Brain Functional Magnetic Resonance Imaging (fMRI) Study On Manual Acupuncture At LI4 (Hegu)

OBJECTIVES: Acupuncture, an ancient therapeutic technique, is emerging as an important modality of complementary medicine in china. The efficacy of acupuncture treatment is not yet widely appreciated. Demonstration of regionally specific, quantifiable acupuncture effects on relevant structures of the human brain would facilitate acceptance and integration of this therapeutic modality into the practice of modern medicine. For future studies on mechanisms of acupuncture action in therapeutic interventions, functional magnetic resonance imaging (fMRI) was used to investigate the brain activation of 13 healthy volunteers in response to manual acupuncture at LI4 (Hegu) versus Superficial tactile stimulation.MATERIALS AND METHODSSubjects: Thirteen right-handed, healthy volunteer adults, 7 male and 5 female, ages 22-24 participated in the experiment. All of the volunteers had not experienced acupuncture before, and none had a history of psychiatric or neurologic disorders or head trauma with loss of consciousness, nor intake of tranquilizing drugs in the previous 3 days.Experimental protocol: Each subject was put into the scanner and instructed to close his or her eyes and relax throughout the imaging session. Four MRI scan runs were performed, two runs for manual acupuncture and two for Superficial tactile stimulation. The Superficial tactile stimulation was always performed before manual acupuncture for all subjects. Both of the manual acupuncture and Superficial tactile stimulation were performed at acupoint LI4 on the right hand. Intermittent acupuncture stimulation was delivered using a sterile disposable stainless steel needle (0.30 mm in diameter). The frequency of stimulation was matched as closely as possible across subjects. For manual acupuncture, the needle was rotated manually clockwise and counterclockwise at a rate of about 180 times per minute (3 cycles per second, 3 Hz). A Superficial tactile stimulation was applied on the palm surface of LI4 with the opposite to the needle tip. To match typical clinical administration paradigms, the intensity for manual acupuncture was chosen to elicit a moderate degree of the unique acupuncture sensation called de qi. Despite our efforts to match stimulation intensity, the sensations reported by subjects were different in the two modalities.A block design was adopted for each functional run. We adopted a 3minute and 12 seconds scan time for each functional run. This started with 30 seconds of rest, followed by 24 seconds of stimulation, then 30 seconds of rest, followed by 2 times of stimulation, and 3 times of rest again. The interval between two functional runs was approximately 3 minutes for the same acupuncture modality and at least 5 minutes between different acupuncture modalities. Acupuncture was performed by the same acupuncturist on all subjects.After scanning was completed, subjects were questioned as to the sensation that they experienced when acupuncture stimuli were applied during each run.Apparatus and scanning procedures: fMRI scanning was conducted on a 1.5 T General Electric (GE Medical Systems) Signa scanner using a three-axis local gradient coil with an insertable transmit-receive radio frequency coil optimized for wholebrain echo-planar imaging (EPI). Functional imaging used a gradient-echo EPI sequence with the following parameters: 50-ms echo time, 3-second repetition time, 240mm×180mm field of view, 64×64 pixel matrix, 10 mm slice thickness, and 2.5mm interslice gap. Eight (8) contiguous axial slice locations were imaged encompassing the whole brain down to the level of the pons. Sixty-four (64) sequential images were collected at each of the slice locations. High-resolution, T1-weighted anatomic reference images were obtained as a set of 128 contiguous slices using a three-dimensional fast-spoiled gradient-echo sequence (FSPGR). For each scan, the room lights were dimmed and the subjects instructed to close their eyes. Padding was placed around the head. Each 64-image EPI series began with one baseline images (3 seconds) to allow the MR/signal to reach equilibrium, followed by 63 images on which analysis was performed.Data analysis: All data processing was conducted with the software package AFNI (Analysis of Functional Neurolmage). Motion correction was first applied to the functional data. One subject whose fMRI time series had perceptible, residual head movements based on cinematic viewing was excluded from further analysis. Then, the two runs for each modality of stimulation were concatenated to produce a single long functional run. Next, for each concatenated functional run (one for manual acupuncture and one for Superficial tactile stimulation) of each subject, the time points during acupuncture manipulations (n=48) were compared, on a voxel by voxel basis, against all other time points (n=60). This procedure generated statistical parametric maps of t deviates reflecting differences between stimulation and baseline at each voxel location for each subject.To perform the group analysis, individual anatomic (SPGR) scans and statistical parametric maps were then transformed into the standard stereotaxic space of Talairach. To compensate for normal variation in anatomy across subjects, functional images were blurred using a 4-mm root mean square Gaussian filter to compensate for intersubject variability in anatomic and functional anatomy. A t test was then applied to the group detect the effects of manual acupuncture and Superficial tactile stimulation versus baseline on a voxel by voxel basis as described above for the individual fMRI data. A t test was also applied to detect voxel by voxe difference between manual acupuncture and Superficial tactile stimulation.In the group average data, a p value of＜0.05 was selected as the cutoff for statistical significance. Only clusters that consisted of more than three continuous voxels were counted as activation. In the individual data, a p value of 0.05 was also selected as the cutoff for statistical significance. Only clusters that consisted of more than three continuous voxels were counted as activation.Talairach three-dimensional brain is chosen as a "standard brain" for anatomic reference. Anatomic labels for activated areas were derived by interactive three dimensional inspection of stereotaxically registered functional and anatomical data using MCW-AFNI software and by reference to the atlas of Talairach. Activation areas were given anatomic labels only when the borders of the area followed borders of a gyral or sulcal structure in the Talairach atlas and the label was supported by three-dimensional inspection of the individual Talairach anatomic data.RESULTSSubject i ve effects : During manual acupuncture, all 13 subjects whose fMRI data were used for analysis developed the de qi sensation around the acupoint or extend along the arm, the sensation is individual different. During Superficial tactile stimulation, none experienced de qi sensation, the sensation was mainly soreness and distension.fMRI resu ]tS : Manual acupuncture on the right hand produced prominent increases of fMRI signals in bilateral involvement of Anterior frontal region(BA9,46), Middle frontal gyrus(BA6), Precentral gyrus (BA4), Inferior parietal lobule(BA39,40), Superior temporal gyrus(BA22), Middle temporal gyrus(BA21), Occipital obule(BA 17,18,19), Posterior cingulate cortex(BA 17,18,19), Parahippocampus(BA35,36), Lentiform nucleus, putamen, and thalamus; Left-side involvement of Inferior frontal gyrus(BA44) and the secondary somatosensory cortex(BA43); Right-side involvement of Transverse temporal gyrus(BA41,42), insula (BA 13) and amygdale. While signal decreases were observed primarily in bilateral involvement of medial frontal gyrus and anterior cingulate gyrus(BA24).Superficial tactile stimulation to the same area produced minor increases of fMRI signals in bilateral involvement of Superior temporal gyrus(BA22), Angular gyrus(BA39),Precuneus(BA 17), Left-side of insula(BA13), Right-side of Middle temporal gyrus(BA21); In contrast, signal decreases were observed primarily in anterior cingulate gyrus(BA32), and medial frontal gyrus.CONCLUSION : This initial study show the brain regions including Frontal gyrus, and subcortical limbic structures can always been evoked by acupuncture, and the activity pattern has positive corresponding with acupuncture intensities (de qi sensation), these regions may play an important role in acupuncture process, fMRI show a network of bilateral conical and subcortical limbic structures active, by which acupuncture achieve diverse therapeutic effects, propagated sensation along channels has some correlation with neural pathway but not the same.