Neuroimaging Research Branch, Intramural Research Program National Institute on Drug Abuse, Baltimore, Maryland.
JAMA Psychiatry. 2015 Jun;72(6):584-92. doi: 10.1001/jamapsychiatry.2015.1.
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.
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.
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.
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).
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.
冲动性和强迫性一直被认为是药物成瘾的关键心理结构。尽管可卡因成瘾中已经发现纹状体-皮质网络相互作用失调，但这些脑网络与成瘾之间的关系尚不清楚。
检验可卡因成瘾与静息状态功能连接（rsFC）改变有关的假设，该连接通过血氧水平依赖功能磁共振成像信号的自发波动来测量，并探讨纹状体 rsFC、特质冲动性与可卡因成瘾中无控制药物使用之间的关系。
设计、地点和参与者：这是一项在国家药物滥用研究所门诊磁共振成像设施进行的病例对照、横断面研究。本研究中使用的数据于 2005 年 12 月 8 日至 2011 年 9 月 30 日期间收集。参与者包括 56 名未经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 名健康对照者（HC），这些对照者在年龄、性别、受教育年限、种族、估计智力和吸烟状况方面与 CU 相匹配。
采用基于体素的统计参数分析，对 CU 和 HC 之间 6 个纹状体亚区功能连接的 rsFC 强度差异进行测试。
观察到 rsFC 强度增加主要发生在纹状体-额叶回路中；与 HC 相比，CU 组中纹状体与扣带回、纹状体、颞叶、海马/杏仁核和岛叶区域之间的 rsFC 减少。纹状体-背外侧前额叶皮质连接强度的增加与近期可卡因使用量呈正相关（未校正 P <.046），与 CU 中的特质冲动性升高呈正相关（未校正 P <.012），反映纹状体-背侧前扣带皮质与纹状体-前前额叶/眶额皮质回路之间平衡的指标与可卡因使用失控显著相关（校正 P <.012）。
可卡因成瘾与多个特定的纹状体-皮质回路中的 rsFC 紊乱有关。具体而言，依赖的一个特征是强迫性可卡因使用，与增加的纹状体-前前额叶/眶额皮质和减少的纹状体-背侧前扣带皮质连接平衡有关；特质冲动性既是可卡因使用的一个风险因素，也是其后果，与 CU 中背侧纹状体-背外侧前额叶皮质连接的增加有关。这些发现为成瘾的神经生物学机制提供了新的见解，并为治疗提供了潜在的新的治疗靶点。
