Intermittent Theta Burst Stimulation On Anhedonia In Depression

Objective:Anhedonia is a core symptom of major depressive disorder(MDD)and is a difficult and painful area for antidepressant treatment.Anhedonia is associated with dysfunctional reward neural circuits,especially the functional connections between the dorsolateral prefrontal cortex(DLPFC)and the subcortical nucleus accumbens.Transcranial Magnetic Stimulation(TMS)has a role in modulating the function of brain networks and is one of the treatment options for refractory depression.In recent years,TMS stimulation protocols using high-frequency 10 Hz-rTMS targeting L-DLPFC have been found to be effective for symptoms of self-rated anhedonia.The new optimized intermittent theta burst stimulation(iTBS)can greatly simplify the treatment process and improve clinical instrumentation utilization,so it is necessary to explore whether iTBS has equivalent efficacy to rTMS in intervening with pleasure deficits.Method:This study was designed as a single-blind controlled trial to investigate the intervention effect of iTBS stimulation on anhedonia in depressed patients.33 subjects were included,17 participated in conventional 10 Hz-rTMS treatment and 16 in iTBS treatment.Using the subjects’ MRI imaging data of the nucleus accumbens(NAcc)as a seed point,individualized left dorsolateral prefrontal cortex(1DLPFC)targets were calculated from brain imaging data.Patients received once-daily treatment for 15 days.Clinical symptoms,behavioral and EEG assessments were performed before and after treatment.Clinical assessments included The Hamilton Anxiety Scale(HAMA),the Hamilton Depression Rating Scale(HAMD),the Beck Depression Inventory(BDI),the Temporal Experience of Pleasure Scale(TEPS),and Apathy Evaluation Scale(AES);behavioral and EEG data were collected by the Monetary Incentive Delay(MID)paradigm.One month after the end of the intervention,follow-up BDI,TEPS,and AES symptom data were collected by electronic scales.This study focused on the analysis of scale,behavioral,and EEG data of subjects using a two-factor repeated measures ANOVA for comparison.Results:Ⅰ.Clinical symptom intervention results:between-group differences on demographic variables such as gender,age,education,duration of disease,and clinical symptoms at baseline did not reach significance levels.ANOVA showed significant time main effects on HAMD,HAMA,TEPS,TEPS-ant,TEPS-con,and AES,with both groups being significantly elevated after stimulation.On the BDI scale,there was a significant interaction of "time × group",F(1,31)=8.159,P=0.008,ηp2=0.208.For the rTMS group,the BDI score was significantly lower after treatment(P=0.006);for the iTBS group,the BDI score was significantly lower after treatment(P<0.001).Ⅱ.Clinical symptoms follow-up results:on TEPS,TEPS-ant,TEPS-con,and AES,the time main effect was significant.On BDI,the time and group interaction was significant,F(2,36)=4.054,P=0.026,ηp2=0.184.simple effects analysis showed that for the rTMS group,the difference between intervention and follow-up scores was not significant(P=0.535);the results were similar for the iTBS and rTMS groups(P=0.267).Bonferroni post hoc test found no significant difference between groups.Ⅲ.MID task behavioral results:no significant interaction or main effect was seen in ANOVA on correctness and response time.Ⅳ.MID task EEG results:Because there were significant differences between the two groups at baseline on the motivational pleasure deficit dimension,motivational pleasure deficit symptoms were included as covariates.On the CNV component,ANOVA revealed significant time*group interactions in the no-reward,low-reward,and high-reward conditions,and simple effects analysis,with no significant differences between the two groups at the pre-and post-test levels,but significant differences between the 10 Hz-rTMS group at the preand post-test levels,with wave amplitude correcting towards post-intervention(P=0.042;P=0.035;P=0.026).On the Fb-P3 component,the ANOVA showed that in the 10Hz-rTMS group,wave amplitude increased after the intervention in both low and high reward conditions(P=0.003;P=0.059).Conclusion:This study used intermittent Theta burst stimulation to intervene in depressed patients with anhedonia.The results showed that individualized and precisely targeted intermittent Theta burst stimulation had the same significant improvement in depressive anxiety and pleasure deficit symptoms compared to conventional 10 HZ high frequency stimulation,and maintained the treatment effect until one month follow-up.Behaviorally,however,there was no significant improvement in either group before or after the intervention.On the EEG component,the rTMS group showed an intervention effect,which was missing in the iTBS group.These results provide further evidence that the NAcc-DLPFC reward circuit is an important neurobiological mechanism of pleasure deficits.