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28 A Graph Theoretical Approach to Understanding Associations between Structural Connectivity and Improvements in Behavior of Children Born Very Preterm Following a Positive Parenting Intervention
- Sandra Glazer, Nehal Parikh, Weihong Yuan, Ernest Pedapati, Peter Chiu, Shari Wade
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 903-904
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Objective:
Children born very preterm (VPT; <32 weeks gestation) are at increased risk for long-term neurocognitive sequelae such as behavioral problems. These problems may be caused by disrupted brain development, particularly white matter abnormalities that affect network efficiency, as shown via diffusion magnetic resonance imaging (dMRI). There is evidence that short-term interventions for pediatric clinical populations can lead to behavioral improvements as well as associated neuroplasticity. Adapted from a previous parenting intervention for families of young children with traumatic brain injury, the novel Building Better Brains and Behavior (B4) program teaches responsive parenting skills for families of children born preterm. It is hypothesized that parent-reported externalizing symptoms will improve from pre- to postintervention and that these improvements will be mirrored by an increase in neural efficiency.
Participants and Methods:VPT children between the ages of 3-8 with documented behavioral problems were recruited to participate in a single-arm pilot clinical trial. Families began with a baseline visit in which the Child Behavior Checklist (CBCL) was administered as a measure of behavior problems, and the child underwent dMRI. Parents then participated in the 7-session intervention integrating self-guided, online learning modules with live virtual coaching sessions with a therapist. Twenty three participants enrolled, 15 of which completed the intervention and baseline MRI scan; 4 children were excluded from analysis due to not meeting eligibility criteria, leaving 11 participants for analysis of intervention effects (8 males, Mage=5.42). At program completion, families returned for a follow-up that entailed another CBCL questionnaire and dMRI scan. Eight children completed the post-intervention scan and five were retained for analysis (4 males, Mage=5.83). Imaging data was analyzed using the Brain Connectivity Toolbox, which generated graph theoretical metrics to characterize the topological organization of anatomical networks.
Results:A paired samples t-test showed significant reduction of externalizing behavior problems pre-intervention (M=61.12, SD=10.02) to post-intervention (M=55.00, SD=11.62; f(10)=3.09, p=0.01). At baseline, externalizing behavior problems were positively correlated with normalized clustering coefficient, r(10)=0.59, p=0.04, and small-worldness, r(10)=0.64, p=0.03. Change in externalizing symptoms pre- to post-intervention was positively correlated with baseline global efficiency, r(4)=0.94, p=0.02, and negatively correlated with mean local efficiency, r(4)=-0.89, p=0.03, and normalized characteristic path length, r(4)=-0.89, p=0.03.
Conclusions:Preliminary results indicate that VPT children who exhibit higher levels of externalizing symptoms show higher normalized clustering coefficient (which is expected of networks with less integration), and higher small-worldness (which is unexpected). Greater behavioral improvements were associated with higher baseline characteristic path length as expected, but lower baseline global efficiency; this may indicate that children who had lower global efficiency to begin with benefitted from the intervention the most. Due to the small sample size and lack of corrections for multiple comparisons, these results are not definitive and further research is needed to elucidate associations between structural connectivity and behavioral intervention in children born very preterm.
3046 Reduced structural and functional connectivity in infants with prenatal opioid exposure
- Stephanie Merhar, Adebayo Braimah, Traci Beiersdorfer, Brenda Poindexter, Nehal Parikh
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- Journal:
- Journal of Clinical and Translational Science / Volume 3 / Issue s1 / March 2019
- Published online by Cambridge University Press:
- 26 March 2019, p. 52
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OBJECTIVES/SPECIFIC AIMS:. This study aims to understand the effects of prenatal opioid exposure on structural and functional connectivity in the neonatal brain. Our central hypothesis is that infants with prenatal opioid exposure will have decreased structural and functional connectivity as compared to non-exposed controls. Our overarching goal is to improve neurodevelopmental and behavioral outcomes in infants with prenatal opioid exposure. METHODS/STUDY POPULATION:. Infants with prenatal opioid exposure were recruited from 2 birth hospitals in our area. Control infants were recruited from the larger community. Infants underwent MRI between 4-6 weeks of age in the Cincinnati Children’s Hospital Imaging Research Center. MRI sequences included 3D structural T1 and T2-weighted imaging, resting state functional connectivity MRI, and multi-shell DTI (36 directions at b=800 and 68 directions at b=2000). Tract-based spatial statistics (TBSS) was used to identify differences in fractional anisotropy (a measure of white matter integrity) between groups. Group independent component analysis was used to identify differences in resting-state networks between groups RESULTS/ANTICIPATED RESULTS:. There were 5 subjects enrolled in the study with evaluable imaging, 3 infants with prenatal opioid exposure and 2 unexposed controls. Structural MRI was normal in all cases. Infants with prenatal opioid exposure had reduced structural connectivity as measured by fractional anisotropy (FA) in the genu and splenium of the corpus callosum as compared with controls. The orange/red color represents areas in which the FA of the opioid-exposed group was lower than controls and green represents the white matter skeleton common to both groups. Infants with prenatal opioid exposure also had significantly reduced within-network functional connectivity strength (z-transformed partial correlation coefficient 0.358 vs 0.199, p = 0.03) in the sensorimotor network as compared with controls. DISCUSSION/SIGNIFICANCE OF IMPACT:. In this small pilot study, both structural and functional connectivity were reduced in opioid-exposed infants compared with controls. This data suggests that differences in structural and functional connectivity may underlie the later developmental and behavioral problems seen in opioid-exposed children. These findings must be validated in a larger population with correction for confounding factors such as maternal education