| [Background]With the rapid development of medical technology, education level and economy, population aging has become a social trend. Anti-aging and senile diseases have attracted the attention and concern of governments and people all over the world. By the end of 2012, China’s population, aged over 65 years old, accounted for 1/5 of the world’s elderly population. China has become the country with the largest population of the elderly. Aging can cause cognitive impairment, visual and auditory decline, sensory motor function and balance function decline. Aging often causes a lot of age-related diseases, such as degenerative disease of the brain, osteoporosis, cancer, cardiovascular disease, muscle atrophy, diabetes and so on. Numerous researches have unequivocally demonstrated that aging is accompanied by loss of brain tissue, especially the gray matter tissue. Furthermore, there were evidences that, in addition to regional brain atrophy, aging is usually accompanied by an average decline in cognitive function such as processing speed, encoding of information into episodic memory, and working memory, executive function. And age-related cognitive decline has an influence on quality of life and life satisfaction. The theory of Traditional Chinese Medicine argues that the aging of the human body refers to the degenerative changes of viscera. Aging mainly attributes to kidney deficiency, and the growth and aging process is a process of enriching and deficiency of the kidney. Therefore, the core of anti-aging is the treatment of kidney deficiency. Acupuncture as one method of Traditional Chinese Medicine has its advantages in anti-aging research, and acupoint Taixi as the primary acupoint of kidney meridian is an important acupoints in the treatment of kidney deficiency.Functional magnetic resonance imaging (fMRI) can instantly reflect brain activity with advantages such as non-invasive, high spatial resolution, repeatable inspection. It is widely used in the research on the specificity of acupuncture and brain science research. The traditional fMRI is mainly adopted to explore brain function when performing specific tasks, and finally obtained the results of brain activation or brain functional connectivity. This technique is often referred to Task-State fMRI. In addition, the resting-state fMRI is used to study spontaneous activity of the brain when the subjects keep awake, and do not perform any specific task or accept any external stimulus. The resting-state fMRI has been widely used in brain mechanism researches. The rationale behind this approach is that the brain, rather than being idle during rest, displays instead vigorous and persistent functional activity.There is a constant exchange of information between the various brain regions, which together constitute the interconnected brain network. There are three forms of brain network connectivity between brain areas, which are structural connectivity, functional connectivity and effective connectivity. Functional connectivity can reflect the interaction between different brain regions, and the effective connectivity can reflect the flow direction and intensity of information the interaction between brain regions. There are several approaches for the analysis of resting-state fMRI data, among which the most common is graph theory analysis. For brain network, we defined brain regions or voxels as nodes, functional connectivity or structural connectivity of brain regions or voxels as edge, so that we can use graph to represent brain networks. And graph theory analysis and its relative indices are used to study the topological properties of brain networks. For the effective connectivity of the brain, one commonly used analytical method is Grainger causality analysis (GCA).Based on the causal model of time series of two brain regions of functional magnetic resonance data, GCA is used to study the effect of one brain region on another, so as to reveal the effective connectivity between the brain areas.At present, a great deal of aging related resting-state fMRI researches demonstrated that aging-related decrements in resting state functional connectivity (RSFC) preferentially affect default-mode network (especially the posterior cingulate cortex and hippocampus) and dorsal attention network which are closely related to attention, memory and executive function. A very recent study found that age was negatively correlated with RSFC between the anterior cingulate cortex and bilateral insula. These regions have been related to a salience network, which is supposed to participate in the integration of sensory data from multiple modalities and in decision-making processes. Based on graph theory