li>
	<li>For unilateral M1 stimulation place the second electrode (for anodal tDCS: the cathode) over the contralateral supra-orbital area (corresponding to electrode Fp2 in the EEG 10/20 international system). Make sure the cable is oriented towards the back of the participant.</li>
	<li>For bilateral M1 stimulation skip step 4.4. Place the second electrode (for anodal tDCS: the cathode) on the opposite M1 following the head marking ipsilateral to the limb used in the study. Make sure the cable is oriented towards the back of the participant.</li>
	<li>Cover the head twice with an elastic bandage circularly in the medio-lateral direction to stabilize the M1 electrode, then use the remaining bandage to cover the head circularly in the anterior-posterior direction to stabilize both electrodes.</li>
	<li>Use an adhesive tape to fix the end of the bandage.</li>
	<li>Secure the cables with an adhesive tape on the participant&#39;s neck or shirt.</li>
	<li>Connect electrode cables to the NEBS device.</li>
</ol>
<img alt="Figure 2" src="/files/ftp_upload/53367/53367fig2.jpg" /> 
Figure 2.&#160;Materials used for NEBS protocols. Conventional materials used in non-invasive electrical brain stimulation protocols include an NEBS device, electrode cables, conductive rubber electrodes, perforated sponge bags, rubber sponge cover (optional), isotonic NaCl solution and bandages. <a href="https://www.jove.com/files/ftp_upload/53367/53367fig2large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
5. Stimulation
<ol>
	<li>Switch on the NEBS device.</li>
	<li>Adjust NEBS device settings regarding stimulation type (tDCS or tRNS), intensity (e.g., 1 mA, 1.5 mA or 2 mA), duration (e.g., 10-40 min), ramping up and down (time between beginning of stimulation and maximum intensity, typically 8-15 sec), and additional factors related to stimulation type (e.g., frequency spectrum for tRNS). 
	Note: Conventionally, sham stimulation includes ramping up immediately followed by ramping down. Accordingly, the participant has the sensation of the stimulation but the duration of the stimulation is not sufficient to exert lasting effects on brain function. Some NEBS devices include a study mode which allows blinding of participant and investigator by entering a study specific subject code. The code determines stimulation settings automatically. Alternatively, a second experimenter may set the stimulation settings in each session and cover the display from the experimenter conducting the stimulation.</li>
	<li>Inform the participant about potential side effects associated with NEBS. Common adverse effects include skin itching/tingling or burning sensation underneath the electrodes, headache, and discomfort32. Burning sensation may be a sign of poor electrode contact with the skin.</li>
	<li>Start the stimulation. 
	Note: Common stimulation duration lasts approximately 10-20 min&#160;based on reports investigating changes on cortical excitability (see representative results section). Empirically, the maximum stimulation duration was set to 40 min3.</li>
	<li>Check for continuity of stimulation during ramping up and stimulation. If impedance is too high or electrodes are in bad contact with the skin, the stimulation may terminate automatically. 
	Note: In case the impedance is too high or the participant reports increasing discomfort during the stimulation try to decrease impedance by, e.g., better fixating the electrodes at the stimulation sites or adding conductive medium. NaCl solution may be added by using a syringe directly in the sponges after their placement on the head. 
	Note: For safety reasons some devices report the impedance throughout the stimulation. The NEBS device may shut off if impedance reaches a specific threshold (e.g., 55 kOhms).</li>
	<li>If NEBS is co-applied with execution of a motor task, start the testing/training after stimulation is ramped up and the participant is feeling comfortable with stimulation. In case the study does not include a motor task during stimulation, make sure the participant remains seated and awake during the stimulation period, and wait until stimulation is over.</li>
	<li>Check with the participant for side effects of the stimulation, e.g., by handing out a standardized questionnaire32 or directly asking the participant. In case of studies including multiple days of stimulation, take note of any possible side effects between days. 
	Note: For assessment of blinding efficacy, ask the participant after each stimulation session to guess which stimulation type (sham/condition) the participant underwent. If the experimenter is also blinded, the experimenter could also note his guess regarding the participant&#39;s stimulation type. Compare answers with the actual stimulation type to verify rate of correct guesses33.</li>
	<li>Disinfect electrodes and sponges with non-hazardous substances such as 40-50% alcohol. Thoroughly rinse in water afterwards. Let materials dry before storing.</li>
</ol>

The authors have nothing to disclose.

