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Larsson, Mats
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Publications (7 of 7) Show all publications
Simon, R., Engström, M., Icenhour, A., Larsson, M., Ström, M., Tillisch, K., . . . Walter, S. (2019). On Functional Connectivity and Symptom Relief After Gut-directed Hypnotherapy in Irritable Bowel Syndrome: A Preliminary Study [Letter to the editor]. JOURNAL OF NEUROGASTROENTEROLOGY AND MOTILITY, 25(3), 478-479
Open this publication in new window or tab >>On Functional Connectivity and Symptom Relief After Gut-directed Hypnotherapy in Irritable Bowel Syndrome: A Preliminary Study
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2019 (English)In: JOURNAL OF NEUROGASTROENTEROLOGY AND MOTILITY, ISSN 2093-0879, Vol. 25, no 3, p. 478-479Article in journal, Letter (Other academic) Published
Abstract [en]

n/a

Place, publisher, year, edition, pages
Seoul, Korea: Korean Society of Neurogastroenterology and Motility, 2019
National Category
Clinical Medicine Basic Medicine
Identifiers
urn:nbn:se:liu:diva-159267 (URN)10.5056/jnm19069 (DOI)000476655500017 ()31327225 (PubMedID)
Note

Funding Agencies|Region Ostergotland; Bengt-Ihre Fond

Available from: 2019-08-07 Created: 2019-08-07 Last updated: 2019-08-15Bibliographically approved
Lowén, M. B. O., Mayer, E., Tillisch, K., Labus, J., Naliboff, B., Lundberg, P., . . . Walter, S. (2015). Deficient habituation to repeated rectal distensions in irritable bowel syndrome patients with visceral hypersensitivity. Neurogastroenterology and Motility, 27(5), 646-655
Open this publication in new window or tab >>Deficient habituation to repeated rectal distensions in irritable bowel syndrome patients with visceral hypersensitivity
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2015 (English)In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 27, no 5, p. 646-655Article in journal (Refereed) Published
Abstract [en]

Background Irritable bowel syndrome (IBS) patients show evidence of altered central processing of visceral signals. One of the proposed alterations in sensory processing is an altered engagement of endogenous pain modulation mechanisms. The aim was to test the hypothesis that IBS patients with (IBS-S) and without visceral hypersensitivity (IBS-N) differ in their ability to engage endogenous pain modulation mechanism during habituation to repeated visceral stimuli.

Methods Brain blood oxygen level dependent (BOLD) response was measured during repeated rectal distension and its anticipation in 33 IBS patients with and without visceral hypersensitivity and 18 healthy controls (HCs). BOLD response to early and late phase of the distension series was compared within and between groups.

Key Results While BOLD response was similar during the early phase of the experiment, IBS-S showed greater BOLD response than IBS-N and HCs during the late phase of the distension series. IBS-S showed increasing BOLD response both to the anticipation and delivery of low intensity rectal distensions in brain regions including insula, anterior and mid cingulate cortex. IBS-N showed decreasing BOLD response to repeated rectal distensions in brain regions including insula, prefrontal cortex and amygdala.

Conclusions & Inferences These findings are consistent with compromised ability of IBS-S to respond to repeated delivery of rectal stimuli, both in terms of sensitization of sensory pathways and habituation of emotional arousal. The fact that both IBS subgroups met Rome criteria, and did not differ in terms of reported symptom severity demonstrates that similar symptom patterns can result from different underlying neurobiological mechanisms.

Keywords
irritable bowel syndrome, brain-gut interaction, fMRI, visceral sensitivity
National Category
Gastroenterology and Hepatology Neurosciences
Identifiers
urn:nbn:se:liu:diva-122143 (URN)10.1111/nmo.12537 (DOI)000364742000007 ()25777251 (PubMedID)
Note

Funding agencies: County Council of Ostergotland, Sweden; National Institute of Health [DK 64531]

Available from: 2015-10-20 Created: 2015-10-20 Last updated: 2018-01-11Bibliographically approved
Lowén, M. (2015). Irritable Bowel Syndrome: Studies of central pathophysiological mechanisms and effects of treatment. (Doctoral dissertation). Linköping: Linköping University Electronic Press
Open this publication in new window or tab >>Irritable Bowel Syndrome: Studies of central pathophysiological mechanisms and effects of treatment
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background and aims

