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TECHNOLOGY, COMPUTING, AND SIMULATION

Electroencephalogram-Entropy and Acupuncture

Research Unit of Biomedical Engineering in Anesthesia and Intensive Care Medicine, Medical University of Graz, Austria

Address correspondence and reprint requests to Gerhard Litscher, PhD, MDsc, Research Unit of Biomedical Engineering, in Anesthesia and Intensive Care Medicine, Medical University Graz, Auenbruggerplatz 29, A-8036 Graz, Austria. Address e-mail to gerhard.litscher{at}meduni-graz.at.

	Abstract

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Computer-based measuring of the level of sedation and hypnosis is difficult and has proven to be challenging. The electroencephalogram (EEG) has been proposed as a potential method. Response entropy (RE) and state entropy (SE) are multifactor, dimensionless parameters of a new technology of EEG monitoring, and we investigated them for the first time in acupuncture research within this study. Both parameters have been alleged to reflect changes in the clinical state of sedation. Two different acupuncture schemes were tested in a randomized crossover trial with nine healthy volunteers (mean age ± sd, 28.8 ± 3.6 yr; 25–36 yr). Applying and stimulating acupuncture needles or performing laserneedle acupuncture at special sedation points decreased RE and SE significantly (P 0.01; paired t-test) compared with the reference interval before acupuncture. In contrast, acupuncture of points for increasing "Qi-energy" did not decrease parameters of entropy. Specific acupuncture schemes produce specific, reproducible, and quantifiable effects on entropy parameters in the EEG. Therefore, entropy measurements during acupuncture seem to be worthy of further evaluation with a larger series of subjects.

	Introduction

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Bioelectrical neuromonitoring is gaining attention in anesthesia and critical care. Electroencephalogram (EEG) entropy is an important numerical descriptor of the EEG.

The term "entropy" has its origin in the field of thermodynamics. Entropy is a variable of state and describes the quantity or degree of randomness or disorder in a system. In mathematics, it is the second principle of thermodynamics (principle of entropy). Because of the similar definition of entropy in thermodynamics, the mean information capacity per character in the field of computer sciences is also called entropy (1,2).

Neuronal systems also show characteristics of nonlinear behavior (3). Therefore, the EEG cannot be considered only as the total of sine oscillations but, rather, as a "chaotic" pattern. Thus, it seems to be profitable to apply mathematic methods of nonlinear dynamics to the EEG (4). Computer-aided analysis of entropy in EEGs should enable routine control of anesthetic effects in the brain (5–11).

There are few studies on electrophysiological modalities, such as EEG during acupuncture, and the effects of acupuncture on these parameters are relatively unknown (12–14). However, a number of environmental and physiological factors may affect neuromonitoring indices. It has been reported that nonpharmacological interventions, such as acupressure or acupuncture, can reduce neuromonitoring parameters significantly (15).

For the first time, the new method of entropy in EEGs was applied in this study, and evidence regarding an acupuncture scheme consisting of "sedative acupoints" compared with an acupuncture scheme that is considered to activate energy was validated. The study was conducted in a group of healthy volunteers (n = 9) to determine whether manual needle acupuncture and laser acupuncture stimulations applied to two groups of acupuncture points (sedative versus enhancement of energy) have effects on either state entropy (SE) or response entropy (RE) or both.

	Methods

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An S/5 Entropy-Module, M-Entropy (Datex Ohmeda Instrumentarium Corp., Helsinki, Finland) was used for monitoring entropy. The nearly automatic system is based on the registration of EEG signals as well as frontal electromyography (FEMG) and measures the irregularities of both signal components (16).

The EEG/FEMG electrodes are integrated in a special entropy sensor, which can be easily applied to the frontal region of the head (Fig. 1A). After independent controlling of sensor integrity and electrode impedances, immediate registration of data can be performed.

View larger version (68K): [in this window] [in a new window]   Figure 1. Entropy-monitoring at the Center for Medical Research (ZMF I) at the Medical University of Graz using (a) needle- and (b) laserneedle acupuncture with the Datex Ohmeda S/5 Entropy-Module.

SE and RE were used as evaluative parameters. SE was determined in a frequency range between 0.8 and 32 Hz and RE between 0.8 and 47 Hz (Fig. 2).