This protocol describes typical materials and procedural steps for modulation of hand motor function and skill learning using NEBS, specifically unilateral and bilateral M1 stimulation for anodal tDCS, and unilateral tRNS. Before choosing a particular NEBS protocol for a human motor system study, e.g., in the context of motor learning, methodological aspects (safety, tolerability, blinding) as well as conceptual aspects (montage or current type specific effects on a particular brain region) need to be taken into...

Non-invasive electrical brain stimulation (NEBS), the administration of electrical currents to the brain through the intact skull, can modify brain function and behavior1-3. To optimize the therapeutic potential of NEBS strategies understanding the underlying mechanisms leading to neurophysiological and behavioral effects is still needed. Standardization of application across different laboratories and full transparency of stimulation procedures provides the basis for comparability of data which supports reliable interpretation of results and evaluation of the proposed mechanisms of action. Transcranial direct current stimulation (tDCS) or transcranial alternating current stimulation (tACS) differ by parameters of the applied electrical current: tDCS consists of an unidirectional constant current flow between two electrodes (anode and cathode)2-6 while tACS uses an alternating current applied at a specific frequency7. Transcranial random noise stimulation (tRNS) is a special form of tACS that uses an alternating current applied at random frequencies (e.g., 100-640 Hz) resulting in quickly varying stimulation intensities and removing polarity-related effects4,6,7. Polarity is only of relevance if the stimulation setting includes a stimulation offset, e.g., noise spectrum randomly changing around a +1 mA baseline intensity (usually not used). For the purpose of this article, we will focus on work using tDCS and tRNS effects on the motor system, closely following a recent publication from our lab6.
The underlying mechanisms of action of tRNS are even less understood than of tDCS but likely different from the latter. Theoretically, in the conceptual framework of stochastic resonance tRNS introduces stimulation-induced noise to a neuronal system which may provide a signal processing benefit by altering the signal-to-noise ratio4,8,9. TRNS may predominantly amplify weaker signals and could thus optimize task-specific brain activity (endogenous noise9). Anodal tDCS increases cortical excitability indicated by alteration of the spontaneous neuronal firing rate10 or increased motor evoked potential (MEP) amplitudes2 with the effects outlasting the stimulation duration for minutes to hours. Long-lasting increases in synaptic efficacy known as long-term potentiation are thought to contribute to learning and memory. Indeed, anodal tDCS enhances synaptic efficacy of motor cortical synapses repeatedly activated by a weak synaptic input11. In accordance, improved motor function/skill acquisition is often revealed only if stimulation is co-applied with motor training11-13, also suggesting synaptic co-activation as a prerequisite of this activity-dependent process. Nevertheless, causality between increases in cortical excitability (increase in firing rate or MEP amplitude) on one hand and improved synaptic efficacy (LTP or behavioral function such as motor learning) on the other hand has not been demonstrated.
NEBS applied to the primary motor cortex (M1) has attracted increasing interest as safe and effective method to modulate human motor function1. Neurophysiological effects and behavioral outcome may depend on the stimulation strategy (e.g., tDCS polarity or tRNS), electrode size and montage4-6,14,15. Aside from subject-inherent anatomical and physiological factors the electrode montage significantly influences electric field distribution and may result in different patterns of current spreading within the cortex16-18. In addition to the intensity of the applied current the size of the electrodes determines the current density delivered3. Common electrode montages in human motor system studies include (Figure 1): 1) anodal tDCS as unilateral M1 stimulation with the anode positioned on the M1 of interest and the cathode positioned on the contralateral forehead; the basic idea of this approach is upregulation of excitability in the M1 of interest6,13,19-22; 2) anodal tDCS as bilateral M1 stimulation (also referred to as &#34;bihemispheric&#34; or &#34;dual&#34; stimulation) with the anode positioned on the M1 of interest and the cathode positioned on the contralateral M15,6,14,23,24; the basic idea of this approach is maximizing stimulation benefits by upregulation of excitability in the M1 of interest while downregulating excitability in the opposite M1 (i.e., modulation of interhemispheric inhibition between the two M1s); 3) For tRNS, only the above mentioned unilateral M1 stimulation montage has been investigated4,6; with this montage excitability enhancing effects of tRNS have been found for the frequency spectrum of 100-640 Hz4. The choice of brain stimulation strategy and electrode montage represents a critical step for an efficient and reliable use of NEBS in clinical or research settings. Here these three NEBS procedures are described in detail as used in human motor system studies and methodological and conceptual aspects are discussed. Materials for unilateral or bilateral tDCS and unilateral tRNS are the same (Figure 2).
<img alt="Figure 1" src="/files/ftp_upload/53367/53367fig1.jpg" /> 
Figure 1.&#160;Electrode montages and current direction for distinct NEBS strategies.&#160;(A) For unilateral anodal transcranial direct current stimulation (tDCS), the anode is centered over the primary motor cortex of interest and the cathode positioned over the contralateral supra-orbital area. (B) For bilateral motor cortex stimulation, anode and cathode are located each over one motor cortex. The position of the anode determines the motor cortex of interest for anodal tDCS. (C) For unilateral transcranial random noise stimulation (tRNS), one electrode is located over the motor cortex and the other electrode over the contralateral supra-orbital area. The current flow between electrodes is indicated by the black arrow. Anode (+, red), cathode (-, blue), Alternating current (+/-, green). <a href="https://www.jove.com/files/ftp_upload/53367/53367fig1large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>

