Edited by: Andreas Stengel, Charité – Universitätsmedizin Berlin, Germany
Reviewed by: Peng Liu, Xidian University, China; Brunno Machado De Campos, Campinas State University, Brazil
*Correspondence: Katarzyna Skrobisz,
This article was submitted to Psychosomatic Medicine, a section of the journal Frontiers in Psychiatry
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The study focuses on evaluation of the Default Mode Network (DMN) activity in functional magnetic resonance imaging (fMRI) in resting state in patients with functional dyspepsia (FD) and irritable bowel syndrome (IBS), Crohn's disease and colitis ulcerosa (IBD) in comparison to healthy volunteers. We assume that etiology of both functional and non-specific inflammatory bowel diseases is correlated with disrupted structure of axonal connections. We would like to identify the network of neuronal connections responsible for presentation of symptoms in these diseases. 56 patients (functional dyspepsia, 18; Crohn's disease and colitis ulcerosa, 18; irritable bowel syndrome, 20) and 18 healthy volunteers underwent examination in MRI of the brain with assessment of brain morphology and central nervous system activity in functional imaging in resting state performed in 3T scanner. Compared to healthy controls' DMN in patients with non-specific digestive tract diseases comprised additional areas in superior frontal gyrus of left hemisphere, in left cingulum and in the left supplementary motor area. Discovered differences in the DMNs can be interpreted as altered processing of homeostatic stimuli. Our study group involved patients suffering from both functional and non-specific inflammatory bowel diseases. Nevertheless a spectrum of changes in the study group (superior frontal gyrus of the left hemisphere, in the left cingulum and in the left supplementary motor area) we were able to find common features, differentiating the whole study group from the healthy controls.
Functional disorders of the gastrointestinal tract (FGIDs) may explain from 25% up to 40% gastrointestinal tract (GI) derived symptoms in young adults (
Functional disorders of the gastrointestinal tract are diagnosed after exclusion of so called alert symptoms and structural diseases on bases of Rome III Criteria (
A number of studies contributed to the knowledge of neural underpinning of patients' sensations in gastric diseases and show two major findings. Abnormal interhemispheric interactions have been encountered in patients with FGIDs (
There is a limited number of studies which examined the role of DMN in inflammatory bowel diseases, among others, Liu et al. (
We decided to focus on the default mode network as the one most activated during processing the self-specific stimuli (
All patients gave written consent to participate in the study. Study has been approved by The Bioethical Committee of The Military Medical Council (Street Koszykowa 78, 00-909 Warsaw) (document 107/12 dated 22.06.2012).
Study group included patients with functional dyspepsia (FD), irritable bowel syndrome (IBS), and with non-specific inflammatory bowel diseases (IBDs) (Crohn's disease and ulcerative colitis)—FD, 18 (K, 13; M, 5; age range, 20–40 years; mean age, 33.28 years); IBS, 20 (K, 14; M, 6; age range, 23–44 years; mean age, 33.1 years); IBD, 18 (K, 10; M, 8; age range, 21–43 years; mean age, 26.83 years).
Patients suffering from FGIDs have been enrolled according to Rome III Criteria summarized in
Summary of Rome III Criteria on FGIDs.
Diagnostic criteria* | |
---|---|
1. Functional dyspepsia | Must include one or more of the following:
–Bothersome postprandial fullness, –Early satiation, –Epigastric pain and/or burning. |
1a. Epigastric pain syndrome (EPS) | Must include all of the following:
–Pain or burning localized to the epigastrium of at least moderate severity, at least once a week, –Intermittent character of pain/burning, –Pain/burning should not be generalized or localized to other abdominal or chest regions, –Pain/burning should not be relieved by defecation or passage of flatus. |
1b. Postprandial distress syndrome (PDS) | Must include one or both of the following:
–Bothersome postprandial fullness, occurring after ordinary-sized meals, at least several times a week, –Early satiation that prevents completing a regular meal, at least several times a week |
2. Irritable bowel syndrome (IBS) | Recurrent abdominal pain or discomfort** at least 3 days/month in the last 3 months associated with two or more of the following:
–Improvement with defecation, –Onset associated with a change in frequency of stool, –Onset associated with a change in form (appearance) of stool. |
*Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis.