analysis, the researchers found that elderly subjects presented decreased RSFC in left preemptor area and right cingulated motor cortex. Although RSFC decreases are the most common pattern reported in rs-fMRI studies of the elderly population, findings of increased functional connectivity related to aging have also been described. This maybe related to compensatory responses to decreased functioning, aging-related developmental changes in the architecture of brain networks or a reflection of brain degenerative effects due to aging.FMRI study on the acupoint Taixi is to explore the acupuncture specificity.An fMRI research found that acupuncture at Taixi in health subjects can activate brain areas related to auditory and cognitive function. These brain areas mainly distributed in the right temporal gyrus and precuneus. The above results are in accord with Traditional Chinese Medicine theory "kidney opens into the ear" "the kidney being in charge of the bone and producing marrow and being interlinked to brain". Previous studies often used multiple block design and ignoring the effect after acupuncture. They often used the resting stage after needing as a baseline for acupuncture, which ignored the effect of needling on the results. Therefore, traditional experimental paradigm in the research of acupuncture specificity has several limitations.[Objective]This fMRI study makes a comparison of brain activation and brain network connectivity induced by normal acupuncture and shallow acupuncture at Taixi.And this research aimed to explore the brain central mechanisms of acupuncture at Taixi in the elderly, which can provided theoretical basis for acupuncture effect in anti-aging.[Method]1 SubjectAccording to the inclusion and exclusion criteria, twelve healthy elderly right-handed volunteers were recruited from communities. All the subjects were randomly to receive normal acupuncture(12 cases) and shallow acupuncture(12 cases) at Taixi.2 Experimental paradigmThis research adopted new experimental paradigm. Functional runs lasting for 15 min were divided into four phases. At the beginning, a resting state (REST) scan was conducted for 6min without any stimulation for a baseline control. Secondly, an acupuncture needle was inserted in acupoint KI3 (Taixi) on the right leg, and retained for 1 min. Thirdly, the needle was manipulated for 2min and then the needle was out. At last, another REST scan was conducted for 6min without any stimulation again. At the end of each acupuncture scan, the subjects were questioned about aching, pressure, soreness, heaviness, fullness, warmth, coolness, numbness, tingling, dull or sharp pain, and any other sensations they felt during the stimulation. A 10-point visual analogue scale (VAS), which was scaled at 0= no sensation,1-3= mild,4-6= moderate,7-8= strong,9= severe, and 10= unbearable sensation, was adopted to self-rate the intensities about the "Deqi" sensation. The presentation sequence of two runs (normal acupuncture and shallow acupuncture) was randomized and balanced throughout the population, and every participant performed only one run each week in order to avoid potential long-lasting effect after acupuncture administration.3 Acupuncture designAn acupuncture needle was inserted in acupoint KI3 (Taixi) on the right leg. A silver needle with 0.35mm in diameter and 25mm in length (silver content above 85%, Acupuncture Supplies Company in Suzhou, China) were chosen for acupuncture in this study. After sterilizing, the needle was inserted vertically to a depth of 1-2cm in normal acupuncture, but of 1-2mm in shallow acupuncture. And the needle was retained for 1 min when the subjects experience the sense of soreness, tingling and fullness. Then the needle was manipulated for 2min by rotating the needle at a rate of 120 times per min in frequency and at 60° in angle. All the acupuncture manipulation in this experiment was done independently by a experienced acupuncturist. The other operations were the same in both groups besides the needling depth.4 Sequences and parameter of fMRI scanningAll the MRI data were collected from a 3.0T Phillips MRI scanner. The MRI scan of this study consists of anatomical scans and functional scans of acupuncture stimulation. The images were parallel to the anterior commissure (AC)-posterior commissure (PC) plane and covered the whole brain. Thirty axial slices were obtained using a T2-weighted single-shot, gradient-recalled echo planar imaging sequence [field of view (FOV)=220 mm×220 mm, matrix=64×64, thickness=4mm, repetition time (TR)=2000ms, echo time (TE)=30ms, flip angle=77°. After the functional run, high-resolution structural information on each subject was acquired using