title: Thalamocortical functional connectivity and behavioral disruptions in neonates with prenatal cocaine exposure.
abstract: Prenatal cocaine exposure (PCE) affects neurobehavioral development, however, disentangling direct drug-related mechanisms from contextual effects (e.g., socioeconomic status) has proven challenging in humans. The effects of environmental confounds are minimal immediately after birth thus we aimed to delineate neurobehavioral correlates of PCE in a large cohort of neonates (2-6weeks of age, N=152) with and without drug exposure using resting state functional magnetic resonance imaging (rsfMRI) and developmental assessments at 3months with the Bayley Scales of Infant & Toddler Development, 3rd edition. The cohort included healthy controls and neonates with similar poly-drug exposure±cocaine. We focused on the thalamus given its critical importance in early brain development and its unique positioning in the dopamine system. Our results revealed PCE-related hyper-connectivity between the thalamus and frontal regions and a drug-common hypo-connective signature between the thalamus and motor-related regions. PCE-specific neonatal thalamo-frontal connectivity was inversely related to cognitive and fine motor scores and thalamo-motor connectivity showed a positive relationship with composite (gross plus fine) motor scores. Finally, cocaine by selective-serotonin-reuptake-inhibitor (SSRI) interactions were detected, suggesting the combined use of these drugs during pregnancy could have additional consequences on fetal development. Overall, our findings provide the first delineation of PCE-related disruptions of thalamocortical functional connectivity, neurobehavioral correlations, and drug-drug interactions during infancy.
authors.affiliation: Biomedical Imaging Research Institute (BIRI), Department of Biomedical Sciences and Imaging, Cedars-Sinai Medical Center, Los Angeles, USA; University of North Carolina Chapel Hill, Department of Radiology and Biomedical Research Imaging Center, Chapel Hill, NC 27599, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Salzwedel
authors.affiliation: University of North Carolina Chapel Hill, Department of Psychiatry, Neurobiology, and Psychology, Chapel Hill, NC 27599, USA. Electronic address: Karen_Grewen@med.unc.edu.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Grewen
authors.affiliation: University of North Carolina Chapel Hill, Department of Psychology and Neuroscience, FPG Child Development Institute, Chapel Hill, NC 27599, USA.
authors.forename: Barbara D
authors.initials: BD
authors.lastname: Goldman
authors.affiliation: Biomedical Imaging Research Institute (BIRI), Department of Biomedical Sciences and Imaging, Cedars-Sinai Medical Center, Los Angeles, USA; University of North Carolina Chapel Hill, Department of Radiology and Biomedical Research Imaging Center, Chapel Hill, NC 27599, USA. Electronic address: Wei.Gao@csmc.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
mesh_terms: D001931:Brain Mapping; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology*; D003042:Cocaine / Q000009:adverse effects*; D005260:Female; D005865:Gestational Age; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D009043:Motor Activity; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D009483:Neuropsychological Tests; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology* / Q000523:psychology*; D013788:Thalamus / Q000187:drug effects* / Q000503:physiopathology*
chemical_list: D003042:Cocaine
keywords: Behavior; Connectivity; Neonate; Prenatal cocaine exposure; Thalamus; fMRI