An examination of resting-state functional connectivity in patients with active Crohn's disease.

Background: Alterations in resting state functional connectivity (rs-FC) in Crohn's Disease (CD) have been documented in default mode network (DMN) and frontal parietal network (FPN) areas, visual, cerebellar, salience and attention resting-state-networks (RSNs), constituting a CD specific neural phenotype. To date, most studies are in patients in remission, with limited studies in active disease. Methods: Twenty five active CD cases and 25 age-, BMI- and gender-matched healthy controls (HC) were recruited to a resting-state-functional Magnetic Resonance Imaging (rs-fMRI) study. Active disease was defined as C-reactive protein>5 mg/dL, faecal calprotectin>250 µg/g, or through ileocolonoscopy or MRE. rs-fMRI data were analysed using independent component analysis (ICA) and dual regression. Differences in RSNs between HCs and active CD were assessed, and rs-FC was associated with disease duration and abdominal pain. Results: Increased connectivity in the FPN (fusiform gyrus, thalamus, caudate, posterior cingulate cortex, postcentral gyrus) and visual RSN (orbital frontal cortex) were observed in CD versus HC. Decreased activity was observed in the salience network (cerebellum, postcentral gyrus), DMN (parahippocampal gyrus, cerebellum), and cerebellar network (occipital fusiform gyrus, cerebellum) in CD versus HCs. Greater abdominal pain scores were associated with lower connectivity in the precuneus (visual network) and parietal operculum (salience network), and higher connectivity in the cerebellum (frontal network). Greater disease duration was associated with greater connectivity in the middle temporal gyrus and planum temporale (visual network). Conclusion: Alterations in rs-FC in active CD in RSNs implicated in cognition, attention, emotion, and pain may represent neural correlates of chronic systemic inflammation, abdominal pain, disease duration, and severity.

The relationship between Central Nervous System morphometry changes and key symptoms in Crohn's disease.

Alterations in grey matter volume (GMV) and cortical thickness (CT) in Crohn's disease (CD) patients has been previously documented. However, the findings are inconsistent, and not a true representation of CD burden, as only CD patients in remission have been studied thus far. We investigate alterations in brain morphometry in patients with active CD and those in remission, and study relationships between brain structure and key symptoms of fatigue, abdominal pain, and extraintestinal manifestations (EIM). Magnetic Resonance Imaging brain scans were collected in 89 participants; 34 CD participants with active disease, 13 CD participants in remission and 42 healthy controls (HCs); Voxel based morphometry (VBM) assessed GMV and white matter volume (WMV), and surface-based analysis assessed cortical thickness (CT). We show a significant reduction in global cerebrospinal fluid (CSF) volume in CD participants compared with HCs, as well as, a reduction in regional GMV, WMV and CT in the left precentral gyrus (motor cortex), and an increase in GMV in the frontal brain regions in CD compared with HCs. Atrophy of the supplementary motor area (SMA) was associated with greater fatigue in CD. We also show alterations in brain structure in multiple regions in CD associated with abdominal pain and extraintestinal inflammations (EIMs). These brain structural alterations likely reflect neuroplasticity to a chronic systemic inflammatory response, abdominal pain, EIMs and fatigue. These findings will aid our understanding of the cross-linking between chronic inflammation, brain structural changes and key unexplained CD symptomatology like fatigue.

Mapping brain activity of gut-brain signaling to appetite and satiety in healthy adults: A systematic review and functional neuroimaging meta-analysis.

Understanding how neurohormonal gut-brain signaling regulates appetite and satiety is vital for the development of therapies for obesity and altered eating behavior. However, reported brain areas associated with appetite or satiety regulators show inconsistency across functional neuroimaging studies. The aim of this study was to systematically assess the convergence of brain regions modulated by appetite and satiety regulators. Twenty-five studies were considered for qualitative synthesis, and 14 independent studies (20-experiments) found eligible for coordinate-based neuroimaging meta-analyses across 212 participants and 123 foci. We employed two different meta-analysis approaches. The results from the systematic review revealed the modulation of insula, amygdala, hippocampus, and orbitofrontal cortex (OFC) with appetite regulators, where satiety regulators were more associated with caudate nucleus, hypothalamus, thalamus, putamen, anterior cingulate cortex in addition to the insula and OFC. The two neuroimaging meta-analyses methods identified the caudate nucleus as a key area associated with satiety regulators. Our results provide quantitative brain activation maps of neurohormonal gut-brain signaling in heathy-weight adults that can be used to define alterations with eating behavior.

Mechanisms of umami taste perception: From molecular level to brain imaging.

