Shinozuka Kenneth, Tewarie Prejaas K B, Luppi Andrea, Lynn Christopher, Roseman Leor, Muthukumaraswamy Suresh, Nutt David J, Carhart-Harris Robin, Deco Gustavo, Kringelbach Morten L
Centre for Eudaimonia and Human Flourishing, Linacre College, University of Oxford, Oxford, United Kingdom.
Department of Psychiatry, University of Oxford, Oxford, United Kingdom.
Imaging Neurosci (Camb). 2025 Jan 3;3. doi: 10.1162/imag_a_00420. eCollection 2025.
Psychedelics are serotonergic drugs that profoundly alter consciousness, yet their neural mechanisms are not fully understood. A popular theory, RElaxed Beliefs Under pSychedelics (REBUS), posits that psychedelics flatten the hierarchy of information flow in the brain. Here, we investigate hierarchy based on the imbalance between sending and receiving brain signals, as determined by directed functional connectivity. We measure properties of directed functional hierarchy in a magnetoencephalography (MEG) dataset of 16 healthy human participants who were administered a psychedelic dose (75 micrograms, intravenous) of lysergic acid diethylamide (LSD) under four different conditions: eyes-closed with or without music and eyes-open with or without a video stimulus. Across the whole brain, LSD diminishes the asymmetry of directed connectivity when averaged across time. Additionally, we demonstrate that machine learning classifiers distinguish between LSD and placebo more accurately when trained on one of our hierarchy metrics than when trained on traditional measures of functional connectivity. Taken together, these results indicate that LSD weakens the hierarchy of directed connectivity in the brain by increasing the balance between senders and receivers of neural signals.
致幻剂是一类能深刻改变意识的血清素能药物，但其神经机制尚未完全明确。一种流行的理论——致幻剂作用下的放松信念（REBUS）认为，致幻剂会使大脑中信息流的层级扁平化。在此，我们基于由定向功能连接所确定的大脑信号发送与接收之间的不平衡来研究层级结构。我们在16名健康人类参与者的脑磁图（MEG）数据集中测量定向功能层级的特性，这些参与者在四种不同条件下接受了迷幻剂量（75微克，静脉注射）的麦角酸二乙酰胺（LSD）：闭眼且有无音乐、睁眼且有无视频刺激。在整个大脑中，LSD在对时间进行平均时会减少定向连接的不对称性。此外，我们证明，与基于传统功能连接测量进行训练相比，当使用我们的层级指标之一进行训练时，机器学习分类器能更准确地区分LSD和安慰剂。综上所述，这些结果表明，LSD通过增加神经信号发送者与接收者之间的平衡，削弱了大脑中定向连接的层级结构。
