Published: March 19th, 2021
This article provides a straightforward protocol for acquiring good quality electroencephalography (EEG) data during simultaneous EEG and functional magnetic resonance imaging by utilizing readily available medical products.
Simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), EEG-fMRI, combines the complementary properties of scalp EEG (good temporal resolution) and fMRI (good spatial resolution) to measure neuronal activity during an electrographic event, through hemodynamic responses known as blood-oxygen-level-dependent (BOLD) changes. It is a non-invasive research tool that is utilized in neuroscience research and is highly beneficial to the clinical community, especially for the management of neurological diseases, provided that proper equipment and protocols are administered during data acquisition. Although recording EEG-fMRI is apparently straightforward, the correct preparation, especially in placing and securing the electrodes, is not only important for safety but is also critical in ensuring the reliability and analyzability of the EEG data obtained. This is also the most experience-demanding part of the preparation. To address these issues, a straightforward protocol that ensures data quality was developed. This article provides a step-by-step guide for acquiring reliable EEG data during EEG-fMRI using this protocol that utilizes readily available medical products. The presented protocol can be adapted to different applications of EEG-fMRI in research and clinical settings, and may be beneficial to both inexperienced and expert operators.
Functional magnetic resonance imaging (fMRI) provides a measure of neuronal activity through hemodynamic responses by measuring blood-oxygen-level-dependent (BOLD) changes during an electrographic event. Simultaneous electroencephalography (EEG) and fMRI (EEG-fMRI) is a non-invasive research tool that combines the synergic properties of scalp EEG (good temporal resolution) and fMRI (good spatial resolution), allowing better localization of the site responsible for the generation of electrographic events detectable in EEG. It was first developed in the 1990s for the use in the epilepsy field1,2 and has subsequently been used in neuroscience research since the 2000s3,4. With the increase in knowledge regarding the safety5 and continuous development of techniques for the removal of MRI-induced artifacts on EEG3,6,7,8,9,10, it is currently a tool that is widely utilized in both neuroscience and clinical research11.
EEG-fMRI is acquired either at rest or during a task, depending on the research question. In general, resting state acquisition allows the identification of structures involved in the generation of a particular EEG feature (e.g., waveform, rhythm, frequencies, power) and helps in understanding the variable spontaneous brain activities11. A number of neuroscience studies and most clinical studies, especially those on epilepsy12, acquire EEG-fMRI at rest11. Task-based acquisition allows the identification of cerebral areas and the brain electrical activities assigned or related to a specific task and helps establish the link between the electrical activities and cerebral areas associated with the task. Task-based acquisition is mainly utilized in neuroscience studies11 and some clinical studies13. Most task-based EEG-fMRI acquisitions use an event-related design. The type of modeling used for integrating EEG and fMRI data determines whether the efficiency or detection power should be maximized in designing the task14. Please see the studies by Menon et al.14 and Liu et al.15,16 for details on the task design.
Although data acquisition during EEG-fMRI may appear straightforward, the preparation is experience-demanding. A protocol for guiding proper preparation for data acquisition is important to ensure both the safety and yield (i.e., analyzable and reliable data). Despite the existence of various techniques to remove MRI-induced EEG artifacts, inconsistent artifacts in the EEG recorded, especially those related to machinery-induced vibration of the wires and subjects' gross movements, are still difficult to completely remove; therefore, these artifacts need to be minimized during data acquisition.
This article presents a straightforward protocol that utilizes readily available MRI-compatible medical products. The protocol provides important steps that ensure data quality, particularly the quality of EEG data, which is key to the success of an EEG-fMRI study. This protocol was developed based on the 20-year experience of the EEG-fMRI research team at the Montreal Neurological Institute12,17 and was further modified for use at Osaka University, which benefits both inexperienced and expert operators.
The research ethics committee of Osaka University Hospital and the safety committee of the Center for Information and Neural Networks (CiNET) approved the protocol (Osaka University Hospital Approval Nos. 18265 and 19259; CiNET Approval Nos. 2002210020 and 2002120020). All subjects provided written informed consent for their participation.
