Most of the recent work in psychedelic neuroscience has been done using non-invasive neuroimaging, with data recorded from the brains of adult volunteers under the influence of a variety of drugs. While this data provides holistic insights into the effects of psychedelics on whole-brain dynamics, the effects of psychedelics on the meso-scale dynamics of cortical circuits remains much less explored. Here, we report the effects of the serotonergic psychedelic N,N-diproptyltryptamine (DPT) on information-processing dynamics in a sample of in vitro organotypic cultures made from rat cortical tissue. Three hours of spontaneous activity were recorded: an hour of pre-drug control, and hour of exposure to 10$\mu$M DPT solution, and a final hour of washout, once again under control conditions. We found that DPT reversibly alters information dynamics in multiple ways: first, the DPT condition was associated with higher entropy of spontaneous firing activity and reduced the amount of time information was stored in individual neurons. Second, DPT also reduced the reversibility of neural activity, increasing the entropy produced and suggesting a drive away from equilibrium. Third, DPT altered the structure of neuronal circuits, decreasing the overall information flow coming into each neuron, but increasing the number of weak connections, creating a dynamic that combines elements of integration and disintegration. Finally, DPT decreased the higher-order statistical synergy present in sets of three neurons. Collectively, these results paint a complex picture of how psychedelics regulate information processing in meso-scale cortical tissue. Implications for existing hypotheses of psychedelic action, such as the Entropic Brain Hypothesis, are discussed.

翻译：近期致幻剂神经科学领域的研究多采用非侵入性脑成像技术，通过记录成年志愿者在多种药物影响下的脑部数据。这类数据虽能整体揭示致幻剂对全脑动力学的影响，但其对皮层回路中尺度动力学的作用机制仍鲜有探索。本研究基于大鼠皮层组织制备的器官型离体培养样本，报道了血清素能致幻剂N,N-二丙基色胺（DPT）对信息处理动力学的影响。实验记录了三小时的自发放电活动：给药前对照时段（1小时）、暴露于10μM DPT溶液时段（1小时）及撤药后对照时段（1小时）。结果发现，DPT通过多种途径可逆地改变信息动力学：首先，DPT处理组自发放电活动的熵值升高，同时信息在单个神经元中的存储时间缩短；其次，DPT降低了神经活动的可逆性，增加了熵的产生，表明系统偏离平衡态；第三，DPT改变了神经回路结构，减少了进入每个神经元的信息流总量，但增加了弱连接数量，形成兼具整合与分离特征的动态模式；最后，DPT降低了三神经元集合中存在的高阶统计协同作用。综合这些结果，揭示了致幻剂如何调控中尺度皮层组织信息处理的复杂机制，并讨论了其对现有致幻剂作用假说（如熵脑假说）的启示意义。