■导致可卡因和其他物质使用障碍的生物学机制涉及一系列皮质和皮质下系统。先前关于开发和维持物质使用的工作主要集中在皮质纹状体回路上,相对较少关注大规模功能性大脑网络内部和之间的变化,以及多巴胺系统的相关方面。不同大脑区域之间的时间共激活的全脑模式,被称为功能性连接体,支持行为的个体差异。严重的,相对于其他代谢型受体类别,功能性连接体与物质使用及其与多巴胺受体密度的特异性相关尚待确定。
■我们在多个尺度上全面表征了全脑功能连接的差异,包括个人连接,regions,以及可卡因使用障碍参与者(CUD;n=69)和健康匹配对照(n=62)的网络,Further,我们研究了观察到的CUD功能连接特征与广泛的规范性神经递质受体和转运蛋白结合的空间分布之间的关系,如通过18个不同的规范性正电子发射断层扫描(PET)图评估的.
■我们的分析确定了CUD个体与匹配的健康比较参与者之间功能连接差异的广泛分布(占总边缘的8.8%;8,185个边缘;pFWE=0.025)。我们在很大程度上发现较低的连通性优先连接默认网络和皮质下区域,在具有CUD的参与者的默认网络中,网络内连通性更高。此外,我们发现CUD的特征与多巴胺D2/3受体的标准空间密度之间存在一致且可复制的关联.
■我们的分析揭示了CUD个体连通性改变的广泛概况,其延伸到整个功能连接体,并涉及多个回路。该曲线与规范的多巴胺D2/3受体密度强烈耦合。强调用于研究体内脑功能的连接组学方法的翻译潜力,大脑功能的CUD相关方面在空间上与疾病相关的神经递质系统耦合。
■问题:有和没有可卡因使用障碍的个体之间的全脑功能连接是否存在群体差异,以及这些连接模式在多大程度上与多巴胺(D2/3)受体密度的空间分布有关?发现:可卡因使用障碍的存在与全脑功能连接改变有关,这些改变在空间上与多巴胺(D2/3)受体的密度有关。含义:可卡因使用障碍的功能性连接体与大脑中多巴胺受体密度之间存在优先且可复制的联系。
UNASSIGNED: The biological mechanisms that contribute to cocaine and other substance use disorders involve an array of cortical and subcortical systems. Prior work on the development and maintenance of substance use has largely focused on cortico-striatal circuits, with relatively less attention on alterations within and across large-scale functional brain networks, and associated aspects of the dopamine system. The brain-wide pattern of temporal co-activation between distinct brain regions, referred to as the functional connectome, underpins individual differences in behavior. Critically, the functional connectome correlates of substance use and their specificity to dopamine receptor densities relative to other metabotropic receptors classes remains to be established.
UNASSIGNED: We comprehensively characterized brain-wide differences in functional connectivity across multiple scales, including individual connections, regions, and networks in participants with cocaine use disorder (CUD; n=69) and healthy matched controls (n=62), Further, we studied the relationship between the observed functional connectivity signatures of CUD and the spatial distribution of a broad range of normative neurotransmitter receptor and transporter bindings as assessed through 18 different normative positron emission tomography (PET) maps.
UNASSIGNED: Our analyses identified a widespread profile of functional connectivity differences between individuals with CUD and matched healthy comparison participants (8.8% of total edges; 8,185 edges; pFWE=0.025). We largely find lower connectivity preferentially linking default network and subcortical regions, and higher within-network connectivity in the default network in participants with CUD. Furthermore, we find consistent and replicable associations between signatures of CUD and normative spatial density of dopamine D2/3 receptors.
UNASSIGNED: Our analyses revealed a widespread profile of altered connectivity in individuals with CUD that extends across the functional connectome and implicates multiple circuits. This profile is robustly coupled with normative dopamine D2/3 receptors densities. Underscoring the translational potential of connectomic approaches for the study of in vivo brain functions, CUD-linked aspects of brain function were spatially coupled to disorder relevant neurotransmitter systems.