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

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $209,647

## Abstract

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.

## Key facts

- **NIH application ID:** 10512793
- **Project number:** 3R01MH067924-17S1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** BEATRIZ LUNA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $209,647
- **Award type:** 3
- **Project period:** 2022-04-08 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10512793

## Citation

> US National Institutes of Health, RePORTER application 10512793, Brain Mechanisms Underlying Plasticity in the Specialization of Cognitive Systems through the Adolescent Period: Covid Supplement (3R01MH067924-17S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10512793. Licensed CC0.

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