Sensitivity of functional connectivity to periaqueductal gray localization, with implications for identifying disease-related changes in chronic visceral pain: A MAPP Research Network neuroimaging study.

Previous studies examining the resting-state functional connectivity of the periaqueductal gray (PAG) in chronic visceral pain have localized PAG coordinates derived from BOLD responses to provoked acute pain. These coordinates appear to be several millimeters anterior of the anatomical location of the PAG. Therefore, we aimed to determine whether measures of PAG functional connectivity are sensitive to the localization technique, and if the localization approach has an impact on detecting disease-related differences in chronic visceral pain patients. We examined structural and resting-state functional MRI (rs-fMRI) images from 209 participants in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network study. We applied three different localization techniques to define a region-of-interest (ROI) for the PAG: 1) a ROI previously-published as a Montreal Neurological Institute (MNI) coordinate surrounded by a 3 mm radius sphere (MNI-sphere), 2) a ROI that was hand-traced over the PAG in a MNI template brain (MNI-trace), and 3) a ROI that was hand-drawn over the PAG in structural images from 30 individual participants (participant-trace). We compared the correlation among the rs-fMRI signals from these PAG ROIs, as well as the functional connectivity of these ROIs with the whole brain. First, we found important non-uniformities in brainstem rs-fMRI signals, as rs-fMRI signals from the MNI-trace ROI were significantly more similar to the participant-trace ROI than to the MNI-sphere ROI. We then found that choice of ROI also impacts whole-brain functional connectivity, as measures of PAG functional connectivity throughout the brain were more similar between MNI-trace and participant-trace compared to MNI-sphere and participant-trace. Finally, we found that ROI choice impacts detection of disease-related differences, as functional connectivity differences between pelvic pain patients and healthy controls were much more apparent using the MNI-trace ROI compared to the MNI-sphere ROI. These results indicate that the ROI used to localize the PAG is critical, especially when examining brain functional connectivity changes in chronic visceral pain patients.

Cardiovagal modulation in pediatric functional gastrointestinal disorders.

BACKGROUND AND OBJECTIVES: Though reduced cardiovagal modulation accompanies adult IBS, adolescents with functional gastrointestinal disorders (FGID) have not been studied. We aim to investigate whether adolescents with FGID have reduced cardiovagal modulation. METHODS: After 10-minute supine rest, we recorded ECG for 5-minute supine and 5-minute standing without support in healthy and FGID-affected adolescents. After analysis with Kubios 2.2 for high-frequency (hf) and low-frequency (lf) heart rate variability (HRV), Wilcoxon signed-ranks test compared individual paired supine and standing HRV data, while Kruskal-Wallis and Mann-Whitney U tests compared HRV across groups. RESULTS: A total of 50 FGID subjects (90% females; median age 17 years [range 11-21]) and 22 healthy comparison group (HC) (59% females; median age 14 years [range 10-18]) participated. Both absolute and relative supine hfHRV exceeded standing in both groups. Absolute supine lfHRV was higher than standing in FGID patients and not in HCs, while relative supine lfHRV power was actually lower in both groups. Compared to HC, FGID group showed significantly lower absolute HRV, while relative HRV did not differ between groups. CONCLUSIONS: Cardiovagal modulation is lower in adolescents with FGID. This difference impacts these subjects significantly. Whether this finding reflects a cause or a consequence of FGID is unknown.