| Objective:Depression is a serious mental illness.The weighted lifetime prevalence rate of patients with depression in China is 6.8,while the weighted 12-month prevalence rate is 3.6%.Depression not only affects the study,work and life of patients,but also causes a huge burden to the family and social economy.Repetitive transcranial magnetic stimulation(Repetitive Transcranial Magnetic Stimulation,rTMS)is safe and well tolerated in the treatment of depression,and the incidence of adverse reactions is low.However,at present,the mechanism of rTMS antidepressant is not clear,loss of pleasure is one of the core symptoms of depression,but the current drug treatment effect is limited.In this paper,we will study the brain imaging mechanism of the efficacy of rTMS in the treatment of depression and loss of pleasure.The ratio low frequency amplitude(Fractional Amplitude of Low-frequency Fluctuations,fALFF)technique of resting state functional magnetic resonance imaging(Fractional Amplitude of Low-frequency Fluctuations,fALFF)was used to analyze the brain functional activity of patients with depression before and after rTMS treatment,to explore the changes of rTMS stimulation site as the functional connection of the whole brain(Function Connection,FC),and to understand the neural mechanism of rTMS in the treatment of depression..Methods:Patients with mild to moderate depression in the Department of Psychiatry of the first affiliated Hospital of Kunming Medical University from October 2020 to March 2021 were divided into two groups:one group received 3-week rTMS treatment(rTMS group),the other received 3-week pseudo-rTMS treatment(sham group).At the same time,age-sex matched healthy control group(Health Control,HC)was collected.Resting fMRI scan was performed in both rTMS group and sham group before treatment,and fMRI scan was performed again after 3 weeks of rTMS treatment.17 items of Hamilton Depression scale(Hamilton Depression-17 item Scale,HAMD)and Snyce-Hamilton pleasure scale(Snaith-Hamilton Pleasure Scale,SHAPS)were evaluated in patients with depression before and at the end of 1,2 and 3 weeks of treatment.The imaging data were processed by DPARSF software based on Matlab platform.The fALFF values of the whole brain of the subjects were calculated and compared.Taking the left dorsolateral prefrontal lobe as the seed point,the whole brain functional connection method based on voxel was used to analyze the functional connection mode of left dorsolateral prefrontal lobe in resting state of fMRI in patients with depression treated with rTMS.Pearson correlation analysis was used to explore the relationship between the value of fALFF in different brain regions and Z value in depressive patients treated with rTMS and clinical symptoms.Results:The main results were as follows:(1)A total of 36 patients(5 males and 29 females)were enrolled in the rTMS group,including 22 patients in the sham group,20 patients completed 3 weeks of treatment,19 patients completed resting fMRI at baseline,17 patients completed resting fMRI 3 weeks after rTMS treatment,14 patients in sham group completed 3 weeks treatment,and 14 patients completed resting fMRI after 3 weeks of baseline and sham treatment.There were 23 cases in the control group.There was no significant difference in sex,age and years of education among rTMS group,sham group and HC group.(2)Comparison of the curative effect between the two groups:the effect of rTMS treatment in rTMS group and rTMS pseudo-stimulation on HAMD score reduction rate in sham group was different.The HAMD score reduction rate in rTMS group was better than that in sham group,in which HAMD in rTMS group decreased from 18.1012.51 to 4.95 ± 1.82,and HAMD in rTMS group decreased from 19.93 12.34 to 9.5013.01,with a score reduction rate of 52.42±13.14%.The comparison between the two groups was analyzed by repeated measurement variance of two factors.The results were statistically significant(P<0.05).There was no significant difference in SHAPS score reduction rate between rTMS group and sham group(P>0.05).In the treatment of depression with rTMS,the antidepressant symptoms were obvious,but the loss of pleasure was not obvious.(3)The fALFF values of fALFF:rTMS group and HC group before and after treatment were compared by two-sample t-test analysis.The results showed that there was no significant difference in fALFF between rTMS group and HC group at baseline,but after 3 weeks,the FALFF value of dorsolateral superior frontal gyrus in rTMS group was lower than that in HC group.Compared with sham group and HC group,the fALFF value of middle frontal gyrus in sham group was lower than that in HC group at baseline,but there was no significant difference between sham group and HC group after 3 weeks.The fALFF value of rTMS group was compared with that of 3 weeks after treatment,the results showed that the FALFF values of right Talar fissure(right posterior cingulate)and right postcentral gyrus in rTMS group were higher than those in baseline after 3 weeks,while in sham group,there was no significant difference in fALFF between sham group and baseline after 3 weeks.