• brain
• chronic primary pain
• magnetic resonance imaging (mri)
• diffusion mri
• white matter

• Humans
• Chronic Pain/diagnostic imaging
• Chronic Pain/physiopathology
• Diffusion Magnetic Resonance Imaging/methods
• Brain/diagnostic imaging
• Brain/physiopathology
• White Matter/diagnostic imaging
• White Matter/pathology

• Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Fonds de Recherche du Québec - SantéPascal Tétreault, Arthritis Society; Pascal Tétreault, Fonds de Recherche du Québec - Santé; Guillaume Léonard, Unifying Neuroscience and Artificial Intelligence - Québec

• Five-factor model
• Functional somatic disorders
• Functional somatic syndromes
• Meta-analysis
• Personality

• Humans
• Personality/physiology
• Somatoform Disorders/physiopathology
• Somatoform Disorders/psychology
• Neuroticism

• FA
• IBD
• IBS
• brain connectivity
• fractional anisotropy
• irritable bowel syndrome

• chronic pain
• diffusion-weighted imaging
• white matter
• neurite orientation dispersion and density imaging
• pediatric pain
• pain catastrophizing

• Humans
• White Matter/diagnostic imaging
• White Matter/pathology
• Male
• Female
• Chronic Pain/diagnostic imaging
• Chronic Pain/pathology
• Chronic Pain/psychology
• Adolescent
• Neurites/pathology
• Catastrophization/psychology
• Child
• Diffusion Magnetic Resonance Imaging
• Diffusion Tensor Imaging
• Brain/pathology
• Brain/diagnostic imaging
• Young Adult

• R01 HD083270 NICHD NIH HHS
• R01HD083270 Eunice Kennedy Shriver National Institute of Child Health and Human Development

• DTI
• acupuncture
• brain function
• irritable bowel syndrome
• white matter fiber bundles

• diagnosis
• gastrointestinal tract
• irritable bowel syndrome
• pituitary
• volume calculation

• burning mouth syndrome
• diffusion tensor imaging
• gray matter-based spatial statistics
• neurite orientation dispersion and density imaging
• tract-based spatial statistics

• Humans
• Diffusion Tensor Imaging/methods
• Gray Matter/diagnostic imaging
• Brain/diagnostic imaging
• Neurites
• Burning Mouth Syndrome/diagnostic imaging
• Starch Synthase
• Diffusion Magnetic Resonance Imaging
• White Matter/diagnostic imaging

• Mendelian randomization
• causal effect
• irritable bowel syndrome
• mediation analysis
• psychiatric disorders

• National Natural Science Foundation of China
• National Key Research and Development Program of China

• Biological sciences
• Cognitive neuroscience
• Neuroscience

Chronic inflammatory bowel disorders (IBD) are idiopathic diseases associated with altered intestinal permeability, which in turn causes an exaggerated immune response to enteric antigens in a genetically susceptible host. A rise in psych cognitive disorders, such as anxiety and depression, has been observed in IBD patients. We here report investigations on a model of chemically induced experimental colitis by oral administration of sodium dextran sulfate (DSS) in C57BL/6 mice. We investigate, in vivo, the crosstalk between the intestine and the brain, evaluating the consequences of intestinal inflammation on neuroinflammation and hippocampal adult neurogenesis. By using different DSS administration strategies, we are able to induce acute or chronic colitis, simulating clinical characteristics observed in IBD patients. Body weight loss, colon shortening, alterations of the intestinal mucosa and fecal metabolic changes in amino acids-, lipid- and thiamine-related pathways are observed in colitis. The activation of inflammatory processes in the colon is confirmed by macrophage infiltration and increased expression of the proinflammatory cytokine and oxidative stress marker (Il-6 and iNOS). Interestingly, in the hippocampus of acutely DSS-treated mice, we report the upregulation of inflammatory-related genes (Il-6, Il-1β, S-100, Tgf-β and Smad-3), together with microgliosis. Chronic DSS treatment also resulted in neuroinflammation in the hippocampus, indicated by astrocyte activation. Evaluation of stage-specific neurogenesis markers reveals deficits in the dentate gyrus after acute and chronic DSS treatments, indicative of defective adult hippocampal neurogenesis. Finally, based on a possible causal relationship between gut-related inflammation and brain cancer, we investigate the impact of DSS-induced colitis on oncogenesis, using the Ptch1^+/−/C57BL/6 mice, a well-established medulloblastoma (MB) mouse model, finding no differences in MB development between untreated and DSS-treated mice. In conclusion, in our experimental model, the intestinal inflammation associated with acute and chronic colitis markedly influences brain homeostasis, impairing hippocampal neurogenesis but not MB oncogenesis.

