A Review of the International System Electrodes Grass
Purpose. We provide a comprehensive verification of a new subcutaneous EEG recording device which promises robust and unobtrusive measurements over ultra-long time periods. The arroyo is evaluated against a state-of-the-art surface EEG electrode technology. Materials and Methods. An electrode powered past an inductive link was subcutaneously implanted on v subjects. Surface electrodes were placed at sites corresponding to the subcutaneous electrodes, and the EEG signals were evaluated with both quantitative (ability spectral density and coherence analysis) and qualitative (blinded subjective scoring by neurophysiologists) assay. Results. The power spectral density and coherence assay were very similar during measurements of resting EEG. The scoring past neurophysiologists showed a higher EEG quality for the implanted organisation for different subject states (eyes open and optics closed). This was near likely due to higher amplitude of the subcutaneous signals. During periods with artifacts, such as chewing, blinking, and center motion, the 2 systems performed equally well. Conclusions. Subcutaneous measurements of EEG with the test device showed high quality equally measured by both quantitative and more subjective qualitative methods. The bespeak might be superior to surface EEG in some aspects and provides a method of ultra-long term EEG recording in situations where this is required and where a small number of EEG electrodes are sufficient.
1. Introduction
Electroencephalography (EEG) is a standard procedure to obtain information most the metabolic and electric status of the encephalon. The EEG is widely used in both the diagnostics and the monitoring of the country of human being cognitive system, ranging from epilepsy and dumb consciousness to sleep disorders. The clinical application of EEG is now well described; notwithstanding, the quality of long-term ambulatory monitoring of EEG is however compromised by inconvenient equipment and unstable electrodes, thus requiring continuous supervision.
The positions of the electrodes on the scalp are given co-ordinate to international conventions, such equally the x/20 system [ane]. Standard scalp EEG-recordings are suitable for many applications in neurology; notwithstanding, for long-term continuous monitoring it is desirable to perform recordings without causing discomfort to the patient, and outside clinical facilities [2]. In addition, EEG recorded over a prolonged period of time may provide deeper insight and open completely new avenues of research and applications compared to conventional EEG. Examples include the diagnosis of infrequent seizures and characterization of more than frequent pathological events, together with the monitoring of drug titration and the development of brain-estimator interface techniques [iii]. Continuous EEG recording is a prerequisite for the monitoring of, for example, vigilance level [four] or sleep stages [five]. This also provides the footing for early on detection of the onset of epileptic seizures [vi] or indices of impending severe hypoglycaemia [seven, viii].
For continuous EEG recordings to become a reality the device should be convenient to employ, not hamper daily activities, and at the same time provide EEG of high quality with a minimum of electric racket and device-related artifacts. Standard clinical EEG recording systems are not suited for this purpose, equally the electrode leads and bulky batteries are inconvenient, electrodes are hands dislodged, gel-based electrodes tend to dry out, and artifacts are oftentimes seen in outpatient monitoring [9].
To this stop, the visitor HypoSafe is developing an EEG recording organization which consists of a miniaturized subcutaneous implant placed behind the ear and an external part which provides the implant with ability, receives and stores the EEG indicate, and conducts real-fourth dimension data analysis if required. Both data and ability transmission use an inductive link, and so that the inner device does not require an internal energy supply. This ultra-long term habiliment capability, lack of artifacts, and a perfect electrode contact make the organisation robust and convenient. In preliminary experiments the study subjects found the device comfortable and aside from a temporary transient soreness at the implantation site, no adverse events have been reported. Subjects informed that they slept well with the implantable electrode.
The current paper presents a comparative analysis of EEG signal quality of the commencement generation of a miniaturized subcutaneously implanted recorder [ten] against standard scalp electrodes used in conjunction with a state-of-the-art recording system. The EEG was analysed both qualitatively and quantitatively over recordings of unlike brain states and during physical activity.
ii. Materials and Methods
The considered dataset originates from a continuous EEG recording, and co-ordinate to a protocol which aims to test the robustness and performance of an EEG based hypoglycaemia alarm for blazon i diabetes patients. The project was canonical by the regional upstanding committee and the Danish Health and Medicines Authority and registered at ClinicalTrials.gov (identifier number NCT01238016). For optimal office of the device, before implantation in diabetes patients, a serial of implantations were conducted in healthy volunteers. The population reported in this paper consists of these healthy individuals, who all wore the device for one month. They were consulted weekly during the study menstruum and whatever reported adverse events were recorded.
