This work was funded in part by NIMH R01 MH112815. This work was also supported by the Temerty Family Foundation, Grant Family Foundation and Campbell Family Mental Health Research Institute at the Centre for Addiction and Mental Health.

All the experimental procedures presented here have been approved by our Local Ethical Committee following guidelines of the Declaration of Helsinki.
1. Head Registration for Neuronavigated TMS &#8212; EEG
<ol>
	<li>Obtain a high resolution whole head T1-weighted structural MRI for each participant. Scan according to the neuronavigation manufacturer guidelines.</li>
	<li>Upload the images on the navigation system. Check if MRIs are correctly scanned. Choose the cardinal points (pre-auricular points, the nasion and the tip of the nose). Insert the stimulation targets (based on anatomy or based on the head coordinates, MNI, or Talairach coordinates).</li>
	<li>Place the head tracker in such a way so that it will not move during the stimulation session and allow free moving of the TMS coil. Have the participant insert the earplugs before the registration starts.</li>
	<li>Align the participant&#39;s head to the 3-D MRI model. Touch on the participant&#39;s head with the digitizing pen at the cardinal points that were selected on the images of the MRI stack. Select and mark additional points over the parietal, temporal and occipital areas of the head to reduce the registration error over those areas.</li>
	<li>Validate the registration. Place the digitizing pen on the participant&#39;s head. Check its representation on the computer. If it is not on the corresponding point in the MR, repeat step 1.4.</li>
	<li>Calibrate the TMS coil in use (in some systems this step is not needed).
	<ol>
		<li>Attach the trackers to the coil.</li>
		<li>Place the coil on the calibration block so all trackers are visible from the camera.</li>
		<li>Press the calibration button on the computer screen and keep the coil in the calibration position for 5 s.</li>
	</ol>
	</li>
</ol>
2. TMS-EEG Experiment
<ol>
	<li>Place the EEG cap on the head and prepare the electrodes
	<ol>
		<li>Choose a cap that fits the head well. Ensure that all electrodes are tightly touching the scalp and are functional. If more than 2 electrodes do not work, then use another cap of the same or smaller size.</li>
		<li>Place the Cz electrode at vertex, half way between the line connecting the nasion and inion and the Iz electrode over the inion. 
		&#8203;NOTE: Place the vertical (above and under the eye contralateral to the stimulation eye) and/or horizontal electrodes (left from the left eye and right from the right, a little above each zygomatic bone) for electrooculography (EOG).</li>
		<li>Adjust the blunt tip of the syringe and fill it with electroconductive gel. Place the tip inside the hole of the electrode, and then lightly press the plunger flange until there is some paste on the skin. Scrub the scalp lightly using cross-like moves with the blunt tip. Ensure that the paste is not spilling out over the top to avoid bridging (short-circuit between the electrodes).</li>
	</ol>
	</li>
	<li>Place the EMG electrodes. Place two disposable disc electrodes (diameter of about 30 mm) over the right abductor pollicis brevis muscle (APB) for a belly tendon montage. Place the ground according to the manufacturer&#39;s guidelines.</li>
	<li>Start the head registration. Follow steps 1.3&#8211;1.6. Use the MNI or Talairach coordinates of the DLPFC.</li>
	<li>Hot spot and motor threshold.
	<ol>
		<li>Add a sponge (artificial fiber made from polyutherane) under the coil in order to minimize the coil vibration over the electrodes during the TMS pulses. Note that the foam should be about 10 mm thick.</li>
		<li>Instruct the participant to be at rest &#8212; comfortable and with relaxed hands, legs and spinal column.</li>
		<li>Find the hot spot. Target the motor knob24 as the initial landmark of cortical representation of APB in M1 and move the coil until there is corresponding APB movement. Use TMS intensities evoking MEPs of around 500 &#181;V over APB. Optimize the coil orientation by changing its angle and tilt to evoke the biggest response over the hot spot.</li>
		<li>Save the coil positioning in the neuronavigator software and reduce the output intensity in steps of 2&#8211;3%. Give 10 pulses and if more than 5 out of 10 MEP responses over 50 &#181;V are obtained, then continue reducing the intensity.</li>
		<li>When less than 5 out of 10 responses are evoked, increase the intensity by steps of 1&#8211;2%. MT is represented as the intensity that produces MEPs larger than 50 &#181;V 5 out of 10 times25. The inter-stimulus interval (ISI) for MT should be longer than 1 s, usually set at 3, 4 or 5 s.</li>
	</ol>
	</li>
	<li>Adjust the intensity using the following steps:
	<ol>
		<li>Start at 120% of MT intensity to produce MEPs over M1 from 500 to 1,500 &#181;V. Record 10 pulses with this stimulator&#39;s output so the average response is 1 mV. Increase or decrease the intensity in steps of 1&#8211;2% until reaching an average of 1 mV.</li>
		<li>For stimulation intensity, choose the intensity as a percentage of stimulator&#39;s output, e.g., 110%, 120%, etc.</li>
		<li>Find the corresponding induced field in V/m (if the system allows). Place the coil over DLPFC; adjust the stimulator&#39;s output until the calculation of the induced field becomes the same as the one over M1 for the same cortical depth.</li>
	</ol>
	</li>
	<li>Digitize the EEG electrodes, so that their position is registered to the brain anatomy. 
	NOTE: This is a very important step for locating the distribution of neuronal activation and for accurate repositioning of the electrodes in the follow-up session.</li>
	<li>Record the TMS-EEG
	<ol>
		<li>Replace the earplugs with the earplugs with air tubes to connect to audio masking (e.g., white noise) if available and add headphones over them. Play the audio masking only during TMS pulse delivery. 
		NOTE: This step can be applied to step 2.4.2 without playing the audio masking and with care so the head trackers are not moved.</li>
		<li>Mount the coil on the coil holder and make sure that the coil does not move or press the electrodes under it. Make sure that the sponge is between the electrodes and the coil.</li>
		<li>Remove all active screens out of the sight of the participant. Give instructions to the participant to stare on a fixed point, not to change his/her head position during TMS delivery and not to blink between the TMS pulses.</li>
		<li>Switch off any fluorescent lights. Run single pulse TMS, SICI, ICF and LICI in a random order for each participant. Give 100 single and paired pulses. Use various ISI&#39;s of 3&#8211;4 s (&#177;20%) or a constant of 3&#8211;5 s (see Note). Give a break of 3&#8211;5 min between each condition so the participant can relax and stretch. 
		NOTE: SICI and ICF involve a paired-pulse TMS paradigm with a subthreshold conditioning stimulus (CS) and a suprathreshold test stimulus (TS). The CS used in this protocol is 80% of MT and the TS at the intensity evoking a 1 mV MEP peak-to-peak26. The inter-pulse interval used for optimal SICI is at 2 ms and for ICF at 12&#8211;1327. The LICI paradigm involves the pairing of a supra-threshold CS at the intensity evoking the 1 mV MEP peak-to-peak followed by another suprathreshold TS again using the intensity that evoked a 1 mV MEP peak-to-peak and at an inter-pulse interval of 100 ms. The ISI for both single and paired pulse paradigms is determined by the stimulator&#39;s charging time (our system can allow paired pulses every 4 s), the amount of sessions (longer experiments would require smaller ISI to not overburden the participants) and the analysis that is going to take place. In this study, we used a constant ISI of 5 s due to our stimulator&#39;s restrictions and also because we would need several cycles of low frequency band (theta rhythm) for the time-frequency and power spectrum analysis.</li>
	</ol>
	</li>
</ol>

