Orbito-frontal cortex functional connectivity mediates the relationship between fetal growth and childhood impulsivity

Abstract The prenatal period is critical for a healthy development, and exposure to adversity during it may provoke alterations of several biological tissues and systems, resulting in health outcomes that may take place into childhood and adulthood. The orbito-frontal cortex (OFC), central in cognitive processes, is sensitive to negative environmental effects in the intrauterine environment. We investigated the association between OFC function and decision-making behavior in response to a poor-quality prenatal environment. We evaluated a subsample of the MAVAN longitudinal Canadian birth cohort gathering data on anthropometric measurements at birth, and resting-state functional MRI (rsfMRI) and decision-making (using the Information Sampling Task from the CANTAB battery) measured later in life. We performed a mediation analysis to investigate the direct and indirect effect of being born small for gestational age (SGA) on the Information Sampling Task performance, through OFC-related functional connectivity. Being born SGA is associated with decreased functional connectivity between the left hemisphere OFC and the middle frontal gyrus (OFC–MFG). Additionally, increased OFC–MFG connectivity is linked to better IST performance. Thus, SGA individuals have an altered OFC– MFG functional connectivity, which impacts on their performance on a decision-making task. Lower OFC–MFG functional connectivity and impulsive decision-making were associated to the SGA condition, reflecting a poor-quality prenatal environment. These findings highlight the importance of the prenatal period for a healthy development and suggest that neuroimaging focusing on the affected areas may identify individuals at higher risk of developing psychopathologies, and direct for proper interventions. Competing Interest Statement The authors have declared no competing interest. Funding Statement This study was funded by the Fonds de recherche du Quebec - Sante and Canadian Institutes of Health Research (CIHR, PJT-166,066 and PJT-173,237, PI Silveira PP) and supported by by the JPB Foundation through a grant to the JPB Research Network on Toxic Stress: A Project of the Centre on the Developing Child at Harvard University. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Research Ethics Board approval was received from the Douglas Mental Health University Institute (IUSMD-03-45, IUSDM-13-09). In the current study, only children from Montreal were included. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present work are contained in the manuscript.