Gastric-Selective Associations of Caudate Functional Connectivity with Gastrointestinal Rhythms in Parkinson's...

Background/Objectives: Gastrointestinal dysmotility (GID) is a frequent non-motor manifestation of Parkinson's disease (PD). However, its peripheral electrophysiological characteristics, as well as the underlying neural mechanisms within the brain-gut axis, remain insufficiently understood. This study aimed to delineate spatiotemporal abnormalities in gastrointestinal pacing activity in PD and to explore their associations with cerebral functional connectivity (FC). Methods: Multichannel electrogastroenterography (EGEG) recordings, including both preprandial and postprandial states from gastric (leads 1-4) and intestinal (leads 5-8) regions, were obtained from patients with PD and healthy controls (HCs), alongside resting-state functional MRI (rs-fMRI). The striatal-thalamic circuit was selected as the seed region for FC analysis. Between-group differences in EGEG-derived spatiotemporal metrics were assessed using analysis of covariance (ANCOVA), while FC differences were examined using two-sample t-tests. Partial correlation analyses were conducted to evaluate associations among neuroimaging measures, aberrant gastrointestinal electrophysiological indices, and clinical variables. Regional specificity of correlations was further tested by comparing dependent correlation coefficients. In addition, multivariate brain-gut connectivity was assessed using partial canonical correlation analysis (pCCA) with 1000 permutation tests. Results: Relative to HCs, PD patients exhibited a significant reduction in the proportion of normal slow waves in both gastric and intestinal regions during preprandial and postprandial states (pFDR < 0.05). FC analysis revealed increased connectivity between the left thalamus and right insula in PD, whereas interhemispheric connectivity of the caudate nuclei and putamina was significantly reduced. Additionally, FC between the left pallidum and left precentral gyrus was attenuated in the PD group. Partial correlation analysis demonstrated a positive association between postprandial normal slow-wave fraction and interhemispheric caudate connectivity (r = 0.63, pFDR = 0.047). Furthermore, left thalamus-right insula connectivity correlated with both total Non-Motor Symptoms Scale (NMSS) scores (r = 0.57, pFDR = 0.042) and gastrointestinal subscale scores (r = 0.63, pFDR = 0.037). At the multivariate level, pCCA revealed a strong association between lentiform nucleus connectivity and preprandial gastric slow-wave rhythms (canonical r = 0.892, p = 0.004). Conclusions: In PD, caudate nucleus FC shows a preferential association with gastric rather than intestinal electrophysiological activity. Multivariate analyses further demonstrate a significant network-level association between lentiform nucleus connectivity and baseline gastric pacing rhythms, extending regional findings to a broader network interaction. Together, these results provide multimodal correlational evidence reflecting parallel central and peripheral alterations in PD, highlighting synchronized alterations in central networks and peripheral gastrointestinal rhythmicity.