Characterizing a Translational Mechanism of Sensitive Period Neuroplasticity and Cognitive Sequalae in Human Infant Visual Development

PROJECT SUMMARY/ABSTRACT Motivation: Sensitive periods are temporal windows of elevated neuroplasticity, facilitating adaptation to and learning from early environments across a range of domains. In non-human animal models, excitation/inhibition (E/I) balance, or the expression of the primary excitatory (glutamate) to inhibitory (GABA) neurotransmitters, governs the degree of neuroplasticity throughout the sensitive period. Until recent methodological advances, measuring E/I balance minimally invasively in the human brain was infeasible, and thus our understanding of the role of E/I balance in human sensitive period neurobiology is extremely limited. Normative individual and clinical phenotypic differences exist in learning outcomes supported by sensitive periods. Research in non- human animal models suggests a range of clinical outcomes may result from differences in sensitive period neuroplasticity. Therefore, the proposed research will have a broader impact by first furthering understanding of normative sensitive period mechanisms, so future work can understand clinical deviations in these mechanisms. Here, we focus on an early visual cortical sensitive period because it is well-characterized and translatable across species. The proposed project investigates if E/I balance indexes sensitive period neuroplasticity in human infant visual cortical development as it does in non-human animal models. Methods: In this accelerated longitudinal study, infants will participate in visits at 2-to-4 months, 7-to-9 months, and 10- to-12 months. At all visits, infants will participate in a visual-evoked potential (VEP) electroencephalography (EEG) task as a readout of visual neurodevelopmental maturation throughout the sensitive period. Also at all visits, the MEGA-PRESS magnetic resonance spectroscopy (MRS) sequence will be collected from infants during natural sleep to extract concentrations of glutamate and GABA in a visual cortical seed. To measure visually-mediated cognitive outcomes, infants will participate in the cognitive scale of the Bayley Scales of Infant Development at the last visit. Aims: Aim 1 of the proposed project will characterize age-related changes in the MRS-derived E/I balance over the sensitive period using Generalized Additive Models for Location, Scale, and Shape. Aim 2 will relate individual differences in the MRS-derived E/I balance to the VEP readout of visual cortex function over the sensitive period using longitudinal multilevel modeling. Aim 3 will test if individual differences in the MRS- derived E/I balance from 2 to 9 months predicts emerging visually-mediated cognition at 10-to-12 months, at the end of the sensitive period, using longitudinal multilevel modeling. Training: To support the applicant’s goal of being an independent developmental neuroscientist using multimodal infant neuroimaging and to complete the proposed project, the applicant will develop expertise in 1) infant MRS, 2) advanced longitudinal modeling, and will 3) accelerate her professional development. The applicant is well-poised to complete this project and advance towards her career goals with a strong mentorship team, detailed training plan, and position at an R1 research institution.