<table><tbody><tr><td>NEBS device (DC Stimulator plus)</td><td>Neuroconn</td><td></td><td></td></tr><tr><td>Electrode cables</td><td>Neuroconn</td><td></td><td></td></tr><tr><td>Conductive-rubber electrodes</td><td>Neuroconn</td><td></td><td>5x5 cm</td></tr><tr><td>Perforated sponge bags</td><td>Neuroconn</td><td></td><td>5x5 cm</td></tr><tr><td>Non-conductive rubber sponge cover</td><td>Amrex-Zetron</td><td>FG-02-A103</td><td>Rubber pad 3&quot;*3&quot;</td></tr><tr><td>NaCl isotonic solution&amp;nbsp;</td><td>B. Braun Melsungen AG&amp;nbsp;</td><td>A1151</td><td>Ecoflac, 0,9%</td></tr><tr><td>Cotton crepe bandage</td><td>Paul Hartmann AG</td><td>931004</td><td>8x5m, textile elasticity</td></tr><tr><td>Adhesive tape (Leukofix)</td><td>BSN medical</td><td>02122-00</td><td>2,5cm*5m</td></tr><tr><td>Skin preparation paste</td><td>Weaver</td><td>10-30</td><td></td></tr><tr><td>Magnetic stimulator</td><td>Magstim</td><td>3010-00</td><td>Magstim 200</td></tr><tr><td>EMG conductive paste</td><td>GE Medical Systems</td><td>217083</td><td></td></tr><tr><td>EMG bipolar electrodes</td><td>e.g., Natus Medical Inc. Viking 4&amp;nbsp;</td><td></td><td></td></tr><tr><td>EMG amplifier</td><td>e.g., Natus Medical Inc. Viking 4&amp;nbsp;</td><td></td><td></td></tr><tr><td>Cable for EMG signal transmission</td><td>e.g., Natus Medical Inc. Viking 4</td><td></td><td></td></tr><tr><td>Data acquisition unit&amp;nbsp;</td><td>Cambridge Electronic Design (CED)</td><td>MK1401-3</td><td>AD converter</td></tr><tr><td>Computer for signal recording and offline analysis</td><td></td><td></td><td></td></tr><tr><td>Signal 4.0.9</td><td>Cambridge Electronic Design (CED)</td><td></td><td>Software</td></tr><tr><td>non-permanent skin marker</td><td>Edding</td><td>8020</td><td>1 mm, blue</td></tr></tbody></table>

non-invasive electrical brain stimulation montages for modulation of human motor function

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

To investigate the effects of NEBS on the human motor system it is important to consider appropriate outcome measures. One advantage of the motor system is the accessibility of the cortical representations by electrophysiological tools. Motor evoked potentials are frequently used as an indicator of motor cortical excitability. After application of 9 or more minutes of anodal tDCS at a current density of 29 &#181;A/cm2, motor cortical excitability is increased for at least 30 mi...

