Research articleFunctional Magnetic Resonance Imaging (fMRI) of Neural Responses to Visual and Auditory Food Stimuli Pre and Post Roux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG)☆,☆☆
Introduction
Of the current treatments for obesity, bariatric surgery produces the largest weight loss (Chang et al., 2014, Clemens et al., 2015, Colquitt et al., 2014, Munzberg et al., 2015, Picot et al., 2009, Spaniolas et al., 2016). With the marked increase in number of bariatric surgeries to 179,000 annually in the US (Matarese and Pories, 2014; Surgery ASfMaB, 2017), greater understanding of the mechanisms of action is essential. Major obesity surgeries currently performed include the Roux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG), which result in similar weight loss after 5 years (Chang et al., 2014). They also induce appetite-related hormonal changes postsurgery, suggesting a hormonal role in reducing food intake (Mohos et al., 2014, Rubino et al., 2004).
Functional neuroimaging offers a non-invasive approach to studying neural aspects of obesity (Carnell et al., 2014, Geliebter et al., 2006). Participants with obesity (vs. of normal weight) show increased brain activity in reward areas (e.g. ventral striatum, putamen) in response to palatable high-energy dense (HED) food cues compared to low-energy dense (LED) ones (Carnell et al., 2014, Jensen and Kirwan, 2015). In patients with obesity, at 1 month post RYGB, we previously found reduced activity in dopaminergic reward pathways (ventral tegmental area [VTA], ventral striatum, putamen, dorsolateral prefrontal cortex [dlPFC]) in response to HED vs. LED cues, suggesting some normalization of food stimuli response (Ochner et al., 2011). However, there were no control groups included in that study. RYGB also induces hormonal changes (e.g. GLP-1), which could in turn modify neural activity in response to food cues, but hormonal changes were also not assessed. Goldman et al. examined neural responses to visual food vs. neutral cues postsurgery and found that food craving activated the dorsomedial prefrontal cortex (dmPFC) whereas resistance to food craving elicited activity of the dlPFC, but that study was cross-sectional at postsurgery only (Goldman et al., 2013). Scholtz et al. reported lower fMRI reward activation in the orbitofrontal cortex (OFC), amygdala, caudate nucleus, and hippocampus in response to HED visual stimuli after RYGB vs. gastric banding (GB) in another cross-sectional postsurgical study (Scholtz et al., 2014). In a collaborative study with the University of Pennsylvania, we compared changes in fMRI to visual food cues 6 months after RYGB and SG and found decreased activation of the VTA for HED > LED stimuli, relative to a non-treatment (NT) control; however, that study lacked a nonsurgical weight loss (WL) control group (Faulconbridge et al., 2016).
Functional connectivity (FC) expands upon the univariate single brain region analysis to explore connectivity between multiple brain regions. Psychophysiological Interaction (PPI) reveals how a single brain region (seed region) interacts with others (target regions). Previous studies using PPI involving subjects with obesity have explored connectivity in reward areas such as the VTA or the nucleus accumbens (NAcc) but have not addressed potential changes after bariatric surgery (Carnell et al., 2014, Filbey and Yezhuvath, 2017, Garcia-Garcia et al., 2013, Nummenmaa et al., 2012, Stoeckel et al., 2009).
We examined fMRI responses to auditory and visual stimuli following RYGB and SG compared to two controls: dietary WL and NT. We also conducted a PPI analysis based on the activation findings. We anticipated decreased postoperative responsivity to HED vs. LED cues in reward areas in both surgery groups. Since nonsurgical weight loss is often followed by weight regain, we expected that WL would show increased brain responsivity in reward areas vs. the surgery groups (Lager et al., 2017, Sepulveda et al., 2017). We also expected to see differences in connectivity between the RYGB and SG vs. WL and NT groups, given evidence that individuals with obesity have altered brain networks (Gupta et al., 2015). We used a whole brain approach to yield new insights, as opposed to a region of interest (ROI) approach for more confirmational investigation. We also examined postprandial plasma GLP-1, an anorexigenic peptide which increases postprandially following RYGB and to a lesser extent following SG (Manning et al., 2015a, Manning et al., 2015b, Ochner et al., 2010, Salehi and D'Alessio, 2014, Svane and Madsbad, 2014). We anticipated that the changes in postprandial GLP-1 concentrations in the surgical groups would correlate with changes in brain activity in reward areas of the brain.
