Effects of Transcranial Alternating Current Stimulation on the Primary Motor Cortex by Online Combined Approach with Transcranial Magnetic Stimulation
Summary
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.
Abstract
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.
Introduction
Transcranial Electrical Stimulation (tES) is a neuromodulatory technique which allows the modification of neuronal states through different current waveforms1. Among different types of tES, transcranial Alternating Current Stimulation (tACS) enables the delivery of sinusoidal external oscillatory potentials in a specific frequency range and the modulation of physiological neural activity underlying perceptual, motor and cognitive processes2. Using tACS, it is possible to investigate potential causal links between endogenous oscillatory activity and brain processes.
In vivo, it has been shown that spiking neural activity is synchronized at different driving frequencies, suggesting that neuronal firing can be entrained by electrically applied fields3. In animal models, weak sinusoidal tACS entrains the discharged frequency of the widespread cortical neuronal pool4. In humans, tACS combined with online Electroencephalography (EEG) allows the induction of the so-called "Entrainment" effect on endogenous oscillatory activity by interacting with brain oscillations in a frequency-specific manner5. However, combining tACS with neuroimaging methods for a better understanding of the online mechanisms is still questionable because of AC-induced artifacts6. In addition, it is not possible to directly record the EEG signal over the stimulated target area without using a ring-like electrode which is a questionable solution7. Thus, there is a lack of systematic studies on this topic.
So far, there is no clear evidence about the lasting effects of tACS after stimulation cessation. Only a few studies have shown weak and unclear after-effects of tACS on the motor system8. Moreover, EEG evidence is still not clear about the after-effects of tACS9. On the other hand, most tACS studies showed prominent online effects10,11,12,13,14,15,16,17,18, which are difficult to measure at a physiological level because of technical constraints. Thus, the overall goal of our method is to provide an alternative approach to test online and frequency-dependent effects of tACS on the motor cortex (M1) by delivering single pulse Transcranial Magnetic Stimulation (TMS). TMS allows researchers to "probe" the physiological state of the human motor cortex19. Moreover, by recording Motor Evoked Potentials (MEP) on the subject's contralateral hand, we can investigate the effects of the ongoing tACS11. This approach lets us accurately monitor changes in corticospinal excitability by measuring MEP amplitude during online electrical stimulation delivered at different frequencies in an artifact-free fashion. In addition, this approach can also test online effects of any other waveform of tES.
To demonstrate the combined tACS-TMS effects, we will show the protocol by applying 20 Hz AC stimulation over the primary motor cortex (M1) while online neuronavigated single pulse TMS is delivered interspersed by random intervals from 3 to 5 s in order to test M1 cortical excitability.
Protocol
Representative Results
Discussion
This approach represents a unique opportunity to directly test online effects of tACS of the primary motor cortex by measuring corticospinal output through MEPs recording. However, the placement of the TMS coil over the tACS electrode represents a critical step that should be accurately performed. Therefore, we would firstly suggest experimenters find a target point by single pulse TMS, then mark it on the scalp and, only after that, place the tACS electrode over the hotspot. Moreover, the availability of a neuronavigati…
Disclosures
The authors have nothing to disclose.
Acknowledgements
This study was supported by Russian Science Foundation grant (contract number: 17-11-01273). Special thanks to Andrey Afanasov and colleagues from Multifunctional Innovation Centre for Television Technics (National Research University, Higher School of Economics, Moscow, Russian Federation) for video recording and video editing.
Materials
| BrainStim, high-resolution transcranial stimulator | E.M.S., Bologna, Italy | EMS-BRAINSTIM | |
| Pair of 1,5m cables for connection of conductive silicone electrodes | E.M.S., Bologna, Italy | EMS-CVBS15 | |
| Reusable conductive silicone electrodes 50x50mm | E.M.S., Bologna, Italy | FIA-PG970/2 | |
| Reusable spontex sponge for electrode 50x100mm | E.M.S., Bologna, Italy | FIA-PG916S | |
| Rubber belts – 75 cm | E.M.S., Bologna, Italy | FIA-ER-PG905/8 | |
| Plastic non traumatic button | E.M.S., Bologna, Italy | FIA-PG905/99 | |
| Brainstim | E.M.S., Bologna, Italy | ||
| MagPro X100 MagOption – transcranial magnetic stimulator | MagVenture, Farum, Denmark | 9016E0731 | |
| 8-shaped coil MC-B65-HO-2 | MagVenture, Farum, Denmark | 9016E0462 | |
| Chair with neckrest | MagVenture, Farum, Denmark | 9016B0081 | |
| Localite TMS Navigator – Navigation platform, Premium edition | Localite, GmbH, Germany | 21223 | |
| Localite TMS Navigator – MR-based software, import data for morphological MRI (DICOM, NifTi) | Localite, GmbH, Germany | 10226 | |
| MagVenture 24.8 coil tracker, Geom 1 | Localite, GmbH, Germany | 5221 | |
| Electrode wires for surface EMG | EBNeuro, Italy | 6515 | |
| Surface Electrodes for EEG/EMG | EBNeuro, Italy | 6515 | |
| BrainAmp ExG amplifier – bipolar amplifier | Brain Products, GmbH, Germany | ||
| BrainVision Recorder 1.21.0004 | Brain Products, GmbH, Germany | ||
| Nuprep Skin Prep Gel | Weaver and Company, USA | ||
| Syringes | |||
| Sticky tape | |||
| NaCl solution |
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