1. Preparation of the experimental setup
2. Applying the EEG cap and ECG electrode
3. Apply the carbon wire loop (if a bipolar amplifier is available)
4. Securing the cap and carbon wire loops
5. Placing the subject in the MR scanner
6. Configuration of the wires and amplifiers
7. EEG-fMRI data acquisition
Upon placing the EEG cap using this protocol, the impedance of each electrode usually drops below 20 kΩ (Figure 1). Representative EEG signals obtained from a subject (20-year-old man) who participated in a neurocognitive study, and a different subject (19-year-old woman) who participated in an epilepsy study using this protocol in the same MR scanner are shown in Figure 2 and Figure 3, respectively. The subject who underwent neurocognitive testing was instructed to keep the eyes open but stay still while performing a visual task as instructed. The subject for the epilepsy study was instructed to close the eyes and sleep, as epileptic activities are typically more frequent during sleep. The EEG signals acquired from both studies were similar before processing (Figure 2); the MRI gradient artifact obscured the real EEG signals. The EEG signals from both studies were processed offline as follows: MRI artifacts were removed using the subtraction method24; and BCG, movements, and Helium pump artifacts were removed using the regression of signals recorded from the carbon wire loops7,9. The resultant EEG signals (Figure 3B) from both studies were of analyzable quality without visible contamination of BCG artifacts (Figure 3A). Epileptic activities were clearly seen on the EEG during the epilepsy study (Figure 3B). On the EEG acquired during the neurocognitive study, blinking, eye movement, and muscle artifacts were seen, especially in the frontal leads (Fp1 and Fp2) after artifact removal (Figure 3B) due to the nature of the study, and may be further removed using other methods depending on the need. No artifact originating from machinery vibrations was seen on post-processed EEG signals acquired during both studies (Figure 3B comparable to EEG signals acquired outside MRI as shown in Figure 3C). No artifact originating from the EEG electrodes was seen on the MR images acquired simultaneously (Figure 4).
Figure 1: Representative EEG electrodes impedance that dropped below 5 kΩ upon application of a 32-channel EEG cap on a subject who participated in a neurocognitive study. Each round colored circle represents an EEG electrode, with the electrode name written within the circle; the position of each circle represents the position of each electrode on the EEG cap. The color bar and the numbers on the right represent the range of the impedance being measured (0-5 kΩ in this case); green color indicates that the impedance value is lower than the Good level value, and red color indicates Bad level. In this example, electrodes CP1, O1, Oz, O2, and ECG are indicated in light green, which means that the impedances of these electrodes were 2 kΩ; the rest of the electrodes are indicated in dark green, which means that the impedances of these electrodes were 0 kΩ. Please click here to view a larger version of this figure.
Figure 2: EEG signal before processing. Note that the MRI gradient artifact obscured the real EEG signals. Please click here to view a larger version of this figure.
Figure 3: Representative EEG signals from subjects who participated in neurocognitive and epilepsy studies. EEG signals on the top row were from a neurocognitive study and those on the bottom row were from an epilepsy study. EEG signals were processed offline. (A) EEG signals after MRI gradient artifact removal. The boxes in light blue indicate BCG artifacts. (B) EEG signals after artifact removal using regression of signals recorded from the carbon wire loops. (C) EEG signals recorded outside MRI using the same EEG equipment. EEG signals were shown in referential montage (reference at FCz); EEG in bipolar montage (each channel represents the voltage difference between a pair of adjacent electrodes) of the same segment is also shown for EEG acquired during an epilepsy study to ease the visualization of epileptic activities. The blue arrowheads (B and C, top row) indicate blinking (high-amplitude slow downward deflections/diphasic potentials at Fp1 and Fp2), the black arrowhead (B, top row) indicates eye movement resulting from a saccade or a spontaneous change of gaze (small, rapid deflections at Fp1 and Fp2), and the green rectangles (B, top row) indicate alpha rhythm seen on the EEG acquired during a neurocognitive study. The low-amplitude and high-frequency activities predominantly at Fp1 and Fp2 are muscle artifacts (thickening of the EEG tracing, top row). The red arrowheads (B and C, bottom row) indicate the time points at which epileptic activities were identified on EEG acquired during an epilepsy study (sharp downward or upward deflections that are sometimes followed by a slow wave). Please click here to view a larger version of this figure.
Figure 4: Representative MRI data acquired from a subject using this protocol. Note that the EEG electrodes did not cause visible artifacts on the MR images acquired simultaneously. (A) magnetization prepared rapid acquisition with gradient echo image; (B) echo planar imaging. Please click here to view a larger version of this figure.