Watch this Scientific Journal Video about Non-Invasive Electrical Brain Stimulation Montages for Modulation of Human Motor Function at JoVE.com

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

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

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

non-invasive-electrical-brain-stimulation-montages-for-modulation

Research

JoVE Journal

Behavior

13.0K Views.  Albert Ludwigs University Freiburg. Non-invasive electrical brain stimulation can modulate cortical function and behavior, both for research and clinical purposes. This protocol describes different brain stimulation approaches for modulation of the human motor system.

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

Multifunctional Setup for Studying Human Motor Control Using Transcranial Magnetic Stimulation, Electromyography, Motion Capture, and Virtual Reality

The study of neuromuscular control of movement in humans is accomplished with numerous technologies. Non-invasive methods for investigating neuromuscular function include transcranial magnetic stimulation, electromyography, and three-dimensional motion capture. The advent of readily available and cost-effective virtual reality solutions has expanded the capabilities of researchers in recreating &#8220;real-world&#8221; environments and movements in a laboratory setting. Naturalistic movement analysis will not only garner a greater understanding of motor control in healthy individuals, but also permit the design of experiments and rehabilitation strategies that target specific motor impairments (e.g. stroke). The combined use of these tools will lead to increasingly deeper understanding of neural mechanisms of motor control. A key requirement when combining these data acquisition systems is fine temporal correspondence between the various data streams. This protocol describes a multifunctional system&#8217;s overall connectivity, intersystem signaling, and the temporal synchronization of recorded data. Synchronization of the component systems is primarily accomplished through the use of a customizable circuit, readily made with off the shelf components and minimal electronics assembly skills.

Transcranial magnetic stimulation, electromyography, and 3D motion capture are commonly used non-invasive techniques for investigating neuromuscular function in humans. In this paper, we describe a protocol that synchronously samples data generated by all three of these tools along with the unique addition of virtual reality stimulus presentation and feedback.

The study of neuromuscular control of movement in humans is accomplished with numerous technologies. Non-invasive methods for investigating neuromuscular ...

Utilizing Transcranial Magnetic Stimulation to Study the Human Neuromuscular System

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

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

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

Medicine

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 ...

Continuous Theta Burst Stimulation of the Posterior Medial Frontal Cortex to Experimentally Reduce Ideological Threat Responses

Decades of behavioral science research have documented functional shifts in attitudes and ideological adherence in response to various challenges, but little work to date has illuminated the neural mechanisms underlying these dynamics. This paper describes how continuous theta burst transcranial magnetic stimulation may be employed to experimentally assess the causal contribution of cortical regions to threat-related ideological shifts. In the example protocol provided here, participants are exposed to a threat prime-an explicit reminder of their own inevitable death and bodily decomposition-following a downregulation of the posterior medial frontal cortex (pMFC) or a sham stimulation. Next, disguised within a series of distracter tasks, participants' relative degree of ideological adherence is assessed-in the present example, with regard to coalitional prejudice and religious belief. Participants for whom the pMFC has been downregulated exhibit less coalitionally biased responses to an immigrant critical of the participants' national in-group, and less conviction in positive afterlife beliefs (i.e., God, angels, and heaven), despite having recently been reminded of death. These results complement prior findings that continuous theta burst stimulation of the pMFC influences social conformity and sharing and illustrate the feasibility of investigating the neural basis of high-level social cognitive shifts using transcranial magnetic stimulation.

Threats reliably evoke shifts in high-level ideological investment, but little work to date has explored the neural mechanisms underlying these dynamics. This paper describes how continuous theta burst transcranial magnetic stimulation may be employed to test the contribution of the posterior medial frontal cortex (and/or other regions) to threat-related ideological shifts.

Decades of behavioral science research have documented functional shifts in attitudes and ideological adherence in response to various challenges, but ...

Brain State-dependent Brain Stimulation with Real-time Electroencephalography-Triggered Transcranial Magnetic Stimulation

The effect of a stimulus to the brain depends not only on the parameters of the stimulus but also on the dynamics of brain activity at the time of the stimulation. The combination of electroencephalography (EEG) and transcranial magnetic stimulation (TMS) in a real-time brain state-dependent stimulation system allows the study of relations of dynamics of brain activity, cortical excitability, and plasticity induction. Here, we demonstrate a newly developed method to synchronize the timing of brain stimulation with the phase of ongoing EEG oscillations using a real-time data analysis system. This real-time EEG-triggered TMS of the human motor cortex, when TMS is synchronized with the surface EEG negative peak of the sensorimotor &#181;-alpha (8-14 Hz) rhythm, has shown differential corticospinal excitability and plasticity effects. The utilization of this method suggests that real-time information about the instantaneous brain state can be used for efficacious plasticity induction. Additionally, this approach enables personalized EEG-synchronized brain stimulation which may lead to the development of more effective therapeutic brain stimulation protocols.

