Author name cluster

Emeran A. Mayer

Possible papers associated with this exact author name in Arrow. This page groups case-insensitive exact name matches and is not a full identity disambiguation profile.

13 papers

1 author row

YNICL Journal 2021 Journal Article

Altered brain structural connectivity in patients with longstanding gut inflammation is correlated with psychological symptoms and disease duration

Joanna Turkiewicz
Ravi R. Bhatt
Hao Wang
Priten Vora
Beatrix Krause
Jenny S. Sauk
Jonathan P. Jacobs
Charles N. Bernstein

OBJECTIVE: We aimed to identify differences in network properties of white matter microstructure between asymptomatic ulcerative colitis (UC) participants who had a history of chronic gut inflammation, healthy controls (HCs) and a disease control group without gut inflammation (irritable bowel syndrome; IBS). DESIGN: Diffusion weighted imaging was conducted in age and sex-matched participants with UC, IBS, and HCs (N = 74 each), together with measures of gastrointestinal and psychological symptom severity. Using streamline connectivity matrices and graph theory, we aimed to quantify group differences in brain network connectivity. Regions showing group connectivity differences were correlated with measures showing group behavioral and clinical differences. RESULTS: UC participants exhibited greater centrality in regions of the somatosensory network and default mode network, but lower centrality in the posterior insula and globus pallidus compared to HCs (q < 0.05). Hub analyses revealed compromised hubness of the pallidus in UC and IBS compared to HCs which was replaced by increased hubness of the postcentral sulcus. Surprisingly, few differences in network matrices between UC and IBS were identified. In UC, centrality measures in the secondary somatosensory cortex were associated with depression (q < 0.03), symptom related anxiety (q < 0.04), trait anxiety (q < 0.03), and symptom duration (q < 0.05). CONCLUSION: A history of UC is associated with neuroplastic changes in several brain networks, which are associated with symptoms of depression, trait and symptom-related anxiety, as well as symptom duration. When viewed together with the results from IBS subjects, these findings suggest that chronic gut inflammation as well as abdominal pain have a lasting impact on brain network organization, which may play a role in symptoms reported by UC patients, even when gut inflammation has subsided.

Details DOI

YNICL Journal 2019 Journal Article

Interactions between gut permeability and brain structure and function in health and irritable bowel syndrome

Suzanne T. Witt
Olga Bednarska
Åsa V. Keita
Adriane Icenhour
Michael P. Jones
Sigrid Elsenbruch
Johan D. Söderholm
Maria Engström

Changes in brain-gut interactions have been implicated in the pathophysiology of chronic visceral pain in irritable bowel syndrome (IBS). Different mechanisms of sensitization of visceral afferent pathways may contribute to the chronic visceral pain reports and associated brain changes that characterize IBS. They include increased gut permeability and gut associated immune system activation, and an imbalance in descending pain inhibitory and facilitatory mechanisms. In order to study the involvement of these mechanisms, correlations between gut epithelial permeability and live bacterial passage, and structural and functional brain connectivity were measured in women with moderate-to-severe IBS and healthy women. The relationships between gut permeability and functional and anatomical connectivity were significantly altered in IBS compared with the healthy women. IBS participants with lower epithelial permeability reported increased IBS symptoms, which was associated with increased functional and structural connectivity in endogenous pain facilitation regions. The findings suggest that relationships between gut permeability and the brain are significantly altered in IBS and suggest the existence of IBS subtypes based on these interactions.

Details DOI

YNICL Journal 2017 Journal Article

Brain functional connectivity is associated with visceral sensitivity in women with Irritable Bowel Syndrome

Adriane Icenhour
Suzanne T. Witt
Sigrid Elsenbruch
Mats Lowén
Maria Engström
Kirsten Tillisch
Emeran A. Mayer
Susanna Walter

Increased perception of visceral stimuli is a key feature of Irritable Bowel Syndrome (IBS). While altered resting-state functional connectivity (rsFC) has been also reported in IBS, the relationship between visceral hypersensitivity and aberrant rsFC is unknown. We therefore assessed rsFC within the salience, sensorimotor and default mode networks in patients with and without visceral hypersensitivity and in healthy controls (HCs). An exploratory resting-state functional magnetic resonance imaging study was performed in 41 women with IBS and 20 HCs. Group independent component analysis was used to derive intrinsic brain networks. Rectal thresholds were determined and patients were subdivided into groups with increased (hypersensitive IBS, N = 21) or normal (normosensitive IBS, N = 20) visceral sensitivity. Between-group comparisons of rsFC were carried-out using region-of-interest analyses and peak rsFC values were extracted for correlational analyses. Relative to normosensitive IBS, hypersensitive patients showed increased positive rsFC of pregenual anterior cingulate cortex and thalamus within the salience network and of posterior insula within the sensorimotor network. When compared to both hypersensitive IBS and HCs, normosensitive IBS showed decreased positive rsFC of amygdala and decreased negative rsFC in dorsal anterior insula within the DMN. DMN and sensorimotor network rsFC were associated with rectal perception thresholds, and rsFC in posterior insula was correlated with reported symptom severity in IBS. Our exploratory findings suggest that visceral sensitivity in IBS is related to changes in FC within resting-state networks associated with interoception, salience and sensory processing. These alterations may play an important role in hypervigilance and hyperalgesia in IBS.

