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Kable JA1,2, Mesa DA3, Coleman TP3, Coles CD1,2, Jones KL4,, Yevtushok L5, Kulikovsky Y5, Wertelecki W5,7, Chambers CD4,6 , & and the CIFASD

1 Departments of Psychiatry and Behavioral Science and 2Pediatrics, Emory University School of Medicine, Atlanta, GA, USA; 3Departments of Bioengineering, 4Pediatrics and 6Family Medicine and Public Health, University of California San Diego, San Diego, CA, USA; 5OMNI-Net for Children International Charitable Fund, Rivne Regional Medical Diagnostic Center, Rivne Province, Ukraine; 7Department of Medical Genetics, University of South Alabama, Mobile, AL, USA.

Early identification of individuals who are neurodevelopmental impaired as a function of their prenatal alcohol exposure (PAE) remains challenging as a result of limitations in standardized tests of early neurocognitive functioning. The assessment of infant neurophysiological encoding and memory of environmental events using cardiac orienting responses (ORs) has been found to be a promising alternative as ORs obtained from both humans and animal have been sensitive to the impact of PAE. ORs enable the heart to gate oxygen to the central nervous system to allow for higher level information processing and are characterized by a specific pattern of heart rate deceleration in the presence of novel stimuli. Using animal models, electrical stimulation of either the ventral-medial or dorsal lateral prefrontal cortex can elicit an OR, suggesting that ORs can provide an early index of the efficiency of prefrontal cortical functioning involved in gating energy resources between basic attention and arousal systems. ORs collected in the first year of life have been found to be impacted by PAE but have not yet been evaluated in older children. The offspring of women (N=372) enrolled in a randomized clinical trial of multivitamin/mineral usage during pregnancy carried out in the Ukraine were evaluated using habituation/dishabituation learning paradigms at 6, 12, and 3.5 to 4.5 years to assess the predictive validity of ORs collected in the first year of life and the sensitivity of ORs to detecting the impact of PAE in older children. In each paradigm, baseline heart rate (HR) was collected for 30 sec prior to stimulus onset and by sampling HR for 12 sec post-stimulus onset for each trial. Using supervised logistic regression classifier models to predict 12-month development, negative predictive values ranged from 0.72 to 0.84 and positive predictive values ranged from 0.54 to 0.66 using 6-month ORs. Indices of neurophysiological encoding and memory collected in the toddler and preschool period continued to be sensitive to the effects of PAE. ORs provide a relatively quick assessment of the efficiency of prefrontal cortical activity and can be applied readily in diverse cultural settings, making them an ideal tool for global applications.