نهمین کنگره نقشه برداری مغز

نمایش مقاله

Title:

Bilateral Prefrontal rTMS Modulates Anterior Cingulate Activation and Cingulo-Insular Resting-State Connectivity in Major Depressive Disorder

Subject:

Clinical Applications of Brain Mappin

Presenter Author:
Name:	Maryam Zivariderakhshande

Author:
Name 1:	Maryam Zivariderakhshande - Corresponding - Presenter
Affiliation 1:	MSc student in Medical Imaging, Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences

Name 2:	Dr anita Ebrahimpour
Affiliation 2:	Assistant Professor , Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences

Name 3:
Affiliation 3:

Name 4:
Affiliation 4:

Name 5:
Affiliation 5:

Name 6:
Affiliation 6:

Name 7:
Affiliation 7:

Name 8:
Affiliation 8:

Name 9:
Affiliation 9:

Name 10:
Affiliation 10:

Abstract

Original Research

introduction :

: Repetitive transcranial magnetic stimulation (rTMS) is an effective, non-invasive neuromodulatory intervention for major depressive disorder (MDD), yet the neuroimaging biomarkers and underlying neural mechanisms remain incompletely understood. MDD is characterized not only by emotional dysregulation but also by prominent cognitive deficits, particularly working memory (WM) impairments. Bilateral rTMS targeting the dorsolateral prefrontal cortex (DLPFC), combining high-frequency stimulation to the left DLPFC and low-frequency stimulation to the right DLPFC, aims to restore prefrontal functional balance. This study aimed to reveal the effects of bilateral DLPFC-rTMS on the improvement of depressive symptoms and cognitive function, and to investigate the functional neuroimaging changes induced by rTMS by measuring both task-related brain activation during a working memory task and intrinsic resting-state functional connectivity (rs-FC) in patients with MDD.

Methods:

10 patients diagnosed with MDD received a 20-session course of bilateral DLPFC-rTMS (5 sessions per week for 4 weeks; high-frequency left DLPFC and low-frequency right DLPFC). Clinical assessments, including the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI), were evaluated before and after the treatment course. All participants underwent functional magnetic resonance imaging (fMRI) at baseline and post-treatment, both at rest and while performing the Sternberg working memory task. Task-related brain activation was analyzed using SPM with small volume correction (SVC) and false discovery rate (FDR) correction. Seed-to-voxel resting-state functional connectivity was evaluated using MATLAB's CONN toolbox with the anterior cingulate cortex (ACC) defined as the seed region of interest.

Results:

Bilateral rTMS led to significant clinical improvements, reflected by marked reductions in both depression (BDI) and anxiety (BAI) scores after treatment (p < 0.001). Task-based fMRI analysis showed a significant post-treatment increase Post > Pre in task-related brain activation within the anterior cingulate cortex during working memory (peak MNI: [-2, 32, 16], T = 19.18, Z = 5.15, cluster size = 44 voxels, p_FDR-corr = 0.002). Furthermore, resting-state seed-to-voxel connectivity analysis in CONN revealed significant functional connectivity changes between the ACC seed and a cluster in the right hemisphere (peak MNI: [+46, +8, -4], cluster size = 59 voxels, cluster-level p_FDR-corr = 0.011, mainly covering the right insular cortex (59% of cluster voxels), right central opercular cortex (10%), right temporal pole (5%), and right frontal operculum (5%).

Conclusion:

our findings demonstrate that a 4-week bilateral DLPFC-rTMS protocol provides substantial clinical relief while driving coordinated neurofunctional reorganization across both task-engaged and intrinsic brain states in MDD. The localized upregulation of ACC activation during the Sternberg task underscores the restoration of top-down cognitive control and neural efficiency required for working memory. Concurrently, the modulation of resting-state connectivity between the ACC and the right insular cortex points to functional normalization within the salience and cingulo-opercular networks, which play a critical role in mediating dynamic switching between self-referential processing and externally guided cognitive networks. Taken together, these convergent task-based and resting-state neuroimaging results enrich our understanding of the neural mechanisms underlying bilateral rTMS and provide compelling evidence that frontocingulate-insular functional remodeling serves as a robust neuroimaging biomarker for therapeutic and cognitive recovery in depression.

Keywords:

Major depressive disorder (MDD); Repetitive transcranial magnetic stimulation (rTMS); Working memory; Resting-state functional connectivity