View larger version (55K): [in this window] [in a new window]   Figure 2. State-entropy (SE) is calculated at a frequency range between 0.8 and 32 Hz and primarily includes components from the electroencephalogram (EEG). Response-entropy (RE) is determined in the range of 0.8–47 Hz and simultaneously registers EEG and frontal electromyography (FEMG; electromyogram of facial muscles).

Thus, the higher frequency FEMG signals have a faster reaction time in RE (<2 s) compared to SE (15–30 s). Both RE (0–100) and SE (0–91) are standardized, dimensionless values between 100 and 91 (awake) and 0 (no EEG and FEMG activity) with SE RE. Hence, SE can never be more than RE (16).

The basis for calculation of SE is the power spectrum of the EEG (P(f_i)), which is transferred into a standardized power spectrum P_n(f_i) with the selected frequency range (f₁ and f₂) by multiplication with a standardized constant C_n (Fig. 3a).

View larger version (20K): [in this window] [in a new window]   Figure 3. Formulae for calculation of entropy (modified according to (16)).

Spectral entropy for a particular frequency range results from the formula in Figure 3b. Thereafter, the entropy variable is standardized at a range between 1 (maximum irregularity) and 0 (total regularity). Formula c in Figure 3, N[f₁,f₂], corresponds to the number of frequency components in range f₁–f₂. As already mentioned, the EMG is also considered when calculating RE. In the equations d and e in Figure 3, the frequency range from 0.8 to 32 Hz is referred to as R_low, the range from 32 to 47 Hz as R_high, and the entire range from 0.8 to 47 Hz as R_low+high. The standardized entropy value for SE is defined according to equation d and RE according to equation e in Figure 3. The difference between RE and SE can be considered as a measurement value for EMG activity (16).

Entropy values (SE and RE) were investigated in 36 measurements performed on nine healthy volunteers with a mean age (± sd) of 28.8 ± 3.6 yr (range, 25–36 yr; five women and four men). Volunteers were only informed about the procedure to a certain degree to avoid influences on the study design. Information was given only concerning the different modalities of stimulation. The volunteers were not informed about the goal of the study and the fact that sedative acupoints or a stimulation that increases the blood flow velocity in the middle cerebral artery were used. All persons gave their written consent. Our study was approved by the Ethical Committee of the Medical University of Graz, Graz, Austria. The volunteers declared that they did not take any medication, and their neurological and mental status were normal.

A standardized, partially double-blind (laserneedle acupuncture) randomized, crossover study design including the following steps was used:

Ten minutes before starting the procedure, the volunteers were positioned in a comfortable and relaxed manner on a bed. During this time, the entropy sensor was applied. Thereafter, randomized needle or laserneedle acupuncture was performed with a pause of at least 20 min between each application. On different days, the procedure was repeated using the different acupuncture scheme, respectively.

Two different acupuncture schemes were tested on different days using the same volunteer. The first scheme (A) contained so-called sedative points and included the following acupuncture points in detail: Shenting (GV 24), Yintang (Ex.1), Sedative Point 1 (Ex.8, Anmian I), Sedative Point 2 (Ex.9, Anmian II), and Shenmen (He.7). Points Shenting and Yintang and their cerebral effects are described comprehensively in the scientific literature (17). Sedative Point 1 is located at the median point of the connecting line between SJ 17 (Yi Feng) and Yi Ming (Ex.7) (18). Sedative Point 2 lies at the median point of the connection line between GB.20 (Feng Chi) and Yi Ming (Ex.7) (18). The main indication for the latter two points is sleeplessness (18). Scheme A, as described above, was supplemented with point Shenmen (He.7) on the hand (Figs. 4 and 5, left).

View larger version (44K): [in this window] [in a new window]   Figure 4. Box-plot illustration of alteration in state (SE) and response (RE) entropy values in nine healthy volunteers 2 min before (a), during ([b], immediately after applying the needles; [c] 2 min after b; [d] 5 min after b; [e] 10 min after b; and [f] 15 min after applying needles), and 2 min after (g) needle acupuncture using two different acupuncture schemes (A and B). Note the significant decrease in entropy when using Scheme A (sedation points). The horizontal line in the box indicates the position of the median. The end of the bars define the 25th and 75th percentile, and the error bars mark the 10th and 90th percentile.

