Activated and deactivated functional brain areas in the Deqi state: A functional MRI study.

We compared the activities of functional regions of the brain in the Deqi versus non-Deqi state, as reported by physicians and subjects during acupuncture. Twelve healthy volunteers received sham and true needling at the Waiguan (TE5) acupoint. Real-time cerebral functional MRI showed that compared with non-sensation after sham needling, true needling activated Brodmann areas 3, 6, 8, 9, 10, 11, 13, 20, 21, 37, 39, 40, 43, and 47, the head of the caudate nucleus, the parahippocampal gyrus, thalamus and red nucleus. True needling also deactivated Brodmann areas 1, 2, 3, 4, 5, 6, 7, 9, 10, 18, 24, 31, 40 and 46.

Research Highlights

The present study measured brain activity during true needling accompanied by Deqi sensation (soreness, numbness, heaviness, and distension) in physician and subjects, and compared it to brain activity accompanying non-sensation during sham needling.

Functional MRI identified activated and deactivated brain areas in the Deqi state.

Abbreviations

fMRI, functional MRI; BA, Brodmann area

INTRODUCTION

Deqi, also called needling sensation, is a special phenomenon that occurs following needling. When a needle is inserted, the physician feels a subsidence of the tip of the needle, while the person who receives the needling feels local soreness, numbness, heaviness and distension, or a spread of the sensation along a certain route[12]. Deqi is a unique sensation essential for clinical efficacy according to traditional Chinese medicine. It has been proven by recent clinical practice[134], but there is a lack of scientific evidence of Deqi.

Deqi relies on subjective descriptions from both patient and acupuncturist, and can therefore not be objectively assessed. Recent studies of Deqi have mainly focused on two aspects: (1) objective quantitative determination of Deqi, and (2) the essence of Deqi[5].

Large-sample studies of subjective sensations in the Deqi state have found that the nature of Deqi (a comfortable feeling in the patient) is distinct from pain[5678]. In addition to the visual analogue scale, special scales have been developed for the identification of Deqi and for assessment of its strength[910]. Furthermore, it has been shown that Deqi should be induced by insertion of the needle to a certain depth and stimulation with twirling manipulation[11]. This is different from the shallow insertion with sham twirling used in studies utilizing the visual analogue scale.

In addition to the studies of the subjective experience of Deqi, some research has focused on identifying anatomical correlates of Deqi induction. Shi et al[12] used light and electron microscopy to observe guinea pig tissue after needling, and reported that Deqi experienced by the acupuncturist was related to insertion into local connective tissue. Kimura et al[13] found that when the needle was withdrawn immediately upon the onset of Deqi, the transparent tissues attached to the needle tip contained many collagen fibers and mast cells, as confirmed by electron microscopy and immunohistochemistry. Analysis of the relationship between Deqi and peripheral afferent nerve fibers showed that Deqi induction was associated with needle insertion into slow conduction fibers[141516].

Some studies have focused on changes in brain activity in the state of Deqi. Yin et al[17] observed that the strength of the subjective feeling was correlated to the power of α and δ activity on electroencephalography. Takamoto et al[18] found that blood oxygen concentration decreased in the supplementary motor area upon Deqi induction, based on functional near-infrared spectroscopy. Using functional MRI (fMRI), Asghar et al[19] observed that Deqi was associated with decreased activity of limbic subcortical structures and cerebellum compared with activity during uncomfortable pain. The sensation of Deqi is different in human beings than in animals[20]. Studies should focus on the brain, because it is pivotal in integrating afferent signals induced by the needling and mediating the therapeutic actions on target organs[2021].

fMRI is superior for space-time discrimination, and is well suited to identifying changes in cerebral function in the Deqi state[21]. In contrast to the previous study[19], which compared Deqi with uncomfortable pain, the present study focused on comparing non-feeling with typical Deqi, to test the hypothesis that Deqi produces a specific pattern of cerebral activation/deactivation compared with sham needling.

