| BackgroundDepression is one of the most common mood disorders characterized by persistent low mood,anhedonia,lack of motivation and various somatic symptoms.Somatic symptoms refer to bodily complaints including headache,dizziness,flustered,chest stuffy and abdominal distension without any medical reasons.Somatic symptoms account for the primary reason for depressive patients to go to general hospitals for treatment,which can cause poor response to antidepressants and misdiagnosis.Due to high misdiagnosis rate and difficulty in treatment,somatic symptoms cause heavy economic burden to the family and society.The neural mechanism of somatic symptoms remains elusive.Probing the neural mechanism is crucial for accurate diagnosis and effective treatment.Prior evidence indicated that amygdala is the critical region for emotional and somatic information processing.These results suggest that the amygdala is the core brain region for emotional and physical information processing,and the dysfunction of amygdala-related circuit may be implicated in the neural substrate of somatic symptoms.As the most effective treatment for depression,electroconvulsive therapy（ECT）can significantly improve the somatic symptoms of depressive patients.Previous studies suggested that ECT can significantly regulate the function of neural circuits.However,whether ECT regulates the somatic symptoms-related circuit remains unclear.Though remarkable efficacy,ECT often cause significant cognitive impairment.Therefore,it is urgent to find a non-invasive and effective intervention method.Transcranial Direct Current Stimulation（t DCS）is a noninvasive brain stimulation method that modulates cortical excitability and has been applied in the treatment of neuropsychiatric disorders.Whether t DCS can improve somatic symptoms in depressive patients via regulating somatic symptoms-related circuits is unclear.ObjectivesIn this study,we explored the neural circuit of somatic symptoms in depressive patients based on specific hypothesis.Then we probed the substrates of ECT relieving somatic symptoms based on the circuit.The cardinal role of this circuit in somatic symptoms was further validated.Subsequently,we targeted the circuit via t DCS to improving somatic symptoms in depressive patients.Combined with rs-f MRI data,the therapeutic effect and underlying neural mechanism of t DCS on somatic symptoms were explored.（1）Amygdala is implicated in somatosensory information encoding and interoception processing.Because of the functional heterogeneity,the amygdala can be divided into three subregions with respective role in emotion,cognition and somatic information processing.Based on the resting-state functional connectivity（RSFC）of the amygdala subregion,this study identified cortical regions associated with somatic symptoms and provided the basis for subsequent identification of targets.（2）Based on the determined neural circuit,this study explored the substrate of ECT reducing somatic complaints.The core role of this circuit in somatic symptoms was further confirmed.（3）This study aimed to explore the efficacy of t DCS treating somatic symptoms using a randomized and double-blinded controlled trail.Further,we explored the neural mechanism of t DCS relieving somatic symptoms.Methods（1）We recruited 46 depressive patients and matched healthy controls（HCs）to complete rs-f MRI scanning.Depressive and somatic symptoms were assessed using the Hamilton Depression Rating Scale（HDRS-17）and the 15-item somatic symptom severity scale of the Patient Health Questionnaire（PHQ-15）,respectively.We investigated the relationship between the RSFC of amygdala subdivisions and somatic symptoms.Then,we extracted the FC value from HCs and compared the differences between groups.（2）Rs-fMRI scans and clinical symptoms were assessed in 45 patients with major depressive disorder（MDD）before and after ECT and in 43 demographically matched HCs once.The basolateral amygdala was used as the seed for functional connectivity analysis.Longitudinal analysis was conducted before and after ECT to find functional connectivity alterations.Then,correlation analysis was conducted with the improvement rate of somatic symptoms.（3）Randomized double-blind t DCS trail was conducted in depressive patients with somatic symptoms to explore the efficacy of t DCS on somatic symptoms,emotional symptoms.Meanwhile,combined with rs-f MRI data,we explored the neural mechanism of t DCS in improving somatic symptoms.Results（1）The somatic symptoms were negatively correlated with the left basolateral amygdala-dorsomedial prefrontal cortex（dm PFC）RSFC（r =-0.591,p<0.001）,which was significantly lower than HCs（0.083±0.129 vs.0.139±0.125,p<0.05）.On the other hand,the somatic symptoms of depressive patients were positively correlated with the left basolateral amygdala-ventromedial prefrontal cortex RSFC（r = 0.476,p=0.001）,which was lower than HCs（0.142±0.222 vs.0.238±0.221,p<0.05）.（2）ECT significantly increased the left basolateral amygdala-dm PFC RSFC in patients with MDD（0.048±0.104 vs.0.151±0.131,p<0.001）.The changed RSFC value was correlated with the improvement rate of somatic symptoms（r=0.364,p=0.018）.RSFC was lower at baseline than HCs and normalized after ECT.（3）TDCS targeting dm PFC significantly alleviated somatic symptoms and emotional symptoms of depressive patient.There was a significant time*group interaction effect between the real and sham group（F=4.551,p=0.037;F=9.413,p=0.003）.Functional connectivity between the target and the left amygdala,right anterior cingulate gyrus,and inferior temporal gyrus increased after t DCS treatment.The increase of functional connectivity was correlated with the improvement of somatic symptoms.ConclusionDecreased basolateral amygdala-dm PFC functional connectivity may be the neural mechanism of somatic symptoms of depression.The increased basolateral amygdala-dm PFC functional connection may be the neural circuit mechanism of ECT relieving somatic symptoms in depressive patients.Stimulating dm PFC via t DCS can significantly improve the somatic and emotional symptoms of depressive patients,which provides targeted intervention guidance for depressive patients with residual somatic symptoms.TDCS can regulate limbic systems such as anterior cingulate gyrus and amygdala by stimulating dm PFC,which may be the underlying neural mechanism for t DCS to improve somatic symptoms. |
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