Frontal cortical thinning and subcortical volume reductions in early adulthood obesity

https://doi.org/10.1016/j.pscychresns.2013.06.004Get rights and content

Abstract

Obesity depends on homeostatic and hedonic food intake behavior, mediated by brain plasticity changes in cortical and subcortical structures. The aim of this study was to investigate cortical thickness and subcortical volumes of regions related to food intake behavior in a healthy young adult sample with obesity. Thirty-seven volunteers, 19 with obesity (age=33.7±5.7 (20–39) years body-mass index (BMI)=36.08±5.92 (30.10–49.69) kg/m2) and 18 controls (age=32.3±5.9 (21–40) years; BMI=22.54±1.94 (19.53–24.97) kg/m2) participated in the study. Patients with neuropsychiatric or biomedical disorders were excluded. We used FreeSurfer software to analyze structural magnetic resonance images (MRI) and obtain global brain measures, cortical thickness and subcortical volume estimations. Finally, correlation analyses were performed for brain structure data and obesity measures. There were no between-group differences in age, gender, intelligence or education. Results showed cortical thickness reductions in obesity in the left superior frontal and right medial orbitofrontal cortex. In addition, the obesity group had lower ventral diencephalon and brainstem volumes than controls, while there were no differences in any other subcortical structure. There were no statistically significant correlations between brain structure and obesity measures. Overall, our work provides evidence of the structural brain characteristics associated with metabolically normal obesity. We found reductions in cortical thickness, ventral diencephalon and brainstem volumes in areas that have been implicated in food intake behavior.

Introduction

Obesity is a major public health concern in developed countries. Its prevalence worldwide has more than doubled in the last three decades. According to the World Health Organization, in 2008 there were 500 million obese adults over the age of 20 (World Health Organization, 2012b), and in recent years a vast literature on studies on eating behavior has developed.

Obesity results from a chronic imbalance between energy intake and energy expenditure in which the brain plays a fundamental role in modulating hunger and eating behavior (Berthoud and Morrison, 2008). Food intake depends on a complex neural system regulated by two major interacting systems. Firstly, the involvement of homeostatic processes mediated by the hypothalamus and brainstem is well recognized (Suzuki et al., 2010). The hypothalamus plays a major role in appetite regulation and has been related to obesity in animal and human models (Thaler et al., 2012). The brainstem is also involved in food intake modulation, through midbrain dopamine projections to the hypothalamus (Suzuki et al., 2010). However, the hedonic component of feeding behavior provides reinforcement that regulates eating behavior. Hedonic processes, which are not directly implicated in the homeostatic value of food, are basically mediated by mesocorticolimbic pathways that include the prefrontal cortex (Van Vugt, 2010, Hollmann et al., 2011). The prefrontal cortex integrates motivational and cognitive control processes in decision-making contexts, which are necessary for making choices about food consumption (Kouneiher et al., 2009).

Interestingly, converging evidence from magnetic resonance imaging (MRI) studies suggests a relation between body-mass index (BMI) and brain frontal cortex morphology in lean-to-obese samples, with the great majority of results pointing to negative correlations between BMI and gray matter volumes in frontal regions, including the following: inferior frontal gyrus (Taki et al., 2008, Walther et al., 2010, Kurth et al., 2013), orbitofrontal cortex (Raji et al., 2010, Walther et al., 2010, Kurth et al., 2013), frontal pole (Kurth et al., 2013), precentral gyrus (Taki et al., 2008, Walther et al., 2010), and superior frontal gyrus (Taki et al., 2008, Kurth et al., 2013). Moreover, Yokum et al. (2012) reported trend-level reduced gray matter volume in superior frontal gyrus and middle frontal gyrus, related to future BMI increases. In comparisons of obese and lean subjects, gray matter reductions in frontal regions have been related to obesity specifically in inferior frontal gyrus (Brooks et al., 2013), orbitofrontal cortex (Maayan et al., 2011), middle frontal gyrus (Pannacciulli et al., 2006), dorsolateral prefrontal cortex (Brooks et al., 2013), medial prefrontal cortex, supplementary motor area (Brooks et al., 2013), anterior cingulate cortex (Raji et al., 2010, Hassenstab et al., 2012), and frontal operculum (Pannacciulli et al., 2006).