• Amino Acids
• Animals
• Brain Neoplasms
• Brain-Gut Axis
• Carcinogenesis
• Colitis/pathology
• Colon/pathology
• Cytokines/metabolism
• Dextran Sulfate/toxicity
• Disease Models, Animal
• Hippocampus/metabolism
• Inflammation
• Inflammatory Bowel Diseases
• Interleukin-6/metabolism
• Lipids/adverse effects
• Mice
• Mice, Inbred C57BL
• Neurogenesis
• Sulfates
• Thiamine
• Transforming Growth Factor beta/metabolism

• Bias, Top-down
• Diffusion MRI
• Expectation
• Functional MRI
• Functional connectivity
• Mindfulness
• Pain catastrophizing
• Pain, perception
• Prediction
• System segregation
• Threat

• Brain/diagnostic imaging
• Brain Mapping
• Humans
• Magnetic Resonance Imaging
• Nerve Net/diagnostic imaging
• Pain/diagnostic imaging
• Pain Perception

• R01 AT006344 NCCIH NIH HHS
• R21 AT003673 NCCIH NIH HHS
• CIHR

• diffusion tensor imaging
• functional constipation
• track-based spatial statistics
• white matter

• engram
• inflammation
• insular cortex
• memory
• neurons
• psychosomatic

Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disease characterized by recurrent abdominal pain and bowel dysfunction. However, the majority of previous neuroimaging studies focus on brain structure and connections but seldom on the inter-hemispheric connectivity or structural asymmetry. This study uses multi-modal imaging to investigate the abnormal changes across the 2 cerebral hemispheres in patients with IBS.

Structural MRI, resting-state functional MRI, and diffusion tensor imaging were acquired from 34 patients with IBS and 33 healthy controls. The voxel-mirrored homotopic connectivity, fractional anisotropy, fiber length, fiber number, and asymmetry index were calculated and assessed for group differences. In addition, we assessed their relevance for the severity of IBS.

Compared with healthy controls, the inter-hemispheric functional connectivity of patients with IBS showed higher levels in bilateral superior occipital gyrus, middle occipital gyrus, precuneus, posterior cingulate gyrus, and angular gyrus, but lower in supplementary motor area. The statistical results showed no significant difference in inter-hemispheric anatomical connections and structural asymmetry, however negative correlations between inter-hemispheric connectivity and the severity of IBS were found in some regions with significant difference.

The functional connections between cerebral hemispheres were more susceptible to IBS than anatomical connections, and brain structure is relatively stable. Besides, the brain areas affected by IBS were concentrated in default mode network and sensorimotor network.

• Brain
• Default mode network
• Irritable bowel syndrome
• Neuroimaging

• BDNF
• NT-3
• behavior
• refined grains
• whole grains

• functional connectome
• functional dyspepsia
• graph theory
• resting-state fMRI
• white matter

• Anxiety disorder
• Depressive disorder
• Irritable bowel syndromes
• Personality

• Anxiety/complications
• Anxiety/epidemiology
• Cross-Sectional Studies
• Depression/epidemiology
• Gastrointestinal Diseases/complications
• Gastrointestinal Diseases/epidemiology
• Humans
• Psychiatric Status Rating Scales
• Severity of Illness Index
• Sweden
• Young Adult

• Märta och Nicke Nasvells fund
• Ekhaga Foundation
• Fredrik och Ingrid Thurings Stiftelse
• Stiftelsen Söderström Königska Sjukhemmet
• Svenska Läkaresällskapet
• The Medical Training and Research Agreement from Uppsala University

• diffusion kurtosis imaging
• functional dyspepsia
• functional gastrointestinal disorders
• irritable bowel syndrome

• PEP
• RSA
• autonomic nervous system
• baevsky stress index
• colonic motility
• high-amplitude pressure waves
• parasympathetic
• sympathetic

• brain/gut interaction
• functional bowel disorder
• irritable bowel syndrome
• magnetic resonance imaging