Due to unique characteristics, umami substances have gained much attention in the food industry during the past decade as potential replacers to sodium or fat to increase food palatability. Umami is not only known to increase appetite, but also to increase satiety, and hence could be used to control food intake. Therefore, it is important to understand the mechanism(s) involved in umami taste perception. This review discusses current knowledge of the mechanism(s) of umami perception from receptor level to human brain imaging. New findings regarding the molecular mechanisms for detecting umami tastes and their pathway(s), and the peripheral and central coding to umami taste are reviewed. The representation of umami in the human brain and the individual variation in detecting umami taste and associations with genotype are discussed. The presence of umami taste receptors in the gastrointestinal tract, and the interactions between the brain and gut are highlighted. The review concludes that more research is required into umami taste perception to include not only oral umami taste perception, but also the wider "whole body" signaling mechanisms, to explore the interaction between the brain and gut in response to umami perception and ingestion.

Thermal taster status: Temperature modulation of cortical response to sweetness perception.

Temperature is known to impact taste perception, but its reported effect on sweet taste perception in humans is inconsistent. Here, we assess whether thermal taste phenotype alters the temperature modulation of the brains' response to sweet samples and sweet taste perception. Participants (n = 24 balanced for thermal tasters (TT) and thermal non-tasters (TnT), 25 ± 7 years (mean ± SD), 10 males) underwent a thermal taste phenotyping session to study responses to cooling and warming of the tongue using a thermode. In a separate session, functional Magnetic Resonance Images (fMRI) were collected during sweet samples (87 mM sucrose) delivery at two temperatures ('cold' (5 ± 2 °C) and 'ambient' (20 ± 2 °C)) and the perceived sweetness intensity rated.In the phenotyping session, TTs had heightened perceptual temperature sensitivity to cooling and warming of the tongue using a thermode compared to TnTs. Although there was no significant effect during the fMRI session, the fMRI response to the 'cold sweet' sample across all participants was significantly increased in anterior insula/frontal operculum and mid-insula compared to the 'ambient sweet' sample, likely to reflect the perceptual difference to temperature rather than taste perception. TTs showed significantly increased fMRI activation patterns compared with TnTs and an interaction effect between thermal taster status and sample temperature, with TTs showing selectively greater cortical responses to 'cold sweet' samples compared to TnTs in somatosensory regions (SI and SII).The increase in cortical activation in somatosensory cortices to the 'cold sweet' stimulus correlated with perceptual ratings of temperature sensitivity to the thermode. The results highlight the importance of investigating the effects of thermal taster phenotype across a range of temperatures representing the reality of consumer consumption to beverages.

A nociresponsive specific area of human somatosensory cortex within BA3a: BA3c?

It is well recognized that in primates, including humans, noxious body stimulation evokes a neural response in the posterior bank of the central sulcus, in Brodmann cytoarchitectonic subdivisions 3b and 1 of the primary somatosensory cortex. This response is associated with the 1st/sharp pain and contributes to sensory discriminative aspects of pain perception and spatial localization of the noxious stimulus. However, neurophysiological studies in New World monkeys predict that in humans noxious stimulation also evokes a separate neural response-mediated by C-afferent drive and associated with the 2nd/burning pain-in the depth of the central sulcus in Brodmann area 3a (BA3a) at the transition between the somatosensory and motor cortices. To evoke such a response, it is necessary to use multi-second duration noxious stimulation, rather than brief laser pulses. Given the limited human pain-imaging literature on cortical responses induced by C-nociceptive input specifically within BA3a, here we used high spatial resolution 7T fMRI to study the response to thermonoxious skin stimulation. We observed the predicted response of BA3a in the depth of the central sulcus in five human volunteers. Review of the available evidence suggests that the nociresponsive region in the depth of the central sulcus is a structurally and functionally distinct cortical area that should not be confused with proprioceptive BA3a. It is most likely engaged in interoception and control of the autonomic nervous system, and contributes to the sympathetic response to noxious stimulation, arguably the most intolerable aspect of pain experience. Ablation of this region has been shown to reduce pain sensibility and might offer an effective means of ameliorating some pathological pain conditions.

Variation in thermally induced taste response across thermal tasters.

Thermal tasters (TTs) perceive thermally induced taste (thermal taste) sensations when the tongue is stimulated with temperature in the absence of gustatory stimuli, while thermal non tasters (TnTs) only perceive temperature. This is the first study to explore detailed differences in thermal taste responses across TTs. Using thermal taster status phenotyping, 37 TTs were recruited, and the temporal characteristics of thermal taste responses collected during repeat exposure to temperature stimulation. Phenotyping found sweet most frequently reported during warming stimulation, and bitter and sour when cooling, but a range of other sensations were stated. The taste quality, intensity, and number of tastes reported greatly varied. Furthermore, the temperature range when thermal taste was perceived differed across TTs and taste qualities, with some TTs perceiving a taste for a small temperature range, and others the whole trial. The onset of thermal sweet taste ranged between 22 and 38°C during temperature increase. This supports the hypothesis that TRPM5 may be involved in thermal sweet taste perception as TRPM5 is temperature activated between 15 and 35°C, and involved in sweet taste transduction. These findings also raised questions concerning the phenotyping protocol and classification currently used, thus indicating the need to review practices for future testing. This study has highlighted the hitherto unknown variation that exists in thermal taste response across TTs, provides some insights into possible mechanisms, and importantly emphasises the need for more research into this sensory phenomenon.