(4)Functional connection before and after treatment:at baseline,the functional connection between the left dorsolateral prefrontal lobe and the right thalamus and lentiform putamen in the rTMS group was stronger than that in the HC group,but there was no significant difference between the rTMS group and the HC group 3 weeks after treatment.There was no significant difference in functional connection between sham group and HC group at baseline and 3 weeks later.Self-comparison of FC images before and after treatment:paired t-test was used to analyze the functional connections between left dorsolateral prefrontal lobe and right orbital inferior frontal gyrus,posterior cerebellar lobe,left orbital inferior frontal gyrus and inferior parietal angular gyrus in rTMS group after 3 weeks,but there was no significant difference in brain functional connections between sham group and baseline after 3 weeks.(5)Comparison of fALFF and FC images between cured group and uncured group in rTMS group:the values of fALFF in the right postcentral gyrus and right posterior cingulum extending to the right posterior cingulate in the cured group were higher than those in the cured group before and after treatment by paired t-test.The results showed that after 3 weeks,the values of fALFF in the right postcentral gyrus and right posterior cingulate in the cured group were higher than those in the cured group.Compared with the uncured group at baseline,there was no significant difference in the value of fALFF in the uncured group after 3 weeks.Comparison of FC before and after treatment:paired t-test analysis showed that compared with the baseline,the functional connection between the left dorsolateral prefrontal lobe and the left and right superior cerebellum and the right orbital inferior frontal gyrus decreased after 3 weeks in the cured group,and the functional connection between the left dorsolateral prefrontal lobe and the left peritalar fissure cortex decreased in the uncured group after 3 weeks.(6)Correlation between imaging indexes and curative effect:the fALFF values of different brain regions in the rTMS group before and after treatment were analyzed by pearson correlation analysis.The results showed that there was no significant correlation between the β-fALFF values of the right postcentral gyrus and the right posterior cingulate fissure(right posterior cingulate)and the HAMD score reduction rate(r=0.270,0.102)and SHAPS score reduction rate(r=0.270,-0.003)in the rTMS group.The Z value of brain regions with different functional connections and clinical efficacy in rTMS group were extracted and analyzed by Pearson correlation analysis.The results showed that in rTMS group,the β Z value of functional connection between left dorsolateral prefrontal lobe and right orbital inferior frontal gyrus,posterior cerebellar lobe,left orbital inferior frontal gyrus and inferior parietal angular gyrus was not significantly correlated with HAMD score reduction rate(r=0.148,-0.284,-0.164,r=0.069)and SHAPS score reduction rate(r=0.065,-0.311,-0.266,-0.384),respectively..Conclusion:(1)After 3 weeks of rTMS treatment in rTMS group and 3 weeks of pseudo-rTMS treatment in sham group,the decrease rate of Hamd in rTMS group was better than that in sham group,but the therapeutic effect on the symptoms of anaesthesia was not obvious in both groups.(2)Compared with HC group,the decrease of FALFF in dorsolateral superior frontal gyrus in rTMS group after 3 weeks may be one of the neuroimaging mechanisms for the improvement of depressive symptoms in rTMS treatment,while the increase in FALFF in sham group after 3 weeks may be related to the improvement of depression symptoms by pseudo-rTMS stimulation as a placebo.Compared with the baseline,the increase of FALFF in the right Talar fissure(right posterior cingulate)and right postcentral gyrus in the rTMS group may be one of the mechanisms for the improvement of depressive symptoms.(3)The normalization of the functional connection between the left dorsolateral prefrontal lobe and the right lenticular putamen and thalamus in the rTMS group after rTMS treatment may be one of the neuroimaging mechanisms of the efficacy of rTMS in the treatment of depression.At the same time,in rTMS group,the functional connections between left dorsolateral prefrontal lobe and left and right orbitofrontal lobe,left inferior parietal angular gyrus and posterior cerebellar lobe decreased after rTMS treatment.The improvement of clinical symptoms in patients with depression may be related to the intensity of functional connection between left dorsolateral prefrontal lobe and these brain regions. |
