Turner Jasmin M, Byrge Lisa, Richardson Hilary, Galdi Paola, Kennedy Daniel P, Kliemann Dorit
Department of Psychological and Brain Sciences, The University of Iowa, 340 Iowa Avenue, Iowa City, IA, 52242, USA.
Department of Psychological and Brain Sciences, University of North Florida, 1 UNF Drive, Jacksonville, FL, 32224, USA.
Mol Autism. 2025 Aug 22;16(1):42. doi: 10.1186/s13229-025-00669-x.
Difficulty in social inferences is a core feature in autism spectrum disorders (ASD). On the behavioral level, it remains unclear whether reasoning about others' mental states (Theory of Mind, ToM) and empathic responses to others' physical states may be similarly or differentially affected in autism. On the neural level, these inferences typically engage distinct brain networks (ToM versus Pain networks), but their functional specialization remains not well understood in autism. This study aimed to investigate the functional specialization, heterogeneity, and brain-behavior relationships of the ToM and Pain networks in autistic compared to neurotypical (NT) participants. We hypothesized differential functional network specialization (i.e., functional connectivity), increased heterogeneity, and less typical network responses specifically in the ToM network, with relatively similar responses in the Pain network in ASD.
Using functional magnetic resonance imaging (fMRI), we investigated neural responses in 107 adults (autistic: 34 (female = 11), NT: 73 (female = 23); matched for age, intellectual functioning, sex, motion) while they passively watched a short, animated movie including events that evoke reasoning about characters' mental states and bodily sensations. Preregistered analyses included regression models to assess inter-region correlation of within- and across-network connectivity, inter-subject correlation to quantify similarity to the average neurotypical, as well as to within- and across-group timecourse responses, and brain-behavior relationships relevant for social inferences.
Functional specialization of ToM and Pain networks were overall intact, with distinct network responses in both groups. The autistic group showed differential ToM network responses and reduced similarity to the average typical response for both networks. Network responses were more idiosyncratic and heterogenous in the autistic group. Brain-behavior relationships differed between groups for ToM behavior only.
Effects between groups were overall small. Samples were acquired across two sites, yet the sample size restricts subgroup analyses that may further inform autistic heterogeneity and limits generalizability.
We found weak evidence for greater differential responses in brain networks underlying ToM inferences than those involved in empathic responses in autism, consistent with a prior empathy imbalance hypothesis. We outline suggestions for replicating, generalizing and extending these results in future research.
社交推理困难是自闭症谱系障碍（ASD）的核心特征。在行为层面，自闭症患者对他人心理状态的推理（心理理论，ToM）和对他人身体状态的共情反应是否受到相似或不同的影响仍不清楚。在神经层面，这些推理通常涉及不同的脑网络（ToM网络与疼痛网络），但其功能特化在自闭症中仍未得到很好的理解。本研究旨在调查与神经典型（NT）参与者相比，自闭症患者中ToM网络和疼痛网络的功能特化、异质性以及脑-行为关系。我们假设在ASD中，ToM网络存在不同的功能网络特化（即功能连接）、异质性增加以及不太典型的网络反应，而疼痛网络的反应相对相似。
使用功能磁共振成像（fMRI），我们调查了107名成年人（自闭症患者：34名（女性 = 11名），NT：73名（女性 = 23名）；年龄、智力功能、性别、运动匹配）在被动观看一部简短动画电影时的神经反应，该电影包含引发对角色心理状态和身体感觉推理的事件。预先注册的分析包括回归模型，以评估网络内和网络间连接的区域间相关性、受试者间相关性，以量化与平均神经典型的相似性，以及组内和组间的时间进程反应，以及与社交推理相关的脑-行为关系。
ToM网络和疼痛网络的功能特化总体上是完整的，两组均有明显的网络反应。自闭症组表现出不同的ToM网络反应，并且与两个网络的平均典型反应的相似性降低。自闭症组的网络反应更具特异性和异质性。两组之间仅在ToM行为的脑-行为关系上存在差异。
组间效应总体较小。样本在两个地点采集，但样本量限制了可能进一步揭示自闭症异质性并限制普遍性的亚组分析。
我们发现，与自闭症中涉及共情反应的脑网络相比，ToM推理背后的脑网络存在更大差异反应的证据较弱，这与先前的共情失衡假说一致。我们概述了在未来研究中复制、推广和扩展这些结果的建议。