**“Discomfort” stands for uncomfortable sensation, not described as pain.
The control group of 18 healthy volunteers consisted of nine women and nine men (age range, 24–47 years; mean age, 34.27 years).
The exclusion criteria comprised lack of fulfillment of Rome III Criteria for FGIDs, head trauma in anamnesis, severe additional diseases, depression, mental disorders, pregnancy, and/or lactation and well established contraindications to MRI.
Patients from both study and control group underwent a GAST questionnaire developed by one of the authors (GP). GAST questionnaire focuses on type of functional GI disease, anamnesis with emphasis on history of symptoms and concomitant diseases as well as sociodemographic data.
All patients subjected to research have been thoroughly introduced to its principles and given detailed information on examination procedures, especially on MR, also in order to reduce stress levels and avoid potential panic or claustrophobic attacks.
Functional and anatomical data sets were acquired in a 3T Achieva TX Scanner (Philips Healthcare, Best, the Netherlands) with the use of the eight-channel head coil. To evaluate brain morphology and exclude subjects with brain pathology standard T1 and T2 sequences were applied. No contrast agent was administered. T2* Gradient Echo-Planar Imaging (FFE-EPI: TR, 1,500 ms; TE, 27 ms; flip angle, 60°; matrix, 80 × 80; slice thickness, 3 mm with 0-mm gap, 210 volumes in series; TA 5 min 15 s; FOV, 240 mm × 240 mm), and 3D high-resolution T1 sequence (T1-TFE: TR, 7.44 ms; TE, 3.6 ms; slice thickness, 1 mm; matrix, 260 × 240; FOV, 260 mm × 240 mm) were applied for functional imaging and anatomical reference, respectively. During the resting state, acquisition subjects were asked to consciously attend to the fixation point presented in the center of the visual field and not to think of anything specific. The fixation point was presented
Data analyses were performed using the SPM12 toolbox (Wellcome Department of Imaging Neuroscience, London, UK,
In group resting state data analysis, the Group ICA of fMRI Toolbox [GIFT v4.0, icatb.sourceforge.net] (
principal component analysis (PCA), which reduced each of the subject's fMRI data to predefined number of components;
ICA algorithm (Infomax) application;
back reconstruction for each individual subject's data, resulting in time courses and spatial maps of components.
For each of the groups 20 components were resembled. The Default Mode Network was identified with the use of spatial matching to the GIFT's binary DMN template. All independent components were converted to z-maps (
The automated matching of the Default Mode Network resulted in a component replicable amongst groups as shown in
The two-sample t-test comparisons revealed significant effect only when contrasting the IBD group with the CON group. The IBD group showed auxiliary area of DMN connectivity in one cluster in the superior frontal gyrus of the left hemisphere (peak coordinates = −18, 57, 30, Z = 3.64, k = 28, corrected cluster pFDR = 0.030). The cluster is visualized in red in
When comparing all the patients and the controls, two clusters reached significance. First one located in the left cingulum (peak coordinates = 3, −15, 39; Z = 4.17; k = 23; corrected cluster pFDR = 0.004), second one located in the left supplementary motor area (peak coordinates 0 15 54, Z=3.77, k=14, corrected cluster pFDR=0.021). In both cases the DMN of the patients showed increased connectivity in those areas. The clusters are visualized in yellow in
When restricting the comparison to functional gastroenterological diseases only—one cluster reached significance. It was located in left supplementary motor area (peak coordinates = −3, 12, 57; Z = 3.87; k = 14; cluster corrected pFDR = 0.043) and roughly overlaps with one of the clusters of “the gastroenterological diseases vs control” reported in previous paragraph. The direction of the alternation remained unchanged (the DMN of the functional gastrointestinal patients was increased in the area as compared with the controls). The cluster is visualized in green in
All results are summarized in
Summary results of the intergroup comparisons.
