Shenting And Yintang: Quantification Of Cerebral Effects Of Acupressure, Manual Acupuncture, And Laserneedle Acupuncture Using High-Tech Neuromonitoring Methods
Gerhard Litscher, MDsc

ABSTRACT
Background In the field of computer-assisted monitoring during anesthesia, specialized cerebral neurophysiologic monitoring includes several indexes.
Objective To investigate cerebral effects of sensory (acupressure, acupuncture) and optical (laserneedle acupuncture) stimulation of the acupoints Shenting and Yintang, on electroencephalographic bispectral index (BIS) and A-line ARX-index (AAI).
Design, Setting, and Patients A partly randomized controlled crossover trial of 57 healthy volunteers (mean [SD] age, 26.1 [3.6] years; 35 women and 22 men) were investigated during the awake state. The acupuncture points Shenting and Yintang and a placebo control point were stimulated.
Main Outcome Measures The main evaluation parameters were the BIS and the AAI during different conditions and time intervals. The whole study session lasted 2-3 hours. BIS and AAI represent a single number, which should decrease continuously with decreasing level of consciousness. In addition, functional magnetic resonance imaging (fMRI) investigations were performed.
Results Values for BIS (P<.001) and AAI (not significant) both decreased during acupressure on Shenting and Yintang. BIS was also significantly (P<.05) affected by laserneedle acupuncture and acupressure on the control point. Significant effects were also seen in frontal brain activation (fMRI) due to laserneedle stimulation of Shenting.
Conclusions Our findings demonstrate electroencephalographic similarities of acupressure-induced sedation (Shenting and Yintang) and general anesthesia as assessed by BIS and AAI.
KEY WORDS
Shenting, Yintang, Electroencephalogram, Bispectral Index, A-line ARX-index, Acupressure, Acupuncture, Laserneedle Acupuncture

INTRODUCTION
Multimodal cerebral neuromonitoring may detect stimulation-induced alterations of cerebral functions for which any single monitor may be unreliable. Specialized cerebral neurophysiologic monitoring includes electroencephalographic (EEG), bispectral analysis and calculation of the A-line ARX-index (AAI), as well as functional magnetic resonance imaging (fMRI).

In the field of computer-assisted monitoring during anesthesia, multimodal neuromonitors are primarily used to make anesthesia as safe as possible for every patient.¹ The bispectral index (BIS) is an important numerical descriptor of the EEG and is mainly used for assessing depth of anesthesia.² If anesthetists rely on BIS to detect patient awareness, then it is very important to exclude other influences that could give false readings. A number of environmental and physiologic factors may affect BIS performance. The interpretation of the middle latency auditory evoked potentials (MLAEP) is based on the decrease of the peak amplitudes, and increase of peak latencies that take place during increased doses of volatile or intravenous anesthetic agents. This morphological change of the MLAEP is mapped into an index, the AAI.³

Recently, it was reported by our group and others that also nonpharmacological interventions such as acupressure or acupuncture can reduce BIS and AAI values significantly.^4-7

Shenting (GV 24) is located 0.5 cun directly above the midpoint of the anterior hairline. Indications for its use are epilepsy, anxiety, palpitations, insomnia, headache, vertigo, and rhinorrhea. The extra point Yintang is plainly on the Du meridian, lying as it does directly above the nose between the inner ends of the eyebrows in the position of the "third eye" of some cultures. It is not clear from literature why it is considered as an extra point because it has been in use for hundreds of years.⁸

This study was a randomized, controlled, partly blinded (laser-needle acupuncture) crossover trial to investigate the cerebral effects of 3 nonpharmacological interventions (acupressure, manual needle acupuncture, and laserneedle acupuncture) on the 2 acupoints Shenting and Yintang.

Figure 1. Different conditions of the crossover study design: (a) acupoint Shenting (GV 24), (b) acupressure at the acupoint Yintang (Ex.1), (c) manual needle acupuncture at Yintang, (d) laserneedle acupuncture at Yintang, (e) acupressure at a control point, and (f) laboratory at the Medical University of Graz. Photographs printed with permission by the volunteers.

