Port Russell G, Gaetz William, Bloy Luke, Wang Dah-Jyuu, Blaskey Lisa, Kuschner Emily S, Levy Susan E, Brodkin Edward S, Roberts Timothy P L
Lurie Family Foundations MEG Imaging Center, Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Autism Res. 2017 Apr;10(4):593-607. doi: 10.1002/aur.1686. Epub 2016 Oct 1.
Autism spectrum disorder (ASD) is hypothesized to arise from imbalances between excitatory and inhibitory neurotransmission (E/I imbalance). Studies have demonstrated E/I imbalance in individuals with ASD and also corresponding rodent models. One neural process thought to be reliant on E/I balance is gamma-band activity (Gamma), with support arising from observed correlations between motor, as well as visual, Gamma and underlying GABA concentrations in healthy adults. Additionally, decreased Gamma has been observed in ASD individuals and relevant animal models, though the direct relationship between Gamma and GABA concentrations in ASD remains unexplored. This study combined magnetoencephalography (MEG) and edited magnetic resonance spectroscopy (MRS) in 27 typically developing individuals (TD) and 30 individuals with ASD. Auditory cortex localized phase-locked Gamma was compared to resting Superior Temporal Gyrus relative cortical GABA concentrations for both children/adolescents and adults. Children/adolescents with ASD exhibited significantly decreased GABA+/Creatine (Cr) levels, though typical Gamma. Additionally, these children/adolescents lacked the typical maturation of GABA+/Cr concentrations and gamma-band coherence. Furthermore, children/adolescents with ASD additionally failed to exhibit the typical GABA+/Cr to gamma-band coherence association. This altered coupling during childhood/adolescence may result in Gamma decreases observed in the adults with ASD. Therefore, individuals with ASD exhibit improper local neuronal circuitry maturation during a childhood/adolescence critical period, when GABA is involved in configuring of such circuit functioning. Provocatively a novel line of treatment is suggested (with a critical time window); by increasing neural GABA levels in children/adolescents with ASD, proper local circuitry maturation may be restored resulting in typical Gamma in adulthood. Autism Res 2017, 10: 593-607. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
自闭症谱系障碍（ASD）被认为是由兴奋性和抑制性神经传递失衡（E/I失衡）引起的。研究已经在患有ASD的个体以及相应的啮齿动物模型中证实了E/I失衡。一种被认为依赖于E/I平衡的神经过程是γ波段活动（Gamma），这一观点得到了健康成年人中运动、视觉Gamma与潜在GABA浓度之间观察到的相关性的支持。此外，在ASD个体和相关动物模型中也观察到了Gamma降低的情况，尽管ASD中Gamma与GABA浓度之间的直接关系仍未得到探索。本研究对27名发育正常的个体（TD）和30名患有ASD的个体进行了脑磁图（MEG）和编辑磁共振波谱（MRS）检查。将听觉皮层局部锁相Gamma与儿童/青少年和成年人静息状态下颞上回相对皮质GABA浓度进行了比较。患有ASD的儿童/青少年尽管Gamma正常，但GABA+/肌酸（Cr）水平显著降低。此外，这些儿童/青少年缺乏GABA+/Cr浓度和γ波段相干性的典型成熟过程。此外，患有ASD的儿童/青少年也未能表现出典型的GABA+/Cr与γ波段相干性关联。儿童期/青少年期这种耦合的改变可能导致患有ASD的成年人中观察到的Gamma降低。因此，患有ASD的个体在儿童期/青少年期关键时期表现出局部神经元回路成熟不当，此时GABA参与了此类回路功能的配置。令人兴奋的是，提出了一种新的治疗方法（具有关键时间窗）；通过提高患有ASD的儿童/青少年的神经GABA水平，可能恢复局部回路的正常成熟，从而在成年期产生典型的Gamma。《自闭症研究》2017年，10：593 - 607。©2016国际自闭症研究协会，威利期刊公司
