
Results of the Systematic Review Divided up by Methodology
First author, year | Participants | Technique | Task | Main results |
---|---|---|---|---|
Hong,19 2013 | 60 IBS vs 108 HC | fMRI, ALFF | Resting-state | Female HC and IBS showed hyperactivation in amygdala and hippocampus compared with male HC and IBS. Female IBS showed hyperactivation in INS and hypoactivation in S1 compared to male IBS. |
Gupta,20 2014 | 58 IBS vs 110 HC | fMRI | Resting-state | History of EAL was associated with altered FC in the salience/executive control network in IBS patients; male IBS patients demonstrated additional EAL-related alterations in the cerebellar network. |
Hong,26 2014 | 48 IBS vs 48 HC | fMRI | Resting-state | Male IBS showed increased FC than female IBS of the dorsal aINS bilaterally with mPFC and dorsal pINS; (2) female IBS showed greater negative FC than male IBS of L dorsal aINS with L precuneus; clinical characteristics correlated to the FC between INS and dorsal mPFC in male IBS, with the precuneus in female IBS. |
Ke,30 2015 | 31 IBS vs 32 HC | fMRI, ReHo analysis | Resting-state | IBS patients showed increased FC in S1 and thalamus and decreased FC in the ACC and PFC. |
Ma,17 2015 | 21 IBS vs 21 HC | fMRI, ALFF | Resting-state | IBS patients showed hypoactivity in the L SFG, R hippocampus, R MFG, bilateral M1, and R superior temporal pole; hyperactivation in the L MCC and L calcarine; increased FC in cingulate and frontal cortex. |
Qi,18 2016 | 30 IBS vs 31 HC | fMRI, ALFF | Resting-state | IBS showed hypoactivity in DMN regions (mPFC, PCC, bilateral inferior parietal cortices), MFG, R orbital part of the SFG, dorsal ACC, ventral ACC; hyperactivity in bilateral pINS and cuneus; decreased positive FC between mPFC and R orbital SFG, between ventral ACC and PCC; decreased negative FC between mPFC and L pINS; increased negative FC between mPFC and cuneus. |
Qi,27 2016 | 31 IBS vs 32 HC | fMRI | Resting-state | IBS showed higher positive FC between the amygdala and INS, midbrain, parahippocampal gyrus, S1/M1, and SMA. |
Qi,21 2016 | 65 IBS vs 67 HC | fMRI, IVMHC | Resting-state | IBS showed higher interhemispheric FC between bilateral thalami, cuneus, PCC, lingual gyri and inferior occipital/cerebellum lobes; lower interhemispheric FC between bilateral ventral ACC and inferior parietal lobules. |
Qi,24 2016 | 31 IBS vs 32 HC | fMRI | Resting-state | IBS showed decreased DMN inter-regional FC between precuneus and ACC, medial orbital SFG, and MTG, together with decreased DMN global efficiency (E glob). |
Gupta,23 2017 | 16 IBS vs 16 HC | fMRI | Resting-state | Regions of the salience network, (MCC, MTG, STG) were positively correlated with proinflammatory genes ( |
Icenhour,29 2017 | 41 IBS vs 20 HC | fMRI | Resting-state | H-IBS, compared to N-IBS, showed increased positive FC of pregenual ACC and thalamus and of pINS within the sensorimotor network; N-IBS showed decreased positive FC of amygdala and decreased negative FC in dorsal aINS within the DMN. FC between DMN and sensorimotor network correlated with rectal perception thresholds, while FC in pINS correlated with symptom severity. |
Longarzo,28 2017 | 19 IBS vs 26 HC | fMRI | Resting-state | In IBS patients, correlation emerged: between hypochondriasis and FC between PCC and L supramarginal gyrus/STG; interoception and FC between L ventral aINS and supramarginal gyrus bilaterally. |
Weng,22 2017 | 32 IBS vs 32 HC | fMRI | Resting-state | IBS showed decreased long- and short-range FCD in bilateral anterior MCC and inferior parietal lobules; decreased long-range FCD in R aINS; decreased short-range FCD in bilateral PFC, subgenual ACC and caudates; increased long- and short-range FCD in S1/M1; increased long-range FCD in R SMA; increased short-range FCD in occipital lobe. |
Witt,25 2019 | 32 IBS vs 15 HC | fMRI | Resting-state | IBS patients only showed an increased FC of the R amygdala, correlated with decreased gut permeability. |
