667 - Brain Functional Connectivity Correlates with Neurobehavioral Impairments in Opioid-Exposed Neonates

Publication Number: 667.4098

Josepheen De Asis-Cruz, Children's National Health System, Washington DC, DC, United States; Stephanie L. Merhar, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; Kushal Kapse, Children's National Health System, Washington, DC, United States; Yao Wu, Children's National Hospital, Washington, DC, United States; Carla Bann, RTI International, Apex, NC, United States; Jamie E. Newman, RTI International, Carrboro, NC, United States; Nicole Mack, RTI International, Chicago, IL, United States; Sara B.. DeMauro, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States; Namasivayam Ambalavanan, University of Alabama School of Medicine, Birmingham, AL, United States; Scott A. Lorch, The Children's Hospital of Philadelphia, Philadelphia, PA, United States; Deanne Wilson-Costello, Case Western Reserve University School of Medicine, Cleveland, OH, United States; Brenda Poindexter, Children's Healthcare of Atlanta, Atlanta, GA, United States; Myriam Peralta-Carcelen, University of Alabama at Birmingham, School of Medicine, Birmingham, AL, United States; Jonathan Davis, Tufts Medical Center, Boston, MA, United States; Catherine Limperopoulos, Children's National Health System, Washington DC, DC, United States

Background: Antenatal opioid exposure is associated with neurobehavioral dysregulation in neonates. In the Outcomes of Babies with Opioid Exposure (OBOE) study, using the Neonatal Neurobehavioral Scale, 2nd edition (NNNS-II), we observed persistent differences between exposed and unexposed neonates in the nonoptimal reflexes (NOR) and quality of movement (QOM) subscales. The in vivo brain correlates of these neurobehavioral findings are unknown.

Objective: To investigate the relationship between brain functional connectivity and neurobehavior in opioid-exposed neonates.

Design/Methods: First, we confirmed previously reported differences in Quality of Movement (QOM) and Regulation of State (NOR) scores between opioid-exposed and unexposed groups in this subset of subjects with both rs-fMRI and NNNS-II data available (n=256). In the exposed neonates (n=156), we preprocessed rs-fMRI data using a neonatal pipeline and computed pairwise correlation of regional brain signals in 93 areas spanning the whole brain. These Fisher-z transformed Pearson correlation values represent connectivity strength between brain areas. Connectivity strength was then correlated to NOR and QOM subscales of the NNNS-II. Statistical tests used a false discovery rate-corrected p< 0.05 threshold.

Results: We confirmed higher NOR (exposed vs unexposed: 3.2±1.1 vs. 2.8±1.0) and lower QOM (6.6±1.1 vs 6.9±1.1) scores in opioid-exposed neonates. See Table 1 for characteristics of opioid-exposed neonates. In this group, connectivity strength in 6.4% of connections was associated with NOR, with 36% of these involving the hippocampus, amygdala, and parahippocampal gyrus and 22% involving the mid- and superior occipital cortices. Higher NOR subscale scores correlated with greater connectivity strength in connections involving these regions. Approximately 0.6% of connections were associated with QOM, with the superior temporal pole involved in 52% of these connections. Higher connectivity strength in connections involving the superior temporal pole correlated with lower QOM scores.

Conclusion(s): In a large sample of opioid-exposed neonates, associations between disrupted neurobehavior and brain connectivity were found in the limbic/paralimbic, occipital, and superior temporal areas. These circuits are crucial for visual-spatial integration, action execution, and biological motion processing, suggesting a neural basis for the altered neurobehavior in exposed neonates. We are currently conducting longitudinal MRI and behavioral assessments to evaluate the functional significance of these early brain-behavior interactions on short and longer-term outcomes.

Table 1. Characteristics of opioid-exposed neonates.
pas2025_fc_oboe_Table1.pdf

Figure 1. Early brain-behavior interactions in opioid-exposed neonates.
pas2025_fc_oboe_Figure1.pdfConnections shown on the left panel positively correlate with nonoptimal reflex subscale scores on the NNNS-II in opioid-exposed neonates. The most involved regions include the limbic, paralimbic, and occipital areas. The right panel displays connections where connectivity strength is negatively associated with quality of movement subscale scores, with the left superior temporal pole frequently implicated. Abbreviations: R, right; L, left; AMYG, amygdala; PHG, parahippocampal gyrus; HIP, hippocampus; MOG, middle occipital gyrus; SOG, superior occipital gyrus; TPOsup, superior temporal pole.

Table 1. Characteristics of opioid-exposed neonates.
pas2025_fc_oboe_Table1.pdf

Figure 1. Early brain-behavior interactions in opioid-exposed neonates.
pas2025_fc_oboe_Figure1.pdfConnections shown on the left panel positively correlate with nonoptimal reflex subscale scores on the NNNS-II in opioid-exposed neonates. The most involved regions include the limbic, paralimbic, and occipital areas. The right panel displays connections where connectivity strength is negatively associated with quality of movement subscale scores, with the left superior temporal pole frequently implicated. Abbreviations: R, right; L, left; AMYG, amygdala; PHG, parahippocampal gyrus; HIP, hippocampus; MOG, middle occipital gyrus; SOG, superior occipital gyrus; TPOsup, superior temporal pole.