Reduced Language Lateralization in Autism and the Broader Autism Phenotype as Assessed with Robust Individual-Subjects Analyses

One of the few replicated functional brain differences between individuals with autism spectrum disorders (ASD) and neurotypical (NT) controls is reduced language lateralization. However, most prior reports relied on comparisons of group-level activation maps or functional markers that had not been validated at the individual-subject level, and/or used tasks that do not isolate language processing from other cognitive processes, complicating interpretation. Furthermore, few prior studies have examined functional responses in other brain networks, as needed to determine the spatial selectivity of the effect. Using functional magnetic resonance imaging (fMRI), we compared language lateralization between 28 adult ASD participants and carefully pairwise-matched controls, with the language regions defined individually using a well-validated language "localizer" task. Across two language comprehension paradigms, ASD participants showed less lateralized responses due to stronger right hemisphere activity. Furthermore, this effect did not stem from a ubiquitous reduction in lateralization of function across the brain: ASD participants did not differ from controls in the lateralization of two other large-scale networks-the Theory of Mind network and the Multiple Demand network. Finally, in an exploratory study, we tested whether reduced language lateralization may also be present in NT individuals with high autism-like traits. Indeed, autistic trait load in a large set of NT participants (n= 189) was associated with less lateralized language responses. These results suggest that reduced language lateralization is robustly associated with autism and, to some extent, with autism-like traits in the general population, and this lateralization reduction appears to be restricted to the language system. Lay Summary How do brains of individuals with autism spectrum disorders (ASD) differ from those of neurotypical (NT) controls? One of the most consistently reported differences is the reduction of lateralization during language processing in individuals with ASD. However, most prior studies have used methods that made this finding difficult to interpret, and perhaps even artifactual. Using robust individual-level markers of lateralization, we found that indeed, ASD individuals show reduced lateralization for language due to stronger right-hemisphere activity. We further show that this reduction is not due to a general reduction of lateralization of function across the brain. Finally, we show that greater autistic trait load is associated with less lateralized language responses in the NT population. These results suggest that reduced language lateralization is robustly associated with autism and, to some extent, with autism-like traits in the general population.

自闭症谱系障碍（ASD）患者与神经典型（NT）对照个体之间少数几个可重复的功能性大脑差异之一是语言偏侧化降低。然而，大多数先前的报告依赖于组水平激活图或功能性标记的比较，这些在个体受试者水平上未得到验证，并且/或者使用的任务没有将语言处理与其他认知过程区分开来，这使得解释变得复杂。此外，很少有先前的研究检查其他大脑网络中的功能反应，而这是确定该效应的空间选择性所必需的。利用功能性磁共振成像（fMRI），我们比较了28名成年ASD参与者和精心配对的对照个体之间的语言偏侧化，使用经过充分验证的语言“定位”任务对语言区域进行个体定义。在两种语言理解范式中，由于右侧大脑半球活动更强，ASD参与者表现出较弱的偏侧化反应。此外，这种效应并非源于大脑功能偏侧化的普遍降低：在另外两个大规模网络——心理理论网络和多需求网络的偏侧化方面，ASD参与者与对照个体没有差异。最后，在一项探索性研究中，我们测试了在具有高自闭症样特质的NT个体中是否也可能存在语言偏侧化降低。实际上，在一大组NT参与者（n = 189）中，自闭症特质负荷与较弱的语言偏侧化反应相关。这些结果表明，语言偏侧化降低与自闭症密切相关，并且在一定程度上与普通人群中的自闭症样特质相关，而且这种偏侧化降低似乎仅限于语言系统。 通俗总结 自闭症谱系障碍（ASD）患者的大脑与神经典型（NT）对照个体的大脑有何不同？最一致报道的差异之一是ASD患者在语言处理过程中偏侧化降低。然而，大多数先前的研究使用的方法使得这一发现难以解释，甚至可能是人为造成的。利用可靠的个体水平偏侧化标记，我们发现，确实由于右侧大脑半球活动更强，ASD个体表现出语言偏侧化降低。我们进一步表明，这种降低不是由于大脑功能偏侧化的普遍降低。最后，我们表明在NT人群中，较高的自闭症特质负荷与较弱的语言偏侧化反应相关。这些结果表明，语言偏侧化降低与自闭症密切相关，并且在一定程度上与普通人群中的自闭症样特质相关。