Pantelis Lioumis has been a paid consultant for Nexstim Plc. (Helsinki, Finland) outside the submitted work (i.e., for the motor and speech mapping rTMS applications before 2017). Reza Zomorrodi is a member of the advisory board of Vielight Inc. (Toronto, Canada). Zafiris J. Daskalakis receives research support from the Canadian Institutes of Health Research (CIHR), National Institutes of Health - US (NIH), Weston Brain Institute, Brain Canada and the Temerty Family through the CAMH Foundation and the Campbell Research Institute. He received research support and in-kind equipment support for an investigator-initiated study from Brainsway Ltd. and he is the site principal investigator for three sponsor-initiated studies for Brainsway Ltd. He received in-kind equipment support from Magventure for this investigator-initiated study. Daniel M. Blumberger receives research support from the Canadian Institutes of Health Research (CIHR), National Institutes of Health - US (NIH), Weston Brain Institute, Brain Canada and the Temerty Family through the CAMH Foundation and the Campbell Research Institute. He received research support and in-kind equipment support for an investigator-initiated study from Brainsway Ltd. and he is the site principal investigator for three sponsor-initiated studies for Brainsway Ltd. He received in-kind equipment support from Magventure for this investigator-initiated study. He received medication supplies for an investigator-initiated trial from Indivior. He has participated in an advisory board for Janssen.