View larger version (44K): [in this window] [in a new window]   Figure 5. Box-plot illustration of changes in state (SE) and response (RE) entropy values in nine healthy volunteers (a) before, (b–f) during, and (g) after laserneedle acupuncture using two different acupuncture schemes (A and B). See Figure 4 for further explanations.

Acupuncture was performed by a professional acupuncturist (Lu Wang, MD, see Acknowledgments). After exact localization, based on the experience of the acupuncturist, sterile Chinese metal, one-use needles (0.25 x 25 mm; Suzhou Medical Appliance Factory, Suzhou, China) were punctured vertically and deeply during the respective triggering of the De-Qi sensation. In both schemes (A + B), a brief stimulation (duration, 30 s) of the needles was performed twice, from proximal to distal, in the same order as the acupoints mentioned in the text. A neutral technique with middle strength stimulation and constant pulling and pressing of the needle during stimulation was used in both schemes. The needles were removed after 15 min, and a concluding phase of 5 min followed.

Adequate laserneedle stimulation was performed as far as possible. Laserneedle acupuncture allows simultaneous stimulation of individual acupoint combinations. As a result, variations in acupuncture on the body, ear, or hand are possible, as performed in other published studies (20–24) by our research group. Methodical details can also be found in these previous studies. In this study, laserneedles emitted continuous laser light at a wavelength of 685 nm with an output of 30–40 mW per laserneedle.

Results were presented graphically using box-plot illustrations (SigmaStat; Jandel Scientific Corp., Erkrath, Germany). In addition, the paired t-test was used. The level of significance was determined by P 0.05.

	Results

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Nine of 10 volunteers participated in all 4 examinations and completed the study. One volunteer did not participate in the manual needle acupuncture investigation and was therefore not integrated in the statistical analysis. Figure 4 shows the results of SE and RE in 2 different acupuncture schemes (A and B) using needle acupuncture on nine test persons. Before needle acupuncture, the mean values (± sd) were SE = 86.6 ± 2.1 and RE = 97.6 ± 0.90. Ten minutes after the beginning of needling and immediately after stimulation with acupuncture Scheme A (Fig. 4e, left), the values decreased to SE = 75.8 ± 8.3 and RE = 85.1 ± 7.8. Two minutes after removing the needles (Fig. 4g, left) the reference values had not yet been reached (SE, 83.3 ± 5.0; RE, 92.0 ± 5.9). The decrease in measurement values compared with the reference value (Fig. 4a, left) reached the level of significance (P 0.01; paired t-test) for both types of entropy (SE and RE) when using Scheme A.

The second energetic acupuncture scheme (Fig. 4B, right) yielded a totally different result. Although the initial values of SE = 87.4 ± 1.2 and RE = 97.2 ± 0.8 were similar to those before needling using Scheme A, no significant reduction in values during or after acupuncture (10 min, SE = 85.6 ± 2.1 and RE = 95.4 ± 2.0; after, SE = 85.0 ± 2.9 and RE = 96.8 ± 1.4) occurred.

The behavior under painless laserneedle acupuncture was characterized by high needle equivalency (Fig. 5). Adequate responses were present. Before laserneedle acupuncture using Scheme A, the values of SE were 86.1 ± 1.6 and RE = 97.1 ± 1.4. Ten minutes after beginning laserneedle acupuncture, the values were SE = 80.7 ± 5.0 and RE = 90.9 ± 3.8. After ending stimulation, the measurement data for SE were 86.6 ± 1.4 and 96.2 ± 1.4 for RE. During manual needle acupuncture, stimulation using Scheme B did not lead to significant changes during and after stimulation (before, SE = 86.0 ± 3.2 and RE = 97.1 ± 1.3; 10 min, SE = 85.8 ± 1.9 and RE = 96.1 ± 1.2; after, SE = 86.2 ± 2.1 and RE = 96.4 ± 1.0).

Whereas an average decrease in both entropy values of 12.7% occurred during needle acupuncture using acupuncture Scheme A, laserneedle acupuncture under the same conditions showed a mean reduction in entropy of 6.4% (Table 1).

