Table 1_Aberrant cortical–subcortical-cerebellar connectivity in resting-state fMRI as an imaging marker of schizophrenia and psychosis: a systematic review of data-driven whole-brain functional connectivity analyses.docx

IntroductionSchizophrenia is extremely heterogenous, and the underlying brain mechanisms are not fully understood. Many attempts have been made to substantiate and delineate the relationship between schizophrenia and the brain through unbiased exploratory investigations of resting-state functional magnetic resonance imaging (rs-fMRI). The results of numerous data-driven rs-fMRI studies have converged in support of the disconnection hypothesis framework, reporting aberrant connectivity in cortical–subcortical-cerebellar circuitry. However, this model is vague and underspecified, encompassing a vast array of findings across studies. It is necessary to further refine this model to identify consistent patterns and establish stable imaging markers of schizophrenia and psychosis. The organizational structure of the NeuroMark atlas is especially well-equipped for describing functional units derived through independent component analysis (ICA) and uniting findings across studies utilizing data-driven whole-brain functional connectivity (FC) to characterize schizophrenia and psychosis.
MethodsToward this goal, a systematic literature review was conducted on primary empirical articles published in English in peer-reviewed journals between January 2019–February 2025 which utilized cortical–subcortical-cerebellar terminology to describe schizophrenia-control comparisons of whole-brain FC in human rs-fMRI. The electronic databases utilized included Google scholar, PubMed, and APA PsycInfo, and search terms included (“schizophrenia” OR “psychosis”) AND “resting-state fMRI” AND (“cortical–subcortical-cerebellar” OR “cerebello-thalamo-cortical”).
ResultsTen studies were identified and NeuroMark nomenclature was utilized to describe findings within a common reference space. The most consistent patterns included cerebellar-thalamic hypoconnectivity, cerebellar-cortical (sensorimotor & insular-temporal) hyperconnectivity, subcortical (basal ganglia and thalamic)—cortical (sensorimotor, temporoparietal, insular-temporal, occipitotemporal, and occipital) hyperconnectivity, and cortical–cortical (insular-temporal and occipitotemporal) hypoconnectivity.
DiscussionPatterns implicating prefrontal cortex are largely inconsistent across studies and may not be effective targets for establishing stable imaging markers based on static FC in rs-fMRI. Instead, adapting new analytical strategies, or focusing on nodes in the cerebellum, thalamus, and primary motor and sensory cortex may prove to be a more effective approach.

引言
精神分裂症具有极强的异质性，其潜在的脑机制尚未完全阐明。诸多研究尝试通过对静息态功能磁共振成像（resting-state functional magnetic resonance imaging，rs-fMRI）开展无偏探索性研究，以证实并阐明精神分裂症与大脑之间的关联。众多数据驱动的rs-fMRI研究结果已趋于一致，支持“连接异常假说”框架，报道了皮层-皮层下-小脑环路存在连接异常。然而，该模型较为模糊且界定不清，涵盖了不同研究中的大量研究结果。因此，有必要进一步优化该模型，以识别出一致的脑活动模式，并确立精神分裂症与精神病性障碍的稳定影像学标志物。NeuroMark图谱的组织结构尤其适用于描述通过独立成分分析（independent component analysis，ICA）得到的功能单元，且可整合不同研究中利用数据驱动全脑功能连接（functional connectivity，FC）来表征精神分裂症与精神病性障碍的研究结果。
方法
为实现这一目标，本研究开展了系统性文献综述，纳入2019年1月至2025年2月期间发表于同行评审期刊的英文原创实证论文，这些研究使用皮层-皮层下-小脑相关术语，对人类rs-fMRI数据中的全脑功能连接（FC）进行精神分裂症与健康对照的比较分析。检索的电子数据库包括Google Scholar、PubMed以及APA PsycInfo，检索式为：（“精神分裂症” OR “精神病性障碍”）AND “静息态功能磁共振成像” AND （“皮层-皮层下-小脑” OR “小脑-丘脑-皮层”）。
结果
最终共纳入10项研究，并采用NeuroMark命名法在统一参考空间内描述研究结果。最为一致的脑连接模式包括：小脑-丘脑连接减弱、小脑-皮层（感觉运动皮层与岛叶-颞叶皮层）连接增强、皮层下（基底神经节与丘脑）-皮层（感觉运动皮层、颞顶皮层、岛叶-颞叶皮层、枕颞皮层以及枕叶皮层）连接增强，以及皮层-皮层（岛叶-颞叶皮层与枕颞皮层）连接减弱。
讨论
涉及前额叶皮层的连接模式在不同研究中一致性较差，基于rs-fMRI静态功能连接来建立稳定影像学标志物时，或许无法将其作为有效靶点。相较而言，采用新型分析策略，或聚焦于小脑、丘脑以及初级运动与感觉皮层的节点，可能是更为有效的研究路径。