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

ABSTRACT: Irritable bowel syndrome (IBS) is the most common chronic visceral pain disorder. The pathophysiology of IBS is incompletely understood; however, evidence strongly suggests dysregulation of the brain-gut axis. The aim of this study was to apply multivariate pattern analysis to identify an IBS-related morphometric brain signature that could serve as a central biological marker and provide new mechanistic insights into the pathophysiology of IBS. Parcellation of 165 cortical and subcortical regions was performed using FreeSurfer and the Destrieux and Harvard-Oxford atlases. Volume, mean curvature, surface area, and cortical thickness were calculated for each region. Sparse partial least squares discriminant analysis was applied to develop a diagnostic model using a training set of 160 females (80 healthy controls and 80 patients with IBS). Predictive accuracy was assessed in an age-matched holdout test set of 52 females (26 healthy controls and 26 patients with IBS). A 2-component classification algorithm comprising the morphometry of (1) primary somatosensory and motor regions and (2) multimodal network regions explained 36% of the variance. Overall predictive accuracy of the classification algorithm was 70%. Small effect size associations were observed between the somatosensory and motor signature and nongastrointestinal somatic symptoms. The findings demonstrate that the predictive accuracy of a classification algorithm based solely on regional brain morphometry is not sufficient, but they do provide support for the utility of multivariate pattern analysis for identifying meaningful neurobiological markers in IBS.

SUBMITTER: Labus JS

PROVIDER: S-EPMC4504800 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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

Labus Jennifer S JS Van Horn John D JD Gupta Arpana A Alaverdyan Mher M Torgerson Carinna C Ashe-McNalley Cody C Irimia Andrei A Hong Jui-Yang JY Naliboff Bruce B Tillisch Kirsten K Mayer Emeran A EA

Pain 20150801 8

Irritable bowel syndrome (IBS) is the most common chronic visceral pain disorder. The pathophysiology of IBS is incompletely understood; however, evidence strongly suggests dysregulation of the brain-gut axis. The aim of this study was to apply multivariate pattern analysis to identify an IBS-related morphometric brain signature that could serve as a central biological marker and provide new mechanistic insights into the pathophysiology of IBS. Parcellation of 165 cortical and subcortical region ...[more]

PMID: 25906347

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Project description:Successfully predicting the susceptibility of individuals to placebo analgesics will aid in developing more effective pain medication and therapies, as well as aiding potential future clinical use of placebos. In pursuit of this goal, we analyzed healthy and chronic pain patients' patterns of responsiveness during conditioning rounds and their links to conditioned placebo analgesia and the mediating effect of expectation on those responses. We recruited 579 participants (380 healthy, 199 with temporomandibular disorder [TMD]) to participate in a laboratory placebo experiment. Individual pain sensitivity dictated the temperatures used for high- and low-pain stimuli, paired with red or green screens, respectively, and participants were told there would be an analgesic intervention paired with the green screens. Over two conditioning sessions and one testing session, participants rated the painfulness of each stimulus on a visual analogue scale from 0 to 100. During the testing phase, the same temperature was used for both red and green screens to assess responses to the placebo effect, which was defined as the difference between the average of the high-pain-cue stimuli and low-pain-cue stimuli. Delta scores, defined as each low-pain rating subtracted from its corresponding high-pain rating, served as a means of modeling patterns of conditioning strength and placebo responsiveness. Latent class analysis (LCA) was then conducted to classify the participants based on the trajectories of the delta values during the conditioning rounds. Classes characterized by persistently greater or increasing delta scores during conditioning displayed greater placebo analgesia during testing than those with persistently lower or decreasing delta scores. Furthermore, the identified groups' expectation of pain relief acted as a mediator for individual placebo analgesic effects. This study is the first to use LCA to discern the relationship between patterns of learning and the resultant placebo analgesia in chronic pain patients. In clinical settings, this knowledge can be used to enhance clinical pain outcomes, as chronic pain patients with greater prior experiences of pain reduction may benefit more from placebo analgesia.

Project description:IntroductionFrequent chronic local pain can develop into chronic widespread pain (CWP). The spread of pain is correlated with pain intensity, anxiety, and depression, conditions that ultimately lead to a poor quality of life. Knowledge is incomplete about CWP's etiology, although it has been suggested that both central hyperexcitability and/or a combination with peripheral factors may be involved. Cerebrospinal fluid (CSF) could act as a mirror for the central nervous system as proteins are signal substances that activate the formation of algesics and control nociceptive processes. To this end, this study investigates the CSF protein expression in women with CWP and in female healthy controls.Materials and methodsThis study included 12 female patients with CWP diagnosed according to the American College of Rheumatology criteria with 13 healthy age- and sex-matched pain-free subjects. All subjects went through a clinical examination and answered a health questionnaire that registered sociodemographic and anthropometric data, pain characteristics, psychological status, and quality of life rating. CSF was collected by lumbar puncture from each subject. Two-dimensional gel electrophoresis in combination with mass spectrometry was used to analyze the CSF proteome. This study identifies proteins that significantly discriminate between the two groups using multivariate data analysis (MVDA) (i.e., orthogonal partial least squares discriminant analysis [OPLS-DA]).ResultsThere were no clinically significant levels of psychological distress and catastrophization presented in subjects with CWP. MVDA revealed a highly significant OPLS-DA model where 48 proteins from CSF explained 91% (R2) of the variation and with a prediction of 90% (Q2). The highest discriminating proteins were metabolic, transport, stress, and inflammatory.ConclusionThe highest discriminating proteins (11 proteins), according to the literature, are involved in apoptotic regulations, anti-inflammatory and anti-oxidative processes, the immune system, and endogenous repair. The results of this explorative study may indicate the presence of neuro-inflammation in the central nervous system of CWP patients. Future studies should be larger and control for confounders and determine which alterations are unspecific/general and which are specific changes.

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

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

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