MATERIAL AND METHODS
Participants
We studied 57 healthy volunteers (mean [SD] age, 26.1 [3.6] years, range 21-39 years; 35 women and 22 men). None had neurological or psychological disorders and they were not taking any medication. They were partly informed about the nature of the investigation and were paid for their participation. The investigators recording EEG and AAI data were blinded to the intervention. Written informed consent was obtained from each participant. The study was approved by the ethics committee of the Medical University of Graz, Austria.

Study Design
This study was performed as a randomized, controlled crossover trial in different parts. Four EEG electrodes for BIS monitoring (F7-Fpz, F8-Fpz, Fz = ground) and 3 electrodes for AAI monitoring (1 at the median forehead, 1 laterally at the right side [positive] of the forehead [reference], and 1 at the right mastoid bone [negative]) were attached to the participants after they arrived at the biomedical engineering laboratory.

Two channels of spontaneous electrical activity were recorded from electroencephalographic (EEG) electrodes (Zipprep self-prepping electrodes; Aspect Medical Systems Inc, Natick, MA). The skin-electrode impedance was < 2 kOhm. Low cutoff frequency was 2 Hz and high cutoff frequency was 30 Hz. The EEG was measured continuously using an Aspect A-1000 system (Aspect Medical Systems Inc, version 3.12).For AAI-monitoring, an AEP-monitor/2 (Danmeter, AAI version 4.2, Odense, Denmark) was used. Acoustic stimuli of 0.2 ms in duration were administered through small earphones at a rate of 9 per second. Click intensity was 75 dB sound pressure level. AAI index is calculated in the 20-80 ms window of the MLAEP, and latency and amplitude changes are weighted equally.

A period of 5 minutes was allowed for each participant to obtain steady state values. Acupressure on the acupoint Shenting was performed in a group of 21 volunteers (mean [SD] age, 25.9 [3.7] years; 12 women and 9 men). In addition, multimodal measurements were made in 25 participants (mean [SD] age, 25.5 [4.0] years; 15 women and 10 men) assigned to 1 of 4 conditions: acupressure at the acupoint Yintang, manual needle acupuncture at Yintang, laserneedle acupuncture at Yintang, or acupressure at a control point (Figure 1). Eleven participants (mean [SD] age, 26.4 [3.3] years; 8 women and 3 men) were investigated using the A-line ARX-monitor (AAI) before, during, and after performing acupressure on the acupoint Yintang. In total, there were 4 treatments and additionally, to investigate a possible placebo effect, we used acupressure at a control point.

To assess the reliability and validity of acupressure and manual needle acupuncture, pressure on both acupoints and the control point was applied by the same Chinese medical doctor experienced in Traditional Chinese Medicine (TCM). The thumb pressure was estimated to be about 3 x 105 Pa (mean force measured <30 N / 1 cm2).

Manual needle acupuncture was performed using sterile single-use needles, 0.30 x 30 mm (Huan Qiu, Suzhou, China). After local disinfections of the skin, the needling method was oblique in a caudal direction (0.5 cm). Stimulation for 20 seconds in intervals of 2 minutes consisted of a combination of rotating and thrusting movements using a special manual acupuncture stimulation technique (sedation method). The needle was removed after 10 minutes.

Laserneedle acupuncture was performed using a new method for optical stimulation. (This method was reported recently by our research group. 9-11) The laserneedle technique represents a new, noninvasive method for optical stimulation of acupuncture points. The laser used in this study emits red light in continuous-wave mode with an output power of 30-40 mW, which results in a radiant exposure energy of about 2.3 kJ/cm2 at the acupuncture point during a stimulation time of 10 minutes.^9-11

Acupressure on the control point (2 cm from lateral end of the left eyebrow) was performed in a similar manner as on the acupoints Shenting and Yintang (duration, 10 minutes).

