Published: June 17th, 2013
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 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 technique that uses weak and direct electric currents delivered continuously through the scalp to induce changes in cortical excitability 1, 2. Using motor evoked potentials as a marker of motor cortex excitability, Nitsche and Paulus3 demonstrated that the direction of the tDCS effects over the brain is polarity-specific: cathodal stimulation induces a decrease in cortical excitability, whereas anodal stimulation induces an increase in cortical excitability. This effect on cortical excitability can last for over an hour following stimulation. These tDCS-induced changes in cortical excitability can result in significant behavioral effects. One important issue is the variability of tDCS effects on behavior. There are several reasons to explain this variability. Studies on fMRI 4 and electroencephalography (EEG) 5,6 reveal that although tDCS has the most activating effect on the underlying cortex, the stimulation evokes widespread changes in other regions of the brain. In addition, it has been shown that tDCS effects depend on the state of baseline cortical activity 7. Therefore, given these sources of variability, the use of better surrogates to measure the effects of tDCS is desirable.
In this context, we propose the use of concomitant EEG monitoring to provide real-time data on the impact of tDCS on cortical excitability for several reasons. First, to optimize the stimulation parameters of tDCS. Second, to provide insights into new targets for therapies. Third, to assure safety during brain stimulation, especially in children. Fourth, to aid in the early detection and treatment of seizures in patients with intractable epilepsy i.e. closed-loop system. Finally, this device might also have a potential application in brain-computer interface systems.
Due to the critical role of monitoring cortical excitability changes related to non-invasive brain stimulation, the purpose of this article is to demonstrate how to combine the use of tDCS with EEG by means of a novel device (StarstimÒ - Neuroelectrics Instrument Controller, v 1.0; Rev 2012-08-01, Neurolelectrics, Barcelona, Spain). It should be noted that this article does not provide details of tDCS application. For a complete understanding of the application of this technique we recommend reading the article on tDCS from DaSilva et al. 11
2. Skin Preparation
3. Head Measurements
4. Electrodes Positioning in the Cap
5. Wearing the Cap and Fixing the Control Box on it
6. Stimulation and Recording Set Up
7. Start the Device
8. Record EEG Data
tDCS is currently being investigated as a therapeutic instrument for varied neurological conditions, which includes major depression 14, 15, post-traumatic stress disorder 16, craving for food 17, marijuana 18, alcohol 19 and smoking 20, as well as pain 21, tinnitus 22, migraine 23, epilepsy 24, Parkinson's disease 25, 26, stroke rehabilitation 27, 28 and cognitive dysfunction 6, 29. Table 1 shows the evidence-based tDCS electrode montages to be used as treatment for different clinical conditions.
In most cases, clinical improvement after tDCS is mainly attributed to its cortical effects. There are several ways to quantify cortical changes and the most frequently used ones are functional magnetic resonance imaging (fMRI), TMS-indexed cortical excitability and the electroencephalography (EEG). In comparison with fMRI, EEG has poorer spatial resolution, but superior temporal resolution 30, reflecting timing of neuronal activity more accurately. In addition, as compared with TMS-indexed cortical excitability, EEG provides a greater spatial resolution. For instance, using the tDCS/EEG device, it is possible to detect ongoing changes on the raw EEG in response to tDCS. Figure 9 shows the attenuation of cortical activity, mainly on the parietal region, after the tDCS was turned on (channels C3 and C4). Note that during stimulation it is not possible to record brain activity in the same channels used for stimulation.
The effects of tDCS on EEG have been recently studied by several authors (see Table 3), but only one has applied tDCS and EEG concomitantly 31. Most of the studies showed significant EEG changes upon tDCS by analyzing the EEG power spectrum in response to active versus sham-tDCS. Using power spectrum analysis, EEG signals can be decomposed into a sum of pure frequency components using FFT analysis. In this way, the signals can be analyzed in terms of its power spectrum, which provides information on the signal's power at each frequency (Table 2).
Figure 7 shows a representative example of an ongoing EEG activity during tDCS (red bracket on the bottom) and after FFT analysis (red circle). The first peak activity corresponds to theta (5-7 Hz) and the second to alpha (8-10 Hz) band frequencies. The amplitude of EEG peaks is measured in μV2.