	Discussion

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Combined with the EEG, entropy is a new, nonlinear statistic parameter that describes the order of coincidental data, such as spontaneous cerebral electrical activity. The EEG shows more randomness and irregularity during the conscious state compared with the phase preceding actual sleep or in anesthetized patients. The entropy concept, as a possible standard to determine the depth of anesthesia or sedation, proposes that the EEG is not a summation of sine oscillations but shows nonlinear, chaotic behavior (4). Entropy values probably correlate with the depth of hypnosis (5–11). High values of entropy show a high irregularity of the signal, which is indicative for the consciousness of the patient. A more regular signal produces lower values of entropy.

For the first time, we investigated two entropy parameters using acupuncture (needles and laserneedles) in this study during the conscious state. Both manual acupuncture stimulation and laser acupuncture at sedative points decrease SE and RE, but there is no significant difference in SE and RE with either manual acupuncture or laser acupuncture stimulation at energy-enhancing acupuncture points. RE reacts to the activation of facial muscles (FEMG) very quickly, whereas SE is always less or equal to RE. SE allows the assessment of the basic hypnotic state in adult patients. SE is not influenced by sudden reactions of the facial muscles because calculation is mainly based on the EEG signal (Fig. 2). The manufacturer of the system gives the following conductance values for entropy as reference values: 100 = conscious and reactive to speech; 60 = clinically relevant anesthesia; 40 = consciousness improbable; and 0 = suppression of electrical cortical activity. These values can vary from person to person. Frequent eye movement, coughing, and movement causes artifacts and can influence registration. The maximum values of entropy in our measurements on conscious volunteers under acupuncture were SE = 89 and RE = 99, and minimum values were SE = 51 and RE = 66. Two volunteers showed intermittent values in SE < 60 (one with needle and one with laserneedle acupuncture; both during application of acupuncture Scheme A), which indicates clinically relevant anesthesia according to the manufacturer. However, RE values were never <60 in any case. The difference in both values of entropy (RE and SE) during conscious measurements (Figs. 4 and 5 and Table 1) results from the muscle activity in the face.

However, the EEG responses in this study seem to be transient. The increase of entropy values after the end of stimulation seems to suggest that there are no stimulation-induced long-term effects. The possible clinical relevance of this phenomenon could not be explained by the chosen study design. Further investigations are required to correlate the significant results with clinical parameters.

Until now, entropy parameters were mainly intraoperatively used to evaluate the hypnotic effect of anesthetics. Measurement of entropy during needle and laserneedle acupuncture performed in this study shows that the brain plays a key role in acupuncture (17,19–25). Several preliminary investigations regarding this topic showed that acupressure can induce major effects in brain-specific neuromonitoring (15,20). For the first time, this study design could prove that two different acupuncture schemes can influence different parameters in the brain. The so-called "sedation point scheme" (A) showed a significant decrease in both entropy parameters (RE+SE), which can be interpreted as a sedation effect in the EEG. In the same volunteer, a different acupuncture scheme (B), which according to traditional Chinese medicine leads to a general increase in Qi-energy, did not yield this effect. Moreover, several preliminary tests showed that the latter scheme leads to a significant increase in blood flow velocity in the middle cerebral artery (19–21,25), which was also manifested in the entropy measurements as rigid variability at a high base level (median, SE = 86 and RE = 96) (Fig. 4 and 5, left, and Table 1). In addition, this study proves that laserneedle acupuncture is needle equivalent regarding the values of entropy described and has an important ranking as a painless method of acupuncture.

The author thanks Ms. Lu Wang, MD, for performing acupuncture and Ms. Ingrid Gaischek, MSc, for her valuable support in data registration and analysis (both Research Unit of Biomedical Engineering in Anesthesia and Intensive Care Medicine, Medical University of Graz, Austria). We also thank Mr. Ludwig Bertignol and Mr. Karl-Heinz Aigner-Mühler from Sanitas Medizintechnik, Austria, for providing the Datex Ohmeda S/5 Entropy-Module.

	Footnotes

 
Accepted for publication February 6, 2006.

	References

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999