Neurology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Radiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Mov Disord. 2017 Nov;32(11):1574-1583. doi: 10.1002/mds.27047. Epub 2017 Jun 19.
PD patients treated with dopamine therapy can develop maladaptive impulsive and compulsive behaviors, manifesting as repetitive participation in reward-driven activities. This behavioral phenotype implicates aberrant mesocorticolimbic network function, a concept supported by past literature. However, no study has investigated the acute hemodynamic response to dopamine agonists in this subpopulation.
We tested the hypothesis that dopamine agonists differentially alter mesocortical and mesolimbic network activity in patients with impulsive-compulsive behaviors.
Dopamine agonist effects on neuronal metabolism were quantified using arterial-spin-labeling MRI measures of cerebral blood flow in the on-dopamine agonist and off-dopamine states. The within-subject design included 34 PD patients, 17 with active impulsive compulsive behavior symptoms, matched for age, sex, disease duration, and PD severity.
Patients with impulsive-compulsive behaviors have a significant increase in ventral striatal cerebral blood flow in response to dopamine agonists. Across all patients, ventral striatal cerebral blood flow on-dopamine agonist is significantly correlated with impulsive-compulsive behavior severity (Questionnaire for Impulsive Compulsive Disorders in Parkinson's Disease- Rating Scale). Voxel-wise analysis of dopamine agonist-induced cerebral blood flow revealed group differences in mesocortical (ventromedial prefrontal cortex; insular cortex), mesolimbic (ventral striatum), and midbrain (SN; periaqueductal gray) regions.
These results indicate that dopamine agonist therapy can augment mesocorticolimbic and striato-nigro-striatal network activity in patients susceptible to impulsive-compulsive behaviors. Our findings reinforce a wider literature linking studies of maladaptive behaviors to mesocorticolimbic networks and extend our understanding of biological mechanisms of impulsive compulsive behaviors in PD. © 2017 International Parkinson and Movement Disorder Society.
接受多巴胺治疗的 PD 患者可能会出现适应性冲动和强迫行为，表现为反复参与奖励驱动的活动。这种行为表型暗示了边缘中脑皮质网络功能异常，这一概念得到了过去文献的支持。然而，尚无研究调查过该亚群患者对多巴胺激动剂的急性血液动力学反应。
我们检验了这样一个假设，即多巴胺激动剂会在冲动-强迫行为患者中改变中脑皮质和中脑边缘网络的活动。
使用动脉自旋标记 MRI 测量的脑血流来量化多巴胺激动剂对神经元代谢的影响，分别在多巴胺激动剂和非多巴胺激动剂状态下测量。该研究采用了自身对照设计，纳入了 34 名 PD 患者，其中 17 名有活跃的冲动-强迫行为症状，年龄、性别、疾病持续时间和 PD 严重程度与患者相匹配。
冲动-强迫行为患者在多巴胺激动剂作用下，腹侧纹状体的脑血流显著增加。在所有患者中，腹侧纹状体的脑血流在多巴胺激动剂状态下与冲动-强迫行为的严重程度显著相关（帕金森病冲动-强迫障碍问卷评定量表）。多巴胺激动剂诱导的脑血流的体素分析显示，中皮质（腹内侧前额叶皮质；岛叶皮质）、中边缘（腹侧纹状体）和中脑（SN；导水管周围灰质）区域存在组间差异。
这些结果表明，多巴胺激动剂治疗可以增强易发生冲动-强迫行为的 PD 患者的中皮质边缘和纹状体黑质纹状体网络的活动。我们的研究结果强化了将适应性行为研究与中皮质边缘网络联系起来的更广泛的文献，并扩展了我们对 PD 中冲动强迫行为的生物学机制的理解。© 2017 国际帕金森病和运动障碍协会。