Another example comes from the study by Maeoka et al. 36, in which the authors found a local decrease in alpha and an increase in beta band amplitudes after anodal stimulation of the dorsolateral prefrontal cortex combined with emotional stress.
Figure 10 shows an illustrative example of the effects of tDCS on quantitative EEG (power spectrum). The size of frontal alpha amplitude was significantly higher in response to active-tDCS when compared to sham-tDCS of the left dorsolateral prefrontal cortex.
Therefore, using the automatic FFT analysis (Figure 7) the investigator is able to determine and measure the amplitude of the predominant EEG frequency activities (delta, theta, alpha, beta, gamma) during and after tDCS. Depending on the region of stimulation and other experimental conditions, the amplitude of specific EEG frequency bands is expected to change after tDCS (Table 3). Indeed, adding the FFT analysis function to the EEG recording during tDCS offers a unique opportunity to understand the cortical neuromodulatory effects in real time.
Finally, EEG signals can be analyzed with a technique called a time-frequency based, or spectrogram image. This technique has been considered promising for research purposes; however, this type of EEG analysis is still not fully validated for diagnostic intentions and should be interpreted with caution for this purpose 8.
Figure 8 shows an illustrative example of an EEG spectrogram processed by the same device.
Figure 1. List of required materials for simultaneous EEG monitoring during tDCS: neoprene cap, Control Box, cables, electrodes, measurement tape, saline solution and Bluetooth USB.
Figure 2. Localization of vertex (Cz) on the scalp 11: Measure the distance of nasion to inion and mark halfway using a skin marker.
Figure 3. Stimulation Screenshot: a) Electrical stimulation mode (tDCS, tACS, tRNS, sham); b) Total duration of electrical stimulation; c) Electrode positioning according to channels; d) tDCS and EEG channel configuration; e) tDCS ramping duration; f) EEG recording durations.
Figure 4. Mount Screenshot: Check electrodes impedance before stimulation begins.
Figure 5. Launch Screenshot: a) LAUNCH button; b) Vertical gray bar before tDCS; c) Vertical gray bar during tDCS; d) Vertical gray bar after tDCS; e) Impedance re-checking; f) ABORT button.
Figure 6. EEG Time domain: check the baseline ongoing EEG activity and select EEG band frequencies if needed (yellow arrow at the right bottom).
Figure 7. EEG power spectrum: check the predominant EEG frequency band (red circle) after automatic Fast Fourier Transform (FFT) analysis over the raw ongoing EEG activity (red rectangle on the bottom).
Figure 8. EEG spectrogram: EEG signals (red rectangle on the bottom) can also be transformed into images (red circle) using a technique called time-frequency based.
Figure 9. Attenuation of parietal EEG activity in response to anodal tDCS (Anode = C3; Cathode = C4). Note that during stimulation it not possible to record brain activity in the same channels used for stimulation. Click here to view larger figure.
Figure 10. tDCS effects on EEG power spectrum: Note differences in frontal alpha (a) and beta (b) amplitude in response to active-tDCS when compared to sham-tDCS over the left dorsolateral prefrontal cortex.
|Anode electrode positioning
|Cathode electrode positioning
|Boggio et al., 2008; Loo et al., 2012
|Fregni et al., 2006
|Lindenberg et al., 2010
|Boggio et al., 2007
|M1 (affected side)
|MI (non-affected side)
|Fregni et al., 2006
|Benninger et al., 2010
|Fregni et al., 2006
|Antal et al., 2011
|Boggio et al., 2008
|R/L - DLPFC
|L/R - DLPFC
Table 1. tDCS electrode montages in different clinical conditions. Legends: LTA, left temporoparietal area; V1, Visual cortex; DLPFC, Dorsolateral prefrontal cortex; M1, Motor cortex, R, Right; L, Left.
|Best recording site
|More prominent during…
|Frontal (adults), Posterior (children)
|Deep stages of sleep (3 and 4)
|Diffuse in the scalp
|Awakens, with eyes closed
|Mental effort, deep sleep
|Short term memory tasks and tactile stimulation
Table 2. EEG frequency bands.
|Anode electrode positioning
|Cathode electrode positioning
|EEG Channels (number)
|Ardolino et al., 2005
|Bilateral increase of frontal delta and theta bands.
|Keeser et al., 2011
|Decrease in frontal and prefrontal delta band.
|Marshall et al., 2011
|- Non-REM sleep: frontal decrease of delta band.
