Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Department of Psychiatry, University of North Carolina-Chapel Hill, Chapel Hill, NC, 27514, USA.
Transl Psychiatry. 2021 Jan 11;11(1):33. doi: 10.1038/s41398-020-01170-0.
The social motivation hypothesis of autism posits that autism spectrum disorder (ASD) is characterized by impaired motivation to seek out social experience early in life that interferes with the development of social functioning. This framework suggests that impaired mesolimbic dopamine function underlies compromised responses to social rewards in ASD. Although this hypothesis is supported by functional magnetic resonance imaging (fMRI) studies, no molecular imaging study has evaluated striatal dopamine functioning in response to rewards in ASD. Here, we examined striatal functioning during monetary incentive processing in ASD and controls using simultaneous positron emission tomography (PET) and fMRI. Using a bolus + infusion protocol with the D2/D3 dopamine receptor antagonist [C]raclopride, voxel-wise binding potential (BP) was compared between groups (controls = 12, ASD = 10) in the striatum. Striatal clusters showing significant between-group BP differences were used as seeds in whole-brain fMRI general functional connectivity analyses. Relative to controls, the ASD group demonstrated decreased phasic dopamine release to incentives in the bilateral putamen and left caudate, as well as increased functional connectivity between a PET-derived right putamen seed and the precuneus and insula. Within the ASD group, decreased phasic dopamine release in the putamen was related to poorer theory-of-mind skills. Our findings that ASD is characterized by impaired striatal phasic dopamine release to incentives provide support for the social motivation hypothesis of autism. PET-fMRI may be a suitable tool to evaluate novel ASD therapeutics targeting the striatal dopamine system.
自闭症的社会动机假说认为，自闭症谱系障碍（ASD）的特征是早期对寻求社交体验的动机受损，这干扰了社交功能的发展。这一框架表明，中脑边缘多巴胺功能受损是 ASD 患者对社交奖励反应受损的基础。尽管功能磁共振成像（fMRI）研究支持了这一假说，但尚无分子影像学研究评估 ASD 患者对奖励的纹状体多巴胺功能。在这里，我们使用正电子发射断层扫描（PET）和功能磁共振成像（fMRI）同时评估了 ASD 和对照组在金钱激励处理过程中的纹状体功能。使用 D2/D3 多巴胺受体拮抗剂 [C]raclopride 的推注+输注方案，在纹状体中比较了两组（对照组=12，ASD=10）之间的体素结合潜力（BP）。显示组间 BP 差异的纹状体簇被用作全脑 fMRI 一般功能连接分析的种子。与对照组相比，ASD 组双侧壳核和左侧尾状核的激励性相位多巴胺释放减少，以及从 PET 衍生的右侧壳核种子与楔前叶和脑岛之间的功能连接增加。在 ASD 组中，壳核的相位多巴胺释放减少与较差的心理理论技能有关。我们的发现表明，ASD 的特征是对激励的纹状体相位多巴胺释放受损，这为自闭症的社会动机假说提供了支持。PET-fMRI 可能是评估针对纹状体多巴胺系统的新型 ASD 治疗方法的合适工具。
