Targeting the Primary Visual Cortex-Hippocampus Circuit With Transcranial Magnetic Stimulation to Improve Cognition in Bipolar Disorder: A Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 88
- 试验地点
- 1
- 主要终点
- Cognitive performance will be assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB) Spatial Span (SSP)
研究概览
简要总结
Bipolar disorder is a highly disabling psychiatric illness, and cognitive impairment is common in patients with bipolar depression as well as during remission, contributing substantially to functional disability and poorer prognosis. Currently, effective interventions specifically targeting cognitive deficits remain limited, highlighting the need for novel treatment strategies. Transcranial magnetic stimulation, a noninvasive neuromodulation technique, has shown potential benefits for depressive symptoms and cognitive functioning. Based on structural and functional neuroimaging evidence, this study proposes an individualized intermittent theta burst stimulation (iTBS) protocol targeting the primary visual cortex (V1) and its functional pathway to the hippocampus, combined with online cognitive training. This randomized, double-blind, parallel-group, sham-controlled trial will enroll 88 patients with bipolar disorder in remission phase and allocate them to active or sham stimulation. The intervention will be delivered over 5 days, with follow-up assessments through 6 weeks. The primary outcome is change in cognitive performance as measured by the Cambridge Neuropsychological Test Automated Battery (CANTAB). Secondary outcomes include changes in clinical symptom ratings, magnetic resonance imaging (MRI) biomarkers, and the incidence of adverse events. This study aims to evaluate the efficacy and safety of this targeted intervention and to provide evidence for precision treatment approaches to cognitive impairment in bipolar disorder.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1: Age between 18 and 45 years; 2: Right-handed; 3: Meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for bipolar disorder and are currently in a stable remission phase; 4: Hamilton Depression Rating Scale 24-item (HAMD-24) score < 8; 5: Young Mania Rating Scale (YMRS) score <= 7; 6: The participant and his/her legal guardian are willing to comply with the treatment procedures and provide written informed consent.
排除标准
- •1: Diagnosis of another primary psychiatric disorder judged by the investigators to be the predominant condition, with functional impairment exceeding that attributable to bipolar disorder; 2: Comorbid psychiatric disorders, including obsessive-compulsive disorder, personality disorders, anxiety spectrum disorders, intellectual disability, or substance use (dependence/abuse); 3: Inability to complete self-report symptom rating scales or the CANTAB cognitive assessment; 4: Prominent suicidal ideation (item 3 of the HAMD-24 >= 2); 5: History of severe physical illness or other medical conditions that may affect the central nervous system; 6: Neurological disorders or risk factors for seizures, such as a history of intracranial disease, head injury, abnormal electroencephalogram (EEG) findings, magnetic resonance imaging (MRI) evidence of structural brain abnormalities, or a family history of epilepsy; 8: Contraindications to MRI or transcranial magnetic stimulation, such as the presence of metallic or electronic implants (e.g., intracranial metallic foreign bodies, cochlear implants, cardiac pacemakers, vascular stents); 9: Receipt of electroconvulsive therapy (ECT) within 6 months prior to study enrollment; 10: Currently undergoing transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), or other neuromodulatory interventions; 11: Pregnant or breastfeeding women, and women of childbearing potential with a positive urine pregnancy test.
研究组 & 干预措施
Active iTBS + Online Cognitive Training
Participants will receive active iTBS over the individualized left V1-HPC target using MRI-guided neuronavigation, delivered twice daily for 5 consecutive days (90% RMT; 1,800 pulses per session; ~10 minutes). Each stimulation session will be paired with the same online computerized pattern recall training.
干预措施: Active Intermittent Theta Burst Stimulation (Device)
Active iTBS + Online Cognitive Training
Participants will receive active iTBS over the individualized left V1-HPC target using MRI-guided neuronavigation, delivered twice daily for 5 consecutive days (90% RMT; 1,800 pulses per session; ~10 minutes). Each stimulation session will be paired with the same online computerized pattern recall training.
