Positron emission tomography (PET) is used to observe the cerebral function widely and is a good method to explore the mechanism of acupuncture treatment on the central nervous system. By using this method, we observed the cerebral function of 6 patients suffering from ischemic stroke after receiving EA treatment at Baihui(GV20) and right Qubin(GB7). The results were: (1) the glucose metabolism changed significantly on primary motor area (M1), premotor cortex (PMC), and superior parietal louble (LPs) bilaterally, as well as the Supplementary Motor Area (SMA) on the unaffected hemisphere right after the first EA treatment. (2) The glucose metabolism on bilateral M1 and LPs changed significantly after three weeks of daily EA treatments. (3) The glucose metabolism on other areas such as insula, putamen, and cerebellum changed significantly. It demonstrated that EA at Qubin and Baihui couldactivate the cerebral structures related to motor function on the bilateral hemispheres.We concluded that EA was very helpful for the cerebral motor plasticity after the ischemic stroke. Also based on this study we assumed that the brain plasticity should be a network and that acupuncture participated in some sections of this course.
Acupuncture has been used in stroke rehabilitation in China for over 3000 years. However, its mechanisms are still under discussion. Most researchers used biochemical or anatomical tests to observe the animals or electrophysiological tests to observe human beings and tried to explain the mechanisms [
EA has a nearly 200-year history. French physician Louis Berlioz was the first to apply the electricity on acupuncture needles in his clinical work in 1810. He believed that the current generated by the battery might enhance the therapeutic effect of the acupuncture needles [
So far the researches on stroke recovery mechanisms have found (1) the recovery of an animal experimental focal cerebral ischemia (sensory or motor cortex) was related to the reorganization in the adjacent unaffected cortex around the lesion [
Therefore, we observed cerebral glucose metabolism in stroke patients before and after EA treatments with patients’ fist-clenching movement, in order to explore the effect of head acupoints on multiple cerebral areas above mentioned and to interpret the mechanism of acupuncture on stroke patients’ motor function recovery.
Six right-handed stroke patients (3 males, 3 females) were recruited for the study. Each patient received an explanation of the study protocol and signed an informed consent prior to participating in the study. Patients accepted short-term movement task training before the experiment.
Inclusion criteria were (i) first-ever ischemic stroke (confirmed by computerized tomography (CT) scan or magnetic resonance imaging (MRI)) involving the right basal ganglion region; (ii) age 50–75 years; (iii) admission within 1–3 months of onset; (iv) upper extremity motor function of patients was damaged, but patients could finish the movements that the study required (muscle strength was 3-4); (v) for the diabetic patients with the controlled blood sugar, the blood sugar was tested on the dates of the scan for the correction.
Patients were excluded if they: (i) had severe diabetes and severe heart disease and (ii) were taking any central nervous system depressants or stimulant drugs in the previous month.
PET scanner (ECAT EXACT HR+, Siemens Co. Germany) was used with the scanning mode of three dimensions (3D), and the thickness of each slice was 3 mm with septa retracted and scatters correction. The EXACT HR+ had a 15.2-cm axial FOV, sufficient to image the whole brain in a single scan.
The temperature of the examination room was 22–24°C. The tracer was 18 fluoride-deoxyglucose (18F-FDG, produced by accelerator CTIRDS111, and its purity >95%, 148–185 MBq), which was administered by intravenous injection at 110 mCi/kg (bodyweight). The patients had the earplugs and eye patches on to block auditory and visual stimuli until the end of the scan. Before each scan the patient’s head was placed into a supporting device, localized by laser, and fixed in a position where superior and inferior laser lines were parallel to the orbit mastoid (OM) line and the cerebrum and the cerebellum were covered.
The observation was conducted as the followed steps. (1) The patient laid flat on the examination table and made fist-clenching movements regularly (the affected hand) at a frequency of about 0.5 Hz (metronome interrupter, Nikko, P1440, Japan) continuously for 20 minutes. Five minutes after the movements started, 18 fluorine deoxyglucose (18F-FDG) (4mci) was injected into the vein of the unaffected hand. 40 minutes after the injection, the patients had the PET scans (Figure
(a) First test chart flow diagram. (b) Second test chart flow diagram.
Schematic diagram of GV20 and GB7.
Needling process: the acupuncture pointes were cleaned with 75 percent alcohol. The needles were the single-use, disposable stainless steel acupuncture needles (Huatuo, Suzhou Medical Supplies Co. Ltd; Suzhou, China), with a diameter of 0.25 mm and a length of 25 mm. The needles were inserted horizontally into both acupuncture points, forming a less than 30 angle with the skin surface. Depth of needle insertion was approximately 10 mm. Then two needles were connected to a commercial electro-acupuncture device (model SDZ-V, Suzhou Medical Supplies Co. Ltd; Suzhou, China). The frequency was 2 Hz with continuous waves. The intensity of the stimulation was increased to the point where the patient reported the needling reaction and then it was adjusted gradually to a comfortable intensity and remained at that level for 20 minutes.