2.1. Devices
The Subcutaneous Device. The implantable part of the device consists of an insulated pb (length 100 mm and bore ane mm) with iii embedded platinum-iridium electrodes located 30 mm apart, each with an surface area of 35 mmtwo. The pb is fixed to the implant housing which is 3.0 mm thick and oval shaped, with diameters of 16 and 20 mm, and covered past biocompatible epoxy; run into Figure 1. The outer device consists of a disc for the anterior link (height, width, depth of 28 mm, 20 mm, four mm) connected to a box (meridian, width, depth of 69 mm, 29 mm, 10 mm) containing processing units, retention carte, and a Li-ion battery. EEG data are sampled at 65.ane Hz with an analog high-pass filter with a cutting-off frequency at 0.v Hz and a scroll-off of twoscore dB/decade and a low-laissez passer filter with cut-off at 30 Hz and a coil-off of 80 dB/decade. The common mode rejection ratio was 60 dB, least significant flake beneath 0.vµV, and the input impedance college than twenty MΩ. The bombardment can provide the implant and processor with power for 2 days before it needs to exist recharged, and the storage capacity is sufficient for storage of i month of continuous measurement. The external device gives tactile feedback, and then that the user knows when the inner and outer devices are optimally aligned and in link.
The Command Setup. To verify the quality of EEG data obtained from the test device, standard scalp electrodes (reusable silver EEG loving cup electrodes, 200 cm lead, ten mm cup, Embla Systems Inc., Amsterdam, Netherlands) were placed directly above the electrodes of the inner device, and simultaneous recordings were performed. The skin was initially prepared with Nuprep skin preparation gel, while the Ten20 conductive EEG paste (Weaver and Company, Aurora, CO, United states of america) was used for the disc electrodes, which were fastened with EC2 genuine grass electrode cream (Natus Neurology, Warwick, RI, USA). The EEG data from cup electrodes were sampled with a k.USBamp (Guger Technologies, Republic of austria) at 64 Hz and preprocessed using a digital Butterworth ring-pass filter of eighth order with cut-off frequencies at 0.five Hz and 30 Hz.
All signals were finally resampled to 207 Hz for straightforward comparison.
2.2. Protocol
Five good for you subjects (all male, aged 33 ± eight years) participated in the study. None had a history of diabetes, epilepsy, or whatever other chronic disease and were not taking regular medication. The device was implanted via local analgesia and sterile technique through a xv mm incision backside the ear. The electrode was placed in an open needle and inserted from the top of the incision in the subgaleal infinite in the direction towards a signal between Cz and Pz, co-ordinate to the international 10/20 system. The implant housing of the device was placed in a pocket made past blunt autopsy backside the auricular helix. When the device was in situ the incision was airtight with resorbable sutures.
Approximately 10 days after the insertion, the subjects returned to the clinical research unit, and the outer part of the device was placed on the skin by double adhesive record directly in a higher place the inner device. This adhesive should be changed daily to ensure optimal data transmission. Control electrodes were then placed on the scalp, above subcutaneous electrodes (see Figure 1), and the impedance was checked (should be below 5 kΩ). The subjects were then asked to perform consecutive predefined activities of 30 2nd length; these included rest, closed eyes, jaw clenching, eye blinking, eye movements, arithmetic mental exercise, and jumping on the spot. The full duration of the procedure was 12 minutes.
2.iii. Subjective Assay of Time Series
The recordings were analyzed both visually and quantitatively. The visual inspection was performed in a blinded fashion by two independent neurophysiologists (TWK and MDA). For each of the above tasks, 30 s epochs of EEG were provided and the neurophysiologists were asked to score the time series by a signal calibration and a noise calibration equally shown in Table 1. In the case of more than two points of disagreement inside a single epoch, the neurophysiologists were asked to reevaluate that epoch until agreement. A higher value in the betoken every bit well as the noise scale is preferential. For each task a Mann-Whitney -exam was used of the nothing hypothesis that scorings of the subcutaneous and surface EEG data are independent samples from identical continuous distributions with equal medians, against the culling that they practice not have equal medians.
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| Score | Signal quality | Noise level |
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| v | EEG signal clear, evaluation directly forward | No or very piffling noise present |
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| iv | EEG signal clear, evaluation possible and close to optimal | Some noise present simply does not hamper EEG analysis significantly |
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| 3 | EEG point recognized, evaluation possible notwithstanding not optimal | Moderate amount of noise present, EEG analysis challenging but still possible |
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| two | EEG bespeak recognized, evaluation difficult | Larger amount of noise present, EEG analysis challenging and less reliable |
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| 1 | EEG betoken is not readily recognized | EEG severely noisy, EEG analysis unreliable |
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two.4. Assay of Power Spectral Densities
The nigh apparent encephalon signal response is the alpha attenuation response [11]. When a subject closes the eyes, the absolute as well as relative power in the entire signal will rise in the 8–thirteen Hz frequency band, especially in the posterior electrodes. The power spectrum densities were calculated using Welch's method: the data was carve up into 5-2nd segments with 50% overlap. A Hamming window was applied to each data segment and the power spectral density guess was plant by averaging the resulting periodograms.
