Early Intervention Unit, Department of Psychiatry, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
Functional Brain Imaging Institute of Nanjing Medical University, Nanjing, China.
CNS Neurosci Ther. 2024 Mar;30(3):e14427. doi: 10.1111/cns.14427. Epub 2023 Sep 18.
Neurodevelopmental impairments are closely linked to the basis of adolescent major psychiatric disorders (MPDs). The visual cortex can regulate neuroplasticity throughout the brain during critical periods of neurodevelopment, which may provide a promising target for neuromodulation therapy. This cross-species translational study examined the effects of visual cortex repetitive transcranial magnetic stimulation (rTMS) on neurodevelopmental impairments in MPDs.
Visual cortex rTMS was performed in both adolescent methylazoxymethanol acetate (MAM) rats and patients with MPDs. Functional magnetic resonance imaging (fMRI) and brain tissue proteomic data in rats and fMRI and clinical symptom data in patients were analyzed.
The regional homogeneity (ReHo) analysis of fMRI data revealed an increase in the frontal cortex and a decrease in the posterior cortex in the MAM rats, representing the abnormal neurodevelopmental pattern in MPDs. In regard to the effects of rTMS, similar neuroimaging changes, particularly reduced frontal ReHo, were found both in MAM rats and adolescent patients, suggesting that rTMS may reverse the abnormal neurodevelopmental pattern. Proteomic analysis revealed that rTMS modulated frontal synapse-associated proteins, which may be the underpinnings of rTMS efficacy. Furthermore, a positive relationship was observed between frontal ReHo and clinical symptoms after rTMS in patients.
Visual cortex rTMS was proven to be an effective treatment for adolescent MPDs, and the underlying neural and molecular mechanisms were uncovered. Our study provides translational evidence for therapeutics targeting the neurodevelopmental factor in MPDs.
神经发育障碍与青少年主要精神障碍(MPD)的基础密切相关。视觉皮层可以在神经发育的关键时期调节整个大脑的神经可塑性,这可能为神经调节治疗提供一个有前途的靶点。这项跨物种转化研究检查了视觉皮层重复经颅磁刺激(rTMS)对 MPD 神经发育障碍的影响。
对青少年甲基乙氧甲酰胺(MAM)大鼠和 MPD 患者进行视觉皮层 rTMS。分析大鼠的功能磁共振成像(fMRI)和脑组织蛋白质组学数据以及患者的 fMRI 和临床症状数据。
fMRI 数据的局部一致性(ReHo)分析显示,MAM 大鼠的额皮质增加,后皮质减少,代表 MPD 中的异常神经发育模式。关于 rTMS 的影响,在 MAM 大鼠和青少年患者中都发现了类似的神经影像学变化,特别是额 ReHo 减少,表明 rTMS 可能逆转异常的神经发育模式。蛋白质组学分析表明,rTMS 调节了与额叶突触相关的蛋白质,这可能是 rTMS 疗效的基础。此外,在患者中,rTMS 后额叶 ReHo 与临床症状之间存在正相关关系。
视觉皮层 rTMS 被证明是治疗青少年 MPD 的有效方法,并揭示了其潜在的神经和分子机制。我们的研究为针对 MPD 神经发育因素的治疗提供了转化证据。