Departments of Psychology,
Departments of Psychology.
J Neurosci. 2020 Mar 11;40(11):2269-2281. doi: 10.1523/JNEUROSCI.2376-19.2020. Epub 2020 Feb 3.
A prominent hypothesis regarding the pathophysiology of autism is that an increase in the balance between neural excitation and inhibition results in an increase in neural responses. However, previous reports of population-level response magnitude in individuals with autism have been inconsistent. Critically, network interactions have not been considered in previous neuroimaging studies of excitation and inhibition imbalance in autism. In particular, a defining characteristic of cortical organization is its hierarchical and interactive structure; sensory and cognitive systems are comprised of networks where later stages inherit and build upon the processing of earlier input stages, and also influence and shape earlier stages by top-down modulation. Here we used the well established connections of the human visual system to examine response magnitudes in a higher-order motion processing region [middle temporal area (MT+)] and its primary input region (V1). Simple visual stimuli were presented to adult individuals with autism spectrum disorders (ASD; = 24, mean age 23 years, 8 females) and neurotypical controls ( = 24, mean age 22, 8 females) during fMRI scanning. We discovered a strong dissociation of fMRI response magnitude between region MT+ and V1 in individuals with ASD: individuals with high MT+ responses had attenuated V1 responses. The magnitude of MT+ amplification and of V1 attenuation was associated with autism severity, appeared to result from amplified suppressive feedback from MT+ to V1, and was not present in neurotypical controls. Our results reveal the potential role of altered hierarchical network interactions in the pathophysiology of ASD. An imbalance between neural excitation and inhibition, resulting in increased neural responses, has been suggested as a pathophysiological pathway to autism, but direct evidence from humans is lacking. In the current study we consider the role of interactions between stages of sensory processing when testing increased neural responses in individuals with autism. We used the well known hierarchical structure of the visual motion pathway to demonstrate dissociation in the fMRI response magnitude between adjacent stages of processing in autism: responses are attenuated in a primary visual area but amplified in a subsequent higher-order area. This response dissociation appears to rely on enhanced suppressive feedback between regions and reveals a previously unknown cortical network alteration in autism.
自闭症病理生理学的一个主要假说认为，神经兴奋和抑制之间的平衡增加会导致神经反应增加。然而，以前自闭症个体的群体水平反应幅度的报告一直不一致。关键的是，在自闭症的神经兴奋和抑制失衡的以前神经影像学研究中，没有考虑到网络相互作用。特别是，皮质组织的一个定义特征是其分层和交互结构；感觉和认知系统由网络组成，其中后期阶段继承和建立在早期输入阶段的处理基础上，并且通过自上而下的调制来影响和塑造早期阶段。在这里，我们使用人类视觉系统的既定连接来检查更高阶运动处理区域[颞中区域（MT+）]及其主要输入区域（V1）的反应幅度。在 fMRI 扫描期间，向自闭症谱系障碍（ASD；n=24，平均年龄 23 岁，8 名女性）和神经典型对照（n=24，平均年龄 22 岁，8 名女性）的成年个体呈现简单的视觉刺激。我们发现 ASD 个体中 MT+和 V1 之间的 fMRI 反应幅度存在强烈的分离：具有高 MT+反应的个体 V1 反应减弱。MT+放大的幅度和 V1 衰减的幅度与自闭症严重程度相关，似乎是由于 MT+到 V1 的抑制性反馈增强所致，而在神经典型对照中则不存在。我们的结果揭示了改变的层次网络相互作用在 ASD 病理生理学中的潜在作用。神经兴奋和抑制之间的不平衡，导致神经反应增加，已被认为是自闭症的一种病理生理途径，但缺乏来自人类的直接证据。在当前研究中，我们考虑了在测试自闭症个体中增加的神经反应时，感觉处理阶段之间相互作用的作用。我们使用了众所周知的视觉运动通路的分层结构，来证明自闭症中相邻处理阶段之间的 fMRI 反应幅度的分离：在一个主要的视觉区域中反应减弱，但在一个后续的更高阶区域中反应增强。这种反应分离似乎依赖于区域之间增强的抑制性反馈，并揭示了自闭症中以前未知的皮质网络改变。
