Reduced Functional Connectivity Between the Hypothalamus and High‐order Cortical Regions in Adolescent Patients With Irritable Bowel Syndrome

Abstract

The hypothalamus plays a critical role in maintaining visceral homeostasis. Altered hypothalamus activation has been implicated in functional gastrointestinal disorders, including irritable bowel syndrome (IBS). One important aspect of homeostatic regulation is the cortical modulation of limbic and paralimbic subsystems, including the hypothalamus, which in turn affects the descending regulatory processes mediating visceral homeostasis. Using neuroimaging, we evaluated hypothalamus functional connectivity in adolescent IBS patients and age-matched healthy controls who received rectal distension stimulations. More extensive hypothalamus connectivity was observed in liminal than subliminal condition in controls, but not in IBS patients. Compared with controls, IBS patients showed significantly reduced hypothalamus connectivity in the bilateral prefrontal cortices, supplementary motor and premotor areas, bilateral sensorimotor cortex, and limbic subareas, which are specifically involved in homeostatic regulation. The findings support the generalized homeostatic regulation model that reduced cortical and limbic modulations of hypothalamus functioning underlies disrupted visceral homeostasis in IBS patients.

Shared and Distinct Fractional Amplitude of Low-Frequency Fluctuation Patterns in Major Depressive Disorders With and Without Gastrointestinal Symptoms

“…Patients with functional dyspepsia manifested altered functional connectivity (FC) in the amygdala and insula ( 15 , 16 ). Reduced FC between the hypothalamus and high-order cortical area was found in adolescent IBS patients ( 17 ). Compared to female healthy controls, female IBS patients showed altered FC of the dorsal anterior insular with the medial prefrontal cortex (MPFC) and precuneus ( 18 ).…”

Amygdalar functional connectivity during resting and evoked pain in youth with functional abdominal pain disorders

“…43,63 Previous research has shown the AMY was activated during visceral pain in adults with IBS and not in healthy controls, 65 and changes in hypothalamus FC with the AMY were observed in youth with IBS vs healthy youth undergoing nonpainful rectal distention. 41 AMY FC has also changed after treatment for other pediatric chronic pain conditions, such as CRPS 61 and migraine. 48 Of interest, the AMY is also associated with negative affect, hyperarousal, and stress, and FAPD are highly comorbid with anxiety and other emotional problems, 12,16,18,68 particularly in more persistent and severe cases.…”

Changes in amygdalar functional connectivity following the water load symptom provocation task (WL-SPT) in youth with functional abdominal pain disorders

“…In youth with chronic pain, the AMY is thought to play an important role in aspects of nociceptive processing [57; 61], including pain attention and anticipation of pain [40; 60]. Prior research has shown the AMY was activated during visceral pain in adults with IBS compared to healthy controls [62] and changes in hypothalamus FC with the AMY were observed in youth with IBS versus healthy youth undergoing non-painful rectal distention [38]. AMY FC has also changed following treatment for other pediatric chronic pain conditions, such as CRPS [58] and migraine [45].…”

“…In studies of adolescents with IBS that induced non-painful visceral sensations via rectal distention, increased activation in regions associated with nociceptive processing (e.g., insula) and emotional arousal (e.g., pACC) were observed [39]. Reduced hypothalamic FC was observed in brain regions associated with cognition (bilateral prefrontal cortices), memory (hippocampus) and emotion (AMY) [38]. However, there is presently a lack of understanding of the neural mechanisms of pediatric FAPD using non-invasive visceral pain induction methods.…”