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by abdominal pain and altered bowel habits. The societal costs of the disorder are significant, as are its negative effects on quality of life. Medical treatment options are limited, but psychological treatments such as hypnotherapy have proven to be effective. Important pathophysiological mechanisms include disturbances in brain processing of visceral sensation and expectation of visceral sensation. Increased sensation of stimuli (hypersensitivity) is present in a subset of IBS patients to distensions in the lower part of the gastrointestinal tract, indicating a probable important pathophysiological mechanism in IBS. The overall aim of the thesis was to further study the central pathophysiological mechanisms involved in IBS. Specifically, we aimed to identify differences in brain response to standardized repeated rectal distensions and expectation of these stimuli between IBS patients (with or without perceptual rectal hypersensitivity), and healthy controls. Furthermore, we aimed to investigate IBS patients´ brain responses to standardized rectal distensions and expectation of these stimuli after either a successful course hypnotherapy or educational intervention.

Methods

Functional magnetic resonance imaging (fMRI) data were acquired and analyzed from 15 IBS patients with visceral hypersensitivity, and 18 IBS patients with normal visceral sensitivity (papers I and II). In paper III, fMRI data were analyzed from IBS patients who reported significant symptom reduction after either a course of hypnotherapy, or an educational intervention. FMRI data from IBS patients and healthy controls were also compared.

Results

The findings reported in papers I and II suggest, that the differences in brain response between IBS patients with and without rectal hypersensitivity, can be explained by changes in brain response during the course of the experiment. Even though the brain responses were similar between groups during the early phase of the experiment, they became substantially different during the late phase. The IBS patients with rectal hypersensitivity demonstrated increased brain response in several brain regions and networks involved in visceral sensation and processing. In contrast, IBS patients with normal rectal sensitivity exhibited reduced brain response during the late phase of the experiment. As reported in paper III, similar symptom reduction was achieved for both treatments. The symptomatic improvement was associated with a reduction of response in the anterior insula, indicating an attenuated awareness of the stimuli. The hypnotherapy group had a reduction of response in the posterior insula, indicating less input to the brain, possibly due to changed activity in endogenous pain modulatory systems. In patients who reported significant symptom reduction following treatment, the brain response to rectal distension got more similar to that observed in healthy controls.

Conclusions

The results from papers I and II indicate that a subpopulation of IBS patients lacks the ability to habituate to repeated rectal distensions and expectation of these stimuli. Results from paper III indicate that the abnormal processing of visceral stimuli in IBS can be altered, and that the treatments probably had a normalizing effect on the central processing abnormality of visceral signals in IBS.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2015. p. 62
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1472
National Category
Neurology Radiology, Nuclear Medicine and Medical Imaging Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-122144 (URN)10.3384/diss.diva-122144 (DOI)978-91-7685-983-4 (ISBN)
Public defence
2015-11-06, Berzeliussalen, Campus US, Linköping, 13:00 (English)
Opponent
Supervisors
Available from: 2015-10-20 Created: 2015-10-20 Last updated: 2016-04-24Bibliographically approved
Bednarska, O., Tapper, S., Lundberg, P., Tisell, A., Lowén, M. & Walter, S. (2014). Neurotransmittor Concentration in Pregenual ACC in Stool Consistency Patient Subgroups With IBS. In: : . Paper presented at United European Gastroenterology (UEG), Austria. , 2(Supplement 1)
Open this publication in new window or tab >>Neurotransmittor Concentration in Pregenual ACC in Stool Consistency Patient Subgroups With IBS
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2014 (English)Conference paper, Poster (with or without abstract) (Refereed)
Abstract [en]

Introduction

The Anterior Cingulate Cortex (ACC) is a key region of the central autonomic brain network. Irritable Bowel Syndrome (IBS) is characterized abdominal pain and bowel habit disturbances. Autonomic dysregulation has been reported in IBS as well as altered ACC activation in pregenual ACC during visceral stimulation 1 2. Glutamate is the major excitatory and Gamma-aminobutyric acid (GABA) the major inhibitory neurotransmitter in the brain.