Thirty-two subjects (Shenting or Yintang) had 1 condition (acupressure), and 25 (Yintang) had 4 conditions applied. All participants were in a semi-lying position with closed eyes. The choice of the stimulation procedure was randomized within a participant, and the interval between the different sessions was at least 20 minutes.

Evaluation Parameters
The main evaluation parameters were the BIS and the AAI during different conditions and time intervals (Figure 2). In any one condition, we recorded BIS and AAI values continuously but sampled the data for subsequent analysis at 7 points. A single reading was taken at each point. The stimulation was not stopped at the time of reading. The whole study session lasted 2-3 hours. BIS and AAI represent a single number, which should decrease continuously with decreasing level of consciousness (hypnosis). There are several review articles for the methodological details of signal processing.²

The specific method applied by the MLAEP is an autoregressive with exogenous input (ARX) model. Similar to the BIS, a dimensionless index is generated with the end points 0 and 100 (= awake).

After 5 minutes of stimulation (Figure 2), participants were asked to move their right hand to clarify that they were not asleep. Heart rate and noninvasive blood pressure were also recorded before and after acupressure stimulation at Shenting and Yintang.

Figure 2. Measuring procedure: a = before, b - f = during, g = after stimulation.

The fMRI investigations were performed using a 1.5-T total body system (Intera, Philips Medical Systems, Best, Netherlands). The blood oxygen level-dependent contrast sensitive images were acquired with a T2-weighted gradient echo sequence (single shot planar read-out, flip angle 90°, TE 50 ms, FOV 250 mm, matrix 96 x 96 interpolated at 128 x 128, layer number 30, layer thickness 4 mm). A total of 144 volume images were registered continuously in succession, with a repetition time of 5 seconds.

The fMRI study was based on a block design with alternating resting conditions for 1 minute, and 1 minute of laser needle activation. A total of 6 resting and 6 activation intervals were registered. Each fMRI data registration required 12 minutes.

Statistical Analysis
The BIS and AAI data were tested with Friedman repeated measures analysis of variance on ranks and one-way repeated measures ANOVA using SigmaStat (Jandel Scientific Corp, Erkrath, Germany). As post hoc analysis, Dunnett's method was used. The results were graphically presented as box plots. Changes were considered significant at P<.05.

The fMRI data were analyzed and evaluated with statistical parametric mapping software (SPM 99, Department of Imaging Neuroscience, London, England). All images of the participants were newly organized and the lst picture was used as reference, whereby "sinc-interpolation" was used.

Functional data were spatially smoothed with a 6-mm full width at half maximum isotropic kernel. A boxcar waveform convolved with a synthetic hemodynamic response function was used as the reference waveform. A t test was performed to identify regions showing significantly higher activation during the activation condition vs the resting condition. For significantly activated regions, a statistical threshold of P<.05, corrected at the cluster level for multiple comparisons, was used. The activated regions were located using the Tailairach space.

RESULTS
Shown in Figure 3 are the decreases of BIS values during acupressure applied to the acupoint Shenting in 21 healthy volunteers, and are shown in Figure 4 during acupressure at the acupoint Yintang in 25 participants. The BIS values decreased significantly (P<.001) during acupressure on both acupoints. The release of acupressure caused an increase in BIS back to the baseline values before stimulation.

Summarized in Figure 5 are the BIS results obtained during manual needle acupuncture, laserneedle acupuncture, and acupressure on the control point. Significant (P<.05) changes were found in BIS values during laserneedle acupuncture (measuring points d and e), and during acupuncture on the control point (measuring points d-f). After 7.5 minutes of laserneedle acupuncture at acupoint Yintang, the mean (SD) BIS values were 95.4 (4.1). After 5 minutes of acupressure at the control point, the mean (SD) BIS values were 94.2 (4.8).