three-dimensional MRI sequences with a voxel size of 1 mm3 for anatomical localization (TR=2.1 s, TE=4.6ms, matrix=256×256, FOV=230 mm×230 mm,flip angle=8°, slice thickness=1 mm).5 Data preprocessingBefore data processing, magnetic resonance data format was transfer from "dicom" to "img" by using the conversion software. All the data preprocessing procedures were conducted by the Statistical Parametric Mapping 5 (SPM5). The images were corrected for the acquisition delay between slices, aligned to the first image of each session for motion correction, and spatially normalized to standard MNI template in SPM5. The image data was further processed with spatial normalization based on the MNI space, resample at 2mm×2mm×2 mm, and finally spatially smoothed with a 6mm full-width-at-half maximum (FWHM) Gaussian kernel.6 Statistical analysisSPSS 19.0 software was adopted to analyze the general data. Quantitative data was expressed as with mean± standard deviation (x±s). Relative ratio or percentage was used to express the qualitative data. Quantitative data were compared using t-test, qualitative data by chi square test. P< 0.05 means the difference were significant.General linear model was used to analysis brain activations. Afterwards, we adopted graph theoretical approach to explore the brain functional connectivity at resting-state after RA or MA. There are 39 regions of interest (ROI) and abbreviated area labels in this study. In order to analyze the brain network directly, single nodal point was deleted by artificial setting. In the graph, a pair of nodes and one line were used to show the relationship of ROIs. The methods of building brain network created by Salvador were adopted in our research.Granger causality analysis was used to analyze the effective connectivity of the brain network. The intensity and direction of effective connectivity were obtained in this method, and only significant connectivity is shown in the effect network diagram (P< 0.05).[Results]1 The comparison of acupuncture sensation between normal acupuncture and shallow acupunctureAcupuncture sensation (Deqi) was evaluated at the end of the experiment in each subject. The intensity is expressed as the average score±SE. The sensations of soreness, numbness, fullness and warmth were found to be stronger for RA than for MA.2 The comparison of brain activation between normal acupuncture and shallow acupunctureCompared with the shallow acupuncture group, the positive activation regions in normal acupuncture group distributed in Left central gyrus, central anterior gyrus, middle frontal gyrus and right medial frontal gyrus. And the negative activation regions distributed in right inferior frontal gyrus, left inferior frontal gyrus, superior frontal gyrus, parahippocampal gyrus, culmen and precuneus.3 The comparison of brain functional connectivity between normal acupuncture and shallow acupunctureCompared with the shallow acupuncture group, the brain functional connectivity in normal acupuncture group showed an increase mainly in frontal and temporal lobe. Compared with REST, brain network induced by RA or MA presented the complexity of inner nuclear group connection, which is an increased internal tightness of nuclear group mainly in frontal, parietal and occipital lobe.4 The comparison of brain effective connectivity between normal acupuncture and shallow acupunctureCompared the effective connectivity of network between normal acupuncture and shallow acupuncture at Taixi in elderly adults, the connectivity strength between the hippocampus and caudate nucleus is the greatest, followed by the connectivity between orbital prefrontal cortex and hippocampus.In addition, some brain network connectivities with the strength of causal effect higher than 3 also included information flow from insula to putamen, the middle temporal gyrus to the orbital prefrontal cortex. The connections with causality strength between 2 and 3 were cuneus to precuneus, insula to putamen, thalamus to insula, thalamus to orbital prefrontal cortex and dorsolateral prefrontal cortex to the uvula of cerebellum.The connections with causality strength between 1 and 2 were the primary motor cortex to uvula, hippocampus to dorsolateral prefrontal cortex, anterior cingulate cortex to the hippocampus, putamen to insula, insula to the dorsolateral prefrontal cortex and dorsolateral prefrontal to the middle temporal gyrus.[Conclusions]Compared with shallow acupuncture, normal acupuncture can induce stronger acupuncture sensation,activate cognitive related regions and regulate the aging related functional network and effective network, which make a foundation of acupuncture for anti-aging. |
PDF Full Text Request