Integrated Multimodal Brain Signatures Predict Sex-Specific Obesity Status

Background: While neuroimaging has uncovered mechanisms causing altered ingestive behaviors, few studies have integrated data from multimodal brain imaging to predict sex-specific brain signatures in individuals with obesity. A data-driven approach was used to uncover a correlated signature between differential brain phenotypes and clinical data that predicts sex-specific obesity status.Methods: 183 participants (Female = 118; Male = 65; Obese = 78; Non-obese = 105) underwent multimodal MRI (structural, functional resting-state, and diffusion tensor imaging). A Data Integration Analysis using Latent Components (DIABLO) was conducted using training and test sets to determine whether multimodal brain signatures could differentiate individuals stratified by obesity and sex. Significant brain regions and clinical variables were correlated.Results: The derived models were tested on holdout testing data differentiating obese against nonobese, and obese males against obese females obtaining accuracies of 74% and 74%. Kappa of the respective models were 46%, and 40% while BER of the respective models were 26% and 32%. Pertinent features were extracted with the absolute loadings on each component of the models.Conclusions: Alterations in anatomical and resting state functional connectivity (RSFC) in the default mode (DMN) and reward network suggest the role of dopaminergic dysregulation and impaired homeostatic processing in individuals with obesity. Greater psychological resilience was also correlated with lowered structural integrity in the DMN as the inability to handle large cognitive loads could lead to anxiety and hedonic eating. Females with obesity had greater RSFC in the sensorimotor network suggesting an altered reorientation of attentional resources, while males had lower RSFC in DMN associated with weakening cognitive control circuits. These sex-specific brain signatures suggest the need for targeted diet interventions for the prevention and treatment of obesity.