Human brainstem and hypothalamic responses to nutritional stimuli have been characterised in vivo using physiological functional magnetic resonance imaging (phys-fMRI)(1,2). This permits detailed comparison of spatiotemporal responses to different nutrient stimuli. One important discrepancy between human studies in this area is the method of nutrient administration used (intragastric versus oral). In reality, oral taste sequentially precedes gastrointestinal chemosensation and it is likely there is an interaction between the two sensory phases, which may occur within the CNS. Therefore, using fMRI, the purpose of the study was twofold: first, to establish the effects of oral and sequential gastrointestinal, “sweetness” on brain activation and second, to investigate whether oral sweet taste affects the gut to brain signal. 15 healthy fasted subjects were scanned in a single blind, randomised control trial involving 4 visits. Brain activation responses were mapped following a test solution of either glucose or artificial saliva (oral control) delivered into the mouth. Subjects were asked to hold the solution in the mouth and swallow on cue. Subjects then received an intragastric (IG) bolus of either glucose or saline (IG control). Data were analysed using Statistical Parametric Mapping (SPM8). First level analysis was performed on each subject for each study condition by splitting the scans into 26 consecutive 1 min time bins (one minute prior to and 25 following the IG infusion) at 5 minutes with Blood Oxygen Level Dependent (BOLD) signal averaged across the bin. The BOLD signal in each time bin was compared with the baseline average. A second level random effects ANOVA was used to investigate the effect that oral taste had on the glucose-induced intragastric BOLD signal. There was a significant (qFDR<0.05) interaction between oral taste and gastric infusion in several areas including the hypothalamus, pons and midbrain. Further analysis showed that this interaction was driven by abolition of the glucose-induced BOLD signal after an oral taste of glucose in most brain regions. This abolition was not observed following the artificial saliva condition. A representative time course is shown in figure 1. These findings suggest that pre-stimulation of sweet taste receptors in the mouth abolishes the reduction in BOLD signal previously seen in response to glucose infused directly into the gut lumen. The exact mechanism and physiological significance of this are not known, but sensory inputs transmitted from the oral cavity may directly modulate the gut-to-brain signals activated from the gut lumen by ingested nutrients.