Characterizing Thalamocortical (Dys)connectivity Following D-Amphetamine, LSD, and MDMA Administration
Characterizing Thalamocortical (Dys)connectivity Following D-Amphetamine, LSD, and MDMA Administration
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DOI：
10.1016/j.bpsc.2022.04.003
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发表时间：
2022-09-06
影响因子：
5.9
通讯作者：
Borgwardt, Stefan
中科院分区：
文献类型：
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作者：
Avram, Mihai;Mueller, Felix;Borgwardt, Stefan
背景技术背景：静息态功能性磁共振成像测量的精神病患者的丘脑皮质内在功能连接存在改变。具体而言，丘脑内在功能连接与感觉运动皮层（超连接）增加，与前额叶边缘皮层（低连接）减少。迷幻药如麦角酸二乙基酰胺（LSD）在健康志愿者中引起类似的丘脑皮质与感觉运动区的超连接。目前还不清楚LSD是否也会引起丘脑皮质与前额叶边缘皮质的连接减弱，因为目前的研究结果是模棱两可的。丘脑皮质超连通性与患者的精神病症状和健康志愿者的物质诱导的意识状态改变有关。丘脑皮质连接障碍可能是由改变的神经传递引起的，例如，通过精神病性障碍中的多巴胺能过量和迷幻剂诱导状态中的多巴胺能激动。目前还不清楚丘脑皮质连接障碍是否也是由安非他明类物质引起的，广泛释放单胺（即，多巴胺，去甲肾上腺素），但产生比致幻剂更少的知觉效果。我们在28名健康志愿者中给予LSD、d-苯丙胺和3，4-亚甲二氧基甲基苯丙胺（MDMA），研究它们对丘脑与2个脑网络的内在功能连接的影响（认知-感觉运动和显著性网络，分别对应于感觉运动和前额叶边缘皮层），使用双盲，安慰剂对照，交叉设计。结果：所有的活性物质引起神经-感觉-丘脑超连接与安慰剂相比，尽管主要是不同的药理作用和主观影响。LSD诱导的效应与感知的主观变化相关，表明超连通性和迷幻型感知改变之间存在联系。与d-安非他明和MDMA不同，LSD引起了与显着性网络的低连接，引起了超连接。D-苯丙胺和MDMA诱发类似的丘脑皮层dysconnectivity patterns.CONCLUSIONS：致幻剂，emphagocytoids，和精神兴奋剂引起丘脑皮层超连接与感觉运动区，类似于精神障碍患者的研究结果。
BACKGROUND: Patients with psychotic disorders present alterations in thalamocortical intrinsic functional con-nectivity as measured by resting-state functional magnetic resonance imaging. Specifically, thalamic intrinsic functional connectivity is increased with sensorimotor cortices (hyperconnectivity) and decreased with prefrontal limbic cortices (hypoconnectivity). Psychedelics such as lysergic acid diethlyamide (LSD) elicit similar thalamocortical hyperconnectivity with sensorimotor areas in healthy volunteers. It is unclear whether LSD also induces thalamocortical hypoconnectivity with prefrontal limbic cortices, because current findings are equivocal. Thalamocortical hyperconnectivity was associated with psychotic symptoms in patients and substance-induced altered states of consciousness in healthy volunteers. Thalamocortical dysconnectivity is likely evoked by altered neurotransmission, e.g., via dopaminergic excess in psychotic disorders and serotonergic agonism in psychedelic -induced states. It is unclear whether thalamocortical dysconnectivity is also elicited by amphetamine-type substances, broadly releasing monoamines (i.e., dopamine, norepinephrine) but producing fewer perceptual effects than psychedelics.METHODS: We administrated LSD, d-amphetamine, and 3,4-methylenedioxymethamphetamine (MDMA) in 28 healthy volunteers and investigated their effects on thalamic intrinsic functional connectivity with 2 brain networks (auditory-sensorimotor and salience networks, corresponding to sensorimotor and prefrontal limbic cortices, respectively), using a double-blind, placebo-controlled, crossover design.RESULTS: All active substances elicited auditory-sensorimotor-thalamic hyperconnectivity compared with placebo, despite predominantly distinct pharmacological actions and subjective effects. LSD-induced effects correlated with subjective changes in perception, indicating a link between hyperconnectivity and psychedelic-type perceptual alterations. Unlike d-amphetamine and MDMA, which induced hypoconnectivity with the salience network, LSD elicited hyperconnectivity. D-amphetamine and MDMA evoked similar thalamocortical dysconnectivity patterns.CONCLUSIONS: Psychedelics, empathogens, and psychostimulants evoke thalamocortical hyperconnectivity with sensorimotor areas, akin to findings in patients with psychotic disorders.