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Prenatal Polybrominated Diphenyl Ether and Global Efficiency of the Reading Network in a Community Sample of 5 Year-Old Children

Sat, March 23, 9:45 to 11:15am, Baltimore Convention Center, Floor: Level 3, Room 322

Integrative Statement

Prenatal exposure to Polybrominated Diphenyl Ether (PBDE), compounds extensively used in flame retardants, is associated with reduced language, visual capacity, and reading skill at eight years old. Resting-state functional magnetic resonance imaging (rs-fMRI) measures correlations in neural activity between distant brain regions which reflects functional connectivity between these regions. Prior task- and rs-fMRI studies have identified a left hemisphere reading network (RN) composed of left inferior frontal, temporo-parietal and occipito-temporal regions that supports normal reading. Adults and children with disordered reading show altered activation of these regions during reading and reading-related tasks, and disrupted functional connectivity of this circuit at rest. We used rs-fMRI to examine associations between concentrations of PBDE in maternal blood during pregnancy and functional connectivity of the RN in a community sample of 5 year-old children. We hypothesized that we would detect connectivity within the RN at age 5 and that network architecture, as measured by graph theoretical output, would be associated with word-reading ability and with PBDE concentration.
Forty-seven children were selected from an ongoing longitudinal birth cohort of 316 mother-child pairs in New York City. Useable MRI data was acquired from 33 children. In the CONN toolbox, anatomical CompCor was used for denoising and volumes exceeding >0.5mm frame displacement were regressed out. Twelve regions of interest identified in task fMRI meta-analyses defined the RN; word-reading was assessed with the Woodcock Reading Mastery Word-Identification task on the day of the scan. Maternal serum PBDE concentrations were measured at 12.22.8 weeks gestation (meanSD) using isotope dilution high resolution mass spectrometry. Sum PBDE (PBDE) measured total concentration and weighted quartile sum (WQS) analysis tested which of the PBDE congeners (chemical constituent) associated with reading ability or graph output. One-sample t-test evaluated average network connectivity of the RN. Linear regression evaluated associations between PBDE and reading, and network architecture of the RN, specifically global efficiency (the inverse value of the average length between each hub of the network). Covariates included age, sex, verbal IQ, birthweight, global correlation and mean motion.
RN regions were significantly intercorrelated (t(31)=9.49, p<.0001). As prenatal PBDE increased, global efficiency of the RN decreased (b=-0.02, T=-2.64, p=.014). For every quintile-increase in the exposure index, a -0.01 (-0.02, -0.003) reduction in global efficiency was detected (p=0.0062). This effect was primarily driven by PBDE congener 47, which accounted for 79% of the variance, and by congener 153 which explained 16% of the variance. Greater global efficiency of the RN was associated with better word-reading (r=0.399, p=0.059). PBDE was not associated with word-reading (b=0.92, T=0.16, p=.87). A control analysis demonstrated that PBDE did not associate with global efficiency of a distinct canonical circuit in the brain, the Default Mode Network (DMN; b=-0.001, T=-0.43, p=.67).
Despite being early readers, 5-year-old children showed connectivity within the RN and increased global efficiency was associated with better word-reading. Prenatal PBDE concentrations were inversely associated with global efficiency of the RN but not the DMN, reflecting the specificity of our findings to the RN.

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