Aim & Methods

We aimed to measure neurotransmitter concentration in the pregenual ACC, in stool consistency subgroups with IBS by using quantitative neurotransmitter Magnetic Resonance Spectroscopy (qMRS)Seven patients with IBS-mixed (6 women) and five patients with IBS -diarrhea (4 women) according to Rome 3 were included. Mean age was 34.2 years (SD 5.3) with no significant difference between subgroups.  Patients completed symptom severity score (IBS-SSS). Quantitative MRS was measured in a 3T MRI scanner. A water-suppressed MEGA-PRESS sequence (TR 2.0 s, TE 68 ms) was used with the editing pulses placed at 1.90 ppm (‘ON-dynamics’) and at 7.46 ppm (‘OFF-dynamics’) with a voxel (3x3x3 cm3) placed in the pACC. Each MEGA-PRESS measurement resulted in a sequence of 40 OFF- and ON-dynamics, where each was computed by 8 phase cycles. Directly after each water-suppressed MEGA-PRESS measurement, a shorter 2-dynamic unsuppressed water MEGA-PRESS measurement was performed within the same voxel, which was used to obtain the concentrations in physically well-defined units of [mM]. The GABA concentrations were computed by averaging the difference spectra obtained by subtracting each OFF-dynamic from subsequent ON-dynamic and using LCModel (Version 6.3) for the final quantification. The Glutamate concentrations were obtained by only averaging the OFF-dynamics, which were not affected by the editing pulses. Additionally, all dynamics were phase and frequency corrected prior to the averaging. For group comparison unpaired T-tests were used.

Results

Patients had moderate to severe symptoms with IBS-SSS of 367 (SD 79.7). There was no significant difference between IBS subgroups in terms of IBS-SSS. Mean pACC GABA concentration was 1.66 (SD 0.17) mM in IBS-M and 1.65 (SD 0.27) mM in IBS-D. There was no significant difference between groups (p=0.9). Mean pACC Glutamate concentration was 4.54 (0.35) mM in IBS-M and 5.13 (SD 0.64) mM in IBS-D. There was no significant difference between groups, although a trend with p=0.06 was observed.

Conclusion

Further qMRS data have to be collected in IBS patients as well as healthy controls to evaluate if IBS subgroups demonstrate alterations in pACC glutamate and GABA concentrations

National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-114346 (URN)
Conference
United European Gastroenterology (UEG), Austria
Available from: 2015-02-19 Created: 2015-02-19 Last updated: 2017-01-19Bibliographically approved
Chen, M. P., Walter, S., Lowén, M., Labus, J. S., Kilpatrick, L. A., Mayer, E. A. & Tillisch, K. (2013). Irritable Bowel Syndrome Symptoms Are Related to the Resting Brain's Sensorimotor Network. In: : . Paper presented at Digestive Disease Week 2013, May 18-21, Orlando, USA (pp. S107-S108). , 144(5, Suppl 1)
Open this publication in new window or tab >>Irritable Bowel Syndrome Symptoms Are Related to the Resting Brain's Sensorimotor Network
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2013 (English)Conference paper, Poster (with or without abstract) (Refereed)
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-113417 (URN)10.1016/S0016-5085(13)60394-7 (DOI)
Conference
Digestive Disease Week 2013, May 18-21, Orlando, USA
Available from: 2015-01-19 Created: 2015-01-19 Last updated: 2017-01-17Bibliographically approved
Walter, S., Lowén, M., Mayer, E. A., Tillisch, K., Engström, M. & Craig, A. D. (2013). Su2113 High-Intense Rectal Urgency and Its Representation in the Brain. In: : . Paper presented at Digestive Disease Week 2013, May 18-21 Orlando, USA (pp. S561-S561). , 144(5)
Open this publication in new window or tab >>Su2113 High-Intense Rectal Urgency and Its Representation in the Brain
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2013 (English)Conference paper, Poster (with or without abstract) (Refereed)
Abstract [en]

Background: Several brain imaging studies have demonstrated that visceral distensions activate the insular cortex but there is limited knowledge about which  subregions of the insula underpin the feeling of rectal urgency. An isobaric rectal balloon distension can be subdivided into the inflation phase when pressure is rising (rise) and a stable phase, when the pressure is constant. The rise phase is characterized by a more distinct sensation of urgency (Akervall et al., 1988). We aimed to study the BOLD response during the rise phase of a standardized rectal distension in subregions of the insula, in healthy controls.

