Gradual gastric distention (GD) paradigm.

<p>The deflated balloon was inserted orally and positioned in the stomach 2-cm above the gastro-esophageal junction. The solid and dashed lines depict the emptied (0 ml) and filled (500 ml for GD1 or 700 ml for GD2) balloon conditions. The balloon was filled and emptied with constant flow (5 ml/s) of tap water (warmed at 37°C) in either 90s to 500 ml (GD1) or in 140 s to 700 ml (GD2). The vagus nerve transmits the signal of a full stomach to the solitary and parabrachial nuclei in the brain stem that project to dopaminergic and serotonergic nuclei in midbrain and pons. Other regions implicated in the control of food intake are additionally highlighted (hypothalamus, amygdala, and cerebellum).</p

Association of BOLD signals in hyper- and hypo-activated regions.

<p>Regression plots exemplifying positive and negative cross-correlations of BOLD-fMRI signals (averaged across all volumetric conditions; 125, 375, 500, 600, and 700 ml) in different ROIs (listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0006847#pone-0006847-t001" target="_blank">Table 1</a>). Sample = 24 subjects.</p

BOLD signals in hypo-activated regions vs. BMI.

<p>Scatter plots exemplifying the negative correlations between BMI and the average BOLD-fMRI responses across all volumetric conditions (125, 375, 500, 600, and 700 ml) in dopaminergic brain regions (hypothalamus, midbrain, and amygdala) during gradual GD (N = 24).</p

Brain activation during gradual gastric distention (GD).

<p>Top panel: Statistical maps showing regions with significant brain activation (red-yellow) and deactivation (blue-green) during gradual GD. Bottom panel: correlations between BMI and BOLD-fMRI responses in the brain during gradual GD. Threshold for statistical significance: <i>P</i>_corr<0.05 corrected for multiple comparisons using the family-wise error (FWE) correction. Sample: 24 healthy controls. Data from all 47 GD1 and 43 GD2 fMRI runs were included in SPM2 multiple regression analyses. Activation/correlation patterns reflecting the effect of volume were not significant in any brain region.</p

Drug-word fMRI paradigm.

<p>Drug-word fMRI paradigm.</p

Functional connectivity of midbrain.

<p>Statistical maps of normalized CM coefficients during task epochs of the DW task across word conditions (“Drug” and “Neutral”) for 20 cocaine abusers (left) and 20 healthy matched control subjects (right). Random-effects analyses (two-way repeated measures ANOVA). Red-yellow and blue-green color bars show the <i>t</i>-score windows.</p

Functional connectivity analysis of task-related signal fluctuations during the blocked fMRI paradigm.

<p><b>A</b>: BOLD response elicited by the drug-word paradigm (black curve) and the fitted SPM2 canonic hemodynamic response (red curve). The gray periods identify the plateaus of the model. <b>B</b>: “Word” time series are composed by 37 the time points of plateau 1 (green curve) and the 37 time points of plateau 2 (blue curve). <b>C</b>: Mid-sagittal slice of an MRI structure showing the position of the midbrain seed used for the functional connectivity analysis. D: Mid-saggital slice exemplifying the normalized (z-score) maps reflecting correlations of MRI signals in the brain with those in midbrain. These individual maps were used in group analyses of functional connectivity.</p

Behavioral responses during gradual GD.

<p>Ratings of fullness, discomfort, hunger, and desire for food, collected during the empty and full balloon conditions for GD1 (500 ml) and GD2 (700 ml). (*) P<0.0002.</p

Functional Connectivity during gastric distention.

<p>Statistically significant cross-correlations among time-varying fMRI signals in the 27 ROIs listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0006847#pone-0006847-t001" target="_blank">Table 1</a>; Sample: 24 subjects, 90 fMRI runs; t-test; statistical threshold <i>P</i>_c<0.05 (Bonferroni correction for 351 comparisons).</p

BOLD signals in hyper-activated regions vs. BMI.

<p>Scatter plots exemplifying the positive correlations between the body mass index (BMI) and the average BOLD-fMRI response across all volumetric conditions (125, 375, 500, 600, and 700 ml) in cerebellum and posterior insula during gradual GD (N = 24).</p