Mertz,31 2000 | 18 IBS vs 16 HC | fMRI | Rectal distention exam | In HC and IBS, rectal stimulation led to a greater activity of ACC, PFC, INS, and thalamus. In IBS pain produced an hyperactivation of the ACC. |
Yuan,32 2003 | 26 IBS vs 11 HC | fMRI | Rectal distention exam | In IBS and HC, rectal distention stimulation increased the activity of ACC, PFC, INS and thalamus. During painful stimulation, IBS hyperactivated INS, PFC, and thalamus. |
Wilder-Smith,35 2004 | 10 IBS vs 10 HC | fMRI | Rectal distention exam | IBS-D, during heterotopic stimulation showed significant deactivation in the right aINS; IBS-C showed increased activations of the amygdala and hippocampus; HC only showed deactivation of the PAG. |
Song,36 2006 | 12 IBS vs 12 HC | fMRI | Rectal distention exam | During rectal stimulation, compared to heterotopic stimulation, HC but not IBS showed greater activation in bilateral aINS, S2 and putamen; IBS showed greater activation during rectal plus heterotopic stimulation, compared to rectal stimulation alone, in bilateral S1, R STG, R inferior lobule and bilateral STG. |
Berman,33 2008 | 14 IBS vs 12 HC, female only | fMRI | Rectal distention exam | During cued anticipation of distention, HC showed hypoactivity in INS, supragenual ACC, amygdala, and DBS, while IBS patients showed less anticipatory inactivation. Group differences were significant in R pINS and bilateral DBS. During distention, both groups showed activity increases in INS dorsal ACC, and DBS and decreases in the infragenual ACC. The increases were more extensive in patients, in dorsal ACC and DBS. |
Ringel,48 2008 | 10 IBS vs 10 HC, female, with 5 and 5 respectively having history of abuse | fMRI | Rectal distention exam | In HC and IBS, distention-elicited pain correlated with activation of PCC and MCC, but subjects with IBS and history of sexual abuse showed higher activity in L MCC and PCC, and lower activity in L supragenual ACC. |
Elsenbruch,34 2010 | 15 IBS vs 12 HC, female only | fMRI | Rectal distention exam | IBS showed hyperactivation in aINS and PFC. Anxiety correlated with pain-induced activation of the anterior MCC and pregenual ACC. Depression correlated with activation of PFC and cerebellar areas. |
Elsenbruch,41 2010 | 15 IBS vs 12 HC, female only | fMRI | Rectal distention exam | During rectal stimulation, IBS showed more pronounced stress-induced modulation of neural activation in the INS, MCC, VLPFC. During relaxation, IBS patients demonstrated reduced modulation of distension-induced activation in the INS. |
Hubbard,56 2011 | 14 IBS vs 17 HC, female only | fMRI | Pain expectation + two single oral doses (20 or 200 mg) of the CRF1 antagonist GW876008 vs PLA | During pain expectation, IBS and HC receiving GW876008 showed hypoactivation in the amygdala, hippocampus, INS, ACC, and OFC/mPFC. IBS showed greater BOLD responses in the L locus coeruleus and hypothalamus after PLA compared with HCs, and hypoactivation of the L hypothalamus after drug. |
Kilpatrick,53 2011 | 26 IBS vs 29 HC, female only | fMRI | Affect-matching paradigm | IBS patients with the C/C genotype had increased amygdala responses to nonemotional stimuli, compared with other subjects with C/C genotype. |
Labus,1 2011 | 12 HC vs 14 IBS | fMRI | Rectal distention exam | In HC and IBS-C, ATD lead to an increased response to rectal distention of the amygdala and nodes of emotional arousal and homeostatic afferent networks. The effect was greater during high inflation. |
Aizawa,51 2012 | 30 IBS vs 30 HC | fMRI | Wisconsin Card Sorting Test | IBS showed hypoactivity of the R DLPFC and R hippocampus; hyperactivity of the L pINS at error feedback during set-shifting; less FC from the DLPFC to pre-SMA. |
Larsson,49 2012 | Total: 44 IBS vs 20 HC; imaging: 18 normosensitive and 15 hypersensitive patients with IBS and 18 controls | fMRI | Rectal distention exam | H-IBS had hyperactivation of INS and hypoactivation in pregenual ACC during noxious rectal distensions, compared to HC and N-IBS. During expectation of rectal distension, N-IBS had showed hyperactivation in R hippocampus than HC. |
