Mind-Body treatments such as meditation, yoga or hypnosis have been shown to improve subjective symptoms in several persistent pain disorders including Irritable Bowel Syndrome (IBS). However, objective, reliable measures than can help identify treatment response ("biomarkers") have not been developed. A biomarker can support clinical endpoints and be used to more fully assess mechanisms and outcomes in Mind-Body clinical trials, as well as compare various Complementary and Integrative Medicine treatments, and help to target specific treatments to patients most likely to benefit. Recently identified functional and structural brain imaging abnormalities in patients with IBS and other chronic pain disorders are attractive biomarker candidates but have yet to be validated. For example, alterations in the spatiotemporal pattern of spontaneous brain oscillations during rest and in the functional connections between brain regions during pain expectation as well as changes in the structural density in prefrontal brain areas have been identified in IBS by our group. Correlations of clinical symptom severity with some of these brain abnormalities have also been shown. Based on these preliminary findings, we propose a step-wise process, following established guidelines for biomarker validation, to determine the following:
Aim 1 : Develop and validate structural and functional brain alterations as candidate biomarkers of CAM related treatment change in IBS. Each proposed biomarker will be validated by its ability to differentiate between patients and healthy controls (HC), its correlation with subjective symptom severity, and its stability over time. Our proposed candidate biomarkers include: increased right anterior insula contributions to low frequency power in the resting state, altered connectivity of the amygdala during anticipation of pain, and a structural marker of decreased prefrontal cortex gray matter.
Aim 2 : Validate optimal biomarker candidates from Aim 1 by assessment of their relationship to treatment responsiveness in IBS patients following Mindfulness Based Stress Reduction (MBSR).
Aim 3 : Determine the generality of optimal biomarkers from Aims 1 and 2 by examining relationship of factors such as sex, age, co-morbid pain symptoms, and/or baseline disease severity as moderators of the utility of the biomarker to be associated with initial and three month outcomes.
These Aims will be accomplished in two studies. The first will examine 75 IBS patients and 30 healthy controls during a single imaging session with 30 of the IBS subjects returning for a second session 2-4 weeks later to test the hypotheses for Aim 1. The second study will test 50 IBS patients before and after the MBSR program with imaging and symptom questionnaires to test the hypotheses for Aims 2 and 3.
Identification of objective and biologically based markers of treatment response will facilitate more rapid development and application of effective Mind-Body treatments for chronic pain. This project will lead to new biomarkers based on neuroimaging technology that can be quickly applied in treatment trials as both endpoints and patient selection.
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