Psilocybin desynchronizes the human brain

• 成果类型: Article
• 署名作者: Siegel, Joshua S.; Subramanian, Subha; Perry, Demetrius; Kay, Benjamin P.; Gordon, Evan M.; Laumann, Timothy O.; Reneau, T. Rick; Metcalf, Nicholas V.; Chacko, Ravi V.; Gratton, Caterina; Horan, Christine; Krimmel, Samuel R.; Shimony, Joshua S.; Schweiger, Julie A.; Wong, Dean F.; Bender, David A.; Scheidter, Kristen M.; Whiting, Forrest I.; Padawer-Curry, Jonah A.; Shinohara, Russell T.; Chen, Yong; Moser, Julia; Yacoub, Essa; Nelson, Steven M.; Vizioli, Luca; Fair, Damien A.; Lenze, Eric J.; Carhart-Harris, Robin; Raison, Charles L.; Raichle, Marcus E.; Snyder, Abraham Z.; Nicol, Ginger E.; Dosenbach, Nico U. F.
• 署名单位: Washington University (WUSTL); Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Washington University (WUSTL); Washington University (WUSTL); State University System of Florida; Florida State University; Washington University (WUSTL); University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; University of California System; University of California San Francisco; Imperial College London; University of Wisconsin System; University of Wisconsin Madison; Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL)
• 刊物名称: Nature
• ISSN/ISSBN: 0028-6463
• DOI: 10.1038/s41586-024-07624-5
• 发表日期: 2024-08-01
• 页码: 131-+
• 关键词: life-threatening cancer; functional connectivity; 5-ht2a receptors; Wild Bootstrap; DOUBLE-BLIND; data quality; networks; ORGANIZATION; DEPRESSION; serotonin

摘要

A single dose of psilocybin, a psychedelic that acutely causes distortions of space-time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trials(1-4). In animal models, psilocybin induces neuroplasticity in cortex and hippocampus(5-8). It remains unclear how human brain network changes relate to subjective and lasting effects of psychedelics. Here we tracked individual-specific brain changes with longitudinal precision functional mapping (roughly 18 magnetic resonance imaging visits per participant). Healthy adults were tracked before, during and for 3 weeks after high-dose psilocybin (25 mg) and methylphenidate (40 mg), and brought back for an additional psilocybin dose 6-12 months later. Psilocybin massively disrupted functional connectivity (FC) in cortex and subcortex, acutely causing more than threefold greater change than methylphenidate. These FC changes were driven by brain desynchronization across spatial scales (areal, global), which dissolved network distinctions by reducing correlations within and anticorrelations between networks. Psilocybin-driven FC changes were strongest in the default mode network, which is connected to the anterior hippocampus and is thought to create our sense of space, time and self. Individual differences in FC changes were strongly linked to the subjective psychedelic experience. Performing a perceptual task reduced psilocybin-driven FC changes. Psilocybin caused persistent decrease in FC between the anterior hippocampus and default mode network, lasting for weeks. Persistent reduction of hippocampal-default mode network connectivity may represent a neuroanatomical and mechanistic correlate of the proplasticity and therapeutic effects of psychedelics.