This protocol highlighted the important points for the safe simultaneous EEG-fMRI acquisition of good quality data.
Some common errors resulting in difficult-to-remove artifacts on EEG as well as troubleshooting techniques are as follows. First, choosing subjects that are compliant and cooperative and ensuring their comfort during data acquisition can prevent premature termination due to subject movements (steps 2.1 and 5.4). Second, impedance not dropping below 20 kΩ after repeated abrasion of the scalp (step 2.9) is most likely due to inadequate brushing after use. Thoroughly brushing each opening of the EEG electrodes when washing the cap prevents this problem. Third, inappropriate settings of the hardware and software can result in saturation of the EEG signals that subsequently hamper artifact removal during offline EEG processing. Lastly, to prevent the recording of saturated EEG signals, maintain the impedance of each electrode below 20 kΩ after placing the subject in the MR scanner prior to data acquisition; adequately diminish mechanical vibrations by immobilizing the EEG cap (which also means the subject's head), cables and wires; monitor the raw EEG signal online with the recording software and make sure that the sampling rate and amplitude resolution are correctly set up.
The simultaneous acquisition of EEG and fMRI raises important safety issues related to RF-induced heating and switching gradient-induced currents due to the presence of electrical wires connected to the subject in the rapidly changing magnetic field5. These safety issues have been largely minimized over the years following research findings that have enhanced knowledge of this aspect and led to large improvements in the technology of MRI-compatible EEG equipment. Nevertheless, careless preparation without adequate knowledge or not taking safety precautions places the subjects in danger. For instance, loops that form anywhere within the circuit induce current and possible heat injury. Acquisition with the electrodes at high impedance not only hampers the EEG data quality but also poses a potential hazard to the subject (thermal injury due to high current density). The same hazard applies to broken electrodes. Cables placed in close proximity to the MR bore wall, in other words, far from the center, also pose a potential heating hazard to the subject (heating due to antenna effect)25. This protocol emphasizes the following safety aspects: no loops form within the circuit between the subject and the amplifier, all electrodes have low impedance during the MRI scan, and all cables are placed in the center of the bore. Beginner operators are advised to undergo training and follow the manufacturer's guidelines found in the user manual and demonstration videos20 to avoid any safety concerns.
The major causes of artifacts found on EEG-fMRI are switching gradient of the MRI, BCG, or the subject's gross or subtle movements (face movements, clenching, swallowing etc.). In some MRI setups, artifacts caused by the helium pump and ventilators also significantly compromise the EEG signals. MR gradient artifacts are rather consistent in the waveforms and can be sufficiently corrected using a template-based subtraction technique if they are fully recorded without distortion using amplifiers with a sufficient dynamic range24. BCG artifacts are usually corrected using either the subtraction technique26, independent component analysis6, optimal basis set8, or a combination of these techniques10. Recently, artifact removal using simple regression based on signals acquired simultaneously with carbon wire loops has been developed7,9. The protocol presented here illustrates the technical aspect, with the aim of providing an introductory guide for those who are interested in using this method. This method removes BCG, subtle subject movements, and helium pump artifacts and the resulting EEG signals are reportedly superior to those corrected using other methods7,9. However, larger motion artifacts, especially those containing swaying movements, are not removable even using this method7. Despite the improvement of these artifact-removal methodologies over the years, inconsistent artifacts, including those caused by MRI machinery-induced vibration are still difficult to remove. Moreover, the more extensive the artifact removal procedure, the higher the risk of losing some real EEG signals. Therefore, good preparation that can minimize the inconsistent artifacts remains most important in EEG-fMRI acquisition. In this protocol, these artifacts are minimized by using: (1) an elastic bandage to wrap the head and memory foam pillows to immobilize the head in the head coil, to reduce possible vibration of the wires while maintaining the subject's comfort; (2) cotton and medical adhesive tape to reduce vibration of the ECG electrode wire that may not be fully immobilized by the subject's own weight (partially floating between the subject and the table especially in a thin subject); and (3) sandbags to immobilize the cables placed in the MRI bore. These are important techniques to minimize difficult-to-removed MRI machinery-induced vibration artifacts, which have not been described in the previously published EEG-fMRI protocol20. In that protocol, subjects were placed in the scanner without additional wrapping over the EEG cap and padding around the head, and cables were only taped at a few points without immobilization using sandbags. Based on 20 years of experience at the Montreal Neurological Institute, we realized that those measures may contribute to the susceptibility of the electrode wires and cables to MRI machinery-induced vibration, although they are rarely emphasized in most EEG-fMRI studies6. Minimizing the MRI machinery-induced vibration subsequently leads to better quality and readability of the EEG, which is particularly useful for identifying subtle changes or events in the EEG6, such as small epileptic discharges in epilepsy studies and single-trial ERPs in neurocognitive studies.
