Impaired Functional Connectivity Within and Between Frontostriatal Circuits and Its Association With Compulsive Drug Use and Trait Impulsivity in Cocaine Addiction
Impaired Functional Connectivity Within and Between Frontostriatal Circuits and Its Association With Compulsive Drug Use and Trait Impulsivity in Cocaine Addiction
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DOI：
10.1001/jamapsychiatry.2015.1
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发表时间：
2015-06-01
期刊：
影响因子：
25.8
通讯作者：
Yang, Yihong
中科院分区：
文献类型：
--
作者：
Hu, Yuzheng;Salmeron, Betty Jo;Yang, Yihong
重要性汇聚的证据长期以来一直认为冲动和强迫性都是吸毒成瘾的关键心理结构。尽管在可卡因成瘾中发现了纹状体-皮质网络相互作用的失调，但这些脑网络与成瘾之间的关系还不是很清楚。目的通过静息状态功能连通性(RsFC)来检验这一假说，该假说由依赖于血氧水平的功能磁共振成像信号的相干自发波动来测量，以检验纹状体功能连通性(RsFC)与纹状体-皮质沟通障碍之间的关系，并探讨纹状体rsFC、特质冲动性和可卡因成瘾中不受控制的药物使用之间的关系。本研究使用的数据是在2005年12月8日至2011年9月30日期间收集的。参与者包括56名未寻求治疗的可卡因使用者(CU)(52名可卡因依赖者和3名可卡因滥用者)和56名健康对照(HCS)，这些人在年龄、性别、受教育年限、种族、估计智力和吸烟状况方面匹配。主要结果和测量Voxelise统计参数分析测试CU和HCS之间在与6个纹状体亚区功能连接的脑区的rsFC强度差异。结果与HCS组相比，CU组纹状体-额叶回路rsFC增强，纹状体与扣带回、纹状体、颞叶、海马/杏仁核、岛叶之间rsFC降低。纹状体-背外侧前额叶皮质连接强度的增加与最近可卡因的使用量(未校正的P<；.046)和CU的特质冲动性(未校正的P<；.012)呈正相关，反映纹状体-背侧前扣带回和纹状体-前额/眶前皮质回路之间平衡的指数与对可卡因的使用失去控制显著相关(校正P<；.012)。结论可卡因成瘾与几个特定的纹状体-皮质回路的rsFC紊乱有关。具体地说，强迫性使用可卡因是一种明确的依赖特征，与纹状体-前额叶/眶前叶增加和纹状体-背侧前扣带回连接性降低的平衡有关；特质冲动是可卡因使用的危险因素和后果，与背侧纹状体-背外侧前额叶皮质连接性增加有关，这在CU中是独有的。这些发现为成瘾的神经生物学机制提供了新的见解，并提出了潜在的治疗新靶点。
IMPORTANCE Converging evidence has long identified both impulsivity and compulsivity as key psychological constructs in drug addiction. Although dysregulated striatal-cortical network interactions have been identified in cocaine addiction, the association between these brain networks and addiction is poorly understood.OBJECTIVES To test the hypothesis that cocaine addiction is associated with disturbances in striatal-cortical communication as captured by resting-state functional connectivity (rsFC), measured from coherent spontaneous fluctuations in the blood oxygenation level-dependent functional magnetic resonance imaging signal, and to explore the relationships between striatal rsFC, trait impulsivity, and uncontrolled drug use in cocaine addiction.DESIGN, SETTING, AND PARTICIPANTS A case-control, cross-sectional study was conducted at the National Institute on Drug Abuse Intramural Research Program outpatient magnetic resonance imaging facility. Data used in the present study were collected between December 8, 2005, and September 30, 2011. Participants included 56 non-treatment-seeking cocaine users (CUs) (52 with cocaine dependence and 3 with cocaine abuse) and 56 healthy individuals serving as controls (HCs) matched on age, sex, years of education, race, estimated intelligence, and smoking status.MAIN OUTCOMES AND MEASURES Voxelwise statistical parametric analysis testing the rsFC strength differences between CUs and HCs in brain regions functionally connected to 6 striatal subregions defined a priori. RESULTS Increased rsFC strength was observed predominantly in striatal-frontal circuits; decreased rsFC was found between the striatum and cingulate, striatal, temporal, hippocampal/amygdalar, and insular regions in the CU group compared with the HCs. Increased striatal-dorsal lateral prefrontal cortex connectivity strength was positively correlated with the amount of recent cocaine use (uncorrected P < .046) and elevated trait impulsivity in the CUs (uncorrected P < .012), and an index reflecting the balance between striatal-dorsal anterior cingulate cortex and striatal-anterior prefrontal/orbitofrontal cortex circuits was significantly associated with loss of control over cocaine use (corrected P < .012).CONCLUSIONS AND RELEVANCE Cocaine addiction is associated with disturbed rsFC in several specific striatal-cortical circuits. Specifically, compulsive cocaine use, a defining characteristic of dependence, was associated with a balance of increased striatal-anterior prefrontal/orbitofrontal and decreased striatal-dorsal anterior cingulate connectivity; trait impulsivity, both a risk factor for and a consequence of cocaine use, was associated with increased dorsal striatal-dorsal lateral prefrontal cortex connectivity uniquely in CUs. These findings provide new insights toward the neurobiological mechanisms of addiction and suggest potential novel therapeutic targets for treatment.