Basic Neuroscience Division, McLean Hospital, Belmont, MA, USA.
Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA.
Neuropsychopharmacology. 2022 Nov;47(12):2081-2089. doi: 10.1038/s41386-022-01366-6. Epub 2022 Jun 25.
Dysregulation of frontal cortical inputs to the striatum is foundational in the neural basis of substance use disorder (SUD). Neuroanatomical and electrophysiological data increasingly show that striatal nodes receive appreciable input from numerous cortical areas, and that the combinational properties of these multivariate "connectivity profiles" play a predominant role in shaping striatal activity and function. Yet, how abnormal configuration of striatal connectivity profiles might contribute to SUD is unknown. Here, we implemented a novel "connectivity profile analysis" (CPA) approach using resting-state functional connectivity data to facilitate detection of different types of connectivity profile "misconfiguration" that may reflect distinct forms of aberrant circuit plasticity in SUD. We examined 46 nicotine-dependent smokers and 33 non-smokers and showed that both dorsal striatum (DS) and ventral striatum (VS) connectivity profiles with frontal cortex were misconfigured in smokers-but in doubly distinct fashions. DS misconfigurations were stable across sated and acute abstinent states (indicative of a "trait" circuit adaptation) whereas VS misconfigurations emerged only during acute abstinence (indicative of a "state" circuit adaptation). Moreover, DS misconfigurations involved abnormal connection strength rank order arrangement, whereas VS misconfigurations involved abnormal aggregate strength. We found that caudal ventral putamen in smokers uniquely displayed multiple types of connectivity profile misconfiguration, whose interactive magnitude was linked to dependence severity, and that VS misconfiguration magnitude correlated positively with withdrawal severity during acute abstinence. Findings underscore the potential for approaches that more aptly model the neurobiological composition of corticostriatal circuits to yield deeper insights into the neural basis of SUD.
纹状体皮质输入的失调是物质使用障碍（SUD）的神经基础。神经解剖学和电生理学数据越来越多地表明，纹状体节点从许多皮质区域接收相当大的输入，并且这些多元“连接性特征”的组合特性在塑造纹状体的活动和功能方面起着主要作用。然而，纹状体连接特征的异常构型如何导致 SUD 尚不清楚。在这里，我们使用静息态功能连接数据实施了一种新的“连接特征分析”（CPA）方法，以促进检测可能反映 SUD 中不同形式的异常回路可塑性的不同类型的连接特征“失配”。我们检查了 46 名尼古丁依赖吸烟者和 33 名非吸烟者，结果表明吸烟者的背侧纹状体（DS）和腹侧纹状体（VS）与额叶皮质的连接特征均发生了失配——但以双重不同的方式。DS 失配在满足和急性戒断状态下都是稳定的（表明存在“特质”电路适应），而 VS 失配仅在急性戒断期间出现（表明存在“状态”电路适应）。此外，DS 失配涉及异常的连接强度秩排列，而 VS 失配涉及异常的总强度。我们发现，吸烟者的尾侧腹侧苍白球中唯一显示出多种类型的连接特征失配，其相互作用的幅度与依赖严重程度有关，并且 VS 失配的幅度与急性戒断期间的戒断严重程度呈正相关。这些发现强调了采用更恰当地模拟皮质纹状体回路的神经生物学组成的方法的潜力，以更深入地了解 SUD 的神经基础。
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