Lee,59 2012 | 17 IBS vs 17 HC | fMRI | Rectal distention exam | IBS and HC showed comparable visceral PLA analgesia, but IBS showed hyperactivity in INS, MCC and VLPFC. VLPFC was also more active during anticipation in IBS. |
Bouhassira,37 2013 | 10 IBS patients with facilitation and 10 with inhibition of the RIII reflex vs 11 HC, female only | fMRI | Rectal distention exam | Non-painful and painful rectal distension induced similar changes in brain activity in IBS patients with facilitation and inhibition of the RIII reflex. |
Labus,42 2013 | 47 IBS vs 67 HC | fMRI | Emotion recognition paradigm | Male IBS and HC showed greater overall brain responses to emotional stimuli than females in PFC, INS, and amygdala. |
Lowén,46 2013 | 44 IBS vs 20 HC, female only | fMRI | Rectal distention exam and hypnotherapy | Hypnotherapy or educational intervention were both effective in reducing pain during rectal distention in both IBS and HC group; after the treatment, the brain response to distension was similar in IBS and in HCs. |
Rosenberger,38 2013 | 15 IBS vs 15 HC | fMRI | Rectal distention exam | Within IBS, depression scores correlated with non-painful distension-induced activation in the R cerebellum (Crus I, II, and lobule VIIIb) and with painful distension-induced activation in vermal lobule V; anxiety scores correlated with non-painful induced activation in Crus II. |
Hubbard,52 2015 | 15 IBS vs 14 HC | fMRI | Attention network test | IBS showed shorter reaction times during the alerting and orienting conditions, correlated with hyperactivation of anterior MCC (correlated with duration and severity of GI-symptoms) and INS, and hypoactivation in the R inferior frontal junction and SMA. during the executive control task, IBS showed activation in the dorsal mPFC and deactivation of thalamus. |
Icenhour,45 2015 | 20 IBS vs 23 HC | fMRI | Rectal distention exam with fear acquisition paradigm | IBS showed: during fear acquisition, hyperactivation of PFC and amygdala; during extinction, hyperactivation of cingulate cortex; during reinstatement, hyperactivation of hippocampus. |
Lowén,50 2015 | 33 IBS vs 18 HC | fMRI | Rectal distention exam | In the last trials of a series of rectal distension, N-IBS showed decreasing activation in INS, PFC and amygdala, H-IBS showed greater activation in insula, ACC and MCC. |
Hong,43 2016 | 37 HC vs 37 IBS | fMRI | Pain expectation | Regions within the salience, attention, default mode, and emotional arousal networks were more activated by the cued abdominal threat condition and the uncued condition than in the cued safe condition. During the uncued condition IBS subjects showed hyperactivations in amygdala, aINS, MFG, thalamus and precuneus. |
Wong,55 2016 | 13 IBS vs 11 HC | fMRI | Rectal distention exam | IBS showed, within the scanner environment, significantly increased visceral, but not somatic, pain perception. |
Claassen,39 2017 | 17 IBS vs 21 HC | fMRI | Differential fear conditioning paradigm | IBS patients revealed hyperactivity responses to pain-predictive and safety cues in the vermis, intermediate cerebellum (maximum in lobule VIII), and the posterolateral cerebellar hemisphere (maximum in lobule VI). During extinction and reinstatement, no differences emerged between HC and IBS. During visceral pain-related fear conditioning, IBS patients showed hyperactivations in several areas of the medial, intermediate, and lateral cerebellum. |
Guleria,54 2017 | 20 IBS vs 10 HC | fMRI | Rectal distention exam | IBS patients showed greater cerebral activations in INS, MTG, and cerebellum in the L hemisphere, but lacked of activation in bilateral precuneus/superior parietal lobules. IBS-C activated R MCC, while IBS-D activated L inferior OFC, L calcarine, and bilateral fusiform gyri. |
