Altered neurovascular coupling and associated neurotransmitter profiles in inflammatory bowel disease with distinct depressive symptoms

Neurovascular coupling (NVC) provides a new mechanistic perspective into understanding numerous brain diseases. Previous studies revealed the effects of depressive symptoms on NVC and neurotransmitters in certain neuropsychiatric disorders. However, whether the effects of depressive symptoms on NVC and neurotransmitters would be exhibited in inflammatory bowel diseases (IBD) is hitherto unknown. Forty IBD patients and forty-five healthy controls (HCs) underwent multiparametric magnetic resonance imaging scan. NVC metrics were investigated by exploring Pearson correlation coefficients and ratios between cerebral blood flow (CBF) and functional connectivity strength (FCS). Correlation analysis was applied to evaluate relationships between imaging-related alterations and clinical features as well as neurotransmitter profiles. The effects of depressive symptoms on brain functional alterations and distribution of specific neurotransmitters were explored in IBD subgroups. Multivariate pattern analysis (MVPA) was further applied to select features. Global coupling strength (i.e., short-range CBF-FCS) was significantly higher in IBD than that in HCs. Meanwhile, CBF, FCS and regional NVC (i.e., CBF/FCS) changes in the default mode network, insula, orbitofrontal cortex (OFC), middle cingulate cortex and pre-/postcentral gyrus (Pre-/PostCG) were found in IBD. Image-based machine-learning techniques were capable of differentiating IBD patients from HCs. Significant correlation was found between the decreased long-range FCS in fusiform gyrus and IBD questionnaire score in patients. IBD-related brain functional abnormalities were associated with the specific dopamine, glutamate, acetylcholine and serotonin neurotransmitter profiles. The effects of depressive symptoms on FCS and CBF/FCS were detected in IBD subgroups, mainly located in the OFC, fusiform gyrus, supplementary motor area, PostCG and/or caudate. The effects of depressive symptoms on distribution of aforementioned neurotransmitters were also revealed in IBD subgroups. Furthermore, these findings were implicated in the integration of emotion, cognition and visceral nociceptive perception in IBD patients. This study provides a new perspective for understanding the neuropathological underpinning of IBD by revealing these brain functional abnormalities and corresponding neurotransmitter profiles.