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

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $677,225

## Abstract

Project Abstract/Summary
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). Building on the findings from the first two grants using functional Magnetic Resonance
Imaging, Diffusion Tensor Imaging, and Magnetoencephalography, indicating important specialization in cogni-
tive brain systems during adolescence, we now propose to probe these underlying mechanisms. We aim to
characterize changes in key neurotransmitters (NT): 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 will use 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 12-30
year olds. 7Tesla MRS provides critically greater sensitivity than 3Tesla affording significant increases in the
accuracy of measures of GABA and Glu necessary for probing changes through adolescence, which have yet
to be done. We hypothesize that we will observe decreases 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 will inves-
tigate the association between relative NT changes and systems level effects on known developmental changes
in brain connectivity using resting state connectivity and measures of white matter integrity. We propose that NT
systems changes will be associated with greater network integration and changes in the strength of corticosub-
cortical connectivity through adolescence. Lastly, in Aim 3 we propose to characterize changes in SNR in the
context of developmental improvements in higher-order executive function using a task that probes learning and
working memory, functions that are known to show important improvements through adolescence. Together,
these findings have relevance in elucidating the relative contributions of different NT systems to brain matura-
tional processes providing novel insight into the neurobiological basis of normative neurocognitive development
that is critical for identifying vulnerabilities for abnormal development that can lead to psychopathology.

## Key facts

- **NIH application ID:** 10160952
- **Project number:** 5R01MH067924-17
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** BEATRIZ LUNA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $677,225
- **Award type:** 5
- **Project period:** 2004-07-18 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10160952

## Citation

> US National Institutes of Health, RePORTER application 10160952, Brain Mechanisms Underlying Plasticity in the Specialization of Cognitive Systems through the Adolescent Period (5R01MH067924-17). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10160952. Licensed CC0.

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