An automated method to detect and quantify fungiform papillae in the human tongue: Validation and relationship to phenotypical differences in taste perception.

Determination of the number of fungiform papillae (FP) on the human tongue is an important measure that has frequently been associated with individual differences in oral perception, including taste sensitivity. At present, there is no standardised method consistently used to identify the number of FP, and primarily scientists manually count papillae over a small region(s) of the anterior tip of a stained tongue. In this study, a rapid automated method was developed to quantify the number of FP across the anterior 2cm of an unstained tongue from high resolution digital images. In 60 participants, the automated method was validated against traditional manual counting, and then used to assess the relationship between the number of FP and taste phenotype (both 6-n-propylthiouracil (PROP) and Thermal Taster Status). FP count on the anterior 2cm of the tongue was found to correlate significantly with PROP taster status. PROP supertasters (PSTs) had a significantly higher FP count compared with PROP non-tasters (PNTs). Conversely, the common approach used to determine the number of FP in a small 6mm diameter circle on the anterior tongue tip, did not show a significant correlation irrespective of whether it was determined via automated or manual counting. The regional distribution of FP was assessed across PROP taster status groups. PSTs had a significantly higher FP count within the first centimetre of the anterior tongue compared with the PNT and PROP medium-tasters (PMT), with no significant difference in the second centimetre. No significant relationship was found with Thermal Taster Status and FP count, or interaction with PROP taster status groups, supporting previous evidence suggesting these phenomena are independent. The automated method is a valuable tool, enabling reliable quantification of FP over the anterior 2cm surface of the tongue, and overcomes subjective discrepancies in manual counting.

Prior Consumption of a Fat Meal in Healthy Adults Modulates the Brain's Response to Fat.

BACKGROUND: The consumption of fat is regulated by reward and homeostatic pathways, but no studies to our knowledge have examined the role of high-fat meal (HFM) intake on subsequent brain activation to oral stimuli. OBJECTIVE: We evaluated how prior consumption of an HFM or water load (WL) modulates reward, homeostatic, and taste brain responses to the subsequent delivery of oral fat. METHODS: A randomized 2-way crossover design spaced 1 wk apart was used to compare the prior consumption of a 250-mL HFM (520 kcal) [rapeseed oil (440 kcal), emulsifier, sucrose, flavor cocktail] or noncaloric WL on brain activation to the delivery of repeated trials of a flavored no-fat control stimulus (CS) or flavored fat stimulus (FS) in 17 healthy adults (11 men) aged 25 ± 2 y and with a body mass index (in kg/m2) of 22.4 ± 0.8. We tested differences in brain activation to the CS and FS and baseline cerebral blood flow (CBF) after the HFM and WL. We also tested correlations between an individual's plasma cholecystokinin (CCK) concentration after the HFM and blood oxygenation level-dependent (BOLD) activation of brain regions. RESULTS: Compared to the WL, consuming the HFM led to decreased anterior insula taste activation in response to both the CS (36.3%; P < 0.05) and FS (26.5%; P < 0.05). The HFM caused reduced amygdala activation (25.1%; P < 0.01) in response to the FS compared to the CS (fat-related satiety). Baseline CBF significantly reduced in taste (insula: 5.7%; P < 0.01), homeostatic (hypothalamus: 9.2%, P < 0.01; thalamus: 5.1%, P < 0.05), and reward areas (striatum: 9.2%; P < 0.01) after the HFM. An individual's plasma CCK concentration correlated negatively with brain activation in taste and oral somatosensory (ρ = -0.39; P < 0.05) and reward areas (ρ = -0.36; P < 0.05). CONCLUSIONS: Our results in healthy adults show that an HFM suppresses BOLD activation in taste and reward areas compared to a WL. This understanding will help inform the reformulation of reduced-fat foods that mimic the brain's response to high-fat counterparts and guide future interventions to reduce obesity.

Thermal taster status: Evidence of cross-modal integration.