Differentiating subtypes of chronic pain still remains a challenge—both from a subjective and objective point of view. Personalized medicine is the current goal of modern medical care and is limited by the subjective nature of patient self-reporting of symptoms and behavioral evaluation. Physiology-focused techniques such as genome and epigenetic analyses inform the delineation of pain groups; however, except under rare circumstances, they have diluted effects that again, share a common reliance on behavioral evaluation. The application of structural neuroimaging towards distinguishing pain subtypes is a growing field and may inform pain-group classification through the analysis of brain regions showing hypertrophic and atrophic changes in the presence of pain. Analytical techniques such as machine-learning classifiers have the capacity to process large volumes of data and delineate diagnostically relevant information from neuroimaging analysis. The issue of defining a “brain type” is an emerging field aimed at interpreting observed brain changes and delineating their clinical identity/significance. In this review, 2 chronic pain conditions (migraine and irritable bowel syndrome) with similar clinical phenotypes are compared in terms of their structural neuroimaging findings. Independent investigations are compared with findings from application of machine-learning algorithms. Findings are discussed in terms of differentiating patient subgroups using neuroimaging data in patients with chronic pain and how they may be applied towards defining a personalized pain signature that helps segregate patient subgroups (eg, migraine with and without aura, with or without nausea; irritable bowel syndrome vs other functional gastrointestinal disorders).

• Chronic pain
• IBS
• Machine learning
• Migraine

Objectives: Pain catastrophizing is reliably associated with pain reports during experimental pain in healthy, pain-free subjects and in people with chronic pain. It also correlates with self-reports of clinical pain intensity/severity in a variety of disorders characterized by chronic pain in adults, adolescents and children. However, processes, through which it exerts its effects are yet unclear. In this paper, our primary aim was to synthesize neuroimaging research to open a window to possible mechanisms underlying pain catastrophizing in both chronic pain patients and healthy controls. We also aimed to compare whether the neural correlates of pain catastrophizing are similar in these two groups.

Methods: PubMed and the Web of Science were searched for magnetic resonance imaging (MRI) studies that explored neural correlates of pain catastrophizing.

Results: Twenty articles met the inclusion criteria. The results of our review show a connection between pain catastrophizing and brain areas tightly connected to pain perception (including the somatosensory cortices, anterior insula, anterior cingulate cortex and thalamus) and/or modulation (eg, the dorsolateral prefrontal cortex). Our results also highlight that these processes - in relation to pain catastrophizing - are more pronounced in chronic pain patients, suggesting that structural and functional brain alterations (and perhaps mechanisms) related to pain catastrophizing may depend on prior and/or relatively stable/constant pain experience. However, we also found methodological issues and differences that could lead to divergent results.

Discussion: Based on our results, pain catastrophizing might be related to salience detection, pain processing, and top-down attentional processes. More research is recommended to explore neural changes to specific types of catastrophizing thoughts (eg, experimentally induced and/or state). Furthermore, we provide ideas regarding pain catastrophizing studies in the future for a more standardized approach.

• DLPFC
• anterior insula
• chronic pain
• neuroimaging
• pain catastrophizing

• depression
• human
• irritable bowel syndrome
• melatonin
• mental health
• bmi = body mass index
• ec = enterochromaffin
• gi = gastrointestinal
• gsrs = gastrointestinal symptoms rating scale
• ibs = irritable bowel syndrome
• iqr = interquartile range
• madrs-s = montgomery åsberg depression rating scale–self-assessment
• oc = oral contraceptives
• or = odds ratio
• snri = serotonin-noradrenaline reuptake inhibitors
• ssri = selective serotonin reuptake inhibitors

• Dyspepsia
• Homeostasis
• Irritable bowel syndrome
• Neuroimaging
• Visceral pain

• G0300195 Medical Research Council
• G0600965 Medical Research Council

• diffusion tensor imaging
• irritable bowel syndrome
• microstructural changes
• psychological stress
• voxel‐based morphometry

• Diffusion tensor imaging
• Irritable bowel syndrome
• Tract-based spatial statistics

• DTI
• IBS
• abdominal pain
• functional GI disorders
• pediatrics

• MRI
• brain
• catastrophizing
• cortex
• cortical thickness analysis
• diverticular disease
• gray matter
• magnetic resonance imaging
• pain
• voxel-based morphometry

• Provoked vestibulodynia
• brain
• chronic pain
• diffusion tensor imaging
• irritable bowel syndrome

• Brain
• Diffusion tensor imaging
• Irritable bowel syndrome

• central sensitization
• chronic idiopathic neck pain
• chronic whiplash-associated disorders
• cognitive performance
• cortical thickness
• magnetic resonance imaging
• white matter

• diffusion tensor imaging
• fecal incontinence
• magnetic resonance imaging
• neuroplasticity
• reorganization

• Chronic pain
• Co-alteration network
• Network analysis
• Neuronal alterations
• Pathoconnectomics
• Voxel-based morphometry

