title: Resting-State Brain and the FTO Obesity Risk Allele: Default Mode, Sensorimotor, and Salience Network Connectivity Underlying Different Somatosensory Integration and Reward Processing between Genotypes.
abstract: Single-nucleotide polymorphisms (SNPs) of the fat mass and obesity associated (FTO) gene are linked to obesity, but how these SNPs influence resting-state neural activation is unknown. Few brain-imaging studies have investigated the influence of obesity-related SNPs on neural activity, and no study has investigated resting-state connectivity patterns. We tested connectivity within three, main resting-state networks: default mode (DMN), sensorimotor (SMN), and salience network (SN) in 30 male participants, grouped based on genotype for the rs9939609 FTO SNP, as well as punishment and reward sensitivity measured by the Behavioral Inhibition (BIS) and Behavioral Activation System (BAS) questionnaires. Because obesity is associated with anomalies in both systems, we calculated a BIS/BAS ratio (BBr) accounting for features of both scores. A prominence of BIS over BAS (higher BBr) resulted in increased connectivity in frontal and paralimbic regions. These alterations were more evident in the obesity-associated AA genotype, where a high BBr was also associated with increased SN connectivity in dopaminergic circuitries, and in a subnetwork involved in somatosensory integration regarding food. Participants with AA genotype and high BBr, compared to corresponding participants in the TT genotype, also showed greater DMN connectivity in regions involved in the processing of food cues, and in the SMN for regions involved in visceral perception and reward-based learning. These findings suggest that neural connectivity patterns influence the sensitivity toward punishment and reward more closely in the AA carriers, predisposing them to developing obesity. Our work explains a complex interaction between genetics, neural patterns, and behavioral measures in determining the risk for obesity and may help develop individually-tailored strategies for obesity prevention.
authors.affiliation: Functional Pharmacology, Department of Neuroscience, Uppsala University Uppsala, Sweden.
authors.forename: Gaia
authors.initials: G
authors.lastname: Olivo
authors.affiliation: Functional Pharmacology, Department of Neuroscience, Uppsala University Uppsala, Sweden.
authors.forename: Lyle
authors.initials: L
authors.lastname: Wiemerslage
authors.affiliation: Functional Pharmacology, Department of Neuroscience, Uppsala University Uppsala, Sweden.
authors.forename: Emil K
authors.initials: EK
authors.lastname: Nilsson
authors.affiliation: Functional Pharmacology, Department of Neuroscience, Uppsala University Uppsala, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Solstrand Dahlberg
authors.affiliation: Functional Pharmacology, Department of Neuroscience, Uppsala University Uppsala, Sweden.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Larsen
authors.affiliation: Functional Pharmacology, Department of Neuroscience, Uppsala University Uppsala, Sweden.
authors.forename: Marcela
authors.initials: M
authors.lastname: Olaya Búcaro
authors.affiliation: Functional Pharmacology, Department of Neuroscience, Uppsala University Uppsala, Sweden.
authors.forename: Veronica P
authors.initials: VP
authors.lastname: Gustafsson
authors.affiliation: Functional Pharmacology, Department of Neuroscience, Uppsala University Uppsala, Sweden.
authors.forename: Olga E
authors.initials: OE
authors.lastname: Titova
authors.affiliation: Functional Pharmacology, Department of Neuroscience, Uppsala University Uppsala, Sweden.
authors.forename: Marcus
authors.initials: M
authors.lastname: Bandstein
authors.affiliation: Section of Neuroradiology, Department of Radiology, Uppsala University Uppsala, Sweden.
authors.forename: Elna-Marie
authors.initials: EM
authors.lastname: Larsson
authors.affiliation: Functional Pharmacology, Department of Neuroscience, Uppsala University Uppsala, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Benedict
authors.affiliation: Department of Psychiatry, University of Cape Town Cape Town, South Africa.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Brooks
authors.affiliation: Functional Pharmacology, Department of Neuroscience, Uppsala University Uppsala, Sweden.
authors.forename: Helgi B
authors.initials: HB
authors.lastname: Schiöth
keywords: FTO; MRI; SNP; default mode network; obesity; resting-state; salience network; sensorimotor network