This paper describes real-time electroencephalography-triggered transcranial magnetic stimulation to study and modulate human brain networks.

The effect of a stimulus to the brain depends not only on the parameters of the stimulus but also on the dynamics of brain activity at the time of the ...

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

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

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

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

Neuroscience

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 ...

The Combined Use of Transcranial Direct Current Stimulation and Robotic Therapy for the Upper Limb

Neurologic disorders such as stroke and cerebral palsy are leading causes of long-term disability and can lead to severe incapacity and restriction of daily activities due to lower and upper limb impairments. Intensive physical and occupational therapy are still considered main treatments, but new adjunct therapies to standard rehabilitation that may optimize functional outcomes are being studied.
Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that polarizes underlying brain regions through the application of weak direct currents through electrodes on the scalp, modulating cortical excitability. Increased interest in this technique can be attributed to its low cost, ease of use, and effects on human neural plasticity. Recent research has been performed to determine the clinical potential of tDCS in diverse conditions such as depression, Parkinson&#39;s disease, and motor rehabilitation after stroke. tDCS helps enhance brain plasticity and seems to be a promising technique in rehabilitation programs.
A number of robotic devices have been developed to assist in the rehabilitation of upper limb function after stroke. The rehabilitation of motor deficits is often a long process requiring multidisciplinary approaches for a patient to achieve maximum independence. These devices do not intend to replace manual rehabilitation therapy; instead, they were designed as an additional tool to rehabilitation programs, allowing immediate perception of results and tracking of improvements, thus helping patients to stay motivated.
Both tDSC and robot-assisted therapy are promising add-ons to stroke rehabilitation and target the modulation of brain plasticity, with several reports describing their use to be associated with conventional therapy and the improvement of therapeutic outcomes. However, more recently, some small clinical trials have been developed that describe the associated use of tDCS and robot-assisted therapy in stroke rehabilitation. In this article, we describe the combined methods used in our institute for improving motor performance after stroke.

The combined use of transcranial direct current stimulation and robotic therapy as an add-on for conventional rehabilitation therapy may result in improved therapeutic outcomes due to modulation of brain plasticity. In this article, we describe the combined methods used in our institute for improving motor performance after stroke.

Neurologic disorders such as stroke and cerebral palsy are leading causes of long-term disability and can lead to severe incapacity and restriction of ...

Non-Invasive Modulation and Robotic Mapping of Motor Cortex in the Developing Brain

Mapping the motor cortex with transcranial magnetic stimulation (TMS) has potential to interrogate motor cortex physiology and plasticity but carries unique challenges in children. Similarly, transcranial direct current stimulation (tDCS) can improve motor learning in adults but has only recently been applied to children. The use of tDCS and emerging techniques like high&#8211;definition tDCS (HD-tDCS) require special methodological considerations in the developing brain. Robotic TMS motor mapping may confer unique advantages for mapping, particularly in the developing brain. Here, we aim to provide a practical, standardized approach for two integrated methods capable of simultaneously exploring motor cortex modulation and motor maps in children. First, we describe a protocol for robotic TMS motor mapping. Individualized, MRI-navigated 12x12 grids centered on the motor cortex guide a robot to administer single-pulse TMS. Mean motor evoked potential (MEP) amplitudes per grid point are used to generate 3D motor maps of individual hand muscles with outcomes including map area, volume, and center of gravity. Tools to measure safety and tolerability of both methods are also included. Second, we describe the application of both tDCS and HD-tDCS to modulate the motor cortex and motor learning. An experimental training paradigm and sample results are described. These methods will advance the application of non-invasive brain stimulation in children.

We demonstrate protocols for the modulation (tDCS, HD-tDCS) and mapping (robotic TMS) of the motor cortex in children.

Mapping the motor cortex with transcranial magnetic stimulation (TMS) has potential to interrogate motor cortex physiology and plasticity but carries ...

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 ...