The AAI results after acupressure on the acupoint Yintang are presented in Figure 6; values ranged from 26 to 99 (mean, 54.5) before intervention. After pressure on Yintang, the AAI values steadily decreased during the experimental procedure (mean, 45.0).

Typical results of the fMRI analysis are shown in Figure 7, and Table 1.

Heart rate and blood pressure before and after acupressure at Shenting and Yintang were calculated to be a mean (SD) of 73.2/min (12.4)/min, 109.8 (14.0) mm Hg systolic, and 69.3 (10.6) mm Hg diastolic. After stimulation, the values decreased to 63.7/min (11.9)/min, 107.7 (8.7) mm Hg systolic, and 66.8 (8.6) mm Hg diastolic. An example of multimodal monitoring of standard parameters during acupressure is shown in Figure 8.

DISCUSSION
Acupressure, acupuncture, meditation, hypnosis, and relaxation techniques are all considered to be forms of complementary and alternative medicine. Acupuncture and acupressure have been studied and determined to be valuable in improving the quality of sleep.¹² It has also been shown that pressure on acupoints can decrease postoperative pain,¹³ and that Korean Hand acupressure reduces postoperative nausea and vomiting after gynecological laparoscopic surgery.¹⁴ Acupressure has also been used for prevention of emesis.¹⁵ There are a number of theories as to how acupressure or acupuncture works. All these hypotheses postulate that the brain plays a key role in acupuncture and acupressure.^16-19 Modulation of subcortical structures may be an important mechanism by which acupuncture and acupressure exert complex multisystem effects.¹⁹ Demonstration of regionally specific and quantifiable acupuncture and acupressure effects on relevant structures of the human brain would facilitate acceptance and integration of these therapeutic modalities into the practice of Western medicine.^16-19
 

Figure 3. Box plots of alterations of bispectral index (BIS) values in 21 healthy volunteers before (a), during (b -f), and after (g) acupressure (see Figure 2) on the acupoint Shenting. The ends of the boxes define the 25th and 75th percentiles, with a line at the median and error bars defining the 10th and 90th percentiles. Outliers are shown as circles. Figure 4. Box plots of changes of bispectral index (BIS) values in 25 healthy volunteers during acupressure at the acupoint Yintang. See Figure 3 for definitions. Figure 5. Box plots of changes of bispectral index (BIS) values during manual needle acupuncture (a), laserneedle acupuncture (b), and acupressure at the control point (c). See Figure 3 for definitions. Modified from.4 Figure 5a Figure 5b Figure 5c

The BIS is mainly used intraoperatively to monitor the hypnotic effect of anesthetic drugs. There are several studies proposing target values for EEG parameters to guide the depth of anesthesia. A number of authors have reported a low probability of recall and a high probability of unresponsiveness during surgery at a BIS level of 60.^20,21 BIS values lower than 50 are described as suppressing hemodynamic responses during intubation.²² Chan and Gin²³ reported recently that statistically, it would be extremely unlikely for a patient to be aware when BIS is lower than 50 and, in fact, there has not been a single case of frank awareness at this level. In that context, our results showed that 10 of 25 awake healthy volunteers (40%) had Yintang acupressure-induced BIS values below 50 and 21 of 25 (84%) below 60.4.

It has been shown that different narcotics have a different influence on BIS.^20-29 However, nonpharmacologic influences such as electromyographic activity may contribute to the low specificity of the absolute values of the electrophysiological measurement data.²⁴ In the majority of the cases, the BIS is falsely elevated.²⁴ Our results appear to confirm those of Fassoulaki et al⁵ who also found that acupressure on Yintang resulted in a significant and clinically relevant reduction in BIS values. They also concluded that BIS is therefore of limited clinical relevance for monitoring depth of anesthesia.^25-29 However, Fassoulaki et al⁵ did not investigate the effects of manual needle acupuncture or laserneedle acupuncture.