TMS-EEG enables the direct and noninvasive stimulation of most cortical areas and the acquisition of the resulting neuronal activity with very good spatio-temporal resolution30, especially when neuronavigation is utilized. The benefit of this methodological advance is based on the fact that TMS-evoked EEG signals originate from the electrical neural activity and it is an index of cortico-cortical excitability. This has tremendous potential in neuropsychiatric patient populations where TMS-EEG can ...

Transcranial magnetic stimulation (TMS) is a neurophysiological tool that allows for the non-invasive assessment of cortical neuronal activity through the use of rapid, time-varying magnetic field pulses1. These magnetic field pulses induce a weak current in the superficial cortex beneath the coil which results in membrane depolarization. The ensuing cortical activation or modulation is directly related to the characteristics of the coil, its angle and orientation to the skull2. The waveform of the pulse discharged from the coil and the underlying state of the neurons also influence the resultant cortical activation3.
TMS enables the assessment of cortical functions by evoking behavioral or motor responses or through the interruption of task-related processing. The excitability of cortico-spinal processes can be evaluated through recording electromyographic (EMG) responses elicited from single TMS pulses over the motor cortex, whereas intracortical excitatory (intracortical facilitation; ICF) and inhibitory mechanisms (short and long intracortical inhibition; SICI and LICI) can be probed with paired-pulse TMS. Repetitive TMS can disturb various cognitive processes, but is primarily used as a therapeutic tool for a variety of neuropsychiatric disorders. Furthermore, the combination of TMS with simultaneous electroencephalography (TMS-EEG) can be used to assess cortico-cortical excitability and connectivity4. Finally, if the administration of TMS is delivered with neuronavigation (nTMS), it will allow for precise test-retest paradigms since the exact site of the stimulation can be recorded. Most of the cortical mantle can be targeted and stimulated (including those areas that do not produce measurable physical or behavioral responses) thus the cortex can be functionally mapped.
The EEG signal evoked from single or paired pulse TMS can facilitate the assessment of cortico-cortical connectivity5 and the current state of the brain. The TMS-induced electric current results in action potentials that can activate synapses. The distribution of the postsynaptic currents can be recorded through EEG6. The EEG signal can be used to quantify and locate synaptic current distributions through dipole modelling7 or minimum-norm estimation8, when multichannel EEG is employed, and with the conductivity structure of the head accounted for. Combined TMS-EEG can be employed to study cortical inhibitory processes9, oscillations10, cortico-cortical11 and interhemispheric interactions12, and cortical plasticity13. Most importantly, TMS-EEG can probe excitability changes during cognitive or motor tasks with good test-retest reliability14,15. Importantly, TMS-EEG has the potential to determine neurophysiological signals that may serve as the predictors of response to therapeutic interventions (rTMS or pharmacological effects) in test-retest designs16,17.
The principles of neuronavigation for TMS is based on the principles of frameless stereotaxy. The systems use an optical tracking system18 that employs a light-emitting camera that communicates with light-reflecting optical elements attached to both the head (via a reference tracker) and the TMS coil. Neuronavigation allows for coil localization on the 3-D MRI model with the aid of a digitizing reference tool or pen. The use of neuronavigation facilitates the capture of the coil orientation, location and alignment to the subject&#39;s head as well as the digitization of the EEG electrode positions. These features are essential for test-retest design experiments and for accurate stimulation of a specified location within dorsolateral prefrontal cortex.
In order to utilize a TMS-EEG protocol in a test-retest experiment, there needs to be accurate targeting and consistent stimulation of the cortical region to obtain reliable signals. TMS-EEG recording can be vulnerable to different artifacts. The TMS induced artifact on the EEG electrodes can be filtered with amplifiers that can recover after a delay19,20 or with amplifiers that cannot be saturated21. However, other types of artifact generated by eye movements or blinks, cranial muscle activation in proximity to the EEG electrodes, random electrode movement and their polarization, and by the coil click or somatic sensation must be taken into consideration. Careful subject preparation that ensures electrode impedances below 5 k&#937;, immobilization of the coil over the electrodes and a foam between coil and electrodes to reduce vibration (or a spacer to eliminate low frequency artifacts22), earplugs and even auditory masking should be used to minimize these artifacts23. The protocol presented here introduces a standard process for assessing neurophysiological functioning when the stimulation is applied over the dorsolateral prefrontal (DLPFC). The focus is on common paired-pulse paradigms that have been validated in the studies of M19,15,16.