Method:Twenty right-handed female healthy volunteers (mean age 32.2 yrs, range 21-54) were included. Rectal pressure sensory thresholds were determined before functional Magnetic Resonance Imaging (fMRI) while the subjects were placed in the MR  scanner. Blood Oxygen Level Dependent (BOLD) signals were measured during the rise periods (6.6-7.2 sec) of 20 rectal distensions (45mmHg). Regions of interest (ROIs) included 10 insula subregions: Left (L) and right (R) anterior ventral, anterior dorsal, posterior ventral, posterior dorsal and mid insula. Results were reported as significant if peak p-value were, 0.05 with familywise error (FWE) correction in the ROIs.

Results: The mean values for rectal sensory thresholds for first sensation, first sensation of urgency and maximum tolerable distension were 16 mmHg (SD 3.9), 28mmHg (SD 6.2) and 55 mmHg (SD 12.3), respectively. Complete fMRI data were available from 18 subjects. The rise period of the rectal distension generated significant BOLD activation in the right hemisphere in the anterior dorsal, anterior ventral, mid and posterior ventral parts of the insula. On the left side BOLD activity was generated in mid, posterior ventral and posterior dorsal parts of the insula but not in the anterior insula. Akervall S et al, 1988, Manovolumetry: A new method for investigation of anorectal function. Gut 29:614-623.

National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-113419 (URN)10.1016/S0016-5085(13)62074-0 (DOI)
Conference
Digestive Disease Week 2013, May 18-21 Orlando, USA
Available from: 2015-01-19 Created: 2015-01-19 Last updated: 2017-06-27Bibliographically approved
Larsson, M., Tillisch, K., Craig, B., Engström, M., Labus, J., Naliboff, B., . . . Walter, S. (2012). Brain Responses to Visceral Stimuli Reflect Visceral Sensitivity Thresholds in Patients With Irritable Bowel Syndrome. Gastroenterology, 142(3), 463-472
Open this publication in new window or tab >>Brain Responses to Visceral Stimuli Reflect Visceral Sensitivity Thresholds in Patients With Irritable Bowel Syndrome
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2012 (English)In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 142, no 3, p. 463-472Article in journal (Refereed) Published
Abstract [en]

BACKGROUND & AIMS:

Only a fraction of patients with irritable bowel syndrome (IBS) have increased perceptual sensitivity to rectal distension, indicating differences in processing and/or modulation of visceral afferent signals. We investigated the brain mechanisms of these perceptual differences.

METHODS:

We analyzed data from 44 women with IBS and 20 female healthy subjects (controls). IBS symptom severity was determined by a severity scoring system. Anxiety and depression symptoms were assessed using the hospital anxiety and depression score. Blood oxygen level-dependent signals were measured by functional magnetic resonance imaging during expectation and delivery of high (45 mmHg) and low (15 mmHg) intensity rectal distensions. Perception thresholds to rectal distension were determined in the scanner. Brain imaging data were compared among 18 normosensitive and 15 hypersensitive patients with IBS and 18 controls. Results were reported significant if peak P-values were ≤.05, with family-wise error correction in regions of interest.

RESULTS:

The subgroups of patients with IBS were similar in age, symptom duration, psychological symptoms, and IBS symptom severity. Although brain responses to distension were similar between normosensitive patients and controls, hypersensitive patients with IBS had greater activation of insula and reduced deactivation in pregenual anterior cingulate cortex during noxious rectal distensions, compared to controls and normosensitive patients with IBS. During expectation of rectal distension, normosensitive patients with IBS had more activation in right hippocampus than controls.

CONCLUSIONS:

Despite similarities in symptoms, hyper- and normosensitive patients with IBS differ in cerebral responses to standardized rectal distensions and their expectation, consistent with differences in ascending visceral afferent input.

Place, publisher, year, edition, pages
Elsevier, 2012
Keywords
Barostat; Visceral Sensitivity; Functional MRI; Anticipation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-73455 (URN)10.1053/j.gastro.2011.11.022 (DOI)000300774700024 ()
Note

funding agencies|County Council of Ostergotland, Sweden||Lions Forskningsfond for Folksjukdomar||Bengt Ihresfond, Svenska Lakaresallskapet||Magnus Bergvall fond||National Institutes of Health| DK 64531 DK 48351 K23 DK73451 |

Available from: 2012-01-04 Created: 2012-01-04 Last updated: 2017-12-08Bibliographically approved
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