RESULTS

Quantitative analysis of participants

A total of 12 healthy participants were included in the analysis.

Classification of subjective sensations of physician and subjects

Of the 12 participants, 6 were subjected to needling at Waiguan (TE5) and the others received needling at a sham point. All subjects received true and sham needling. Upon completion of the needling, subjects and physicians were asked to report on their experience during the needling. The subjects were asked to choose between “no feeling”, “soreness, distension or heaviness”, and “uncomfortable sharp pain”, and the physician was asked to choose between “empty” or “tenseness and heaviness” around the tip of the needle.

The physician claimed that he did not experience any tenseness or heaviness during sham needling of either the Waiguan or the sham point, but that there was a feeling of tenseness and heaviness during true needling of either points (Table 1). Patients were assigned to groups according to their reported sensation, and the activity of functional brain areas was compared between the Deqi state (true needling: soreness, numbness, distending; n = 10) and non-Deqi (sham needling: no feeling, n = 7).

Table 1

Needling sensation reported by physician and subjects

Activated brain areas in the Deqi state

True needling with Deqi activated the right Brodmann areas (BA) 3, 6, 8, 9, 10, 11, 20, 37, 39, and 47 compared with sham needling. It also activated the head of caudate nucleus, the parahippocampal gyrus, thalamus red nucleus, and the left BA 3, 6, 9, 10, 13, 21, 40, 43, 47, (Table 2, Figure 1).

Table 2

Activation of brain areas in the Deqi state compared between true and sham needling

Figure 1

Activation of brain areas in the Deqi state compared between true and sham needling.

Row 1: Sagittal plane; row 2: occipital area; row 3: lateral plane; row 4: inferior and superior surfaces. The color shows the activated areas (low to high degree showed by red to yellow).

fMRI showed that true needling with Deqi decreased the activity in the right BA 1, 3, 4, 7, 9, 18 and 24, and the left BA 2, 3, 5, 6, 9, 10, 31, 40 and 46 (Figure 2 and Table 3).

Figure 2

Deactivation of brain areas in the Deqi state compared between true and sham needling.

Row 1: Sagittal plane; row 2: occipital area; row 3: lateral plane; row 4: inferior surface and superior surface. The color shows the deactivated areas (low to high degree showed by red to yellow).

Table 3

Deactivation of brain areas in the Deqi state compared between true and sham needling

DISCUSSION

The experimental design of studies of Deqi is difficult because of the reliance on the subjective experience of both physician and needling receivers. In the physician, Deqi might appear as soon as the needle is inserted, or after twirling, lifting and thrusting. Sensations in the needling receiver can be described as more than ten types of sensations with different degrees of strength. In addition, reports by the physician and the receiver do not always match.

The present study utilized fMRI to assess brain activation in the Deqi state[2022]. Strictly speaking, the study should also have included the following groups: Deqi in both physician and subject; Deqi in physician and non-sensation in subject; Deqi in physician and uncomfortable pain in subject; non-sensation in both physician and subject; non-sensation in physician and Deqi in subject; and non-sensation in physician and uncomfortable pain in the subject. In addition, we should have made a comparison between true and sham points. Asghar et al[19] studied the difference between Deqi and uncomfortable pain, but the present study focused on comparing Deqi with non-sensation, according to the post-needling feeling of both physician and subjects.

In this study, the physician reported Deqi during needling at both true and sham points, and reported non-sensation during sham needling at both true and sham points. However, the experience of the subjects was different. Deqi was mainly reported in the subjects who received needling at true and sham points, whereas non-sensation was reported during sham needling at the true point. Non-sensation, uncomfortable pain and Deqi were all reported during sham needling at the sham point. The results could not be processed statistically since the sample size was too small. However, the subjective feelings of the receivers of sham needling at the sham point varied, and the implications of these findings for clinical practice require further study.

