目的:神经发育障碍与青少年主要精神疾病(MPDs)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有希望的靶标。这项跨物种翻译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。
方法:在青少年甲基氧化甲醇乙酸酯(MAM)大鼠和MPD患者中进行视觉皮层rTMS。分析大鼠功能磁共振成像(fMRI)和脑组织蛋白质组数据以及患者的fMRI和临床症状数据。
结果:功能磁共振成像数据的区域同质性(ReHo)分析显示,MAM大鼠的额叶皮质增加,后皮质减少,代表MPD中异常的神经发育模式。关于rTMS的影响,类似的神经影像学变化,尤其是减少额叶ReHo,在MAM大鼠和青少年患者中都发现了,表明rTMS可能逆转异常的神经发育模式。蛋白质组学分析显示,rTMS调节额叶突触相关蛋白,这可能是rTMS疗效的基础。此外,rTMS后患者的额叶ReHo与临床症状呈正相关.
结论:视觉皮层rTMS被证明是青少年MPD的有效治疗方法,并揭示了潜在的神经和分子机制。我们的研究为MPD中针对神经发育因子的疗法提供了翻译证据。
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.