Brain Mechanisms Underlying Changes in Neural Oscillations through Adolescent Cognitive Maturation

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Project Summary Adolescence is characterized by improvements in executive function, increased plasticity, and the continued refinement of neuronal mechanisms. Importantly, it is also a time when neurobiological mechanisms are actively specializing, where strays from neurotypical development may lead to the emergence of psychopathology. To understand how atypical brain maturation may lead to neuropsychiatric disorders, typical adolescent development needs to be better understood. Previous postmortem human and animal models have shown developmental changes in the excitatory/inhibitory (E/I) balance derived from changes in the excitatory glutamate and inhibitory Gamma-Aminobutyric Acid (GABA) neurotransmitters. Decreases in the E/I balance have been shown to optimize neural systems supporting cognitive control through the stabilization of gamma oscillations, generated by parvalbumin (PV) GABAergic interneurons and measurable through electroencephalography (EEG). However, there is limited understanding of the developmental changes in the E/I balance and its impact on the neuronal mechanisms characterizing this critical period of development. Thus, this project aims to investigate the shift in the E/I balance, as implicated by developmental changes in the balance of glutamate and GABA, to characterize the neuronal underpinnings of neurotypical adolescent cognitive development. To accomplish this, we will 1) assess developmental changes in neural activity underlying working memory and its association with glutamate and GABA using multimodal neuroimaging techniques, including electroencephalography (EEG), 7T Magnetic Spectroscopic Imaging (MRSI) (Aim 1), and stereoelectroencephalography (sEEG) (Aim 2), and 2) use computational modeling to identify the micro-level neuronal underpinnings of adolescent brain development (Aim 3). During this process, the candidate will gain invaluable knowledge in technical methodologies, such as data collection, analysis, computational modeling, clinical neuroscience, and written and oral communication. This study will advance our understanding of neurotypical adolescent development, which is a critical step towards assessing impaired development that can lead to psychopathology, which predominantly emerges in adolescence (e.g., psychosis, mood disorders, substance use disorders). Altogether, this project will support the ability of the candidate to become an expert bioengineering-psychiatry researcher, integrating engineering principles and developmental cognitive neuroscience that can inform the mental health field.