We found a large number of activated and deactivated regions in the brain during the Deqi state. An interesting finding was that the activated regions were concentrated in brain areas that control somatic sensation and motor output, vision, gustation, language, and spatial orientation. The deactivated regions were concentrated to brain areas controlling somatic sensation and motor output, vision, affection, cognition, and spatial orientation, as well as frontal anterior and limbic-parietal association areas. These results indicate that in the state of Deqi, the effect of needling at Waiguan to treat motor and sensory dysfunction of the upper limbs and disorders of the eyes and ears, and to reduce heat and regulate mental disorders, could be manifested more completely.

Another interesting finding was that both activated and deactivated regions appeared in a same BA, such as BA3, 6, 9, 10 and 40, suggesting that those brain areas are very active in Deqi state after needling.

Among areas with changed activity during Deqi, we focused on those showing mixed activation and deactivation. These areas process somatic sensorimotor information and are part of the association areas of the cortex. Under Deqi conditions, needling action included two aspects: effects on certain brain areas to cause curative effects, and strengthening of limbic-cortex associations. In contrast to a previous study[19], we did not find any areas with changed activity in the cerebellum. Similar to the study of Asghar et al[19], Deqi was also found to be related to the association areas of the brain, indicating an effect of needling on functional connectivity of the brain.

In fact, acupoint stimulation has different effects in physiological versus pathological states. Future studies should focus on pathological states. Also, there is a shortage of fMRI studies of needling that use a block design[23]. Subsequent studies could use scans of resting functional connectivity[242526] to reveal the essence of Deqi.

SUBJECTS AND METHODS

Design

A block design, neuroimaging study.

Time and setting

The experiment was performed at the Guangzhou University of Chinese Medicine, and the Southern Medical University, China, from 2008 to 2010.

Subjects

Twelve right-handed healthy volunteers were recruited from different universities in Guangzhou, China. The inclusion criteria were as follows: (1) 21–28 years old undergraduate/postgraduate students majoring in a non-medical subject; (2) non-smokers with regular eating habits without excessive consumption of liquid, tea or coffee, normal sleep, and normal body structure; (3) no metal in his/her body (such as heart stents); (4) no acupuncture treatment within 3 months prior to the experiment; (5) passed a screening test performed 3 months before the experiment (all the volunteers received the screening test by true/sham needling); and (6) agreed to sign the informed consent. The study was ethically approved by declaration of Helsinki.

The subjects included 6 males and 6 females, with an average age of 22.83 ± 2.32 years (range 21–27 years), weight of 55.33 ± 8.44 kg (44–70 kg), and height of 165.42 ± 9.61 cm (155–183 cm).

Methods

True and sham needling

The 12 volunteers were equally assigned to two groups. Subjects in the Waiguan group received sham and true needling at Waiguan, while the subjects in the sham point group received sham and true needling at a sham point.

The Waiguan acupoint was located on the forearm, 2 cun above the transverse crease of the dorsum of the wrist, between the radius and ulna (cun is a unit of length that refers to the width of the interphalangeal joint of the patient's thumb; Figure 3)[27].

Figure 3

Location of Waiguan (TE5) and sham point.

The directions of needling were perpendicular.

True and sham needling was delivered by one acupuncturist who had been in charge of a needling sensation screen three months earlier. The volunteers were blinded to the type of needling they received. True needling: The skin was sterilized locally and the needle was inserted using the tube insertion method. The tubes were purchased from Dongbang AcuPrime Co. (Exeter, England) and the 0.3 cm × 40 cm silver needles from Zhongyan Taihe Co. (Beijing, China). The physician put the auxiliary part of the tube on the skin at the acupoint, inserted the needle into the tube, and tapped the end of the needle to insert its tip into the tube. Then, the tube was removed and the needle punctured to a depth of 15 ± 2 mm. The handle of the needle was twirled to induce the needling sensation. Then, the physician manually applied an even reinforcing and reducing manipulation, by twirling the needle ± 180°, at 60 times/min. Twirling and non-twirling stimulation was alternated in blocks of 30 seconds, and the stimulation was lasted for 360 seconds in total (Figure 4). Sham needling: Sterilization procedures and needling instruments were the same as the above. However, instead of subcutaneous insertion of the needle, the stimulation was designed to provide alternating 30 seconds blocks of touching the skin with the tip of the needle (tactile stimulation) and then lifting the needle. The stimulation lasted for 360 seconds (Figure 5).