Figure 6. Box plots of alterations of A-line ARX-index (AAI) values in 11 healthy volunteers during acupressure at the acupoint Yintang. Target values for "awake," "light anesthesia," and "surgical anesthesia" are indicated.

Our findings show that volunteers subjected to acupressure at Yintang can have similar BIS and AAI values to those of anesthetized patients. While it is unlikely that a patient will receive acupressure or acupuncture during surgery, the question remains as to what causes BIS and AAI readings below 50 in awake subjects. It is unlikely to be a placebo effect because we have shown in several test measurements using placebo points that BIS values are not affected by laserneedle stimulation per se. In a preceding study, there were small, statistically significant but not clinically important, changes with needle acupuncture, laserneedle acupuncture, and acupressure at a control point.⁴ These findings also help confirm that the BIS and AAI reductions induced by acupressure at Shenting and Yintang are not a placebo effect. Reduced electromyographic levels could be partially responsible.²⁴

It is unclear to what degree system algorithms contribute to such findings. BIS is affected by electrical activity nearby, especially diathermy. Therefore, it is possible that local movement in the region of the recording electrode might be responsible for the EEG effects observed. These are apparently less during control point acupuncture than during Shenting or Yintang acupressure, where pressure is applied to a point adjacent to the electrode. Further investigations are necessary to clarify these questions.

Table 1. Regions of significant activation due to laserneedle stimulation at the acupoint Shenting Brain region Brodmann Area Coordinates in Tailarach space (x, y, z) L superior frontal gyrus 11 -15 50 -18 Inferior temporal gyrus   38 -22 -30 L superior temporal gyrus   -15 50 -18 L percental gyrus 6 -58 4 10 L limbic lobe 28 -24 -13 -30 L inferior frontal gyrus   -30 21 -14 L postcentral gyrus   -58 -17 22 L medial frontal gyrus 11 -7 58 -18 L frontal lobe   -17 30 -14 L inferior frontal lobe   -19 32 -22

CONCLUSION
We found in healthy awake volunteers that acupressure at Shenting and Yintang results in statistically significant and clinically relevant reductions in BIS and insignificant reductions in AAI, while needle acupuncture, laserneedle acupuncture, and acupressure at a control point result in statistically significant but clinically unimportant reductions.

Funding/Support
The monitor was provided for this study by Danmeter (Odense) without charge. We thank Managing Director Kim Gommesen for his help.

The author is not part of any agreement concerning the measurement devices and did not receive financial support from the manufacturer.

ACKNOWLEDGEMENTS
The author thanks Dr Lu Wang and Ingrid Gaischek (both from the Department of Biomedical Engineering and Research in Anesthesia and Intensive Care, Medical University of Graz) for their valuable help.

Figure 7. Typical results from functional magnetic resonance imaging (fMRI) investigations in a 29-year-old woman. Note the significant effects of changes in frontal brain activation during laserneedle stimulation at the acupoint Shenting (see Table 1). Figure 8. Multiparametric monitoring during acupressure at Yintang. From left to right: electroencephalographic (EEG) compressed spectral array (CSA), amplitude integrated EEG (CFM, cerebral function monitor), bispectral index (BIS), heart rate (HR), and heart rate variability (HRV).

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AUTHOR INFORMATION
Dr Gerhard Litscher is Doctor of Medical Sciences and Doctor of Technical Sciences, and is Head of the Department of Biomedical Engineering and Research in Anesthesia and Intensive Care at the Medical University of Graz, Austria. Dr Litscher's special interests include Neuromonitoring and acupuncture research.

Gerhard Litscher, PhD, MSc, MDsc*
Department of Biomedical Engineering and Research in Anesthesia and Intensive Care Medicine
Medical University of Graz
Auenbruggerplatz 29
A-8036 Graz
Austria
Phone: +43 316 385-3907
Fax: +43 316 385-3908
E-mail: gerhard.litscher@meduni-graz.at
http://litscher.info
http://litscher.at
www.neuromonitoring.org

*Correspondence and reprint requests

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