Dopamine-Dependent Architecture of Cortico-Subcortical Network Connectivity
Dopamine-Dependent Architecture of Cortico-Subcortical Network Connectivity
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DOI：
10.1093/cercor/bhs136
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发表时间：
2013-07-01
期刊：
影响因子：
3.7
通讯作者：
Beckmann, Christian F.
中科院分区：
文献类型：
--
作者：
Cole, David M.;Oei, Nicole Y. L.;Beckmann, Christian F.
多巴胺能介导的人类奖赏加工的适应不良被认为是多种神经精神疾病的基础，包括成瘾，帕金森病和精神分裂症。这种疾病的发展机制可能取决于大规模皮质-皮质下回路中神经信号的个体差异。在健康志愿者中使用功能性神经成像和药理学挑战的组合，我们确定了对特定皮层下区域和相应的新皮层“静息状态”网络之间的分布式功能相互作用的相反多巴胺激动和拮抗神经调节作用，已知参与认知和奖励处理的不同方面。我们发现，相对于安慰剂，左旋多巴和氟哌啶醇的挑战，分别增加或减少（1）中脑和“默认模式”网络，（2）右尾状核和右侧额顶叶网络，（3）腹侧纹状体和额岛网络之间的功能连接。此外，我们发现了大脑回路对多巴胺调制的反应性与特质冲动性的个体差异之间的药物特异性关联，揭示了不同多巴胺依赖性皮质-皮质下网络之间可分离的药物人格相互作用效应。我们的研究结果确定了多巴胺缺乏症的潜在发病机制和治疗效果的可能系统。
Maladaptive dopaminergic mediation of reward processing in humans is thought to underlie multiple neuropsychiatric disorders, including addiction, Parkinson's disease, and schizophrenia. Mechanisms responsible for the development of such disorders may depend on individual differences in neural signaling within large-scale cortico-subcortical circuitry. Using a combination of functional neuroimaging and pharmacological challenges in healthy volunteers, we identified opposing dopamine agonistic and antagonistic neuromodulatory effects on distributed functional interactions between specific subcortical regions and corresponding neocortical "resting-state" networks, known to be involved in distinct aspects of cognition and reward processing. We found that, relative to a placebo, levodopa and haloperidol challenges, respectively, increased or decreased the functional connectivity between (1) the midbrain and a "default mode" network, (2) the right caudate and a right-lateralized frontoparietal network, and (3) the ventral striatum and a fronto-insular network. Further, we found drug-specific associations between brain circuitry reactivity to dopamine modulation and individual differences in trait impulsivity, revealing dissociable drug personality interaction effects across distinct dopamine-dependent cortico-subcortical networks. Our findings identify possible systems underlying pathogenesis and treatment efficacy in disorders of dopamine deficiency.