Figure 4

Block design of true needling at the Waiguan (TE5) and sham points. s: Second.

Figure 5

Block design of sham needling at the Waiguan (TE5) and sham points. s: Second.

Subjects in both the sham and true needling groups initially received sham needling, and true needling began one week later. Their brains were scanned by fMRI during the sham/true needling. After the scan, the subjects were asked to report on his/her experience during the needling, selecting between “soreness, numbness and distention”, “uncomfortable pain” and “non-sensation”.

Re-grouping

The subjects were re-grouped based on their report on needling sensation. When non-sensation was reported from both the physician and the subject, the subject was assigned to the “non-Deqi group”. When typical Deqi occurred (soreness, numbness and distention reported by the subject; and tenseness and heaviness at the tip of the needle reported by the physician), the subject was assigned to the “Deqi group”. Brain activation and deactivation were compared between the two groups.

fMRI scan

fMRI scanning was performed with a 3.0 T whole-body MRI scanner (GE, Bethesda, MD, USA) and a standard head coil. The subjects were blindfolded (Xinhua Tourism Co., Hangzhou, China) and used earplugs (Aearo Co., Hartford, Connecticut, USA). The subject had a rest on the bed for 5–10 minutes before the scan. The scan covered the entire brain and the images were parallel to the anterior/posterior commissure (AC-PC) line. The scan was divided into two parts. The first part was the collection of three-dimensional anatomy images with T1-weighted three-dimensional gradient echo-pulse fast spin sequence for 3 minutes with axial view T1 fluid-attenuated-inversion-recovery scan; repetition time, 2 300 ms; echo time, 21 ms; time of inversion, 920 ms; slice thickness, 6.0 mm; gap 1.0 mm for 20 layers totally; field of view, 24 cm × 18 cm; matrix, 320 × 256; NEX = 2; field of view echo train length, 9; and band width 50. Another part of the scan was the collection of blood oxygenation level-dependent functional images with single provocation echo-planar imaging sequence for 6.5 minutes with gradient echo/echo-planar imaging/90 (90° pulse); repetition time, 3 000 ms; echo time, 20 ms; flip angle, 90°; field of view, 24 cm × 24 cm; slice thickness, 6.0 mm; slice gap, 1.0 mm; matrix, 96 × 96; NEX = 1; phase per location, 130, 2 600 phases for 6 minutes and 30 seconds.

Data analysis

The fMRI data were processed with the software Statistical Parametric Mapping (SPM2, http://www.fil.ion.ac.uk) and a matched operating platform of Matlab 6.1 (Mathworks, Natick, MA, USA)[28]. Slight movements of the head were corrected by the Realign module; then, the images were normalized to the Montreal Neurological Institute space and smoothed spatially by a Gaussian kernel of 5 mm × 5 mm × 5 mm. The smoothed data were analyzed with a generalized linear model voxel by voxel. The t value of each voxel was calculated by two-sample t-tests, and statistical parametric mapping was based on the t values (P < 0.001, uncorrected, K > 30). Significant changes in different brain regions during non-sensation and Deqi were identified and superposed on the standard brain image mode of each subject's anatomic images. All the images of a group were combined into a standardized model. Then, the two-sample t-test model with the results from fixed effects analysis was used to compare the differences between Deqi and non-sensation. The results were reported by the coordinates of the Talairach space, and activated/deactivated areas were showed with red color in figures.