- REM sleep: global increase of gamma band.
|Wirth et al., 2011
|Global decrease in delta band.
|Zaehle et al., 2011
|- Anodal: local increase of theta and alpha bands.
- Cathodal: local decrease of theta and alpha bands.
|Jacobson et al., 2011
|Decrease in right frontal theta band.
|Polania et al., 2011
|- Global synchronization of all studied bands.
|Maeoka et al., 2012
|Local increase in beta and decreased alpha bands.
Table 3. Studies analyzing the effects of tDCS on EEG recordings.
Initially, subjects should be screened for any contraindications for tDCS 11. Check also for skin lesions or diseases, since there is evidence of tDCS induced lesions according to skin integrity. If tDCS is strongly indicated over a lesioned area, it is possible to do it at lower intensity, i.e. 0.5-1.0 mA. However, it is not guaranteed that this will prevent skin irritations or lesions. Thus, the condition of the skin under the electrodes should be inspected before and after tDCS 2.
Impedance and electrodes
Electrode impedances should be as low as possible. This reduces the risk for internal and external noise interference or distorted signals. Impedances should also be rechecked whenever there is any artifact present in the signal 37.
All electrodes must be of good quality with intact surfaces. Reusable electrodes with inconsistent surfaces can create uneven current densities. All surface electrodes should be applied with sufficient conductive gel to ensure low impedances, and the impedances should be checked for artifacts 37.
A closed-loop system is a system capable of diagnosing electrophysiological abnormalities and treating them promptly 8, 10. An illustrative example is the EEG spike detector for an oncoming seizure. This principle has been successfully applied in patients with severe epilepsy. Morrell and colleagues 9 treated 191 subjects with intractable epilepsy using a brain implanted stimulator and observed a significant reduction in seizure frequency as well as improvements in quality of life. Despite the success, invasive procedures are associated with risks and complications such as local infection or unwanted mood or cognitive effects and therefore an alternative, non-invasive approach is desirable. Hence, the present device may represent an interesting option for those patients who need rapid neurophysiological diagnosis and prompt treatment, such as epileptic patients.
The closed-loop system application might not be restricted to patients with epilepsy only. A number of recent studies have suggested that EEG alterations may be markers of various neuropsychiatric diseases 30. Using a combination of tDCS and EEG could also be useful for optimizing the parameters of stimulation. Such algorithms are still undeveloped, but the combination of findings from EEG and tDCS studies may help in such development.
Compared to TMS, which is another non-invasive brain stimulation technique, tDCS is considered much more suitable for therapeutic purposes mainly because of its low cost and relative portability. In addition, having a system that uses a head cap with pre-determined electrode locations can standardize location of stimulation and improve results. Another advantage of this device is the possibility to stimulate more than one site at the same time, which has been found to be clinically superior than conventional stimulation according to some authors 38, 39.
Although the device shows clear advantages, some limitations need to be addressed in order to improve the device for the future. First, the device cannot stimulate and record EEG signals in the same location simultaneously (See Figure 9). Second, the number of channels available to record EEG is low. The usual recommendation is to use at least 16-channels for an adequate EEG study 40 and even more channels for electro-oculography to detect eye movement artifacts. Indeed, in the past few years there has been a tendency to increase the number of channels in EEG/tDCS studies (Table 3). Although the low number of channels might affect sensibility in detecting dynamic changes in cortical excitability, such system may still be useful for finding algorithms for specific electrode locations.
This work was partially supported by Neuroelectric, Barcelona Spain, which produces the instrument used in this article.
P.S. received funding support from CAPES, Brazil. This work was partially supported with a grant from CIMIT. The authors are also grateful to Uri Fligil for his technical assistance and to Olivia Gozel and Noelle Chiavetta for their help in editing this manuscript.
|Frontal dry electrode front-end
|Gel electrode front-end
|Gel Bottle 60cl
|Stimulation electrode Pi cm2
|Saline solution bottle 100ml
|Sponge electrode fron-end 25 cm2
|Adhesive Electrode Front-end
|USB Bluetooth Dongle
|USB card with software
|microUSB NECBOX charger
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