These studies cover life stages from adolescence to old age, but only one study has specifically focused on an early adulthood sample (Pannacciulli et al., 2006). This developmental stage is crucial for the consolidation of the prefrontal lobe structure and should therefore be investigated in relation to brain structure in obesity.

Obesity is commonly associated with vascular risk factors. However, in the general population, it is difficult to isolate the impact of these factors on brain functioning. The effects of isolated vascular risk factors that are present in metabolic syndrome have been associated with brain structure alterations (Segura et al., 2009). None of the previous studies controlled the possible effects of metabolic syndrome (Pannacciulli et al., 2006, Maayan et al., 2011, Brooks et al., 2013, Hassenstab et al., 2012).

Previous studies have focused mostly on voxel-based morphometry. Analysis of cortical thickness is a relatively new approach that is centered specifically on gray matter. It can help to further our understanding of brain structure, beyond the knowledge obtained from voxel-based morphometry. Volumetry involves a mixture of surface and thickness gray matter parameters. Importantly, cortical thickness measurement allows quantitative assessment of the cortical mantle, independently of the regional surface area (Dale et al., 1999, Fischl et al., 1999). Moreover, it has been suggested that cortical thickness is a highly sensitive parameter with an elevated signal-to-noise ratio (Choi et al., 2008, Hutton et al., 2009, Salat et al., 2004) and provides valid measures at submillimeter resolution (Fischl, 2012). In addition, subcortical volume measures may help to assess whether non-cortical regions are involved in food intake behavior. To our knowledge, only one study has used cortical thickness measures to assess structural brain characteristics in obesity (Hassenstab et al., 2012). This study did not apply a whole brain methodology. Hassenstab et al. (2012) focused on the cognitive control network and reported cortical thickness reductions in obesity in three (dorsal anterior cingulate cortex, posterior parietal cortex and anterior insular cortex) of the four regions that were selected a priori. They found no group differences in the dorsal lateral prefrontal cortex.

All the studies mentioned classified obesity status based on BMI. Only one (Walther et al., 2010) considered waist circumference (WC) for further analyses. It would be interesting to study brain structure evaluating different obesity-related measures such as BMI, WC and years of obesity evolution.

The aim of the current study was to establish whether cortical thickness and subcortical volumetry could identify a pattern of brain characteristics related to obesity in an early adulthood sample without metabolic syndrome considering BMI, WC and years of obesity evolution. We predicted that the obesity group would show frontal thinning and subcortical volume reductions compared to normal-weight participants.

Section snippets

Subjects

Thirty-seven participants, 19 with obesity (BMI=36.08±5.92 (30.10–49.69) kg/m2; 6 male, 13 female) and 18 controls (BMI=22.54±1.94 (19.53–24.97) kg/m2; 7 male, 11 female), were recruited from public medical centers belonging to the Consorci Sanitari de Terrassa (Barcelona, Spain). All subjects were volunteers aged between 20 and 40 who met the inclusion criteria: BMI≥30 for obesity and 18.5≤BMI<25 for the control group, following the World Health Organization's classification for obesity and

Results

There were no significant differences (P>0.05) between the obesity and control groups in age, intelligence, years of education (Table 1), gender (68% females in obesity and 58% females in control groups; χ2=0.217), frequency of smokers (8 smokers/11 non-smokers in the obesity group and 4 smokers/14 non-smokers in the control group; χ2=1.668) or frequency of alcohol drinkers (7 drinkers/12 non-drinkers in the obesity group and 10 drinkers/8 non-drinkers in the control group; χ2=1.303).

Global

Discussion

This is the first article analyzing whole brain cortical thickness and subcortical volumes in a metabolically healthy sample of young obese adults, considering BMI, WC and years of obesity evolution.

We found significant bilateral thinning in the frontal cortex in the obese group relative to the control group. Subcortically, the ventral diencephalon in both hemispheres and the brainstem had significantly lower volumes in the obese group than in controls.

The frontal cortex is regarded as a

Acknowledgments

The authors thank all the participants who made this study possible. They also thank Encarnació Tor for her invaluable help in performing blood analyses. This study was supported by grant PSI2008-05803-C02-00/PSIC from MICINN to Maria Angeles Jurado, grant ADR2011-2012 from the University of Barcelona to Idoia Marqués-Iturria, and grant 2009 SGR0941 from the Government of Catalonia.

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