• Brain/diagnostic imaging
• Brain/physiopathology
• Chronic Pain/diagnostic imaging
• Chronic Pain/physiopathology
• Humans
• Magnetic Resonance Imaging
• Nerve Net/diagnostic imaging
• Nerve Net/physiopathology
• Neuronal Plasticity/physiology

• R01 MH074457 NIMH NIH HHS
• R56 MH074457 NIMH NIH HHS

Trigeminal neuralgia (TN) is a severe chronic neuropathic facial pain disorder. Affect-related behavioral and structural brain changes have been noted across chronic pain disorders, but have not been well-studied in TN. We examined the potential impact of TN (37 patients: 23 with right-sided TN, 14 with left-sided TN), compared to age- and sex-matched healthy controls, on three major white matter tracts responsible for carrying affect-related signals—i.e., cingulum, fornix, and medial forebrain bundle. Diffusion magnetic resonance imaging (dMRI), deterministic multi-tensor tractography for tract modeling, and a model-driven region-of-interest approach was used. We also used volumetric gray matter analysis on key targets of these pathways (i.e., hippocampus, cingulate cortex subregions, nucleus accumbens, and ventral diencephalon). Hypotheses included: (1) successful modeling of tracts; (2) altered white matter microstructure of the cingulum and medial forebrain bundle (via changes in dMRI metrics such as fractional anisotropy, and mean, axial, and radial diffusivities) compared to controls; (3) no alterations in the control region of the fornix; (4) corresponding decreases in gray matter volumes. Results showed (1) all 325 tracts were successfully modeled, although 11 were partially complete; (2) The cingulum and medial forebrain bundle (MFB) were altered in those with TN, with dMRI metric changes in the middle (p = 0.001) and posterior cingulum (p < 0.0001), and the MFB near the ventral tegmental area (MFB-VTA) (p = 0.001). The posterior cingulum and MFB-VTA also showed unilateral differences between right- and left-sided TN patients; (3) No differences were noted at any fornix subdivision; (4) decreased volumes were noted for the hippocampus, posterior cingulate, nucleus accumbens, and ventral diencephalon. Together, these results support the notion of selectively altered affective circuits in patients with TN, which may be related to the experience of negative affect and the increased comorbidity of mood and anxiety disorders in this population.

• DTI
• MRI
• chronic neuropathic pain
• dMRI
• diffusion magnetic resonance
• emotion
• gray matter
• structural neuroimaging

• central nervous system
• chronic pain
• connectivity
• diffusion tensor imaging
• motor skills

Although the precise pathophysiology of irritable bowel syndrome (IBS) remains unknown, it is generally considered to be a disorder of the brain-gut axis, representing the disruption of communication between the brain and the digestive system. The present review describes advances in understanding the pathophysiology and experimental approaches in studying IBS, as well as providing an update of the therapies targeting brain-gut axis in the treatment of the disease.

Causal factors of IBS are reviewed. Following this, the preclinical experimental models of IBS will be introduced. Besides, both current and future therapeutic approaches of IBS will be discussed.

When signal of the brain-gut axis becomes misinterpreted, it may lead to dysregulation of both central and enteric nervous systems, altered intestinal motility, increased visceral sensitivity and consequently contributing to the development of IBS. Interference of the brain-gut axis can be modulated by various psychological and environmental factors. Although there is no existing animal experiment that can represent this complex multifactorial disease, these in vivo models are clinically relevant readouts of gastrointestinal functions being essential to the identification of effective treatments of IBS symptoms as well as their molecular targets. Understanding the brain-gut axis is essential in developing the effective therapy for IBS. Therapies include improvement of GI motor functions, relief of visceral hypersensitivity and pain, attenuation of autonomic dysfunctions and suppression of mucosal immune activation.

Target-oriented therapies that provide symptomatic, psychological and physiological benefits could surely help to improve the quality of life of IBS patients.

• Abdominal pain
• Antidepressants
• Brain–gut axis
• Functional gastrointestinal disorders
• Treatment

• Abdominal Pain/drug therapy
• Abdominal Pain/metabolism
• Abdominal Pain/physiopathology
• Analgesics/therapeutic use
• Animals
• Brain/drug effects
• Brain/metabolism
• Brain/physiopathology
• Chronic Pain/drug therapy
• Chronic Pain/metabolism
• Chronic Pain/physiopathology
• Enteric Nervous System/drug effects
• Enteric Nervous System/metabolism
• Enteric Nervous System/physiopathology
• Gastrointestinal Tract/innervation
• Humans
• Pain Perception/drug effects
• Pain Threshold/drug effects
• Signal Transduction/drug effects