| ObjectiveBased on brain resting-state functional magnetic resonance imaging(fMRI)and functional brain network(fN),this study observed and analyzed the clinical efficacy of the acupuncture treatment in tremor dominant Parkinson’ s disease(TDPD).Based on graph theory of fN,a whole brain binary network with automated anatomic labeling(AAL)of 90 nodes was constructed to investigate the topological attribute change characteristics of fN in TDPD patients during acupuncture treatment and to explore the potential correlation with the clinical data,and further to explore the application value of rs-fMRI technology in complementary therapy of acupuncture of TDPD patients,and provide evidence of corresponding neurophysiological changes for complementary therapy of acupuncture in TDPD.MethodsAccording to the inclusion criteria established in this study,TDPD patients who were admitted to guangdong provincial hospital of traditional Chinese medicine from December 2018 to December 2019 were collected and a randomized controlled trial was adopted.The patients were randomly divided into acupuncture group,sham acupuncture group and drug group for 12-week clinical efficacy observation.(1)In the drug group,only levodopa were used for basic treatment.In the acupuncture group,TDPD patients were acupuncture the Baihui,Fengchi and Chorea-tremor Controlled Zone on the basis of drug treatment.In the sham acupuncture group,0.5-inch shallow acupuncture needles were acupuncture beside the acupoints of the acupuncture group without needle manipulation.The Movement Disorder Society sponsored revision of the Unified Parkinson’ s Disease Rating Scale(MDS-UPDRS),Parkinson’ s Disease Questionnaire-39,PDQ-39(PDQ-39)and Hoehn-Yahr stage(H&Y)were evaluated before and after the treatments.(2)MRI,fMRI and high-resolution 3D-T1WI whole-brain imaging data were collected for all subjects before and after treatment.The gretna software package based on Matlab preprocessed all subjects’ rs-fmri data,constructed 90*90 whole-brain functional connection matrixs,and calculated topology attribute indexes based on graph theory of fN,including global attributes such as clustering coefficient(Cp),shortest path length(Lp),Global efficiency(Eg)and small-world attribute index(σ)and node attributes such as node degree(Dc)node efficiency(NE)node local efficiency(NLE).(3)By comparing the correlation between the difference of the topological attribute index and the clinical scale in the treatment,the potential neurophysiological basis of acupuncture for TDPD was explored.ResultsDuring the experiment,1 case was removed,6 cases were shed,and the final 55 cases were included in the clinical effect observation and statistical analysis of the group,including 20 cases in the acupuncture group,18 cases in the sham acupuncture group,and 17 cases in the drug group.(1)Baseline data analysis:a total of 55 TDPD patients were included in the group study,including 32 males and 23 females,aged from 50 to 83 years old.①There was no significant difference among the three groups in age,gender and education(P>0.05).②There were no statistically significant differences in the daily dose,baseline intelligence and mental status of the three groups(P>0.05).③There were no significant differences among the three groups in MDS-UPDRS and its components,PDQ-39 and H&Y stage at baseline(P>0.05).(2)Clinical Curative Effect Observation:①In acupuncture group,scores of MDS-UPDRS Ⅲ and MDS-UPDRS tremor portion were significantly decreased after treatment(P<0.001).Inter-group analysis suggested that acupuncture group had significant difference compared with sham acupuncture group and control group(P<0.05).②H&Y stage in acupuncture group was significantly lower after treatment(P<0.05).There was no significant difference between the sham acupuncture group and the drug group before and after treatment(P>0.05).There was no significant difference between acupuncture group and sham acupuncture group in inter-group comparison(P>0.05),while there was a significant difference between acupuncture group and drug group in inter-group comparison(P<0..05).For PDQ-39,the scores of acupuncture group significantly decreased after treatment(P<0.001),and there was no significant difference between sham acupuncture group and drug group in inner-group comparison(P>0.05),there was no significant difference between acupuncture group and sham acupuncture group in inter-group comparison(P>0.05),and there was significant difference between drug group and acupuncture group(P<0.05).④There was no significant difference in the MDS-UPDRSⅡ scores in inter and inner group comparions among the three groups.(3)Study on fMRI brain network:①In the global network attributes,there was no statistical difference among the three groups at the baseline level(P>0.05).Moreover,There was no significant difference among the three groups in inter-group comparions of Lp and Eg(P>0.05).②There was a significant difference in difference values of Cpamong the three groups(P>0.05),and there was a significant difference between acupuncture group and drug group in inter-group comparions(P<0.001).while the comparison of the remaining pairwise pairs was not statistically significant(P>0.05).③The left amygdala(L-AMYG),the right amygdala(R-AMYG)and left caudate nucleus(L-CAU)were the brain regions with significant differences in difference values of Dc among the three group in node attributes.Compared with the drug group,the changes of Dc values of L-AMYG during the treatment in the acupuncture group were more significant(P<0.05).Brain regions with significant differences in NLE during the treatment among three groups included right supplementary motor area(R-SMA),right olfactory cortex(R-OLF)and right Superior frontal gyros-medial orbital(R-ORBsupmed).Compared with the drug group,there was a significant difference in difference values of NLE of R-SMA during the treatment in acupuncture group(P<0.05).The brain regions with significant differences in difference values of NE among the three groups included L-AMYG.Compared with the drug group,there was a significant difference in difference values of NE of L-AMYG in the acupuncture group during the treatment(P<0.05).(4)Correlation analysis of brain function network topological properties and clinical data:①There was a negative correlation between ΔDC of L-CAU and ΔMDS-UPDRS Ⅱ in acupuncture group(r=-0.489,P=0.029).There was a negative correlation between △DC of L-CAU and △MDS-UPDRSⅢ during the treatment(/==0.508,P-0.031)in sham acupuncture group.There was a negative correlation between changes of △DC of L-CAU and △MDS-UPDRS during the treatment(r=-0.596,P=0.009)in sham acupuncture group.There was a positive correlation between Δ Dc of R-AMYG and Δ PDQ-39 during the treatment(r=0.478,P=0.045)in sham acupuncture group.Conclusions(1)Complementary therapy of acupuncture with levodopa has significant clinical effect in the treatment of TDPD patients,which is better than that of levodopa,and is manifested as the regulating effect on tremor,motor function and viability.The clinical efficacy evaluation can’ t excluded acupuncture placebo effect.(2)Complementary therapy of acupuncture with levodopa has significant Effect on the adjustment of the global attribute of brain function network in TDPD,which is better than that of levodopa.The specific mechanism may be to regulate the degree of whole-brain network clustering by regulating the abnormal changes of Cp,and then express as the improved for clinical symptoms.(3)Acupuncture can regulate the brain function network of TDPD by regulating the nodal properties of NE and Dc of L-AMYG,Dc of L-CAU and NLE of R-SMA.In the intergroup comparative analysis of some nodes such as R-AMYG,R-OLF and R-ORBsupmed,sham acupuncture therapy and acupuncture therapy showed significant differences in curative effect,which suggested that the changes of acupoint location of scalp acupuncture in acupuncture group and sham acupuncture group may lead to the changes of node attribute activation。(4)The evidence of correlation analysis is insufficient,which suggests that acupuncture may regulate the attributes of brain network nodes by adjusting its Dc values changes,so as to improve activity of daily living in TDPDs,and sham acupuncture may have a potential regulatory effect on L-CAU and R-AMYG,and is associated with motor function and activity of daily living in TDPDs. |
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