fMRI-Based Brain Responses to Quinine and Sucrose Gustatory Stimulation for Nutrition Research in the Minipig Model: A Proof-of-Concept Study

Abstract

The minipig model is of high interest for brain research in nutrition and associated pathologies considering the similarities to human nutritional physiology, brain structures, and functions. In the context of a gustatory stimulation paradigm, fMRI can provide crucial information about the sensory, cognitive, and hedonic integration of exteroceptive stimuli in healthy and pathological nutritional conditions. Our aims were (i) to validate the experimental setup, i.e., fMRI acquisition and SPM-based statistical analysis, with a visual stimulation; (ii) to implement the fMRI procedure in order to map the brain responses to different gustatory stimulations, i.e., sucrose (5%) and quinine (10 mM), and (ii) to investigate the differential effects of potentially aversive (quinine) and appetitive/pleasant (sucrose) oral stimulation on brain responses, especially in the limbic and reward circuits. Six Yucatan minipigs were imaged on an Avanto 1.5-T MRI under isoflurane anesthesia and mechanical ventilation. BOLD signal was recorded during visual or gustatory (artificial saliva, sucrose, or quinine) stimulation with a block paradigm. With the visual stimulation, brain responses were detected in the visual cortex, thus validating our experimental and statistical setup. Quinine and sucrose stimulation promoted different cerebral activation patterns that were concordant, to some extent, to results from human studies. The insular cortex (i.e., gustatory cortex) was activated with both sucrose and quinine, but other regions were specifically activated by one or the other stimulation. Gustatory stimulation combined with fMRI analysis in large animals such as minipigs is a promising approach to investigate the integration of gustatory stimulation in healthy or pathological conditions such as obesity, eating disorders, or dysgeusia. To date, this is the first intent to describe gustatory stimulation in minipigs using fMRI.

fMRI‐Based Brain Responses to Olfactory Stimulation with Two Putatively Orexigenic Functional Food Ingredients at Two Different Concentrations in the Pig Model

“…Here, we implemented the experimental stimulation set‐up to fMRI in order to investigate, within the same imaging session and without prior familiarization to the ingredients, the brain responses under olfactory stimulation with two different feed ingredients at two different concentrations. We have previously shown the potential of fMRI in the pig model for the screening of brain responses to pleasant/unpleasant gustatory stimulations (Coquery et al., ). In the present study, our paradigm was successful in screening the brain responses to each ingredient and allowed for direct comparison between them.…”

“…Imaging was performed during 5 days, with four animals being imaged per day. Image acquisition was performed as previously described (Coquery et al., ) on a 1.5‐T magnet (Siemens Avanto, Erlangen, Germany) at the Rennes Platform for Multimodal Imaging and Spectroscopy (PRISM). Acquisitions were performed using a combination of coils (Body and Spine matrix coils) for optimized signal‐to‐noise ratio acquisition.…”

“…Further details regarding the validity and limitations of the statistical approach used in this model and paradigm are described in Coquery et al. (). …”

“…Based on these behavioral data, we further investigated the impact of one of these ingredients (mainly composed of Citrus sinensis extracts) on brain glucose metabolism via 18 F‐fluoro‐deoxy‐glucose (FDG) positron emission tomography (PET), and in response to olfactogustatory response with or without prior familiarization to the ingredient (Val‐Laillet, Meurice, & Clouard, ). Because the FDG‐PET imaging modality can test only one condition per imaging session, we developed a functional magnetic resonance imaging (fMRI) approach in the pig model to discriminate brain responses to different gustatory stimulations (Coquery et al., ). Here, we adapted this set‐up to olfactory stimulation to evaluate brain responses to the odor of two feed ingredients at different concentrations within the same imaging session.…”

Review: Impact of food, gut–brain signals and metabolic status on brain activity in the pig model: 10 years of nutrition research using in vivo brain imaging

“…More recently, using fMRI, we aimed to compare oral sweet and bitter gustatory stimulation (Table 1; Coquery et al, 2018). The advantage of fMRI for comparing brain responses to different food stimuli is that multiple [123I]-FP-CIT = N-(3-Fluoropropyl)-2β-carbomethoxy-3β-(4-[ 123 I]iodophenyl)nortropane; BBB = blood-brain barrier; CT = computed tomography; DatScan = dopamine transporter scanner; MRS = magnetic resonance spectroscopy; VNS = vagus nerve stimulation; GB = gastric bypass; 18FDG = 18F-fluorodeoxyglucose; PET = positron emission tomography; 99mTc-HMPAO = 99mTc-hexamethylpropyleneamine oxime; SPECT = single-photon computed tomography; fMRI = functional magnetic resonance imaging.…”