Details DOI

YNICL Journal 2016 Journal Article

Multisite, multimodal neuroimaging of chronic urological pelvic pain: Methodology of the MAPP Research Network

Jeffry R. Alger
Benjamin M. Ellingson
Cody Ashe-McNalley
Davis C. Woodworth
Jennifer S. Labus
Melissa Farmer
Lejian Huang
A. Vania Apkarian

The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network is an ongoing multi-center collaborative research group established to conduct integrated studies in participants with urologic chronic pelvic pain syndrome (UCPPS). The goal of these investigations is to provide new insights into the etiology, natural history, clinical, demographic and behavioral characteristics, search for new and evaluate candidate biomarkers, systematically test for contributions of infectious agents to symptoms, and conduct animal studies to understand underlying mechanisms for UCPPS. Study participants were enrolled in a one-year observational study and evaluated through a multisite, collaborative neuroimaging study to evaluate the association between UCPPS and brain structure and function. 3D T1-weighted structural images, resting-state fMRI, and high angular resolution diffusion MRI were acquired in five participating MAPP Network sites using 8 separate MRI hardware and software configurations. We describe the neuroimaging methods and procedures used to scan participants, the challenges encountered in obtaining data from multiple sites with different equipment/software, and our efforts to minimize site-to-site variation.

Details DOI

YNIMG Journal 2016 Journal Article

Pain and Interoception Imaging Network (PAIN): A multimodal, multisite, brain-imaging repository for chronic somatic and visceral pain disorders

Jennifer S. Labus
Bruce Naliboff
Lisa Kilpatrick
Cathy Liu
Cody Ashe-McNalley
Ivani R. dos Santos
Mher Alaverdyan
Davis Woodworth

The Pain and Interoception Imaging Network (PAIN) repository (painrepository. org) is a newly created NIH (NIDA/NCCAM) funded neuroimaging data repository that aims to accelerate scientific discovery regarding brain mechanisms in pain and to provide more rapid benefits to pain patients through the harmonization of efforts and data sharing. The PAIN Repository consists of two components, an Archived Repository and a Standardized Repository. Similar to other ‘open’ imaging repositories, neuroimaging researchers can deposit any dataset of chronic pain patients and healthy controls into the Archived Repository. Scans in the Archived Repository can be very diverse in terms of scanning procedures and clinical metadata, complicating the merging of datasets for analyses. The Standardized Repository overcomes these limitations through the use of standardized scanning protocols along with a standardized set of clinical metadata, allowing an unprecedented ability to perform pooled analyses. The Archived Repository currently includes 741 scans and is rapidly growing. The Standardized Repository currently includes 433 scans. Pain conditions currently represented in the PAIN repository include: irritable bowel syndrome, vulvodynia, migraine, chronic back pain, and inflammatory bowel disease. Both the PAIN Archived and Standardized Repositories promise to be important resources in the field of chronic pain research. The enhanced ability of the Standardized Repository to combine imaging, clinical and other biological datasets from multiple sites in particular make it a unique resource for significant scientific discoveries.

Details DOI

YNICL Journal 2016 Journal Article

Placebo analgesia: Self-report measures and preliminary evidence of cortical dopamine release associated with placebo response

Johanna M. Jarcho
Natasha A. Feier
Jennifer S. Labus
Bruce Naliboff
Suzanne R. Smith
Jui-Yang Hong
Luana Colloca
Kirsten Tillisch

