Investigation of transcranial magnetic stimulation treatment applied to the dorsomedial prefrontal cortex using a double-cone coil and associated microstructural brain changes in treatment-resistant depression patients

Objectives: Major depressive disorder (MDD) is a leading cause of disability worldwide, characterized by symptoms such as a persistently low mood and a loss of interest or pleasure in daily activities. MDD is currently understood to involve abnormalities in the brain's structural and functional connectivity, highlighting its complex pathophysiology. The limited effectiveness of antidepressants and psychotherapies in treating this complex disorder has led clinicians to seek new treatment options. This study investigates the effects of intermittent theta burst stimulation (iTBS), a variant of repetitive transcranial magnetic stimulation (rTMS) that has proven efficacy, on structural brain connectivity and its correlation with clinical responses. Additionally, this study aims to identify biological markers that can assist clinicians in choosing the most appropriate treatment method for each patient. Materials and Methods: This study involved 21 patients diagnosed with treatment-resistant depression who received rTMS treatment. iTBS were applied to these patients using a double-cone coil over 20 or 30 sessions. Before the treatment, the Maudsley Staging Method (MSM) was utilized to assess the resistance level of each patient. Patients were monitored weekly throughout the treatment period using several assessment tools, including the Hamilton Depression Rating Scale (HDRS), Patient Health Questionnaire-9 (PHQ-9), Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR), Beck Scale for Suicide Ideation (BSS), Beck Anxiety Inventory (BAI), and the Clinical Global Impression Scale (CGI) to evaluate their clinical response. Diffusion tensor imaging (DTI) was conducted on patients before and after treatment to investigate white matter microstructures and treatment-induced changes. Results: The iTBS treatment led to changes in the structural connectivity of prefrontal regions, including the anterior cingulate cortex, dorsomedial prefrontal cortex, anteriomedial prefrontal cortex, and orbitofrontal cortex, as well as the amygdala and insula. Additionally, The pre-treatment FA value of the connection between the orbitofrontal cortex and the subgenual cingulate cortex in the left hemisphere has been found to predict treatment response. Conclusion: This study is the first comprehensive investigation of the effects of iTBS applied using a double-cone coil and its relationship to microstructural abnormalities identified through DTI analysis. The research offers valuable insights into the factors influencing treatment response and the impact of iTBS on brain structural connectivity. Keywords: major depressive disorder, treatment-resistant depression, transcranial magnetic stimulation, diffusion tensor imaging