title: The neurobiological drive for overeating implicated in Prader-Willi syndrome.
abstract: Prader-Willi syndrome (PWS) is a genetic imprinting disorder characterized mainly by hyperphagia and early childhood obesity. Previous fMRI studies examined the activation of eating-related neural circuits in PWS patients with or without exposures to food cues and found an excessive eating motivation and a reduced inhibitory control of cognitive processing of food. However, the effective connectivity between various brain areas or neural circuitry critically implicated in both the biological and behavioral control of overeating in PWS is largely unexplored. The current study combined resting-state fMRI and Granger causality analysis (GCA) techniques to investigate interactive causal influences among key neural pathways underlying overeating in PWS. We first defined the regions of interest (ROIs) that demonstrated significant alterations of the baseline brain activity levels in children with PWS (n = 21) as compared to that of their normal siblings controls (n = 18), and then carried out GCA to characterize the region-to-region interactions among these ROIs. Our data revealed significantly enhanced causal influences from the amygdala to the hypothalamus and from both the medial prefrontal cortex and anterior cingulate cortex to the amygdala in patients with PWS (P < 0.001). These alterations offer new explanations for hypothalamic regulation of homeostatic energy intake and impairment in inhibitory control circuit. The deficits in these dual aspects may jointly contribute to the extreme hyperphagia in PWS. This study provides both a new methodological and a neurobiological perspective to aid in a better understanding of neural mechanisms underlying obesity in the general public. This article is part of a Special Issue entitled 1618.
authors.affiliation: School of Life Science and Technology, Xidian University, Xi'an 710071, Shaanxi, China; Department of Psychiatry & McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA. Electronic address: zhangyiuf@gmail.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Life Science and Technology, Xidian University, Xi'an 710071, Shaanxi, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Life Science and Technology, Xidian University, Xi'an 710071, Shaanxi, China.
authors.forename: Guansheng
authors.initials: G
authors.lastname: Zhang
authors.affiliation: School of Life Science and Technology, Xidian University, Xi'an 710071, Shaanxi, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: School of Life Science and Technology, Xidian University, Xi'an 710071, Shaanxi, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Cai
authors.affiliation: School of Life Science and Technology, Xidian University, Xi'an 710071, Shaanxi, China; Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Psychiatry & McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA; Malcom Randall Veterans Affairs Medical Center, Gainesville, FL 32608, USA.
authors.forename: Yi Edi
authors.initials: YE
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Miller
authors.affiliation: Department of Psychology, Remin University of China, Beijing 100872, China.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Wen
authors.affiliation: Department of Biomedical Engineering, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Mingzhou
authors.initials: M
authors.lastname: Ding
authors.affiliation: Department of Psychiatry & McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Gold
authors.affiliation: Department of Psychiatry & McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA; Department of Psychology, Southwest University, Chongqing 400715, China. Electronic address: yijunliu@ufl.edu.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Liu
mesh_terms: D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D002648:Child; D005260:Female; D006801:Humans; D006963:Hyperphagia / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology; D009765:Obesity / Q000503:physiopathology; D011218:Prader-Willi Syndrome / Q000503:physiopathology*; D012146:Rest; D035781:Siblings; D012815:Signal Processing, Computer-Assisted
keywords: Granger causality; Obesity; Overeating; PWS; Resting-state fMRI