To make up one's mind the degree of separation of alpha powers within the 5 s windows between the "eyes closed" and "optics open up" tasks, the -statistic was calculated via Welch'southward test, given by where and denote, respectively, the mean alpha power for the "eyes open" and "optics closed" states, and denote the corresponding variances, and denotes the number of samples (here number of data segments). A positive -statistic indicates that the alpha power is greater for the "optics airtight" recording; the larger the statistic the greater the differentiation from the "eyes open" recording. The respective values were calculated.
2.5. Correspondence betwixt Surface and Subcutaneous Signals
To investigate the similarity betwixt the surface and subcutaneous signals, the normalized correlation coefficient and magnitude squared coherence spectrum were calculated for the states of closed and open up eyes. The normalized correlation coefficient, , was calculated by where denotes the subcutaneous EEG, is the surface EEG, is the number of samples in each calculation, and is the lag in the range to . If , there is no correlation betwixt signals, while shows that the signals are in perfect correlation.
The magnitude squared coherence spectrum, , is a function of the power spectral densities, and , and the cross power spectral density, . It is computed using Welch's averaged periodogram method: Like to the normalized correlation coefficient, the values of the magnitude squared coherence are also in the range of 0 to 1, just with i value for each frequency bin.
iii. Results
three.1. Device Tolerability
I written report subject complained about discomfort at the site of implantation and requested explantation. This was performed 1 calendar week before planned termination of the study and underwent without any farther complications. No further adverse device- or procedure-related rubber issues were raised in the report.
3.2. Qualitative Assay
The neurophysiologists scored the EEG quality to exist higher for the test device than the standard surface-electrode approach when the subjects were at remainder, with both open and closed eyes, likewise as when performing a mental task; come across Effigy 2. This was primarily due to more distinctive EEG responses such as the alpha rhythm associated with the "eyes closed" country. The level of dissonance was adjudged to exist similar for the surface and subcutaneous systems.
(a)
(b)
three.3. Alpha Response
Table 2 shows that the subcutaneous electrodes enable, on average, a better differentiation for three of the 5 subjects (subjects 1, iii, and four). Both the surface and the subcutaneous approaches enabled a statistically significant differentiation for x of all the 15 trials, although non always the aforementioned trials were found statistically significant for the implanted and scalp EEG.
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| Subject | 1 | 2 | 3 | 4 | 5 | |||||
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| System | Surf. | Subc. | Surf. | Subc. | Surf. | Subc. | Surf. | Subc. | Surf. | Subc. |
| value | value | value | value | value | value | value | value | value | value | |
| | ||||||||||
| Trial 1 | seven.02; < .01 | 9.83; < .01 | 2.73; < .01 | −0.09, n.southward. | −ii.2; < .05 | 2.66, < .05 | 0.80, north.s. | −0.xv, n.s. | three.40; < .01 | i.41; n.south. |
| Trial 2 | iii.xl; < .01 | 4.91; < .01 | iii.lxxx; < .01 | 3.55; < .01 | ane.88; due north.s. | 3.96; < .01 | two.33; < .05 | two.41; < .05 | two.59; < .05 | 0.71; n.s. |
| Trial 3 | four.03; < .01 | 4.62; < .01 | 2.48; < .05 | 2.15; < .05 | 1.07; n.s. | 3.89; < .01 | two.13; < .05 | 2.83; < .01 | 1.41; n.s. | 0.91; n.south. |
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3.4. Signal Similarity
Figure 3 shows that the power spectrum densities are very similar for the surface and subcutaneous approaches; the but difference is that the subcutaneous recordings exhibited slightly less power for frequencies below two Hz. These results are supported by the correlation and coherence assay in Figure four. The hateful normalized correlation coefficient was 0.73 between the ii synchronously simply independently recorded signals and the first side lobes were situated at lags ±22, which is equivalent to a wave with a frequency of 9.iv Hz. The coherence spectrum shows that this behavior was primarily due to high coherence in the low frequencies, where the betoken ability and correlation are high.
(a)
(b)
The similarity of the subcutaneous recordings over the ane-calendar month flow besides seems to exist high. Figure v shows the PSDs calculated based on a one-minute noise-costless EEG segment from 24-hour interval one and solar day 26 after the start of the recording.
4. Word
Nosotros have evaluated the quality of EEG recordings from a single-channel miniaturized partly implanted recorder confronting simultaneously obtained recordings from a state-of-the-art surface-electrode EEG organization. By quantitative comparison, we plant a shut correlation between these ii data-sets. Too, the more subjective, however structured, qualitative comparison of the data indicated that the implanted test device provided information of comparable quality.
