Difference in regional neural fluctuations and functional connectivity in Crohn's disease: a resting-state functional MRI study

Abstract

Patients with Crohn's disease (CD) are shown to have abnormal changes in brain structures. This study aimed to further investigate whether these patients have abnormal brain activities and network connectivity. Sixty patients with CD and 40 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (fMRI) scans. Amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC) were used to assess differences in spontaneous regional brain activity and functional connectivity. Compared to the HCs, patients with CD showed significantly higher ALFF values in hippocampus and parahippocampus (HIPP/paraHIPP), anterior cingulate cortex, insula, superior frontal cortex and precuneus. The ALFF values were significantly lower in secondary somatosensory cortex (S2), precentral gyrus, and medial prefrontal cortex. Functional connectivities between left HIPP and left inferior temporal cortex, and right middle cingulate cortex, HIPP, and fusiform area were significantly lower. The functional connectivities between right HIPP and right inferior orbitofrontal cortex and left HIPP were also significantly lower. Patients with CD showed higher or lower spontaneous activity in multiple brain regions. Altered activities in these brain regions may collectively reflect abnormal function and regulation of visceral pain and sensation, external environmental monitoring, and cognitive processing in these patients. Lower functional connectivity of the hippocampus-limbic system was observed in these patients. These findings may provide more information to elucidate the neurobiological mechanisms of the disease.

Keywords: Amplitude of low-frequency fluctuation; Crohn’s disease; Functional connectivity; Resting-state functional MRI.

Figure 1.

Brain regions exhibited significant differences in amplitude of low frequency fluctuations (ALFF) values between CD patients and healthy control subjects using age, gender, anxiety and depression as covariates. The statistical significance was set at voxel-wise P < 0.001 uncorrected with an extent threshold of cluster-wise false discovery rate (FDR) (P < 0.05 at cluster lever, cluster size >45). (A) Brain regions exhibit significantly higher ALFF values in CD patients; (B) Brain regions exhibit significantly lower ALFF values in CD patients. ACC, anterior cingulate cortex; CD, Crohn’s disease; MPFC, medial prefrontal cortex; HC, healthy control; HIPP / paraHIPP, hippocampal / parahippocampal cortex; PCUN, precuneus; PREC, precentral gyrus; S2, secondary somatosensory cortex; SFC, superior frontal cortex.

Figure 2.

Brain regions showed significant differences in the hippocampus-related connectivity between CD patients and healthy control subjects using age, gender, anxiety and depression as covariates. The statistical significance was set at voxel-wise P < 0.001 uncorrected with an extent threshold of cluster-wise false discovery rate (FDR) (P < 0.05 at cluster lever, cluster size >45). (A) Brain regions showing significantly lower connectivity to the left hippocampus in CD patients; (B) Brain regions showing significantly lower connectivity to the right hippocampus in CD patients. CD, Crohn’s disease; HC, healthy control; HIPP, hippocampus; ITC, inferior temporal cortex, MCC, middle cingulate cortex; OFC, orbitofrontal cortex.