Alho Jussi, Lahnakoski Juha M, Panula Jonatan M, Rikandi Eva, Mäntylä Teemu, Lindgren Maija, Kieseppä Tuula, Suvisaari Jaana, Sams Mikko, Raij Tuukka T
Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Institute of Neuroscience and Medicine, Brain, & Behaviour (INM-7), Research Center Jülich, Jülich, Germany; Institute of Systems Neuroscience, Medical Faculty, Heinrich-Heine-universität Düsseldorf, Düsseldorf, Germany; Independent Max Planck Research Group for Social Neuroscience, Max Planck Institute of Psychiatry, Munich, Germany.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2023 Dec;8(12):1197-1206. doi: 10.1016/j.bpsc.2023.06.002. Epub 2023 Jun 17.
Previous functional magnetic resonance imaging studies have reported widespread brain functional connectivity alterations in patients with psychosis. These studies have mostly used either resting-state or simple-task paradigms, thereby compromising experimental control or ecological validity, respectively. Additionally, in a conventional functional magnetic resonance imaging intrasubject functional connectivity analysis, it is difficult to identify which connections relate to extrinsic (stimulus-induced) and which connections relate to intrinsic (non-stimulus-related) neural processes.
To mitigate these limitations, we used intersubject functional connectivity (ISFC) to analyze longitudinal functional magnetic resonance imaging data collected while 36 individuals with first-episode psychosis (FEP) and 29 age- and sex-matched population control participants watched scenes from the fantasy movie Alice in Wonderland at baseline and again at 1-year follow-up. Furthermore, to allow unconfounded comparison and to overcome possible circularity of ISFC, we introduced a novel approach wherein ISFC in both the FEP and population control groups was calculated with respect to an independent group of participants (not included in the analyses).
Using this independent-reference ISFC approach, we found an interaction effect wherein the independent-reference ISFC in individuals with FEP, but not in the control group participants, was significantly stronger at baseline than at follow-up in a network centered in the hippocampus and involving thalamic, striatal, and cortical regions, such as the orbitofrontal cortex. Alleviation of positive symptoms, particularly delusions, from baseline to follow-up was correlated with decreased network connectivity in patients with FEP.
These findings link deviation of naturalistic information processing in the hippocampus-centered network to positive symptoms.
先前的功能磁共振成像研究报告称，精神病患者存在广泛的脑功能连接改变。这些研究大多使用静息态或简单任务范式，从而分别损害了实验控制或生态效度。此外，在传统的功能磁共振成像受试者内功能连接分析中，很难确定哪些连接与外在（刺激诱发）神经过程相关，哪些连接与内在（非刺激相关）神经过程相关。
为了减轻这些局限性，我们使用受试者间功能连接（ISFC）来分析纵向功能磁共振成像数据，这些数据是在36名首发精神病（FEP）患者和29名年龄及性别匹配的健康对照参与者观看奇幻电影《爱丽丝梦游仙境》场景时收集的，分别在基线期和1年随访时进行。此外，为了进行无混淆的比较并克服ISFC可能存在的循环性，我们引入了一种新方法，即FEP组和健康对照组的ISFC均相对于一组独立的参与者（不包括在分析中）进行计算。
使用这种独立参照ISFC方法，我们发现了一种交互效应，即在以海马体为中心、涉及丘脑、纹状体和皮质区域（如眶额皮质）的网络中，FEP患者的独立参照ISFC在基线时显著强于随访时，而对照组参与者则没有这种情况。从基线到随访，FEP患者阳性症状（尤其是妄想）的减轻与网络连接性降低相关。
这些发现将以海马体为中心的网络中自然主义信息处理的偏差与阳性症状联系起来。