Thermal taster status refers to the finding that, in some individuals, thermal stimulation of the tongue elicits a phantom taste. Little is known regarding the mechanism for this, it is hypothesised to be a result of cross-wiring between gustatory and trigeminal nerves whose receptors co-innervate papillae on the tongue. To address this, we use functional magnetic resonance imaging to perform the first study of whether the cortical response to gustatory-trigeminal samples is altered with thermal taster status. We study the response to cold (6°C) gustatory (sweet) samples at varying levels of trigeminal stimulation elicited by CO2 (no CO2 , low CO2 , high CO2 ) in thermal taster (TT) and thermal non-taster (TnT) groups, and evaluate associated behavioural measures. Behaviourally, the TT group perceived gustatory and trigeminal stimuli significantly more intense than TnTs, and were significantly more discriminating of CO2 level. fMRI data revealed elevated cortical activation to the no CO2 sample for the TT group compared to TnT group in taste, oral somatosensory and reward areas. In TnTs, a significant positive modulation in cortical response with increasing level of CO2 was found across taste, somatosensory and reward areas. In contrast, in TTs, a reduced positive modulation with increasing level of CO2 was found in somatosensory areas (SI, SII), whilst a significant negative modulation was found in taste (anterior insula) and reward (ACC) areas. This difference in cortical response to trigeminal stimuli supports cross-modal integration in TTs, with gustatory and trigeminal nerves highly stimulated by cold gustatory samples due to their intertwined nature. Hum Brain Mapp 37:2263-2275, 2016. © 2016 Wiley Periodicals, Inc.

Imaging methodologies and applications for nutrition research: what can functional MRI offer?

Food intake is influenced by a complex regulatory system involving the integration of a wide variety of sensory inputs across multiple brain areas. Over the past decade, advances in neuroimaging using functional MRI (fMRI) have provided valuable insight into these pathways in the human brain. This review provides an outline of the methodology of fMRI, introducing the widely used blood oxygenation level-dependent contrast for fMRI and direct measures of cerebral blood flow using arterial spin labelling. A review of fMRI studies of the brain's response to taste, aroma and oral somatosensation, and how fat is sensed and mapped in the brain in relation to the pleasantness of food, and appetite control is given. The influence of phenotype on individual variability in cortical responses is addressed, and an overview of fMRI studies investigating hormonal influences (e.g. peptide YY, cholecystokinin and ghrelin) on appetite-related brain processes provided. Finally, recent developments in MR technology at ultra-high field (7 T) are introduced, highlighting the advances this can provide for fMRI studies to investigate the neural underpinnings in nutrition research. In conclusion, neuroimaging methods provide valuable insight into the mechanisms of flavour perception and appetite behaviour.

The cortical response to the oral perception of fat emulsions and the effect of taster status.

The rewarding attributes of foods containing fat are associated with the increase in fat consumption, but little is known of how the complex physical and chemical properties of orally ingested fats are represented and decoded in the brain nor how this impacts feeding behavior within the population. Here, functional MRI (fMRI) is used to assess the brain response to isoviscous, isosweet fat emulsions of increasing fat concentration and to investigate the correlation of behavioral and neuroimaging responses with taster status (TS). Cortical areas activated in response to fat, and those areas positively correlated with fat concentration, were identified. Significant responses that positively correlated with increasing fat concentration were found in the anterior insula, frontal operculum and secondary somatosensory cortex (SII), anterior cingulate cortex, and amygdala. Assessing the effect of TS revealed a strong correlation with self-reported preference of the samples and with cortical response in somatosensory areas [primary somatosensory cortex (SI), SII, and midinsula] and the primary taste area (anterior insula) and a trend in reward areas (amygdala and orbitofrontal cortex). This finding of a strong correlation with TS in somatosensory areas supports the theory of increased mechanosensory trigeminal innervation in high 6-n-propyl-2-thiouracil (PROP) tasters and has been linked to a higher risk of obesity. The interindividual differences in blood oxygenation level-dependent (BOLD) amplitude with TS indicates that segmenting populations by TS will reduce the heterogeneity of BOLD responses, improving signal detection power.

Measurement of visual evoked potential during and after periods of pulsed magnetic field exposure.

PURPOSE: To study the effect of switched magnetic fields used in MR scanners on the visual evoked potential (VEP) in human subjects. MATERIALS AND METHODS: We have used an MRI gradient coil, remote from an MRI magnet to produce a time-varying magnetic field (0.5 kHz, peak field approximately 8.7 T/second) in the human brain without the confounding effects of static field exposure or accompanying acoustic noise. The VEP response to a 2-Hz reversal, 8 x 8 checkerboard, occupying 20 degrees of the visual field was recorded from occipital locations O1 and O2. VEP recordings were made every five minutes before, during, and after a 10-minute magnetic field exposure period for seven subjects. RESULTS: In contradiction to studies previously reported in the literature for fields of 50 Hz and 60 mT, no significant effects on the peak amplitude or latency of the VEP P100 O1 and O2 responses were found. CONCLUSION: Switched magnetic fields of a level and frequency comparable to those used in MRI do not have a significant effect on primary retinal or visual processing.