Psilocybin induces spatially constrained alterations in thalamic functional organizaton and connectivity.
Psilocybin induces spatially constrained alterations in thalamic functional organizaton and connectivity.
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DOI：
10.1016/j.neuroimage.2022.119434
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发表时间：
2022-10-15
期刊：
影响因子：
5.7
通讯作者：
Barrett, Frederick S.
中科院分区：
文献类型：
--
作者：
Gaddis, Andrew;Lidstone, Daniel E.;Nebel, Mary Beth;Griffiths, Roland R.;Mostofsky, Stewart H.;Mejia, Amanda F.;Barrett, Frederick S.
关键词：
经典的迷幻药，如裸盖菇素和LSD，以及其他5-羟色胺2A受体（5-HT2AR）激动剂会引起感知和认知的急性改变。一些功能性磁共振成像（fMRI）研究已经证实，丘脑皮质连通性的改变可能是这些影响的基础。这些研究将丘脑视为一个统一的结构，尽管已知不同的丘脑内核的5-HT2AR表达差异和功能特异性。独立成分分析（ICA）先前已被用于从静息状态功能磁共振成像（rsfMRI）数据中确定可靠的群体水平的丘脑功能细分。在这些努力的基础上，我们采用了一种新颖的基于ica的数据最大化方法来检查裸盖菇素诱导的个体参与者的丘脑内功能组织和丘脑皮质连通性的变化。基线rsfMRI数据（n=38）来自长期冥想练习的健康个体，用于生成丘脑功能细分的统计模板。然后将该模板应用于一项新的基于ica的分析，分析裸盖菇素对同一个体子集（n=18）的丘脑内和丘脑外功能组织和连通性的急性影响。我们研究了与主观报告的药物效果的相关性，并与先前报道的分析方法（将丘脑视为单个功能单元）进行了比较。几种丘脑内成分显示出明显的裸盖菇素诱导的空间组织改变，裸盖菇素的影响主要局限于中背核和枕核。个体参与者的变化幅度与报告的主观影响相关。这些成分主要表现为丘脑皮质连通性的减少，主要与视觉和默认模式网络有关。将丘脑视为单一结构的分析显示，丘脑皮质连通性的整体数值增加，与先前使用这种方法的文献一致，但这种增加没有达到统计学意义。我们利用一种新的分析方法来发现裸盖菇素诱导的丘脑内和丘脑外功能组织的变化，以及已知表达5-HT2AR的丘脑内核和皮质网络的连性。使用整个丘脑分析未观察到这些变化，这表明裸盖菇素可能导致丘脑皮质连通性广泛但适度的增加，但被功能相关的丘脑内核的强烈局灶性减少所抵消。
Classic psychedelics, such as psilocybin and LSD, and other serotonin 2A receptor (5-HT2AR) agonists evoke acute alterations in perception and cognition. Altered thalamocortical connectivity has been hypothesized to underlie these effects, which is supported by some functional MRI (fMRI) studies. These studies have treated the thalamus as a unitary structure, despite known differential 5-HT2AR expression and functional specificity of different intrathalamic nuclei. Independent Component Analysis (ICA) has been previously used to identify reliable group-level functional subdivisions of the thalamus from resting-state fMRI (rsfMRI) data. We build on these efforts with a novel data-maximizing ICA-based approach to examine psilocybin-induced changes in intrathalamic functional organization and thalamocortical connectivity in individual participants. Baseline rsfMRI data (n=38) from healthy individuals with a long-term meditation practice was utilized to generate a statistical template of thalamic functional subdivisions. This template was then applied in a novel ICA-based analysis of the acute effects of psilocybin on intra- and extra-thalamic functional organization and connectivity in follow-up scans from a subset of the same individuals (n=18). We examined correlations with subjective reports of drug effect and compared with a previously reported analytic approach (treating the thalamus as a single functional unit). Several intrathalamic components showed significant psilocybin-induced alterations in spatial organization, with effects of psilocybin largely localized to the mediodorsal and pulvinar nuclei. The magnitude of changes in individual participants correlated with reported subjective effects. These components demonstrated predominant decreases in thalamocortical connectivity, largely with visual and default mode networks. Analysis in which the thalamus is treated as a singular unitary structure showed an overall numerical increase in thalamocortical connectivity, consistent with previous literature using this approach, but this increase did not reach statistical significance. We utilized a novel analytic approach to discover psilocybin-induced changes in intra- and extra-thalamic functional organization and connectivity of intrathalamic nuclei and cortical networks known to express the 5-HT2AR. These changes were not observed using whole-thalamus analyses, suggesting that psilocybin may cause widespread but modest increases in thalamocortical connectivity that are offset by strong focal decreases in functionally relevant intrathalamic nuclei.
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DOI：
10.1073/pnas.1525586113
发表时间：
2016-03-08
影响因子：
11.1
作者：
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影响因子：
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DOI：
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1995-01-01
影响因子：
5.8
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HOCHBERG, Y
影响因子：
4.5
作者：
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DOI：
10.1016/j.bpsc.2022.04.003
发表时间：
2022-09-06
影响因子：
5.9
作者：
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Borgwardt, Stefan