Ultra-long term EEG recordings may constitute a complementary approach to standard EEG recordings in order to elucidate occurrence of rare EEG events. In such cases, at that place will inevitably be a tradeoff between the utility of a total-scale EEG recording and the requirement of extended use. The EEG-recorder tested in the present study was developed for the purpose of EEG-based hypoglycaemia detection in type 1 diabetes patients, a task which requires continuous and long-term monitoring [vii, 8]. The nowadays study was undertaken to evaluate the quality of data from the test device, defined equally a high signal-to-noise ratio and picayune or no data loss.
This proof-of-concept study considered a relatively pocket-size subject population. We accept studied five salubrious volunteers who used the EEG device for a period of one month. Intra-subject variation in the EEG or aberrations from the normal EEG was accordingly less essential. Another aspect of the implanted device is that the EEG recording and validation are limited to a unmarried aqueduct and accordingly to a small role of the brain's surface. Notice that anatomic variations in the thickness of the cranium and the overlying soft tissue may influence the subcutaneous and the surface measures differently [12]. The anatomic area considered in this report was called co-ordinate to the requirement of the hypoglycaemia epitome. It is prominent in the temporal area of the brain, where the hypoglycaemia warning device is also positioned [10, 13]. If the examination-device is to be used at other parts of the brain, it will be essential to evaluate the point from these relevant areas.
A strength of the study is that the EEG obtained by subcutaneous and surface methods is evaluated and compared by complementary approaches. The spectral analysis provides a straightforward quantitative comparison showing that the 2 modalities give near-identical signals. Equally the power spectra are almost identical for all frequencies in a higher place ii Hz, i might suspect that the power from the scalp recordings below 2 Hz originates from a nonphysiological phenomenon such as motion of the long wires between the scalp and the amplifier on a nearby table. As those wires are not present for the examination-device, this artifact volition not be present on that device.
Alpha activity was observed during the eyes-closed country in nearly study subjects. Past cross-correlation analysis, information technology is substantiated that the two methods measure near-identical signals. A mean normalized correlation coefficient of 0.73 between the synchronously but independently recorded time series of subcutaneous and surface EEG data is high. The occurrence of significant side-lobes in the cross-correlogram at lags ±22 samples during airtight optics further highlights the high degree of matching between the two signals. The coherence spectrum shows that this is primarily due to high coherence in the low frequencies up to 12 Hz, where the bespeak power is besides highest.
As a complementary approach, the EEG was examined visually by ii independent neurophysiologists. This was achieved in a blinded fashion with respect to the recording technique, in gild to avoid systematic bias. Nosotros constitute that the noise nowadays in each of the approaches was equivalent, irrespective of the recording methodology. Physiological noise might be expected to ascend from at least two sources: (i) due to action of the temporal musculus (EMG) which leads to increased noise especially during periods of chewing and (ii) from the centre muscles during eye movement and blinking. Every bit expected, it was found that these physiological sources of noise were equally represented in the EEG. Dissonance may also arise from instability of the electrode connection to the peel or from induced currents due to electrode movements. These sources of noise are expected to be reduced when the electrode is fully implanted, thus ensuring a rigid connection with the source of the signal. This might be the reason that the reported signal quality of the subcutaneous approach was highest during residual with eyes open, eyes closed, and during a mental task. Had the evaluation continued over days, nosotros would have expected the surface-electrode skin-contact to dethrone, resulting in an inferior performance [14].
To appraise short-term robustness of the recordings we compared data recorded on 24-hour interval ane and 24-hour interval 26. Effigy five shows like power spectral densities, suggesting that the indicate quality does not alter over time. Further comprehensive longitudinal evaluations of the long-term durability will exist published in a afterwards study.
5. Conclusion
We have constitute that the proposed subcutaneous recording system provides data quality which is comparable to state-of-the-fine art in standard surface recording engineering science. This has been verified through both quantitative and more subjective qualitative methods, thus promising a method for a discreet and unobtrusive ultra-long term EEG where a small number of electrodes are sufficient. A blinded visual exam indicates especially loftier EEG quality when no physical movements were performed, and initial studies of the performance of the subcutaneous electrodes over a one-month period suggest its suitability for long-term EEG recordings. Further studies will evaluate the performance of the exam device during multiple months' long trials.
Conflict of Interests
Jonas Duun-Henriksen, Martin Rose, and Rasmus Elsborg Madsen are all full time employed at Hypo-Safe A/South developing and producing devices for unobtrusive subcutaneous EEG monitoring. Claus Bogh Juhl is part fourth dimension employed at Hypo-Safe A/S. None of the remaining authors have whatsoever financial interests in Hypo-Prophylactic A/Due south.
Acknowledgment
The authors would similar to give thanks The Danish Council for Strategic Enquiry for funding of inquiry leading to this paper.
Copyright
Copyright © 2015 Jonas Duun-Henriksen et al. This is an open access article distributed under the Artistic Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Source: https://www.hindawi.com/journals/js/2015/341208/