fMRI Study of Reward Responsiveness of Children with Autism Spectrum Disorder

描述(由申请人提供)： 许多患有自闭症谱系障碍(ASD)儿童的父母担心的一个主要问题是与他们的孩子缺乏情感联系或互惠。这种担忧预示着早期寻求治疗(Twyman等人，2009年)。尽管这是一个重要的痛苦来源，但这种赤字背后的机制直到最近才开始被描述出来。这种缺陷的一个病因模型来自社会动机假说(Dawson等人，1998a；Grelotti等人，2002年；Dawson等人，2004；Dawson等人，2005；Schultz，2005；Monk 2008；Kohls等人，2009)，并认为这种缺陷源于对社会回报缺乏敏感性。了解奖赏反应不仅对行为学干预非常重要(Jerome&Sturmey，2008；Trosclair-Lasserre et al.，2008)，而且对药理学(Walker，2008)也非常重要，因为存在操纵奖赏反应的潜在机制，为干预提供了一个潜在的强大目标。然而，目前尚不清楚是否存在奖赏反应的普遍缺陷，是否需要更显著的奖赏才能触发自闭症的奖赏反应，或者奖赏反应缺陷是否仅限于社会刺激，这表明明显的奖赏缺陷是次要的，而不是主要的，而且可能不太容易受到直接干预。这项研究建议通过使用功能性核磁共振对ASD儿童的奖励内容(社会奖励与非社交奖励)和奖励突出度(特殊兴趣与典型奖励)进行测试，以测试这些替代方案。我们将使用参与者的主要照顾者(PC)的照片作为显著的社会奖励，将陌生人的照片作为典型的社会奖励。我们将使用代表参与者最喜欢的对象/活动的图片作为显著的非社会奖励，并使用代表其他参与者最喜欢的对象/活动的图片作为典型的非社会奖励。参与者将根据Knowlton的深入研究的概率分类任务(Knowlton et al.，1994)执行内隐学习任务，其中任意刺激反应对随着时间的推移以有奖赏和无奖赏的条件被隐含地学习。我们的假设是，患有自闭症的儿童确实能够对社会奖励做出反应并从中学习；然而，社会奖励需要比TD儿童更显著。 公共卫生相关性： 这项研究源于社会动机理论，该理论认为，自闭症儿童从很小的时候起，就不像正常发育的孩子那样，在看到母亲的笑脸时感觉不到奖赏或愉悦。这种未能体验到社会刺激的回报会带来巨大的负面后遗症，这些后遗症即使不是不可能逆转，也很难逆转。我们的工作将有助于更好地描述ASD儿童和TD儿童的奖赏反应，希望能导致改进的药物和行为治疗策略。

DESCRIPTION (provided by applicant): A primary, and often most troubling, concern of many parents of children with autism spectrum disorders (ASD) is the lack of emotional connectedness or reciprocity with their child. Such concerns predict early treatment-seeking (Twyman et al., 2009). Though a significant source of distress, the mechanisms underlying this deficit are only recently starting to be characterized. One model of the etiology of this deficit is drawn from the social motivation hypothesis (Dawson et al., 1998a; Grelotti et al., 2002; Dawson et al., 2004; Dawson et al., 2005; Schultz, 2005; Monk 2008; Kohls et al., 2009) and holds that this deficit arises from a lack of sensitivity to social rewards. Understanding reward responsiveness is extremely important not only for behavioral (Jerome & Sturmey, 2008; Trosclair-Lasserre et al., 2008) interventions but pharmacologic (Walker, 2008), as there are potential mechanisms for manipulating reward responsiveness, providing a potentially powerful target for intervention. However it is unknown whether there is a general deficit in reward responsiveness, whether more salient rewards are required to trigger a reward response in ASD, or whether the reward response deficit is limited to social stimuli, which would suggest that apparent reward deficits are secondary, rather than primary, and potentially less amenable to direct intervention. This study proposes to test these alternatives by manipulating reward content (social vs. non social) and reward salience (special interest vs. typical rewards) using functional MRI in children with ASD. We will use pictures of the participants' primary caregiver (PC) as salient social rewards and pictures of strangers as typical social rewards. We will use pictures representing the participant's favorite object/activity as salient non-social rewards and pictures representing other participants' favorite objects/activities as typical non-social rewards. Participants will perform an implicit learning task based on Knowlton's well studied probabilistic classification task (Knowlton et al., 1994) where arbitrary stimulus response pairs are implicitly learned over time with rewarded and non-rewarded conditions. Our hypothesis is that children with ASD can indeed respond to and learn from social rewards; however, the social rewards need to be of higher salience than for TD children. PUBLIC HEALTH RELEVANCE: This work stems from the social motivation theory which holds that from a young age, children with ASD, unlike typically developing children, fail to feel a sense of reward or pleasure when seeing their mothers smiling face for example. This failure to experience reward to social stimuli has tremendous negative sequelae which are difficult if not impossible to reverse. Our work will help to better characterize the reward responsiveness of children with ASD and of TD children with the hope of leading to improved pharmacological and behavioral treatment strategies.