X | y | z | No. of voxels | T-test/F-test | Z | Cluster corrected pFDR | ||
---|---|---|---|---|---|---|---|---|
IBD vs CON | LH superior frontal gyrus | −18 | 57 | 30 | 28 | 3.86 | 3.64 | .030 |
ALL vs CON | LH cingulum | 3 | −15 | 39 | 23 | 10.18 | 4.17 | .004 |
LH supplementary motor area | 0 | 15 | 54 | 14 | 8.51 | 3.77 | .021 | |
FD and IBS vs CON | LH supplementary motor area | −3 | 12 | 57 | 14 | 11.54 | 3.87 | .043 |
Anatomical labels according to Automated Anatomical Labeling tool. All reported clusters are significant at cluster p < .05 threshold with topological False Discovery Rate small volume correction.
CON, the control group; FD, the functional dyspepsia group; IBS, the irritable bowel syndrome group; IBD, the inflammatory bowel disease group; ALL, all diseases (FD, IBS and IBD); x, y, z, peak coordinates in MNI space; Z, Z-score.
Functional diseases of gastrointestinal tract, frequently encountered worldwide, have a negative influence on the quality of life and cause significant costs in health care systems. Diagnostic criteria are based on Rome III Criteria (
Patients suffering from FIGDs more often present with emotional distress and lower stress tolerance. Patient's constitution and response to stress may influence biological processes within the central nervous system and through autonomic nervous system trigger somatic reactions from digestive tract, leading to decrease in quality of life (
Since 1937 when Papez first described neural pathway in the brain thought to be involved in the cortical control of emotion, the limbic system has been under scrutiny. At first brain studies have been mainly based on observation of its response to damage or stimulation. New possibilities emerged with introduction and development of imaging techniques, such as single-photon emission computed tomography (SPECT), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI). Ample research has been conducted in order to investigate neuroanatomy and recognize which areas of the brain activate while different emotional states are being induced in healthy individuals. Phan et al. (
Our results showed that DMNs in study and the control group differed in left superior frontal gyrus, left cingulum and in the left supplementary motor area. Number of studies focused on functioning of the brain in FGIDs (
Despite that the Default Mode Network in gastric diseases is not yet well examined, there are multiple research explaining role of brain regions, which could give ideas of psychological functioning of this group of patients. Results of our study showed differences in three regions i.e. superior frontal gyrus of the left hemisphere, left cingulum, left supplementary motor area (see
Different DMN activation of superior frontal gyrus (SFG) was found in IBD group comparing to control. Functional brain imaging studies focused on chronic pain emphasis that chronic pain conditions involve mostly medial prefrontal cortical areas as well as subcortical limbic regions. Apkarian et al. (
Last DMN with statistically relevant differences in region of supplementary motor area was noticed in comparison of functional gastric diseases (functional dyspepsia group, irritable bowel syndrome) and control groups. This brain area is considered to play role in facilitating spontaneous motor responses to auditory stimuli, and in supporting a flexible engagement of sensorimotor processes to enable auditory perception and imaginary (
The psychological description of the patients corresponds with this explanation. Patients are characterized as anxious and depressive; also, the comorbidity of the FGIDs and the psychiatric disorders regard mostly the mood and anxiety disorders (
In conclusion, it needs to be stressed that our study group involved patients suffering from both functional and non-specific inflammatory bowel diseases. Nevertheless, with a spectrum of changes in the study group (superior frontal gyrus of the left hemisphere, in the left cingulum and in the left supplementary motor area), we were able to find common features, differentiating the whole study group from the healthy controls.
The datasets generated for this study are available on request to the corresponding author.
The studies involving human participants were reviewed and approved by The Bioethical Committee of The Military Medical Council. The patients/participants provided their written informed consent to participate in this study.
KS: planning and conducting the study, collecting data, drafting the manuscript. GP: collecting the patients and conducting the study. PN and AS: analysis and interpretation of data. KM: drafting the article it critically for important intellectual content. GR: conception and design. ES: final approval of the version to be published.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
We would like to thank Professor Edyta Szurowska for inspiration and scientific guidance.