fMRI Study of Reward Responsiveness of Children with Autism Spectrum Disorder

描述（由申请人提供）： 许多自闭症谱系障碍（ASD）儿童的父母最关心的一个主要问题，也是最令人不安的问题是缺乏与孩子的情感联系或互惠。这种担忧预示着早期寻求治疗（Twyman等人，2009年）。虽然这是一个重大的痛苦来源，但这种赤字背后的机制只是最近才开始被描述出来。这种缺陷的病因学的一个模型是从社会动机假说中得出的（Dawson等人，1998 a; Grelotti等人，2002; Dawson等人，2004; Dawson等人，2005; Schultz，2005; Monk，2008; Kohls等人，2009），并认为这种赤字是由于缺乏对社会回报的敏感性。理解奖励反应不仅对行为非常重要（杰罗姆和Sturmey，2008; Trosclair-Lasserre等人，2008）干预，但药理学（步行者，2008），因为有潜在的机制操纵奖励反应，提供了一个潜在的强大的目标干预。然而，目前尚不清楚是否有一个普遍的赤字奖励反应，是否需要更突出的奖励，以触发奖励反应在ASD，或奖励反应赤字是否仅限于社会刺激，这将表明，明显的奖励赤字是次要的，而不是主要的，并可能不太容易直接干预。本研究提出了测试这些替代品操纵奖励内容（社会与非社会）和奖励显着性（特殊利益与典型的奖励），使用功能性磁共振成像与ASD儿童。我们将使用参与者的主要照顾者（PC）的照片作为显着的社会奖励和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。参与者将基于诺尔顿的充分研究的概率分类任务（诺尔顿等人，1994），其中任意刺激响应对在奖励和非奖励条件下随时间隐式地学习。我们的假设是，自闭症儿童确实可以响应和学习社会奖励，但是，社会奖励需要比TD儿童更高的显着性。 公共卫生相关性： 这项工作源于社会动机理论，该理论认为，从很小的时候起，ASD儿童与通常发育的儿童不同，当看到他们的母亲微笑时，他们无法感受到奖励或快乐。 这种对社会刺激的回报体验的失败具有巨大的负面后果，如果不是不可能的话，也很难逆转。 我们的工作将有助于更好地描述ASD儿童和TD儿童的奖励反应性，希望能够改善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.