Placebo analgesia is measured by self-report, yet current, expected, and recalled efficacy may be differentially related to brain function. Here we used a human thermal pain model to compare self-reports of expected, concurrent, and recalled efficacy of a topical placebo analgesic, and tested associations of the three measures of efficacy with changes in dopamine D2/D3 receptor availability in brain using [(18)F]fallypride with positron emission tomography (PET). Participants (15 healthy women) were assessed on three test days. The first test day included a laboratory visit, during which the temperature needed to evoke consistent pain was determined, placebo analgesia was induced via verbal and experience-based expectation, and the placebo response was measured. On two subsequent test days, PET scans were performed in Control and Placebo conditions, respectively, in counterbalanced order. During Visit 1, concurrent and recalled placebo efficacy were unrelated; during the Placebo PET visit, expected and recalled efficacy were highly correlated (ρ = 0.68, p = 0.005), but concurrent efficacy was unrelated to expected or recalled efficacy. Region of interest analysis revealed dopamine D2/D3 receptor availability was lower in left ventrolateral prefrontal cortex in the Placebo condition (p < 0.001, uncorrected), and greater change in this measure was associated with higher levels of recalled analgesic efficacy (ρ = 0.58, p = 0.02). These preliminary findings underscore the need to consider how self-reported symptom improvement is assessed in clinical trials of analgesics and suggest that dopaminergic activity in the ventrolateral prefrontal cortex may promote recalled efficacy of placebo.

Details DOI

YNICL Journal 2015 Journal Article

Altered resting state neuromotor connectivity in men with chronic prostatitis/chronic pelvic pain syndrome: A MAPP

Jason J. Kutch
Moheb S. Yani
Skulpan Asavasopon
Daniel J. Kirages
Manku Rana
Louise Cosand
Jennifer S. Labus
Lisa A. Kilpatrick

Brain network activity associated with altered motor control in individuals with chronic pain is not well understood. Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a debilitating condition in which previous studies have revealed altered resting pelvic floor muscle activity in men with CP/CPPS compared to healthy controls. We hypothesized that the brain networks controlling pelvic floor muscles would also show altered resting state function in men with CP/CPPS. Here we describe the results of the first test of this hypothesis focusing on the motor cortical regions, termed pelvic-motor, that can directly activate pelvic floor muscles. A group of men with CP/CPPS (N = 28), as well as group of age-matched healthy male controls (N = 27), had resting state functional magnetic resonance imaging scans as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network study. Brain maps of the functional connectivity of pelvic-motor were compared between groups. A significant group difference was observed in the functional connectivity between pelvic-motor and the right posterior insula. The effect size of this group difference was among the largest effect sizes in functional connectivity between all pairs of 165 anatomically-defined subregions of the brain. Interestingly, many of the atlas region pairs with large effect sizes also involved other subregions of the insular cortices. We conclude that functional connectivity between motor cortex and the posterior insula may be among the most important markers of altered brain function in men with CP/CPPS, and may represent changes in the integration of viscerosensory and motor processing.

Details DOI

YNICL Journal 2015 Journal Article

Patterns of brain structural connectivity differentiate normal weight from overweight subjects

Arpana Gupta
Emeran A. Mayer
Claudia P. Sanmiguel
John D. Van Horn
Davis Woodworth
Benjamin M. Ellingson
Connor Fling
Aubrey Love

BACKGROUND: Alterations in the hedonic component of ingestive behaviors have been implicated as a possible risk factor in the pathophysiology of overweight and obese individuals. Neuroimaging evidence from individuals with increasing body mass index suggests structural, functional, and neurochemical alterations in the extended reward network and associated networks. AIM: To apply a multivariate pattern analysis to distinguish normal weight and overweight subjects based on gray and white-matter measurements. METHODS: Structural images (N = 120, overweight N = 63) and diffusion tensor images (DTI) (N = 60, overweight N = 30) were obtained from healthy control subjects. For the total sample the mean age for the overweight group (females = 32, males = 31) was 28.77 years (SD = 9.76) and for the normal weight group (females = 32, males = 25) was 27.13 years (SD = 9.62). Regional segmentation and parcellation of the brain images was performed using Freesurfer. Deterministic tractography was performed to measure the normalized fiber density between regions. A multivariate pattern analysis approach was used to examine whether brain measures can distinguish overweight from normal weight individuals. RESULTS: 1. White-matter classification: The classification algorithm, based on 2 signatures with 17 regional connections, achieved 97% accuracy in discriminating overweight individuals from normal weight individuals. For both brain signatures, greater connectivity as indexed by increased fiber density was observed in overweight compared to normal weight between the reward network regions and regions of the executive control, emotional arousal, and somatosensory networks. In contrast, the opposite pattern (decreased fiber density) was found between ventromedial prefrontal cortex and the anterior insula, and between thalamus and executive control network regions. 2. Gray-matter classification: The classification algorithm, based on 2 signatures with 42 morphological features, achieved 69% accuracy in discriminating overweight from normal weight. In both brain signatures regions of the reward, salience, executive control and emotional arousal networks were associated with lower morphological values in overweight individuals compared to normal weight individuals, while the opposite pattern was seen for regions of the somatosensory network. CONCLUSIONS: 1. An increased BMI (i.e., overweight subjects) is associated with distinct changes in gray-matter and fiber density of the brain. 2. Classification algorithms based on white-matter connectivity involving regions of the reward and associated networks can identify specific targets for mechanistic studies and future drug development aimed at abnormal ingestive behavior and in overweight/obesity.