干预措施: Online Cognitive Training (Behavioral)
Sham iTBS + Online Cognitive Training
Participants will receive sham iTBS over the individualized left V1-HPC target using MRI-guided neuronavigation, delivered twice daily for 5 consecutive days (20% RMT; all other iTBS parameters identical to the active group). Each stimulation session will be paired with the same online computerized pattern recall training.
干预措施: Online Cognitive Training (Behavioral)
Sham iTBS + Online Cognitive Training
Participants will receive sham iTBS over the individualized left V1-HPC target using MRI-guided neuronavigation, delivered twice daily for 5 consecutive days (20% RMT; all other iTBS parameters identical to the active group). Each stimulation session will be paired with the same online computerized pattern recall training.
干预措施: Sham Intermittent Theta Burst Stimulation (Device)
结局指标
主要结局
Cognitive performance will be assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB) Spatial Span (SSP)
时间窗: Time Frame: Assessments will be conducted at baseline prior to randomization (T0), immediately after completion of the intervention (T1), and at 6 weeks (T2) post-intervention follow-up.
SSP is a computerised version of the Corsi Blocks task, assessing working memory capacity. The span length ranges from 0 to 9 items, with higher scores indicating greater short-term memory capacity.
CANTAB Pattern Recognition Memory (PRM)
时间窗: Time Frame: Assessments will be conducted at baseline prior to randomization (T0), immediately after completion of the intervention (T1), and at 6 weeks (T2) post-intervention follow-up.
CANTAB PRM evaluates visual pattern recognition memory. The task comprises two sets of 12 stimuli: one assesses immediate recognition, and the other assesses delayed recognition. Higher corrects indicate better recognition memory performance.
CANTAB Rapid Visual Information Processing (RVP)
时间窗: Assessments will be conducted at baseline prior to randomization (T0), immediately after completion of the intervention (T1), and at 6 weeks (T2) post-intervention follow-up.
RVP assesses sustained visual attention and processing speed. Outcome indices include RVP A' (ranges from 0.00 to 1.00, with higher values indicating better target detection performance, and is derived from the hit rate P(hit) and false-alarm rate P(fa)), Total Hits (number of correct target detections), and Mean Latency (mean reaction time for correct responses).
CANTAB Spatial Working Memory (SWM)
时间窗: Assessments will be conducted at baseline prior to randomization (T0), immediately after completion of the intervention (T1), and at 6 weeks (T2) post-intervention follow-up.
SWM assesses the ability to retain spatial information and manipulate remembered locations within working memory. The error index reflects the number of times a participant returns to boxes in which a token has already been found; higher error counts indicate poorer working memory performance. The strategy score indexes the efficiency of search behavior, with higher scores reflecting a more disorganized search strategy.
次要结局
- Hamilton Depression Rating Scale 24-item (HAMD-24)(Baseline prior to randomization (T0), immediately after completion of the intervention (T1), and at 6 weeks (T2) post-intervention follow-up.)
- Hamilton Anxiety Rating Scale (HAMA)(Baseline prior to randomization (T0), immediately after completion of the intervention (T1), and at 6 weeks (T2) post-intervention follow-up.)
- Young Mania Rating Scale (YMRS)(Baseline prior to randomization (T0), immediately after completion of the intervention (T1), and at 6 weeks (T2) post-intervention follow-up.)
- Self-Rating Depression Scale (SDS)(Baseline prior to randomization (T0), immediately after completion of the intervention (T1), and at 6 weeks (T2) post-intervention follow-up.)
- Self-Rating Anxiety Scale (SAS)(Baseline prior to randomization (T0), immediately after completion of the intervention (T1), and at 6 weeks (T2) post-intervention follow-up.)
- Perceived Deficits Questionnaire-Depression (PDQ-D)(Baseline prior to randomization (T0), immediately after completion of the intervention (T1), and at 6 weeks (T2) post-intervention follow-up.)
- Adverse Event Report Form(During the 5-day intervention period)
- Resting-state fMRI functional connectivity (FC) between V1 and hippocampus(1 day before the intervention and within 2 days after completion of the intervention course.)