Kano,44 2017 | 26 IBS vs 29 HC | fMRI | Rectal distention exam | IBS patients, in uncertain anticipation, showed greater activation of anterior MCC, thalamus, and visual processing areas; the following rectal distention elicited in IBS higher activity in PCC, MCC and the precuneus; lack of rectal distention after the cue of uncertainty lead, in IBS, to a lack in bilateral insula activation. |
Kano,57 2017 | 28 IBS vs 34 HC | fMRI | Rectal distention exam + intravenous CRF administration (2 μg/kg) | HC, but not IBS, showed a negative correlation between ACTH response to CRF and activity in the pregenual ACC during rectal distention. |
Wang,40 2017 | 31 IBS vs 20 HC | fMRI | Rectal distention exam | Activation in parietal areas, PFC, cerebellum, ACC, INS and thalamus increased along with increases in rectal balloon dilation, except in women with IBS and patients with disease duration less than 5 years. |
Kano,47 2019 | 27 IBS vs 33 HC | fMRI | Rectal distention exam | In HC, but not in IBS, a positive correlation between baseline high frequency values of HRV and neural responses to rectal distension was found in the R caudate, bilateral dorsolateral ACC, and pregenual ACC. |
Kano,58 2020 | 26 IBS vs 35 HC | fMRI | Rectal distention exam | During rectal distention, activity in the R INS was positively associated with alexithymia scores to a greater extent in patients with IBS than in HCs. |
Nakai,60 2003 | 12 IBS vs 12 HC | PET | Resting-state - 5-HT Synthesis | 5-HT synthesis was greater in female in the R MTG (multimodal sensory association cortex) compared with the female HC. |
Naliboff,65 2006 | 20 IBS vs 14 HC | PET | Resting-state and rectal distentions exam | IBS, during repeated trials of rectal distention, showed a stable activation of the central pain matrix but a gradually decreasing activation in limbic, paralimbic, and pontine regions; during the anticipation condition, there were significant decreases in amygdala, dorsal ACC, and DBS activation. |
Berman,63 2012 | 11 IBS vs 11 HC | PET | Auditory oddball vigilance task + double-blind ingestion of the α2AR antagonist YOH, agonist CLO or PLA | IBS showed higher plasma NE levels than HCs before and after ingestion of all drugs. IBS patients appeared downregulated the for functional presynaptic α2AR and showed less YOH-mediated reduction of activity in a central arousal circuit in brainstem and amygdala, which inversely correlated with early life trauma. |
Niddam,12 2011 | 15 IBS vs 15 HC | qMRS | Resting-state | IBS showed reduced levels of Glx in hippocampus. |
Bednarska,11 2019 | 30 IBS vs 21 HC, female only | qMRS | Resting-state | IBS showed lower concentrations of Glx in L and R aINS; no group differences for GABA1 concentrations. In IBS, lower R-lateralized Glx concentrations correlated with longer pain duration; lower Glx in L aINS correlated with ess frequent use of adaptive pain-coping. |
Icenhour,13 2019 | 64 IBS vs 32 HC, female only | qMRS + fMRI | Resting-state | IBS and HC showed similar GABA+ and Glx levels in mPFC. Anxiety was positively associated with mPFC GABA+ concentrations in IBS; Glx was unrelated to psychological or gastrointestinal symptoms. IBS with high anxiety showed increased mPFC GABA+ and lower mPFC FC with ACC. |
IBS, irritable bowel syndrome; HC, healthy control; fMRI, functional magnetic resonance imaging; INS, insula; S1, primary somatosensory cortex; EAL, early adverse life events; aINS, anterior insula; mPFC, medial prefrontal cortex; pINS, posterior insula; FC, functional connectivity; ReHo, regional homogeneity; ACC, anterior cingulate cortex; PFC, prefrontal cortex; ALFF, amplitude of low-frequency fluctuation; L, left; SFG, superior frontal gyrus; R, right; MFG, middle frontal gyrus; M1, primary motor cortex; MCC, mid-cingulate cortex; DMN, default mode network; PCC, posterior cingulate cortex; SMA, supplementary motor area; IVMHC, interhemispheric voxel-mirrored homotopic connectivity;