The detection of ERPs in EEG signals is a prerequisite for cognitive neuroscience studies. In contrast to the classic grand average response across trials, ERP single-trial detection, which provides insights into brain dynamics in response to a particular stimulus, is becoming a new target in modern cognitive neuroscience studies and non-invasive brain-computer interface research27. Application of the present protocol may contribute to increasing efficiency in these research fields.
The protocol is best suited for the MRI-compatible EEG system used in this study. Nevertheless, we believe that the important points may also be applicable to other MRI-compatible EEG systems.
The authors report no disclosures relevant to the manuscript.
This study was sponsored by the National Institute of Information and Communications Technology of Japan (NICT).
The authors thank the MRI physicists and technologists at the Center for Information and Neural Networks for their dedication in acquiring good quality MRI data.
Dr. Khoo is funded by Grant-in-Aid for Scientific Research (Nos. 18H06261, 19K21353, 20K09368) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and a grant by the National Institute of Information and Communications Technology of Japan (NICT), and was supported by Mark Rayport and Shirley Ferguson Rayport fellowship in epilepsy surgery and the Preston Robb fellowship of the Montreal Neurological Institute (Canada), a research fellowship of the Uehara Memorial Foundation (Japan). She received a sponsored award from the Japanese Epilepsy Society, support from the American Epilepsy Society (AES) Fellows program, and travel bursary from the International League Against Epilepsy (ILAE).
Dr. Tani is funded by Grant-in-Aid for Scientific Research (No. 17K10895) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and received research support from Mitsui-Kousei Foundation, funding for a trip from Medtronic, royalties from the publication of articles (Gakken Medical Shujunsha, Igaku-shoin), and honoraria from serving as speaker (Medtronic, Daiichi-Sankyo Pharmaceuticals, Eisai Pharmaceuticals).
Dr. Oshino is funded by Grant-in-Aid for Scientific Research (No. 17K10894) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. He received royalties from the publication of articles (Medicalview, Igaku-shoin), and honoraria from serving as speaker (Insightec, Eisai Pharmaceuticals, Daiichi-Sankyo Pharmaceuticals, UCB, Otsuka Pharmaceuticals, Teijin Pharma, Yamasa Corporation).
Dr. Fujita is funded by Grant-in-Aid for Scientific Research (No. 19K18388) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
Dr. Gotman is funded by the Canadian Institutes of Health Research (No. FDN 143208).
Dr. Kishima is funded by Grant-in-Aid for Scientific Research (Nos. 18H04085, 18H05522, 16K10212, 16K10786) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, Cross-ministerial Strategic Innovation Promotion Program (No. SIPAIH18E01), Japan Agency for Medical Research and Development, and Japan Epilepsy Research Foundation.
|BrainAmp EXG MR
|Brain Products, GmBH, Germany
|MRI-compatible bipolar amplifier
|BrainAmp MR Plus
|Brain Products, GmBH, Germany
|MRI-compatible EEG amplifier
|Brain Products, GmBH, Germany
|MRI-compatible EEG cap
|ESPA elastic bandage
|Toyobo co., Ltd.
|elastic bandage for for wrapping the subject's head
|One Shot Plus P EL-II alcohol swab
|Shiro Jyuji, Inc.
|Alcohol swab for preparing the skin
|Brain Products, GmBH, Germany
|MRI-compatible battery pack for electric supply of the amplifiers
|Brain Products, GmBH, Germany
|Phase synchronization between the EEG equipment and the MRI scanner
|USB 2 Adapter (BUA)
|Brain Products, GmBH, Germany
|USB Adaptor to connect the amplifiers to the recording computer
|V19 abrasive conductive gel
|Brain Products, GmBH, Germany
|Abrasive gel for the application of the EEG-cap
|Yu-ki Ban GS Medical adhesive tape
|medical adhesive tape to secure the ECG electrode and carbon wire loops
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