Obesity has reached epidemic proportions globally to become a major public health problem. Obesity-related health problems are numerous including strokes, cardiovascular disease, diabetes mellitus, and increased risk for developing cancer [1]. Reward mechanism of obese patients regarding functional connectivity has been declared by several studies [2, 3], but few studies mentioned about the correlation between functional images and clinical indices. Thus, our study aimed to find out abnormal functional connectivity over obese patients based on amplitude low frequency fluctuation (ALFF) [4] and regional homogeneity (ReHo) [5] using voxel-based analysis, and the correlation between functional images and clinical indices, including body mass index (BMI) and hospital anxiety and depression scale (HADS).

Fifty participants were recruited, including 20 obese patients (BMI = 37.9 ± 5.2) and 30 age-matched healthy controls (BMI = 22.6 ± 3.4). All images were acquired using a 1.5T MRI (Ingenia, Phillips, Netherlands) with an 8 channel head coil. All participants received resting-state functional magnetic resonance imaging (rs-fMRI) scan, and they were instructed not to focus their thoughts on anything in particular and to keep their eyes closed during the resting state MR acquisition. Image parameter were TR/TE = 2000/30 ms, in-plane resolution (pixel size) = 3.9 x 3.9 mm², slice thickness = 5 mm, number of repetition = 400, and 20 axial slices.

Preprocessing was carried out using data processing assistant for resting-state fMRI which is based on statistical parametric mapping (SPM8) and resting-state fMRI data analysis toolkit (REST). The anatomical image was normalized to the Montreal Neurological Institute template, and the resulting parameter file was used to normalize the functional images. Finally, the normalized images were smoothed with a three-dimensional isotropic Gaussian kernel (full-width at half-maximum, FWHM: 6 mm). A temporal filter (0.01–0.12 Hz) was applied to reduce low frequency drifts and high frequency physiological noise. Nuisance regression was performed using white matter, cerebrospinal fluid (CSF), and the six head motion parameters as covariates. Data analysis included assessments of functional connectivity, amplitude low-frequency fluctuations (ALFF), regional homogeneity (ReHo) and voxel-based statistical analysis. Correlations between the functional results and BMI, depression, and anxiety scores were also calculated and discussed.

Our results showed the obese patients had significant decreased functional connectivity in the frontal gyrus, and had significant increased in the anterior cingulated cortex (ACC) compared to healthy controls (Fig. 1). In the results of voxel-based ALFF analysis, higher ALFF of lentiform nucleus and parahippocampa gyrus, and lower ALFF of superior frontal gyrus (SupFG), medial frontal gyrus (MedFG) and cuneus were observed in the obese patients compared to healthy controls (Fig. 2a, 2b, 2c). In the correlation analysis, a positive correlation in the lentiform nucleus, putamen and hippocampus, and a negative correlation in the SupFG, MedFG and cuneus were found between ALFF and BMI (Fig. 2d, 2e). A positive correlation in the precuneus, and a negative correlation in the SupFG and MedFG were found between ALFF and anxiety score (Fig. 2f, 2g). A positive correlation in the thalamus, and a negative correlation in the SupFG and MedFG were found between ALFF and depression score (Fig. 2h, 2i). In the results of voxel-based ReHo analysis, lower ReHo of SupFG, MedFG, middle frontal gyrus (MidFG) and cuneus were observed in the obese patients (Fig. 3a, 3b). In the correlation analysis, a negative correlation in the SupFG and cuneus were found between the ReHo and BMI (Fig. 3c). A negative correlation in the MedFG and cuneus were found between ReHo and anxiety score (Fig. 3d). A negative correlation in the fusiform gyrus, SupFG and MedFG were found between ReHo and depression score (Fig. 3e).Previously study mentioned the obese showed hyper-responsivity to food cues in ACC and visual cortex, which could reflect an overall heightened reward sensitivity to these cues that could increase risk for obese [6]. Our results of functional connectivity were consisted with the study [6]. In the correlation analysis, we revealed significant negative correlation between ALFF/ReHo and clinical indices in the frontal gyrus and cuneus, which plays an important role in inhibitory control and involved in processing visual information in humans, respectively [2]. Previously study mentioned that reward mechanism is composed by desire, value appraisal, and inhibitory control, and dysregulation of reward mechanism is the major cause of obesity [3].We found the brain functional abnormality in the obese patients compared to healthy controls, and the correlation with depression and anxiety. The potential functional imaging markers may provide guidance for managing obesity and disordered eating behaviors, and may change the situation of obesity issue which is prevailing today.