A Study on Functional Connectome and rTMS Intervention of Cognitive Flexibility Impairment in Patients With Major Depressive Disorder

Summary

Persistent cognitive impairment in major depressive disorder (MDD) affects both treatment outcomes and psychosocial functioning, emphasizing the critical need for effective treatment. However, there is still a lack of effective treatment at present. Our previous studies found that the impairment in cognitive flexibility (CF) persisted even in remitted patients with MDD. This impairment was correlated with hypo-connectivity between the left inferior parietal lobule (IPL) and the right dorsal prefrontal cortex (dPFC). Based on these findings, we hypothesize that the hypo-connectivity between the left IPL and the right dPFC is the neural basis of CF impairment, and targeted interventions of this connection may alleviate CF impairment and thus improve treatment outcomes as well as psychosocial functioning of patients with MDD. The present study proposes to employ cognitive training for MDD patients with CF impairment. By comparing changes in CF and brain functional connectivity via task-based fMRI before and after the intervention, we aim to clarify the effect of cognitive training on cognitive performance, treatment outcomes and psychosocial functioning, and identify the critical role of the hypo-connectivity between the left IPL and the right dPFC underlying CF impairment. Furthermore, we will conduct a randomized controlled trial to investigate the effect of individualized dual-target repetitive transcranial magnetic stimulation (rTMS) on CF by targeting the hypo connectivity between the left IPL and the right dPFC. The results will further validate the critical role of this connection in modulating CF performance and provide a reliable intervention target for reducing CF impairment.

Conditions

• Depressive Disorder, Major
• Cognitive Impairment

Interventions

DEVICE

Repetitive Transcranial Magnetic Stimulation

Individualized dual-target rTMS delivered using MRI-guided neuronavigation (Dolphin Robotics). Stimulation parameters: * Targets: Left IPL and right dPFC connectivity hotspots * Protocol: 100 pulse-pairs/session at 0.2Hz * Intensities: Conditioning stimulus 90% RMT, test stimulus 120% RMT * Duration: 8.3 min/session, 5 sessions/week × 4 weeks

BEHAVIORAL

Computerized Cognitive Remediation Therapy

Structured computer-based training targeting cognitive flexibility, consisting of 4-6 exercises per session. Each exercise includes 8-24 progressively challenging tasks. Administered for 45-60 minutes per session, 5 sessions/week over 4 weeks. Delivered via specialized software on desktop computers.

DEVICE

Sham Repetitive Transcranial Magnetic Stimulation

Inactive stimulation using identical equipment with: * Coil tilted at 90° to scalp * Magnetic shielding insert * Matched acoustic artifact All other parameters identical to active rTMS arm.

DRUG

Selective Serotonin Reuptake Inhibitors or Serotonin-Norepinephrine Reuptake Inhibitors

Background antidepressant therapy maintained at stable doses throughout the study. Minimum dose requirements: * SSRIs: Paroxetine ≥20mg/day, Sertraline ≥50mg/day * SNRIs: Venlafaxine ≥75mg/day, Duloxetine ≥60mg/day Dosage adjustments prohibited during trial participation.

Sponsors & Collaborators

• Second Xiangya Hospital of Central South University

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

45 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-09-30

Primary Completion

2028-08-31

Completion

2028-10-31

Countries

• China

Study Locations