Name: combined transcranial magnetic stimulation and electroencephalography of the dorsolateral prefrontal cortex
Uploaded: 2018-08-17T13:30:00
Description: Watch this Scientific Journal Video about Combined Transcranial Magnetic Stimulation and Electroencephalography of the Dorsolateral Prefrontal Cortex at JoVE.com

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
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	<li>Obtain a high resolution whole head T1-weighted structural MRI for each participant. Scan according to the neuronavigation manufacturer guidelines.</li>
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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.

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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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