Details DOI

YNIMG Journal 2012 Journal Article

Evidence for alterations in central noradrenergic signaling in irritable bowel syndrome

Steven Berman
Brandall Suyenobu
Bruce D. Naliboff
Joshua Bueller
Jean Stains
Heng Wong
Mark Mandelkern
Leah Fitzgerald

Background/aims Alterations in noradrenergic (NE) signaling have been implicated in the pathophysiology of irritable bowel syndrome (IBS), and adrenergic receptors are potential treatment targets. Methods To characterize central NE signaling in IBS, 11 patients and 11 healthy controls (HCs) were studied 3 times during an auditory oddball vigilance task after double-blind ingestion of the α2-adrenoreceptor (α2AR) antagonist yohimbine (YOH), the α2AR agonist clonidine (CLO), or placebo (PLA). Regional cerebral glucose metabolism was measured with [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET). Measures of anxiety, early-life trauma, plasma NE and blood pressure were acquired. Results Patients had higher plasma NE levels than HCs before and after ingestion of all drugs (all p<0. 05). YOH increased plasma NE and more anxiety in patients than in HCs. After YOH, NE levels directly correlated with drug-induced increases in anxiety in IBS patients (r=0. 61), but not in HCs. IBS patients showed less YOH-mediated reduction of activity in a central arousal circuit, consistent with fewer functional presynaptic α2AR. In HCs, but not in patients, activation of amygdala and subgenual anterior cingulate cortex (sgACC) was inversely correlated with activation of anterior mid cingulate cortex (aMCC), and state anxiety covaried directly with activity in limbic and right frontotemporal cortices, but indirectly with activity in the left frontotemporal cortex. YOH-mediated reduction of activity in brainstem and amygdala inversely correlated with early life trauma. Conclusions IBS patients showed evidence for increased noradrenergic activity consistent with downregulation of presynaptic inhibitory α2ARs. Activity within central arousal circuits was biased toward greater excitability and reduced corticolimbic inhibition in IBS. Early life trauma may be one mediator of these abnormalities.

Details DOI

YNIMG Journal 2012 Journal Article

One-year test–retest reliability of intrinsic connectivity network fMRI in older adults

Christine C. Guo
Florian Kurth
Juan Zhou
Emeran A. Mayer
Simon B. Eickhoff
Joel H. Kramer
William W. Seeley

“Resting-state” or task-free fMRI can assess intrinsic connectivity network (ICN) integrity in health and disease, suggesting a potential for use of these methods as disease-monitoring biomarkers. Numerous analytical options are available, including model-driven ROI-based correlation analysis and model-free, independent component analysis (ICA). High test–retest reliability will be a necessary feature of a successful ICN biomarker, yet available reliability data remains limited. Here, we examined ICN fMRI test–retest reliability in 24 healthy older subjects scanned roughly one year apart. We focused on the salience network, a disease-relevant ICN not previously subjected to reliability analysis, as well as the default mode network. Most ICN analytical methods proved reliable (intraclass coefficients>0. 4) and were further improved by wavelet analysis. Seed-based ROI correlation analysis showed high scan-wise reliability, whereas graph theoretical analysis and temporal concatenation group ICA proved most reliable at the individual unit-wise level (voxels, ROIs). Including global signal regression in ROI-based correlation analyses reduced reliability. Our study provides a direct comparison between the most commonly used ICN fMRI methods and potential guidelines for measuring intrinsic connectivity in aging control and patient populations over time.

Details DOI

YNIMG Journal 2011 Journal Article

Common component classification: What can we learn from machine learning?

