Early Adverse Life Events and Resting State Neural Networks in Patients With Chronic Abdominal Pain

Abstract

Background Early adverse life (EAL) events and sex have been identified as vulnerability factors for the development of several stress-sensitive disorders, including irritable bowel syndrome (IBS). We aimed to identify disease and sex-based differences in resting state (RS) connectivity associated with EALs in individuals with IBS. Method A history of EALs before age 18 was assessed using the early trauma inventory. RS functional magnetic resonance imaging was used to identify patterns of intrinsic brain oscillations in the form of RS networks in 168 people (58 IBS, 28 females; and 110 healthy controls, 72 females). Partial Least Squares, a multivariate analysis technique was used to identify disease and sex differences and possible correlations between EALs and functional connectivity in six identified RS networks. Results Associations between EALs and RS networks were observed. While a history of EALs was associated with altered connectivity in the salience/executive control network to a similar extent in male and female IBS patients (Bootstrap ratio [BSR]=3.28-5.61; p=.046), male IBS patients demonstrated additional EAL-related alterations in the cerebellar network (BSR=3.92-6.79; p=.022). Conclusion This cross sectional study identified correlations between RS networks and EALs in individuals with IBS. These results suggest that exposure to EALs before age 18 can shape adult RS in both male and female patients in the salience/executive control network, a brain network that has been implicated in the pathophysiology of central pain amplification.

Multivariate morphological brain signatures predict patients with chronic abdominal pain from healthy control subjects

“…Cortical thickening in primary somato-sensensory regions and posterior midcingulate cortex in healthy subjects has been associated with greater sensitivity to experimental temperature and pain stimuli [20]. Recent investigations of resting state data demonstrate an alteration in the salience and sensorimotor networks of IBS patients [23; 25; 26]. Resting state functional alterations in sensorimotor network regions have also been noted in females with other comorbid diseases including vulvodynia [24], fibromyalgia [33] and interstitial cystitis/bladder pain syndrome [31].…”

“…IBS also has a high comorbidity with other chronic pain and affective disorders [64]. Multiple alterations in the central nervous system as measured by structural and functional brain imaging have been demonstrated in IBS compared to HCs and these alterations correlate with self-reported symptom severity measures [18; 23; 25; 29; 37; 60]. Here, we apply MVPA to an objective biological marker, brain morphometry, in order to provide new mechanistic insights into IBS.…”

Disease-related differences in resting-state networks

“…Furthermore the intrinsic connectivity of the regions of the basal ganglia was associated with greater LPVD reports of total vulvar pain and highest daily pain ratings. IBS patients compared to HCs have shown increased connectivity within the salience network specifically the anterior insula, anterior cingulate, and putamen regions [34]. Alterations within the salience network have also been implicated in the pathophysiology of other chronic pain conditions [5; 13; 56; 59].…”

“…Speculum examination of the vagina and bimanual pelvic examination were preformed to exclude other pathology that could contribute to the pain. Age-matched data for female IBS and female healthy control (HC) subjects was obtained from past subjects enrolled in neuroimaging studies at the Center for Neurobiology of Stress between 2010 and 2013 and have been used in previous publications [34; 38; 39]. Healthy control subjects (HCs) were recruited by advertisement and screened via history and medical exam for absence of pain disorders, and were recruited from the UCLA and local Los Angeles community.…”

“…Task free resting-state magnetic resonance imaging (MRI) studies in other chronic pain populations have also demonstrated alterations in these same three networks [6; 16; 34; 38-40; 56; 59; 81], and these alterations have been suggested to contribute to the central pain amplification in these disorders [16; 23; 34; 38; 39; 56]. These resting state networks have not been examined in LPVD.…”