Reduced social motivation is a hallmark of individuals with autism spectrum disorders (ASDs). Although the exact neural mechanisms are unclear, oxytocin has been shown to enhance motivation and attention to social stimuli, suggesting a potential to augment social reinforcement learning as the central mechanism of behavioral interventions in ASD. We tested how reinforcement learning in social contexts and associated reward prediction error (RPE) signals in the nucleus accumbens (NAcc) were modulated by intranasal oxytocin. Male adults with a childhood diagnosis of ASD (n = 15) and healthy controls (n = 24; aged 18-26 years) performed a probabilistic reinforcement learning task during functional magnetic resonance imaging in a single-center (research center in Germany), randomized double-blind, placebo-controlled cross-over trial. The interventions were intranasal oxytocin (Syntocinon®, Novartis; 10 puffs = 20 international units (IUs) per treatment) and placebo spray. Using computational modeling of behavioral data, trial-by-trial RPE signals were assessed and related to brain activation in NAcc during reinforcing feedback in social and non-social contexts. The order of oxytocin/placebo was randomized for 60 participants. Twenty-one participants were excluded from analyses, leaving 39 for the final analysis. Behaviorally, individuals with ASD showed enhanced learning under oxytocin when the learning target as well as feedback was social as compared to non-social (social vs. non-social target: 87.09% vs. 71.29%, 95% confidence interval (CI): 7.28-24.33, p = .003; social vs. non-social feedback: 81.00% vs. 71.29%, 95% CI: 2.81-16.61, p = .027). Correspondingly, oxytocin enhanced the correlation of the RPE signal with NAcc activation during social (vs. non-social) feedback in ASD (3.48 vs. -1.12, respectively, 95% CI: 2.98-6.22, p = .000), whereas in controls, this effect was found in the placebo condition (2.90 vs. -1.14, respectively, 95% CI: 1.07-7.01, p = .010). In ASD, a similar pattern emerged when the learning target was social (3.00 vs. -0.64, respectively, 95% CI: -0.13 to 7.41, p = .057), whereas controls showed a reduced correlation for social learning targets under oxytocin (-0.70 vs. 2.72, respectively, 95% CI: -5.86 to 0.98, p = .008). The current data suggest that intranasal oxytocin has the potential to enhance social reinforcement learning in ASD. Future studies are warranted that investigate whether oxytocin can potentiate social learning when combined with behavioral therapies, resulting in greater treatment benefits than traditional behavior-only approaches.

中文翻译：

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鼻内催产素对患有高功能自闭症谱系障碍的男性成年人的社交强化学习的神经调节：一项随机试验。

降低社会动机是自闭症谱系障碍（ASD）个体的标志。尽管尚不清楚确切的神经机制，但催产素已显示出增强动机和对社会刺激的关注，这表明增强社会强化学习作为ASD行为干预的主要机制的潜力。我们测试了鼻内催产素如何调节社交情境中的强化学习和伏隔核（NAcc）中的相关奖励预测错误（RPE）信号。儿童期诊断为ASD的男性成年人（n = 15）和健康对照者（n = 24；年龄18-26岁）在单中心（德国的研究中心）进行功能性磁共振成像时执行了概率增强学习任务，随机双盲，安慰剂对照的交叉试验。干预措施是鼻内催产素（诺华公司；每次治疗10抽吸= 20国际单位（IUs））和安慰剂喷雾剂。使用行为数据的计算模型，评估了在社会和非社会环境中加强反馈期间，NACC的脑部激活与逐次试验的RPE信号相关。催产素/安慰剂的顺序随机分配给60名参与者。21名参与者被排除在分析之外，剩下39名参与者进行了最终分析。在行为上，与非社交目标相比，当学习目标和反馈为社交目标时，患有催产素的个体在催产素下显示出增强的学习（社交目标与非社交目标：87.09％vs. 71.29％，95％置信区间（CI）： 7.28-24.33，p = 0.003；社交与非社交反馈：81.00％与71.29％，95％CI：2.81-16.61，p = .027）。相应地，催产素增强了ASD在社交（相对于非社交）反馈期间RPE信号与NAcc激活的相关性（分别为3.48和-1.12，95％CI：2.98-6.22，p = .000），而在对照组中，在安慰剂条件下发现了这种效果（分别为2.90和-1.14，95％CI：1.07-7.01，p = .010）。在ASD中，当学习目标为社交时，出现了类似的模式（分别为3.00与-0.64，95％CI：-0.13至7.41，p = .057），而对照组显示催产素下社交学习目标的相关性降低了（ -0.70比2.72，95％CI：-5.86至0.98，p = .008）。目前的数据表明，鼻内催产素有潜力增强自闭症患者的社交强化学习能力。我们有必要进行进一步的研究，以研究催产素与行为疗法结合后是否能增强社交学习能力，