Glucose modulates food-related salience coding of midbrain neurons in humans

Abstract

Although early rat studies demonstrated that administration of glucose diminishes dopaminergic midbrain activity, evidence in humans has been lacking so far. In the present functional magnetic resonance imaging study, glucose was intravenously infused in healthy human male participants while seeing images depicting low-caloric food (LC), high-caloric food (HC), and non-food (NF) during a food/NF discrimination task. Analysis of brain activation focused on the ventral tegmental area (VTA) as the origin of the mesolimbic system involved in salience coding. Under unmodulated fasting baseline conditions, VTA activation was greater during HC compared with LC food cues. Subsequent to infusion of glucose, this difference in VTA activation as a function of caloric load leveled off and even reversed. In a control group not receiving glucose, VTA activation during HC relative to LC cues remained stable throughout the course of the experiment. Similar treatment-specific patterns of brain activation were observed for the hypothalamus. The present findings show for the first time in humans that glucose infusion modulates salience coding mediated by the VTA. Hum Brain Mapp 37:4376-4384, 2016. © 2016 Wiley Periodicals, Inc.

Keywords: functional magnetic resonance imaging; glucose modulation; mesolimbic system; obesity; reward; salience coding; ventral tegmental area.

Figure 1

(A) Six example stimuli, taken from the food‐pics database [Blechert et al., 2014]. (B) Schematic overview of the fMRI experiment which consisted of four inherent experimental phases with 6.4 min duration each, not noticeable to participants. After phase 1, participants of the glucose group received 10 g glucose dissolved in 50 ml saline, intravenously infused within 30 s. The control group did not receive any infusion. 15 LC and 15 HC food cues as well as 30 NF pictures were presented per phase. The task during fMRI was to discriminate between food and NF pictures.

Figure 2

Treatment by Phase by Condition interaction reflecting a greater difference in neural activation elicited by high‐caloric minus low‐caloric food cues for phase 1 relative to phase 3 for the glucose‐treated group vs. the untreated control group. Depicted are significant voxels within the ROIs covering the VTA (for ROI delineation, see Supporting Information Fig. 1) and the hypothalamus. Respective mean parameter estimates are shown in Figures 3 and 4. Statistical parametric maps were overlaid on transverse (left) and sagittal (right) sections of a PD image obtained by averaging over all participants (n = 42). Coordinates refer to MNI space. L: left; R: right.

Figure 3

Averaged magnitude of neural activation [arbitrary unit] derived from 13 significant voxels of the VTA for the glucose group (left) and the control group (right). Activation was greater for HC (in red) than for LC (in green) food cues during phase 1. After phase 1 when the glucose group received a bolus of 10 g glucose intravenously, the VTA's hemodynamic response reversed, with greater activation during LC relative to HC food cues. In the untreated control group, VTA activation was consistently higher in response to HC than LC stimuli. Please see also Supporting Information Figure 2 which includes the NF condition. Error bars represent standard error of the mean.

Figure 4

Magnitude of hypothalamic activation [arbitrary unit] during LC (in green) and HC (in red) food cues averaged across 10 significant voxels. Please see also Supporting Information Figure 3 which includes activation for the NF condition. Error bars represent standard error of the mean.