<table><tbody><tr><td>CED Micro1401-3</td><td>Cambridge Electronic Design Limited</td><td>CED Micro1401-3</td><td>Digital Data Recocrder</td></tr><tr><td>BISTIM&#039;2 Package Option 1</td><td>Magstim</td><td>3234-00</td><td>TMS paired pulse stimulator</td></tr><tr><td>Magstim 200&#039;2 Unit (2 items)</td><td>Magstim</td><td>3010-00</td><td>TMS stimulators</td></tr><tr><td>UI controller</td><td>Magstim</td><td>3020-00</td><td>TMS controller</td></tr><tr><td>BISTIM&#039;2 UI controller</td><td>Magstim</td><td>3021-00</td><td>TMS controller</td></tr><tr><td>BISTIM connecting module</td><td>Magstim</td><td>3330-00</td><td>TMS connecting module</td></tr><tr><td>D70 Alpha Coil - P/N 4150-00 (Alpha 70 mm double coil)</td><td>Magstim</td><td>4150-00</td><td>TMS coil</td></tr><tr><td>Brainsight</td><td>Rogue-Resolutions</td><td>Brainsight 2</td><td>Neuronavigator</td></tr><tr><td>Model 2024F</td><td>Intronix</td><td>2024F</td><td>Electromyograph</td></tr><tr><td>Neuroscan SynAmps RT 64 channel System</td><td>Compumedics Neuroscan</td><td>9032-0010-01</td><td>Electroencephalograph</td></tr><tr><td>Quick-Cap electrode system 64</td><td>Compumedics Neuroscan</td><td>96050255</td><td>EEG Cap</td></tr></tbody></table>

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).

Figure 1A illustrates the TMSevoked potentials after DLPFC stimulation over the F3 electrode after averaging 100 epochs from each session for one healthy volunteer. In this illustration, we highlight the effect of the CS on the TS in comparison to the single pulse condition when TS is applied alone. The CS modulates the N100 deflection in a clear manner even in one subject. In the SICI and LICI sessions, N100 is usually increased and in ICF d...

Watch this Scientific Journal Video about Combined Transcranial Magnetic Stimulation and Electroencephalography of the Dorsolateral Prefrontal Cortex at JoVE.com

Combined Transcranial Magnetic Stimulation and Electroencephalography of the Dorsolateral Prefrontal Cortex

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 ...

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11.7K Views.  Temerty Centre for Therapeutic Brain Intervention at the Centre for Addiction and Mental Health. Het protocol hier gepresenteerd is voor TMS-EEG studies met behulp van intracortical prikkelbaarheid test-hertest ontwerp paradigma's. De bedoeling van het protocol is voor de productie van betrouwbare en reproduceerbare corticale prikkelbaarheid maatregelen voor de beoordeling van neurofysiologische werking verband houden met therapeutische interventies bij de behandeling van neuropsychiatrische ziekten zoals depressie.

Video: Combined Transcranial Magnetic Stimulation and Electroencephalography of the Dorsolateral Prefrontal Cortex

Simultaneous EEG Monitoring During Transcranial Direct Current Stimulation

Transcranial direct current stimulation (tDCS) is a technique that delivers weak electric currents through the scalp. This constant electric current induces shifts in neuronal membrane excitability, resulting in secondary changes in cortical activity. Although tDCS has most of its neuromodulatory effects on the underlying cortex, tDCS effects can also be observed in distant neural networks. Therefore, concomitant EEG monitoring of the effects of tDCS can provide valuable information on the mechanisms of tDCS. In addition, EEG findings can be an important surrogate marker for the effects of tDCS and thus can be used to optimize its parameters. This combined EEG-tDCS system can also be used for preventive treatment of neurological conditions characterized by abnormal peaks of cortical excitability, such as seizures. Such a system would be the basis of a non-invasive closed-loop device. In this article, we present a novel device that is capable of utilizing tDCS and EEG simultaneously. For that, we describe in a step-by-step fashion the main procedures of the application of this device using schematic figures, tables and video demonstrations. Additionally, we provide a literature review on clinical uses of tDCS and its cortical effects measured by EEG techniques.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has shown initial therapeutic effects in several neurological conditions. The main mechanism underlying these therapeutic effects is the modulation of cortical excitability. Therefore, online monitoring of cortical excitability would help guide stimulation parameters and optimize its therapeutic effects. In the present article we review the use of a novel device that combines simultaneous tDCS and EEG monitoring in real time.

