Preliminary efficacy of social reward value training in toddlers with elevated symptoms of autism

婴幼儿自闭症谱系障碍(ASD)的标志之一是选择性注意受损 面对1-6(初步研究，PS#1)。这种损害削弱了他们学习和互动的能力。 与现实世界中的其他人一起适应。7社交领域的注意选择部分依赖于 一个人编码人们的奖赏价值并将这些价值储存在长期记忆中作为稳定的价值的能力。 10“稳定”的价值观(下称“价值观”)是在反复学习的过程中获得的， 一旦获得，它们就会迅速发出信号，优先将目光引导到编码的重要人脸上(高- 值，HV)基于其过去的享乐性或信息性。11基于 当必须快速做出决定时，存储在长期存储器中的值对于生存是必不可少的(例如， 母亲VS陌生人)。关于价值观的学习是由大脑中的奖励学习系统辅助的 涉及基底节(BG)回路。11该回路与ASD12、13和 现有证据表明，自闭症患者在学习奖赏价值方面表现出特定的障碍 社会刺激，如面孔。14(PS#2)基于这一证据，我们认为，在 患有严重自闭症症状(ASD+)的蹒跚学步的孩子，部分原因是社交中的价值学习受损 域，影响他们快速和优先选择HV人脸并忽略低值(LV)人脸的能力 复杂的现实世界环境。因此，他们表现出对面孔的自发注意力减弱。 一般情况下，当他们看脸时，他们可能会将有限的注意力资源分配给高- (例如，母亲或治疗师)和低价值(陌生人)的个人以一种反复试验的方式。我们进一步 ASD+儿童通过社会价值训练加强对特定面孔的注意的假设 (SVT)将增加他们对现实世界环境中这些面孔的关注。在这里，我们打算测试一部小说 ASD+组18个月时的SVT(n=48)。在拟议的初步研究中，ASD+幼儿将接受SVT 使用与凝视相关的眼球跟踪范式。SVT将在两天内实施， 训练效果将通过对HV脸与LV脸的视觉注意力的变化来评估 基线、基线后(第3天)和长期随访(1个月)，使用两项任务：选择实验室 注意(LSA)任务和现实世界选择性注意(RWSA)任务。我们还将评估可接受性和 自闭症的性别、非语言发展水平和严重程度的价值训练和贡献的可行性 症状对训练的反应。利用项目之间的重叠队列1 (新生儿成像)和项目5，我们将检查静息状态功能连接的特征 ASD+幼儿的出生预测对训练的反应。据我们所知，这是第一个直接 通过使用奖励学习系统来定位ASD的标记物，并评估 新生儿连接体作为18个月时训练反应的潜在预测因子。

One of the markers of autism spectrum disorders (ASD) in infants and toddlers is impaired selective attention to faces1-6 (Preliminary Study, PS#1). This impairment diminishes their ability to learn from and interact adaptively with others in real-world environments.7 Attentional selection in the social domain relies, in part, on one’s ability to encode reward values of people and store these values in long-term memory as stable values.8- 10 The ‘stable’ values (henceforth, ‘values’) are learned over the course of repeated learning opportunities, and once acquired, they are signaled rapidly, preferentially directing gaze to encoded faces of importance (high- value, HV) based on their hedonic or informative properties in the past.11 Automatic responses based on values stored in long-term memory are essential for survival when decisions have to be made rapidly (e.g., mother versus stranger). Learning about values is subserved by the reward learning system in the brain involving basal ganglia (BG) circuitry.11 This circuitry is implicated in the pathophysiology of ASD12, 13 and extant evidence suggests that individuals with ASD exhibit specific impairments in learning the reward value of social stimuli such as faces.14 (PS#2) Based on this evidence, we propose that limited attention to faces in toddlers with elevated autism symptoms (ASD+) is, in part, driven by impaired value learning in the social domain, affecting their ability to rapidly and preferentially select HV faces and ignore low-value (LV) faces in the complex real-world environment. Consequently, they exhibit diminished spontaneous attention to faces in general, and when they look at faces, they may distribute their limited attentional resources between high- (e.g., mother or therapist) and low-value (stranger) individuals in a trial-and-error fashion. We further hypothesize that reinforcing attention of children with ASD+ toward specific faces through social value training (SVT) will increase their attention to these faces in real-world environments. Here we propose to test a novel SVT in the ASD+ group at 18 months (n=48). In the proposed pilot study, ASD+ toddlers will undergo SVT using a gaze-contingent eye-tracking paradigm. SVT will be administered over a two-day period and the training effects will be assessed by changes in visual attention to HV faces as compared to LV faces between baseline, post-baseline (day 3), and a long-term follow-up (1 month) using two tasks: a laboratory selective attention (LSA) task and real-world selective attention (RWSA) task. We will also evaluate acceptability and feasibility of the value training and contribution of sex, nonverbal developmental level, and severity of autism symptoms to response to the training. Taking advantage of the overlapping cohorts between Projects 1 (neonatal imaging) and Project 5, we will examine if characteristics of resting-state functional connectivity at birth predict response to training in the ASD+ toddlers. To our best knowledge, this is the first study to directly target a marker for ASD by engaging the reward learning system and to evaluate functional integrity of neonatal connectome as a potential predictor of response to training at 18 months.