Brain Mechanisms Underlying Plasticity in the Specialization of Cognitive Systems through the Adolescent Period: Covid Supplement

Project Abstract/Summary This is a proposal for supplementary support for lost time due to disruptions related to the COVID-19 pandemic that has significantly impacted progress of our scientific aims. The University of Pittsburgh stopped all in person studies during two peaks in the pandemic for a total of seven and a half months in addition to hesitancy by participants to return to in person visits. This supplement will allow us to complete our longitudinal follow-up data critical to addressing the main hypotheses of the proposal by extending salary to critical staff to support assess- ments that were interrupted due to the pandemic and subsequent data analyses and manuscript preparation. This is the second renewal on a line of inquiry characterizing the neural basis of cognitive maturation through the adolescent period, a time of critical vulnerability to the emergence of major psychopathology (e.g., schizo- phrenia, mood disorders). Here we are characterizing changes in key neurotransmitter (NT) systems: gamma- Aminobutyric acid (GABA), glutamate (Glu), and dopamine (DA), which animal and postmortem models show underlie circuit plasticity and undergo unique changes during the adolescent period. Specifically, changes in Glu/GABA processing, modulated by adolescent increases in DA, affect the excitatory/inhibitory (E/I) balance of cognitive brain systems, driving increases in the cortical signal-to-noise ratio (SNR) into adulthood supporting cognitive maturation. Our Central Hypothesis is that the relative changes of these NTs will increase the SNR of neural activity supporting the transition to adult level cognition. In Aim 1, we are using Magnetic Resonance Spectroscopy (MRS) at 7 Tesla to obtain measures of GABA and Glu as well as R2' indirect measures of dopamine (DA) longitudinally in vivo in 10-30 year-olds. We hypothesize that we will observe de- creases in measures of Glu and DA and increases in GABA resulting in decreases in the ratio of DA*Glu/GABA in prefrontal and subcortical regions. In Aim 2, we are characterizing changes in SNR associated with cognitive development. Lastly, in Aim 3 we are characterizing the association between relative NT changes and systems level effects on brain connectivity using resting state and structural white matter connectivity. We hypothesize that NT systems changes will be associated with greater network integration and changes in the strength of cortico-subcortical connectivity through adolescence. We will also assess COVID related perceived stress to control for possible effects on our data as a covariate. Together, these findings have relevance in elucidating the relative contributions of key NT to brain maturational processes providing novel insight into the neurobiolog- ical basis of normative neurocognitive development that is critical for identifying vulnerabilities for abnormal de- velopment that can lead to psychopathology.