Study on iTBS Regulating the Reward Circuit Function to Improve Anhedonia in Depression

Anhedonia, Major Depression, Melancholic Depression, Theta Burst Stimulation

The goal of this clinical trial is to learn if the proposed intermittent theta burst stimulation (iTBS) protocol can effectively improve anhedonia symptoms in depressed patients. The stimulation targets in our protocol include (1) dual-target stimulation at the left dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC). (2) single-target stimulation at the left DLPFC. The main questions it aims to answer are: * Whether iTBS of dual-target stimulation (left DLPFC and OFC) can improve the symptoms of anhedonia and better than single-target stimulation at the left DLPFC? * Whether iTBS of the dual targets of left DLPFC and OFC can improve the symptoms of anhedonia by correcting the abnormal functional connectivity of DLPFC-NAc and OFC-sgACC, regulating the functional abnormalities of NAc and sgACC, and indirectly repairing the overall dysfunction of the reward circuit. * Researchers will compare dual-target stimulation to single-target stimulation and sham dual-target stimulation (a dedicated sham coil is utilized which produces an identical audible click and physical sensation) to see if the proposed iTBS protocol works to treat anhedonia. Participants will: * Take 6 sessions of dual-target iTBS or single-target iTBS every day, for 5 consecutive days. * Visit our hospital at 1 week, 4 weeks, and 8weeks after the iTBS treatment completion, for clinical evaluation and brain image examination.

Anhedonia, defined as the diminished capacity to experience pleasure, is a core symptom of Major Depressive Disorder (MDD). Patients with anhedonia exhibit a pervasive loss of interest or pleasure in all or almost all previously enjoyable activities, which frequently leads to a profound reduction in the desire to engage in rewarding behaviors. Previous studies have reported that anhedonia occurs in 37% to 72% of depressed individuals. Patients with depression accompanied by anhedonia tend to respond poorly to medication and psychotherapy but show relatively better responses to conventional physical treatments such as electroconvulsive therapy (ECT). Research has shown that improving anhedonia significantly enhances social functioning in depressed patients. Therefore, more effective treatments targeting anhedonia are needed. Achieving breakthroughs in therapeutic approaches and understanding their underlying mechanisms will contribute substantially to progress in this field. Theta-burst stimulation (TBS) utilizes a stimulation pattern that closely mimics the natural firing frequencies of cerebral neurons. Accumulating evidence has demonstrated the clinical efficacy of intermittent TBS (iTBS) in alleviating depressive symptoms. Thus, this study aims to investigate and evaluate whether the proposed iTBS protocol can effectively improve anhedonia symptoms in depressed patients by regulating functional abnormalities. The stimulation targets in our protocol include (1) dual-target stimulation at the left dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC). (2) single-target stimulation at the left DLPFC. The main questions it aims to answer are: 1. Whether iTBS of dual-target stimulation (left DLPFC and OFC) can improve the symptoms of anhedonia and better than single-target stimulation? 2. Whether iTBS of the dual targets of left DLPFC and OFC can improve the anhedonia symptom by correcting the abnormal functional connectivity of DLPFC-NAc and OFC-sgACC, regulating the functional abnormalities of NAc and sgACC, and indirectly repairing the overall dysfunction of the reward circuit?

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