Data_Sheet_1_Abnormal temporal variability of rich-club organization in three major psychiatric conditions.docx

IntroductionConvergent evidence has demonstrated a shared rich-club reorganization across multiple major psychiatric conditions. However, previous studies assessing altered functional couplings between rich-club regions have typically focused on the mean time series from entire functional magnetic resonance imaging (fMRI) scanning session, neglecting their time-varying properties.
MethodsIn this study, we aim to explore the common and/or unique alterations in the temporal variability of rich-club organization among schizophrenia (SZ), bipolar disorder (BD), and attention deficit/hyperactivity disorder (ADHD). We employed a temporal rich-club (TRC) approach to quantitatively assess the propensity of well-connected nodes to form simultaneous and stable structures in a temporal network derived from resting-state fMRI data of 156 patients with major psychiatric disorders (SZ/BD/ADHD = 71/45/40) and 172 healthy controls. We executed the TRC workflow at both whole-brain and subnetwork scales across varying network sparsity, sliding window strategies, lengths and steps of sliding windows, and durations of TRC coefficients.
ResultsThe SZ and BD groups displayed significantly decreased TRC coefficients compared to corresponding HC groups at the whole-brain scale and in most subnetworks. In contrast, the ADHD group exhibited reduced TRC coefficients in longer durations, as opposed to shorter durations, which markedly differs from the SZ and BD groups. These findings reveal both transdiagnostic and illness-specific patterns in temporal variability of rich-club organization across SZ, BD, and ADHD.
DiscussionTRC may serve as an effective metric for detecting brain network disruptions in particular states, offering novel insights and potential biomarkers into the neurobiological basis underpinning the behavioral and cognitive deficits observed in these disorders.

引言
越来越多的一致性证据表明，多种重性精神疾病均存在共通的富人俱乐部（rich-club）结构重塑现象。然而，既往针对富人俱乐部脑区间功能连接改变的研究，通常仅关注整个功能磁共振成像（functional magnetic resonance imaging，fMRI）扫描时段的平均时间序列，忽略了其随时间变化的特性。

方法
本研究旨在探究精神分裂症（schizophrenia，SZ）、双相障碍（bipolar disorder，BD）及注意缺陷多动障碍（attention deficit/hyperactivity disorder，ADHD）患者中，富人俱乐部组织的时间变异性所存在的共性与/或特异性改变。本研究采用时间域富人俱乐部（temporal rich-club，TRC）方法，定量评估高连接节点在由156例重性精神疾病患者（SZ/BD/ADHD分别为71/45/40例）及172名健康对照（healthy controls，HC）的静息态fMRI数据构建的时间网络中，形成同步且稳定结构的倾向。本研究在全脑及子网络尺度下，通过调整网络稀疏性、滑动窗口策略、滑动窗口长度与步长以及TRC系数的持续时长，执行了全套TRC分析流程。

结果
相较于对应的健康对照（healthy controls，HC）组，精神分裂症与双相障碍组在全脑尺度及多数子网络中均表现出TRC系数显著降低。与之相反，注意缺陷多动障碍组仅在较长的持续时长中表现出TRC系数降低，而在较短持续时长中则无此现象，这与精神分裂症及双相障碍组的改变模式显著不同。上述研究结果揭示了精神分裂症、双相障碍及注意缺陷多动障碍患者中，富人俱乐部组织时间变异性兼具跨诊断共性与疾病特异性的模式。

讨论
TRC可作为检测特定状态下脑网络异常的有效指标，为阐明上述疾病所伴发的行为与认知缺陷背后的神经生物学基础提供了全新视角与潜在生物标志物。