Department of Electrical and Computer Engineering, University of Houston, Houston, Texas.
Autism Res. 2013 Dec;6(6):542-9. doi: 10.1002/aur.1314. Epub 2013 Aug 27.
An established neural biomarker of autism spectrum disorder (ASD) has the potential to provide novel biological and pharmacological targets for treatment. Lower level of inhibition in brain circuits is a leading biomarker candidate. A physiological investigation of the functional levels of inhibition in the cortex of individuals with autism can provide a strong test of the hypothesis. The amplitude of cortical response to the stimulation of adjacent fingers is controlled by the level of cortical inhibition and provides just such a test. Using magnetoencephalography, we recorded the response of the somatosensory cortex to the passive tactile stimulation of the thumb (D1), and index finger (D2), and to the simultaneous stimulation of both fingers combined (D1,D2) of the dominant (right) hand of young subjects with and without autism. For each participant, we measured the response to the stimulation of both fingers combined (D1,D2) relative to the post hoc sum of the responses to the stimulation of each finger alone (D1+D2) in multiple different ways and linearly regressed the ASD and neurotypical (NT) groups' responses. The resulting slopes were then compared: Smaller slope values imply attenuated response to paired finger stimulation, and enhanced levels of inhibition. The short-latency M40 and mid-latency M80 response slopes of the group with autism obtained in different ways were either significantly smaller, or statistically indistinguishable from NT. The result does not support reduced inhibition in the somatosensory cortex of individuals with autism, contrary to the seminal hypothesis of reduced inhibition. Implications are discussed including refinements of current theory.
自闭症谱系障碍(ASD)的既定神经生物标志物有可能为治疗提供新的生物学和药理学靶点。大脑回路中抑制水平较低是一个主要的候选生物标志物。对自闭症个体大脑皮层抑制功能水平进行生理学研究,可以对这一假设进行强有力的检验。皮层对相邻手指刺激的反应幅度受皮层抑制水平的控制,为这种检验提供了很好的测试手段。我们使用脑磁图记录了年轻的自闭症患者和非自闭症患者的右手优势手的拇指(D1)、食指(D2)和两个手指同时(D1,D2)被动触觉刺激的体感皮层反应。对于每个参与者,我们通过多种不同的方式测量了两个手指同时刺激(D1,D2)的反应相对于每个手指单独刺激(D1+D2)的事后总和,并对 ASD 和神经典型(NT)组的反应进行线性回归。然后比较得到的斜率:较小的斜率值意味着对配对手指刺激的反应减弱,抑制水平增强。自闭症组在不同方式下获得的短潜伏期 M40 和中潜伏期 M80 反应斜率要么显著较小,要么与 NT 无统计学差异。该结果不支持自闭症个体体感皮层抑制减弱,与抑制减弱的开创性假说相反。讨论了包括当前理论的改进等影响。