莫达非尼对小脑-皮层连接性的调节及其与受体和转运体表达的关系

IF 5.7 2区医学 Q1 NEUROSCIENCES

Biological Psychiatry-Cognitive Neuroscience and Neuroimaging Pub Date : 2025-03-01 DOI:10.1016/j.bpsc.2024.11.010

Stefano Delli Pizzi , Federica Tomaiuolo , Antonio Ferretti , Giovanna Bubbico , Valeria Onofrj , Stefania Della Penna , Carlo Sestieri , Stefano L. Sensi

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引用次数: 0

摘要

背景：莫达非尼主要用于治疗嗜睡症，但也可作为标签外的认知增强剂。功能磁共振成像（fMRI）研究表明，莫达非尼能调节主要参与注意力和执行功能的新皮质网络的连接。然而，人们对这种药物对皮层下结构的影响却知之甚少。根据初步研究结果，我们评估了莫达非尼对不同小脑区域与新皮层连接的影响。我们评估了这些影响与神经递质受体/转运体表达的空间关系：方法：我们对50名参与者在服用单次（100毫克）莫达非尼（25人）或安慰剂（25人）前后获得的扫描结果进行了静息态fMRI（rs-fMRI）连通性模式估算。以特定的小脑区域为种子进行体素分析，我们研究了莫达非尼对小脑-皮层连通性的调节作用。接下来，我们对小脑-皮层连通性的调节与通过公开数据库获得的神经递质受体/转运体的表达之间的空间重叠进行了定量评估：莫达非尼增强了Crus I和Vermis IX与前额叶区域的连接。Crus I连接性的变化与多巴胺能D2受体的表达有关。Vermis I-II 显示与背侧前扣带回皮层的耦合增强，并与组胺能 H3 受体的表达相匹配。Vermis VII-VIII 显示与视觉皮层的连接性增强，这种活动与多巴胺能和组胺能神经传递有关：我们的研究揭示了莫达非尼对小脑-皮层连接的调节作用。结论：我们的研究揭示了莫达非尼对小脑-皮层连通性的调节作用，这种调节作用主要涉及Crus I和Vermis，并在空间上与多巴胺能受体、组胺能受体和5-羟色胺转运体的分布重叠。

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Modulation of Cerebellar-Cortical Connectivity Induced by Modafinil and Its Relationship With Receptor and Transporter Expression

Background

Modafinil is primarily used to treat narcolepsy but is also used as an off-label cognitive enhancer. Functional magnetic resonance imaging studies indicate that modafinil modulates the connectivity of neocortical networks primarily involved in attention and executive functions. However, much less is known about the drug’s effects on subcortical structures. Following preliminary findings, we evaluated modafinil’s activity on the connectivity of distinct cerebellar regions with the neocortex. We assessed the spatial relationship of these effects with the expression of neurotransmitter receptors/transporters.

Methods

Patterns of resting-state functional magnetic resonance imaging connectivity were estimated in 50 participants from scans acquired pre- and postadministration of a single (100 mg) dose of modafinil (n = 25) or placebo (n = 25). Using specific cerebellar regions as seeds for voxelwise analyses, we examined modafinil’s modulation of cerebellar-neocortical connectivity. Next, we conducted a quantitative evaluation of the spatial overlap between the modulation of cerebellar-neocortical connectivity and the expression of neurotransmitter receptors/transporters obtained by publicly available databases.

Results

Modafinil increased the connectivity of crus I and vermis IX with prefrontal regions. Crus I connectivity changes were associated with the expression of dopaminergic D₂ receptors. The vermis I–II showed enhanced coupling with the dorsal anterior cingulate cortex and matched the expression of histaminergic H₃ receptors. The vermis VII–VIII displayed increased connectivity with the visual cortex, an activity associated with dopaminergic and histaminergic neurotransmission.

Conclusions

Our study reveals modafinil’s modulatory effects on cerebellar-neocortical connectivity. The modulation mainly involves crus I and the vermis and spatially overlaps the distribution of dopaminergic and histaminergic receptors.

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来源期刊

Biological Psychiatry-Cognitive Neuroscience and Neuroimaging Neuroscience-Biological Psychiatry

CiteScore

10.40

自引率

1.70%

发文量

247

审稿时长

30 days

期刊介绍： Biological Psychiatry: Cognitive Neuroscience and Neuroimaging is an official journal of the Society for Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms, and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal focuses on studies using the tools and constructs of cognitive neuroscience, including the full range of non-invasive neuroimaging and human extra- and intracranial physiological recording methodologies. It publishes both basic and clinical studies, including those that incorporate genetic data, pharmacological challenges, and computational modeling approaches. The journal publishes novel results of original research which represent an important new lead or significant impact on the field. Reviews and commentaries that focus on topics of current research and interest are also encouraged.