Transcranial  direct current stimulation (tDCS) is a technique that delivers weak electric  currents through the scalp. This constant electric current ...

Behavior

Transcranial Direct Current Stimulation and Simultaneous  Functional Magnetic Resonance Imaging

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses weak electrical currents administered to the scalp to manipulate cortical excitability and, consequently, behavior and brain function. In the last decade, numerous studies have addressed short-term and long-term effects of tDCS on different measures of behavioral performance during motor and cognitive tasks, both in healthy individuals and in a number of different patient populations. So far, however, little is known about the neural underpinnings of tDCS-action in humans with regard to large-scale brain networks. This issue can be addressed by combining tDCS with functional brain imaging techniques like functional magnetic resonance imaging (fMRI) or electroencephalography (EEG).
In particular, fMRI is the most widely used brain imaging technique to investigate the neural mechanisms underlying cognition and motor functions. Application of tDCS during fMRI allows analysis of the neural mechanisms underlying behavioral tDCS effects with high spatial resolution across the entire brain. Recent studies using this technique identified stimulation induced changes in task-related functional brain activity at the stimulation site&#160;and also in more distant brain regions, which were associated with behavioral improvement. In addition, tDCS administered during resting-state fMRI allowed identification of widespread changes in whole brain functional connectivity.
Future studies using this combined protocol should yield new insights into the mechanisms of tDCS action in health and disease and new options for more targeted application of tDCS in research and clinical settings. The present manuscript describes this novel technique in a step-by-step fashion, with a focus on technical aspects of tDCS administered during fMRI.

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique. It has successfully been used in basic research and clinical settings to modulate brain function in humans. This article describes the implementation of tDCS and simultaneous functional magnetic resonance imaging (fMRI), to investigate the neural basis of tDCS effects.

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses weak electrical currents administered to the scalp ...

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

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

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

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

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 ...

Extracting Visual Evoked Potentials from EEG Data Recorded During fMRI-guided Transcranial Magnetic Stimulation

Transcranial Magnetic Stimulation (TMS) is an effective method for establishing a causal link between a cortical area and cognitive/neurophysiological effects. Specifically, by creating a transient interference with the normal activity of a target region and measuring changes in an electrophysiological signal, we can establish a causal link between the stimulated brain area or network and the electrophysiological signal that we record. If target brain areas are functionally defined with prior fMRI scan, TMS could be used to link the fMRI activations with evoked potentials recorded. However, conducting such experiments presents significant technical challenges given the high amplitude artifacts introduced into the EEG signal by the magnetic pulse, and the difficulty to successfully target areas that were functionally defined by fMRI. Here we describe a methodology for combining these three common tools: TMS, EEG, and fMRI. We explain how to guide the stimulator&#39;s coil to the desired target area using anatomical or functional MRI data, how to record EEG during concurrent TMS, how to design an ERP study suitable for EEG-TMS combination and how to extract reliable ERP from the recorded data. We will provide representative results from a previously published study, in which fMRI-guided TMS was used concurrently with EEG to show that the face-selective N1 and the body-selective N1 component of the ERP are associated with distinct neural networks in extrastriate cortex. This method allows us to combine the high spatial resolution of fMRI with the high temporal resolution of TMS and EEG and therefore obtain a comprehensive understanding of the neural basis of various cognitive processes.

This paper describes a method for collecting and analyzing electroencephalography (EEG) data during concurrent transcranial magnetic stimulation (TMS) guided by activations revealed with functional magnetic resonance imaging (fMRI). A method for TMS artifact removal and extraction of event related potentials is described as well as considerations in paradigm design and experimental setup.

Transcranial Magnetic Stimulation (TMS) is an effective method for establishing a causal link between a cortical area and cognitive/neurophysiological ...

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 ...

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 ...

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 ...

Combined Transcranial Magnetic Stimulation and Electroencephalography of the Dorsolateral Prefrontal Cortex

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