Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome

 描述（由申请人提供）：虽然有关自闭症谱系障碍（ASD）的研究进展在某些领域已经非常出色，但仍然存在许多关键的知识空白，特别是在开发治疗受影响个体的原发性神经生物学异常方面。例如，几乎所有患有脆性X综合征（FXS）的儿童（ASD最常见的已知遗传原因）都表现出严重的社交焦虑症状，表现为在与他人互动期间的高水平社交凝视回避和其他社交逃避行为。然而，迄今为止，旨在改善这些顽固和社会污名化行为的行为治疗尚未得到评估。我们建议通过评估为期3天的治疗探针来解决这一关键的知识缺口，该探针旨在使用应用行为分析（阿坝）的原则来改善FXS儿童的社会凝视行为。重要的是，我们建议检查这种治疗探针对大脑和行为的影响。 该研究将招募两组受试者：1）10至15岁患有FXS的男孩（N = 40），以及2）年龄和症状匹配的未患有FXS的儿童（N=40）。参与者将前往斯坦福大学进行为期5天的评估。每组中的参与者将随机接受在第2、3和4天每天进行2 x 1小时的社交凝视训练（总训练时间= 6小时）或无训练，无训练将包括相同时间段内的等量治疗师时间和强化，但不进行社交凝视行为的训练。我们将通过在第1天和第5天进行标准化行为和神经影像学评估来测量社会和神经生物学功能的变化。对于行为评估，将在使用眼动仪进行的标准化社交挑战评估期间测量适当的社交行为。对于神经生物学评估，将使用静息状态fMRI测量显著性网络激活。为了评估社会凝视训练在持久性和普遍性方面的长期影响，我们进行了为期4周的随访评估，其中将进行日常社会功能的标准化问卷调查。 这项研究的结果有望提供有关FXS技能训练后的行为效应和大脑行为关联的重要信息，这将为FXS和ASD的社会处理的未来研究奠定基础。因此，这项研究将对现在和未来FXS和其他ASD相关疾病儿童的干预设计和治疗产生重大影响。

 DESCRIPTION (provided by applicant): While research progress pertaining to autism spectrum disorder (ASD) has been extraordinary in some areas, many critical gaps in knowledge remain, particularly with respect to the development of treatments that address primary neurobiological abnormalities in affected individuals. For example, almost all children with fragile X syndrome (FXS), the most common known genetic cause of ASD, exhibit symptoms of severe social anxiety, manifested by high levels of social gaze avoidance and other social escape behaviors during interactions with others. To date, however, behavioral treatments designed to ameliorate these intransigent and socially stigmatizing behaviors have not been evaluated. We propose to address this critical knowledge gap by evaluating a 3-day treatment probe targeted to improving social gaze behavior in children with FXS using the principles of Applied Behavior Analysis (ABA). Importantly, we propose to examine the effects of this treatment probe on brain and behavior. Two groups of subjects will be recruited in the study: 1) Boys with FXS aged 10 to 15 years (N = 40), and 2) age- and symptom-matched children who do not have FXS (N=40). Participants will travel to Stanford for a 5-day evaluation. Participants in each group will be randomized to receive either Social Gaze Training conducted in 2 x 1hr sessions per day on Days 2, 3 and 4 (total training time = 6 hours) or No-Training which will consist of equivalent amounts of therapist time and reinforcement over the same time period, but with no training of social gaze behavior. We will measure change in social and neurobiological functioning by conducting standardized behavioral and neuroimaging assessments on Day 1 and Day 5. For the behavioral assessment, appropriate social behavior will be measured during a standardized social challenge assessment conducted with an eye-tracker. For the neurobiological assessment, salience network activation will be measured using resting-state fMRI. To assess the longer-term effects of social gaze training in terms of durabilit and generalizability, we have included a 4-week follow-up assessment in which standardized questionnaires of everyday social functioning will be administered. The results of this study promises to provide important information regarding both behavioral effects and brain-behavior associations following skills training in FXS that will form the foundation of future studies of social processing in FXS and ASD. This study will therefore have a significant impact on intervention designs and treatments for children with FXS and other disorders associated with ASD symptomatology, both now and in the future.