PET data were processed and analyzed by statistical parametric mapping (SPM99) (Institute of Neurology, University of London, London, UK) and the Matlab 6.1 program (Mathworks Inc., Sherborn, MA, USA) was used. Brain images were anatomically normalized to a standard brain template (FDG-PET version adapted to the MNI-MRI template by Montreal Neurological Institute) by linear (affine) and nonlinear transformations to minimize intersubject anatomical variations by using an SPM routine. To identify brain regions in which the perfusion and glucose metabolism had changed following EA, linear contrasts were used to test for regionally specific differences between groups, producing paired
(1) EA instant effects: the significant increase of glucose metabolism was found on the unaffected side: the Primary motor area (M1), the precentral gyrus (the 4th Area), the supplementary motor area (SMA), the medial frontal gyrus (the 6th area), premotor cortex (PMC), the central frontal gyrus (the 6th Area), and the superior parietal lobule (LPs, the 7th Area) (Table
(a) Talairach coordinates and
Peak | Corrected | Coordinates | |||
---|---|---|---|---|---|
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| |
GPrC (Area4) L | 3.10 | 0.0087 | −8 | −26 | 70 |
GFd (Area6) L | 2.99 | 0.0101 | −16 | −12 | 58 |
LPs (Area7)L | 2.79 | 0.0134 | −32 | −42 | 50 |
GFm (Area6) L | 3.20 | 0.0075 | −36 | 2 | 36 |
GFd (Area6) R | 3.05 | 0.0092 | 10 | −14 | 56 |
GTm (Area37) L | 5.91 | <10−4 | −44 | −68 | 8 |
GTs (Area22) L | 3.75 | 0.0036 | −54 | −48 | 18 |
Cerebellum L | 3.51 | 0.0049 | −8 | −66 | −10 |
Putamen L | 3.01 | 0.0097 | −12 | 16 | −4 |
Peak | Corrected | Coordinates | |||
---|---|---|---|---|---|
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|
|
| |
GPrC (Area4) R | 3.89 | 0.0030 | 32 | −16 | 76 |
GFm (Area6) R | 3.36 | 0.0060 | 26 | 16 | 68 |
LPs (Area7) R | 2.23 | 0.0302 | 2 | −60 | 68 |
GFd (Area9) R | 4.17 | 0.0021 | 6 | 62 | 26 |
GFm (Area10) R | 2. 51 | 0.0200 | 48 | 54 | 4 |
GTm (Area21) R | 5.38 | <10−4 | 60 | 0 | −26 |
GFm (Area6) L | 2.39 | 0.0236 | −34 | 10 | 60 |
(a) EA instant effect: brain glucose metabolism of the stroke patients increases. The red represented the areas with increased glucose metabolism, and the green arrow referred to M1. (b) The glucose metabolism on the left precentral gyrus increased. (c) The glucose metabolism on the right precentral gyrus decreased. (d) The glucose metabolism on the left midfrontal gyrus increased. (e) The glucose metabolism on the right midfrontal gyrus decreased. (f) Three weeks of EA treatment effect: brain glucose metabolism alteration. The red represented the areas with increased glucose metabolism, and the green represented the areas with decreased glucose metabolism. The glucose metabolism alteration areas included bilateral M1, temporal lobe, and so forth. (g) Left superior frontal gyrus glucose metabolism increased. (h) Left precentral gyrus glucose metabolism increased. (i) Right precentral gyrus glucose metabolism decreased.
(2) After three weeks daily EA treatments, the increase of glucose metabolism (Table
(a) Talairach coordinates and
Peak | Corrected | Coordinates | |||
---|---|---|---|---|---|
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|
| |
GPrC (Area4) L | 4.59 | 0.0029 | −46 | −10 | 56 |
GFm (Area6) L | 2.68 | 0.0217 | −68 | 18 | 20 |
LPs (Area7) L | 2.25 | 0.0291 | −14 | 54 | 34 |
GFd (Area9) L | 3.75 | 0.0036 | −54 | −50 | 22 |
Cerebellum R | 3.14 | 0.0082 | 28 | −40 | −50 |
Peak | Corrected | Coordinates | |||
---|---|---|---|---|---|
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|
|
|
| |
GPrC (Area4) R | 3.39 | 0.0058 | 10 | −24 | 78 |
GFd (Area45) R | 2.72 | 0.0147 | 50 | 28 | 4 |
thalamus R | 3.11 | 0.0085 | 20 | −10 | 12 |
GTs (Area22) R | 2.95 | 0.0107 | 74 | −26 | 4 |
GTm (Area21) R | 2.80 | 0.0131 | 60 | −2 | −20 |
Cuneus (Area19) R | 2.61 | 0.0173 | 24 | −90 | 30 |
GTs (Area38) R | 1.96 | 0.0441 | 50 | 16 | −10 |
GFs (Area6) L | 2.39 | 0.0238 | −26 | −8 | 70 |
(3) Besides these areas related to motion directly, the other areas where glucose metabolism had changed included middle temporal gyrus, superior temporal gyrus, putamen, and cerebellum.
