Regulation Of Acupuncture Along Meridians On Resting-state Function Of Insular In Stable Angina Pectoris Management:an FMRI Study

Objects:In this study, we conducted an resting-state fMRI study on stable angina pectoris patients and healthy subjects by focusing on bilateral insular cortex which is a key component of the central autonomic network. Findings revealed different intrinsic neural activity and functional networks of insular on pathological or physiological state and regulating effect of acupuncture therapy on it's function, then provided insight into the mechanism of acupuncture.Methods:1. Twenty-eight participants with stable angina and Twenty-eight gender-and age-basically matched healthy subjects were assigned into group A and group B according to their states. Basic information, four vitals, mental state, lab tests and fMRI data of all participants were collected at the baseline. By comparing ALFF signal between these two groups, we targeted insular which is highly correlated with abnormal cardiac function. Then we further carried out seed-based functional connectivity analysis to find out the feature of functional network and lateralization of bilateral insular.2. All patients with stable angina pectoris were randomly assigned into Group a (puncturing on acupoints from heart and pericardium meridian) and Group b (puncturing on acupoints from large intestine meridian), and received ten sessions of acupuncture treatments on PC-6, HT-5 and LI-5, LI-6, respectively. We adopted angina diary, SAQ, SAS, SDS, ultrasonic cardiogram and Holter to evaluated clinical symptoms, quality of life, emotional state, cardiac function and heart rate variability prior and posterior to acupuncture intervention. All the patients received fMRI scan for the second time after two-week acupuncture intervention. By analyzing clinical and imaging data we wanted to detect the correlation between clinical outcome improvements and fMRI signal changes of insular after acupuncture, then further explore the regulating mechanism of different acupoint selection plan on resting-state functional networks of insular in patients with stable angina pectoris.Results:1. Baseline comparison results were basically comparable between patients and healthy subjects, with their average age revealed significant difference (P<0.001). While baseline comparison were comparable between two groups of patients (P> 0.05).2. At the baseline, it was bilateral insular that had been activated significantly when comparing ALFF signal between patients and healthy subjects, and the right insular was more outstanding than the left side. The functional connectivity between right insular and thalamus, pre-central, post-central gyrus were decreased, while connectivity between left insular and anterior cingulate, left insular and medial prefrontal cortex were increased significantly at morbid condition. These active-deactived patterns remained almost the same after the age factor had been removed.3. After two-week intervention, participants from Group a improved in frequency of onset, VAS and anxiety state overall (P<0.05),also the stable state of angina and awareness of disease dimensions from SAQ has increased significantly (P<0.05), time domain parameter pnn50 from HRV increased remarkably as well (P<0.001). While in Group b, VAS score decreased(P<0.05), and physical activity and treatment satisfaction dimensions from SAQ has increased significantly (P<0.05).Only pnn50 parameter revealed significantly improvement between these two groups after intervention.4. After puncturing on acupoints from heart and pericardium meridians, the left insular was activated. Interestingly, these changes were highly correlated with the improvement of pnn 50 (r=0.750, P<0.05) and frequency of onset (r=-0.863, P< 0.05). Besides, functional connections between left anterior insula, anterior cingulate, cerebellum and medial prefrontal cortex were decreased. In Group b, activation in left cerebellum, right superior occipital gyrus and deactivation in right frontal lobe were found. VAS improvement was related to signal changes frontal lobe positively (r =0.840, P< 0.05), to occipital lobe negatively (r=-0.825, P<0.05). Functionally connectivity between left anterior insular and medial prefrontal cortex was decreased.Conclusions1. Acupuncture improved clinical symptoms and emotional state in patients with stable angina pectoris, puncturing at acupoints from disease-related meridians showed more promise than at point from non-related meridians in improving HRV.2. Patients with stable angina pectoris suffered hyper function of peripheral sympathetic nerve system, while in the central level the right insular which control the sympathetic nerve system was significantly activated. Functional network of bilateral insular also revealed obvious lateralization.3. Puncturing at acupoints from disease-related meridians enhanced peripheral parasympathetic nerve excitability and targeted left anterior insula which control the parasympathetic nerve system by modifying it's intrinsic neural activity, also regulate the functional network between key nodes of central autonomic function network, insular-ACC, insular-cerebellum, insular-mPFG. Compared with puncturing at acupoints from non-related meridians, this point selection plan has more comprehensive and precise effection.