Understanding postsurgical neural activation changes could help guide improved treatments for obesity, including optimizing surgery type as well as developing non-surgical pharmaceutical interventions with new neural targets.
Section snippets
Participants
Participants were recruited from the Center for Weight Loss surgery at a large, university-affiliated hospital in New York City (Table 1). Subjects for the control groups were individuals with obesity of comparable body mass index (BMI) and were recruited by advertising from the local community (Table 1). There were 1164 potential candidates who were screened for inclusion criteria such as age (18–65), weight (< 5% weight fluctuation in previous three months), BMI (40.0 < BMI < 55.0 kg/m2). RYGB
Preprocessing
Functional data were analyzed with SPM8 (Wellcome Department of Imaging Neuroscience, London, United Kingdom). Before statistical analyses, the realigned T2*-weighted volumes were slice-time corrected, spatially transformed to a standardized brain (Montreal Neurological Institute) and smoothed with an 8 mm full-width half-maximum Gaussian kernel.
1st level processing
The first 12 s of each run were discarded to attain magnetic equilibration. The 12 blocks for each subject's 1st level analysis were concatenated to
Results
The subject characteristics are shown in Table 1. Ages differed between RYGB and SG (p = 0.024). The mean change in BMI (kg/m2) was − 9.1 following RYGB and − 8.9 following SG, while the change after WL was − 5.2, and there was little change, as expected, in NT, − 0.8. Pre vs. post BMI changes across groups were significant, F (1,24), 5.83, p = 0.024 (RYGB > NT, RYGB > WL, SG > NT, SG > WL, all p's < 0.00002, but not between the two surgery groups, p = 0.43).
Discussion
Whole brain analysis revealed postsurgical group differences in activation in the dlPFC and PHG/fusiform in response to visual and auditory HED > LED food cues. For both the visual and auditory stimuli presentations, the dlPFC and the PHG/fusiform activation showed similar patterns in the differences within each group, which supports the findings. Although WL reduced BMI significantly less than surgery, we statistically controlled for BMI change. Thus, the dlPFC and PHG/fusiform activation
Conflicts of interest
The authors declare no conflict of interest.
Acknowledgments
We thank Julio Teixeira, MD, for help in recruiting patients at the Center for Weight Loss Surgery, Joy Hirsch, PhD, for help with arranging the fMRI scans, and Sam Tweardy for technical assistance. The study was funded by R01DK080153 (AG).
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2023, Molecular MetabolismCitation Excerpt :These efforts have identified increased functional connectivity of the orbitofrontal cortex (OFC) and decreased functional connectivity of the insula as the major culprits for problematic eating and obesity [151], and led to formulating the ‘triadic model’ to explain increased food consumption, consisting of 1) increased sensitivity for, and reactivity to food reward, 2) decreased inhibitory control in executive decision making often combined with increased impulsivity, and 3) numbing of interoceptive homeostatic metabolic signaling [151–154]. Applied to bariatric surgery, most studies demonstrate normalization of impaired activity and/or connectivity patterns in the obese (before surgery) towards patterns observed in lean controls (VSG [155–158], RYGB [155,159–165]). In one study presurgical functional connectivity predicted the magnitude of weight loss induced by VSG [166], and another study found that activation of cortical areas involved in inhibitory control was significantly greater after RYGB compared to VSG [155].
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Acknowledgments: We thank Julio, MD, for help in recruiting patients at the Center for Weight Loss Surgery, Joy Hirsch, PhD, for help with arranging the fMRI scans, and Sam Tweardy for technical assistance. The study was funded by NIH Grant DK R01080153 (AG).
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Conflicts of interest: The authors declare no conflict of interest.