Ariana Anderson
Jennifer S. Labus
Eduardo P. Vianna
Emeran A. Mayer
Mark S. Cohen

Machine learning methods have been applied to classifying fMRI scans by studying locations in the brain that exhibit temporal intensity variation between groups, frequently reporting classification accuracy of 90% or better. Although empirical results are quite favorable, one might doubt the ability of classification methods to withstand changes in task ordering and the reproducibility of activation patterns over runs, and question how much of the classification machines' power is due to artifactual noise versus genuine neurological signal. To examine the true strength and power of machine learning classifiers we create and then deconstruct a classifier to examine its sensitivity to physiological noise, task reordering, and across-scan classification ability. The models are trained and tested both within and across runs to assess stability and reproducibility across conditions. We demonstrate the use of independent components analysis for both feature extraction and artifact removal and show that removal of such artifacts can reduce predictive accuracy even when data has been cleaned in the preprocessing stages. We demonstrate how mistakes in the feature selection process can cause the cross-validation error seen in publication to be a biased estimate of the testing error seen in practice and measure this bias by purposefully making flawed models. We discuss other ways to introduce bias and the statistical assumptions lying behind the data and model themselves. Finally we discuss the complications in drawing inference from the smaller sample sizes typically seen in fMRI studies, the effects of small or unbalanced samples on the Type 1 and Type 2 error rates, and how publication bias can give a false confidence of the power of such methods. Collectively this work identifies challenges specific to fMRI classification and methods affecting the stability of models.

Details DOI

YNIMG Journal 2011 Journal Article

Impact of mindfulness-based stress reduction training on intrinsic brain connectivity

Lisa A. Kilpatrick
Brandall Y. Suyenobu
Suzanne R. Smith
Joshua A. Bueller
Trudy Goodman
J. David Creswell
Kirsten Tillisch
Emeran A. Mayer

The beneficial effects of mindful awareness and mindfulness meditation training on physical and psychological health are thought to be mediated in part through changes in underlying brain processes. Functional connectivity MRI (fcMRI) allows identification of functional networks in the brain. It has been used to examine state-dependent activity and is well suited for studying states such as meditation. We applied fcMRI to determine if Mindfulness-Based Stress Reduction (MBSR) training is effective in altering intrinsic connectivity networks (ICNs). Healthy women were randomly assigned to participate in an 8-week Mindfulness-Based Stress Reduction (MBSR) training course or an 8-week waiting period. After 8weeks, fMRI data (1. 5T) was acquired while subjects rested with eyes closed, with the instruction to pay attention to the sounds of the scanner environment. Group independent component analysis was performed to investigate training-related changes in functional connectivity. Significant MBSR-related differences in functional connectivity were found mainly in auditory/salience and medial visual networks. Relative to findings in the control group, MBSR subjects showed (1) increased functional connectivity within auditory and visual networks, (2) increased functional connectivity between auditory cortex and areas associated with attentional and self-referential processes, (3) stronger anticorrelation between auditory and visual cortex, and (4) stronger anticorrelation between visual cortex and areas associated with attentional and self-referential processes. These findings suggest that 8weeks of mindfulness meditation training alters intrinsic functional connectivity in ways that may reflect a more consistent attentional focus, enhanced sensory processing, and reflective awareness of sensory experience.

Details DOI

YNIMG Journal 2009 Journal Article

Brain networks underlying perceptual habituation to repeated aversive visceral stimuli in patients with irritable bowel syndrome

Jennifer S. Labus
Bruce D. Naliboff
Steve M. Berman
Brandall Suyenobu
Eduardo P. Vianna
Kirsten Tillisch
Emeran A. Mayer

Patients with irritable bowel syndrome (IBS) show decreased discomfort and pain thresholds to visceral stimuli, as well hypervigilance to gastrointestinal sensations, symptoms, and the context in which these visceral sensations and symptoms occur. Previous research demonstrated normalization of visceral hypersensitivity following repeated exposure to experimental rectal stimuli over a 12-month period that was associated with reduction in cortical regions functionally associated with attention and arousal. Building upon these functional analyses, multivariate functional and effective connectivity analyses were applied to [15O] water positron emission tomography (PET) data from 12 IBS patients (male=4) participating in a PET study before and after 4 visceral sensory testing sessions involving rectal balloon distensions over a 1-year period. First, behavioral partial least squares was applied to test for networks related to reduced subjective ratings observed following repeated application of an aversive rectal stimulus. Next, path analysis within a structural equation modeling framework tested the hypothesis that perceptual habituation to the repeated visceral stimuli resulted in part from the reduced connectivity within a selective attention to threat network over time. Two independent, perception-related networks comprised of interoceptive, attentional and arousal regions were engaged differentially during expectation and distension. In addition, changes in the effective connectivity of an attentional network as well as modulatory amygdala influence suggested that perceptual habituation associated with repeated stimulus delivery results both in an increase in top-down modulation of attentional circuits, as well as in a reduction of amygdala-related interference with attentional mechanisms.

Details DOI