Data_Sheet_1_Altered Functional Connectivity Within and Between Salience and Sensorimotor Networks in Patients With Functional Constipation.DOCX

Functional constipation (FCon) is a common functional gastrointestinal disorder. A considerable portion of patients with FCon is associated with anxiety/depressive status (FCAD). Previous neuroimaging studies mainly focused on patients with FCon without distinguishing FCAD from FCon patients without anxiety/depressive status (FCNAD). Differences in brain functions between these two subtypes remain unclear. Thus, we employed resting-state functional magnetic resonance imaging (RS-fMRI) and graph theory method to investigate differences in brain network connectivity and topology in 41 FCAD, 42 FCNAD, and 43 age- and gender-matched healthy controls (HCs). FCAD/FCNAD showed significantly lower normalized clustering coefficient and small-world-ness. Both groups showed altered nodal degree/efficiency mainly in the rostral anterior cingulate cortex (rACC), precentral gyrus (PreCen), supplementary motor area (SMA), and thalamus. In the FCAD group, nodal degree in the SMA was negatively correlated with difficulty of defecation, and abdominal pain was positively correlated with nodal degree/efficiency in the rACC, which had a lower within-module nodal degree. The salience network (SN) exhibited higher functional connectivity (FC) with the sensorimotor network (SMN) in FCAD/FCNAD, and FC between these two networks was negatively correlated with anxiety ratings in FCAD group. Additionally, FC of anterior insula (aINS)–rACC was only correlated with constipation symptom (i.e., abdominal pain) in the FCNAD group. In the FCAD group, FCs of dorsomedial prefrontal cortex–rACC, PreCen–aINS showed correlations with both constipation symptom (i.e., difficulty of defecation) and depressive status. These findings indicate the differences in FC of the SN–SMN between FCAD and FCNAD and provide neuroimaging evidence based on brain function, which portrays important clues for improving new treatment strategies.

功能性便秘（Functional constipation, FCon）是一种常见的功能性胃肠病。相当一部分功能性便秘患者伴随焦虑/抑郁状态（以下简称FCAD）。既往神经影像学研究多聚焦于单纯功能性便秘患者，未将FCAD与不伴焦虑/抑郁状态的功能性便秘患者（以下简称FCNAD）加以区分，二者脑功能差异尚不明确。为此，本研究纳入41例FCAD患者、42例FCNAD患者及43例年龄与性别匹配的健康对照（healthy controls, HCs），采用静息态功能磁共振成像（resting-state functional magnetic resonance imaging, RS-fMRI）结合图论方法，探究两类便秘亚型与健康对照之间的脑网络连接及拓扑结构差异。FCAD与FCNAD患者的标准化聚类系数及小世界属性均显著降低。两组患者的节点度/节点效率改变主要集中于喙侧前扣带回皮层（rostral anterior cingulate cortex, rACC）、中央前回（precentral gyrus, PreCen）、辅助运动区（supplementary motor area, SMA）及丘脑。在FCAD组中，辅助运动区的节点度与排便困难程度呈负相关，腹痛与喙侧前扣带回皮层的节点度/节点效率呈正相关，而该脑区的模块内节点度更低。突显网络（salience network, SN）与感觉运动网络（sensorimotor network, SMN）之间的功能连接在FCAD及FCNAD患者中均显著升高，且FCAD组中这两个网络间的功能连接与焦虑评分呈负相关。此外，前脑岛（anterior insula, aINS）-喙侧前扣带回皮层的功能连接仅在FCNAD组中与便秘症状（即腹痛）相关。在FCAD组中，背内侧前额叶皮层-喙侧前扣带回皮层、中央前回-前脑岛的功能连接同时与便秘症状（即排便困难）及抑郁状态相关。本研究揭示了FCAD与FCNAD患者在突显网络-感觉运动网络功能连接上的差异，为基于脑功能的神经影像学证据，可为优化新型治疗策略提供重要线索。