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全脑建模用于模拟意识障碍患者的药物干预。

Whole brain modelling for simulating pharmacological interventions on patients with disorders of consciousness.

机构信息

Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Sorbonne Université, Paris, 75013, France.

Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ministry of Science, Technology and Innovation, Buenos Aires, Argentina.

出版信息

Commun Biol. 2024 Sep 19;7(1):1176. doi: 10.1038/s42003-024-06852-9.

DOI:10.1038/s42003-024-06852-9
PMID:39300281
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11413186/
Abstract

Disorders of consciousness (DoC) represent a challenging and complex group of neurological conditions characterised by profound disturbances in consciousness. The current range of treatments for DoC is limited. This has sparked growing interest in developing new treatments, including the use of psychedelic drugs. Nevertheless, clinical investigations and the mechanisms behind them are methodologically and ethically constrained. To tackle these limitations, we combined biologically plausible whole-brain models with deep learning techniques to characterise the low-dimensional space of DoC patients. We investigated the effects of model pharmacological interventions by including the whole-brain dynamical consequences of the enhanced neuromodulatory level of different neurotransmitters, and providing geometrical interpretation in the low-dimensional space. Our findings show that serotonergic and opioid receptors effectively shifted the DoC models towards a dynamical behaviour associated with a healthier state, and that these improvements correlated with the mean density of the activated receptors throughout the brain. These findings mark an important step towards the development of treatments not only for DoC but also for a broader spectrum of brain diseases. Our method offers a promising avenue for exploring the therapeutic potential of pharmacological interventions within the ethical and methodological confines of clinical research.

摘要

意识障碍（DoC）代表了一组具有挑战性和复杂性的神经疾病，其特征是意识出现深刻紊乱。目前针对 DoC 的治疗方法有限。这引发了人们对开发新治疗方法的浓厚兴趣，包括使用迷幻药物。然而，临床研究及其背后的机制在方法学和伦理方面受到限制。为了解决这些限制，我们将具有生物学合理性的全脑模型与深度学习技术相结合，以描述 DoC 患者的低维空间。我们通过包括不同神经递质增强的神经调制水平的全脑动力学后果，并在低维空间提供几何解释，研究了模型药理学干预的效果。我们的研究结果表明，5-羟色胺能和阿片能受体有效地将 DoC 模型推向与更健康状态相关的动力学行为，并且这些改善与大脑中激活受体的平均密度相关。这些发现标志着朝着不仅针对 DoC 而且针对更广泛的大脑疾病的治疗方法迈出了重要一步。我们的方法为在临床研究的伦理和方法限制内探索药理学干预的治疗潜力提供了一个有前途的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3e3/11413186/86dbced5ce02/42003_2024_6852_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3e3/11413186/f903b8476961/42003_2024_6852_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3e3/11413186/ff0217f5d059/42003_2024_6852_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3e3/11413186/2191cd66880e/42003_2024_6852_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3e3/11413186/3467edbfa415/42003_2024_6852_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3e3/11413186/86dbced5ce02/42003_2024_6852_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3e3/11413186/f903b8476961/42003_2024_6852_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3e3/11413186/ff0217f5d059/42003_2024_6852_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3e3/11413186/2191cd66880e/42003_2024_6852_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3e3/11413186/3467edbfa415/42003_2024_6852_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3e3/11413186/86dbced5ce02/42003_2024_6852_Fig5_HTML.jpg

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Re-awakening the brain: Forcing transitions in disorders of consciousness by external in silico perturbation.唤醒大脑：通过外部计算机模拟扰动促使意识障碍发生转变。
PLoS Comput Biol. 2024 May 3;20(5):e1011350. doi: 10.1371/journal.pcbi.1011350. eCollection 2024 May.
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In vivo mapping of pharmacologically induced functional reorganization onto the human brain's neurotransmitter landscape.在体映射人类大脑神经递质景观上的药物诱导功能重组。
Sci Adv. 2023 Jun 16;9(24):eadf8332. doi: 10.1126/sciadv.adf8332. Epub 2023 Jun 14.
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Computational modelling in disorders of consciousness: Closing the gap towards personalised models for restoring consciousness.
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Neuroimage. 2023 Jul 15;275:120162. doi: 10.1016/j.neuroimage.2023.120162. Epub 2023 May 15.
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Low-dimensional organization of global brain states of reduced consciousness.低维组织的意识降低的全球大脑状态。
Cell Rep. 2023 May 30;42(5):112491. doi: 10.1016/j.celrep.2023.112491. Epub 2023 May 11.
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A whole-brain model of the neural entropy increase elicited by psychedelic drugs.迷幻药物引起的神经熵增的全脑模型。
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