(1)
In this study, head acupoints took the role of local treatments. Furthermore, it is very important to select the points on Governor and Foot Gallbladder meridians to treat stroke. Since the Governor meridian goes through the spine upto the neck and brain and is the governor of the Yang of the body; and the Foot Gallbladder meridian goes through the body side up to the top of the head and its meridian sinew intercrosses the musculature of meridians on two sides of the body, and goes along with the Yang Heel Vessel. Their main function is to treat paralysis after stroke and all other kinds of symptoms in the head. Previous research showed that the acupuncture treatments at those points alleviated brain damage after ischemic stroke in the monkeys and rats [
(2) It helped us realize that noninvasive functional examination in vivo could clearly reflect the changes of biological metabolism of cerebral nervous tissue after acupuncture by using PET. Asking the patients to move their hands to activate or deactivate the glucose metabolism was helpful in identifying which cerebral motor areas were engaged and we could obtain the direct evidence from spatial and time aspects, which could reflect the effect of acupuncture on the motor recovery of stroke patients more objectively than in the resting condition.
(a) Instant effect of EA: the results of the study showed that after EA, the bilateral M1, PMC, and LPs, as well as SMA of the unaffected hemisphere had significant changes in glucose metabolism, with remarkable increase in these regions of the unaffected hemisphere and decrease in the affected hemisphere. Acupuncture activated not only the cerebral tissues of the affected hemisphere, but also the related regions of the unaffected hemisphere, particularly SMA. The results confirmed the previous research: the activation of the SMA was considered to be related to the recovery of the motor function [
(b) Effect of three weeks of EA treatments: after three weeks of daily acupuncture treatments, the changes in the region related to the motor ability directly was only the M1, but still showed the same trend as the instant effects: bilateral changes with increased glucose metabolism on the unaffected hemisphere and decreased metabolism on the ipsilesional hemisphere. It showed that the contralateral hemisphere played an important role in the stroke recovery process [
(3) We adopted a functional description to describe the experimental results since different cerebral structures often have the same function. M1 is in the precentral gyrus and paracentral lobule, equivalent to Brodmann area 4 and controls voluntary movements. PMC is located in Area 6 in the front of the precentral gyrus. SMA mainly is located in area 6 in the internal and upper dorsolateral hemisphere. They are related to the state of readiness before exercises. This function division indicated that the region of programming the movement preparation and controlling the movement implementation cannot be limited to a special area and may involve a lot of “modules” in a dynamic network. After EA treatment, these areas had the metabolic changes. It demonstrated that the EA on head acupoints may improve the recovery of motor function through the regulation of “module” of this network.
(4) After EA at Qubin (GB7) and Baihui (GV20), the changes took place not only in the motor areas but also in the insular cortex, temporal lobe, occipital lobe, putamen, and cerebellum. These changes may be related to the specificity of the acupoints. However, some literatures also mentioned that metabolic changes on the areas such as the insular cortex, parietal lobe, thalamus, putamen, and cerebellum were relevant to the movement [
Schematic diagram of the relationship between the structures of the motor system.
(5) The increased or decreased changes of glucose metabolism after acupuncture reflected the degrees of the excitement and inhibition of the related cerebral areas. Those excitement and inhibition had the important role. Because the neurons have an extensive mutual connection, they may excite or inhibit each other and serve to conduct sequential processing and transmission of the complicated information. The inhibition of some neurons may be the aftereffect of excitement of some other neurons or the initiation of the excitement in other sites. The metabolic decrease in some cerebral areas was likely a compensative mode of other areas. Hence, we should pay more attention to which cerebral areas were involved and how much changes happened. When acupuncture activated some areas, it also induced changes in relative areas. It can be thought that the regulation of acupuncture should be a relatively specific network effect and a multiple regulation course.
In conclusion, EA at head points might activate the cerebral motor areas bilaterally and induce the excitation of nerve tissue related to motion, and the activation of other regions demonstrated that the reorganization of the injured motor function was a neural network behavior, and that acupuncture may act on multiple aspects of the neural network, thus further contributing to the recovery of motor function.
This work was supported by the National Natural Science Foundation of China (30972523).