Altered cortical neuronal activity in functional esophageal disorders and its associations with chronic insomnia and peripheral inflammation: a resting-state fMRI study
Background/Objectives Functional esophageal disorders (FEDs) are disorders of gut–brain interaction frequently accompanied by chronic insomnia disorder (CID), but their cortical neuronal basis remains unclear. This study aimed to investigate spontaneous cortical activity in FEDs using resting-state functional magnetic resonance imaging with amplitude of low-frequency fluctuation (ALFF) analysis and to examine its associations with sleep disturbance and peripheral inflammation. Methods Nineteen patients with FEDs, 19 with CID, and 19 healthy controls (HCs) underwent resting-state fMRI and Pittsburgh Sleep Quality Index assessment. Patients with FEDs additionally completed symptom and psychological evaluations and underwent cytokine testing. Whole-brain ALFF was compared among groups, followed by FDR-corrected correlation analyses. An exploratory mediation model was presented in the Supplementary material for hypothesis generation only. Results Compared with HCs, patients with FEDs showed reduced ALFF in the bilateral middle temporal gyri (MTG), right middle occipital gyrus, right precuneus, left postcentral gyrus, and left inferior parietal lobule. Compared with CID, FEDs showed lower ALFF in the bilateral MTG and left superior parietal gyrus. However, because MTG abnormalities have also been reported in chronic insomnia, this finding should not be interpreted as evidence that MTG reduction is exclusive to FEDs. In FEDs, nominally positive correlations were observed between left MTG ALFF and IL-8/TNF-α, and between right MTG ALFF and sleep medication use. An exploratory supplementary mediation model generated a hypothesis regarding a possible indirect association among IL-8, left MTG ALFF, and daytime dysfunction; however, this finding should not be interpreted causally. Across all participants, global and bilateral MTG ALFF values were negatively correlated with PSQI scores after FDR correction. Conclusion FEDs showed reduced spontaneous cortical activity centered on the bilateral MTG, a region that may represent a transdiagnostic sleep- and sensory-related cortical hub rather than an FED-specific marker. This study provides new insights into the central mechanisms of FED and identifies candidate cortical regions for future mechanistic studies. These findings require validation in larger, adequately powered studies.