Therapeutic Efficacy Of Connectivity-directed Transcranial Magnetic Stimulation On Anticipatory Anhedonia

Objective:Depression has become the second largest burden disease in China,and it is expected to rise to the first place in the world in 2030.Impatience is the core symptom of depression,and patients with anhedonia always show poor antidepressant treatment effect.At present,a wide range of antidepressants are difficult to effectively treat the symptoms of anhedonia in depression.rTMS can regulate the excitability of brain region and improve the functional connection between brain regions by stimulating the specific cerebral cortex region continuously at high frequency.Traditional transcranial magnetic stimulation of l DLPFC treatment can improve the symptom on depression patients.However,the effect of improving the symptoms of anhedonia in depression is poor.In this study,based on the study of the neural mechanism of anticipatory anhedonia in patients with depression,the therapeutic effect of individualized precise target rTMS on anticipatory anhedonia in depression was studied.It is assumed that rTMS treatment will effectively improve the anticipatory anhedonia in depression patients by selecting l DLPFC brain region with the strongest positive functional connection with NAcc as the target,and further objectively observe the improvement of patients’motivation and effort level through behavioral and neuroelectrophysiological indicators.Method:This study is a randomized controlled double-blind experiment,in which 56patients with depression were evaluated and screened by temporal pleasure experience scale.They were randomly assigned to two groups,the real rTMS group（32 patients）and sham rTMS group（24 patients）.In the real rTMS group,the l DLPFC region with the strongest functional connection with NAcc was treated with 10Hz rTMS for 15consecutive days,once a day.The sham rTMS group received sham treatment by sham rTMS without magnetic stimulation,and the parameter setting was the same as that of the real rTMS group.Clinical symptom scale,behavior and ERP were evaluated before and after treatment.Hamilton depression scale,Hamilton anxiety scale and temporal pleasure experience scale were used for clinical symptom assessment,and monetary reward delay paradigm was used for behavioral assessment.Use SPSS 22.0 to analyze the data.The clinical scale,behavioral data and ERP data were statistically analyzed by Chi-square test,repeated measurement variance analysis,independent sample t test,paired sample t test and Pearson correlation analysis.Results:At baseline,there were no statistical differences between the two groups（all Ps>0.05）.At the end of rTMS treatment,（1）on the results of clinical symptom scale:the depression symptoms in the real rTMS group improved more significantly,and the number of HAMD relief in the two groups was significantly different（χ²=9.065,P=0.003）.In the measurement of anxiety symptoms,the number of relieving HAMA in the real rTMS group was significantly higher than that in the sham rTMS group（χ²=6.019,P=0.014）.In the two subscales of TEPS scale,the main effect of group is not significant(F_1,54=0.858,P=0.03),but the interaction between time and group is significant(F_1,54=12.675,P=0.001).TEPS-cons score has no significant interaction between time and group(F_1,54=0.367,P=0.55).（2）Behavioral results:the accuracy rate of monetary incentive delaying paradigm task:group main effect is not significant(F _1.42=0.001,P=0.988),condition main effect is significant(F _2,84=23.9,P<0.001),condition×time×group interaction is not significant(F_2,84=0.5,P=0.603),Time×condition interaction effect(F_2,84=6.575,P=0.002).In the reaction time of behavioral tasks,the condition×time×group interaction is not significant(F _2,84=0.1,P=0.951).（3）ERP results showed that cue-N2/cue-P3 components in cue stage changed significantly before and after treatment.Before and after the treatment,the cue-N2 component had time main effect(F_1,42=2.6,P=0.113),group main effect(F_1,42=1.4,P=0.230)and condition main effect(F_2,84=6.345,P=0.003),the interaction effect of time×group×condition was significant(F_1,42=3.551,P=0.040).After treatment,the cue-P3 component had time main effect(F_1,42=1.6,P=0.208),group main effect(F_1,42=0.4,P=0.495),and condition main effect was significant(F_2,84=9.2,P<0.001),time×group×The Fb-P3 component in feedback stage changed significantly(F_2,84=3.6,P=0.046).After the intervention,Fb-P3 had significant time main effect(F_1,42=.9.7,P=0.003),group main effect(F_1,42=0.3,P=0.560)and condition main effect(F_2,84=51.3,P<0.001).The interaction effect between time×group×condition was significant(F_2,84=0.2,P=0.258).Conclusion:10Hz excitatory rTMS stimulated the left DLPFC region with the strongest functional connection with nucleus accumbens,which can effectively improve the symptoms of anticipatory anhedonia and depression symptoms in depressive patients,and improve the average amplitude of cue-P3 component,a related ERP neurophysiological index.