# Refinement of Brain Mechanisms Underlying the Developmental Stabilization from Adolescent to Adult Neurocognitive Processing

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $701,047

## Abstract

Project Summary/Abstract
This is the third renewal in 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., schizophrenia,
mood disorders). We will build on findings from the first three grants using a comprehensive cognitive battery and
multimodal neuroimaging, more recently including high field (7T) Magnetic Resonance Spectroscopic Imaging
(MRSI), Tissue Iron, and Magnetization Transfer, indicating important specialization in cognitive brain systems
during adolescence underlied by changes in neurotransmitters and myelination. We now propose to investigate
the contributions of mechanisms of synaptic plasticity by leveraging advances in high field 7T MRI to characterize
developmental changes in markers of synaptic pruning as well as braking factors of plasticity and their contributions
to the transition from variable executive function in adolescence to stable and reliable cognition in adulthood. Our
Central Hypothesis is that the transition in neurocognition from adolescence to adulthood is underlied by synaptic
pruning in the PFC, triggered by the completion of puberty, establishment of DA availability and formation of peri-
neuronal nets (PNNs), which support the stabilization of cognitive processes and associated brain systems func-
tion. In Aim 1, we will leverage brain phosphorus (31P) Magnetic Resonance Spectroscopy, to characterize in vivo
in humans phospholipid indices of the developmental trajectory of normative loss of synapses, complemented by
1H MRSI measures of age-related decreases in excitatory glutamate function, which we identified in the last grant;
advanced approaches using DWI to assess neural complexity (NODDI); and microRNA markers of mechanisms
of synaptic plasticity. We hypothesize that PME/PDE (from 31P-MRSI), miRs involved in synaptic pruning, NODDI,
and glutamate (from 1H-MRSI) will show associated changes through adolescence stabilizing in the second decade
of life. In Aim 2, we will characterize associations between synaptic pruning and neurocognitive development. We
hypothesize that from adolescence to adulthood, stabilization of executive function (EF), variability in brain activa-
tion, and frontostriatal connectivity will be associated with, and mediated by, synaptic pruning, stabilizing to optimal
processing in adulthood. Finally in Aim 3, we will characterize the role of critical period closing factors into adult-
hood. We hypothesize that stability will coincide with growth plate fusion evidence of the completion of puberty and
will be associated with the stabilization of striatal tissue iron indices of DA availability, peripheral levels of miRs
implicated in PNN formation, and increased myelination, which act as closing factors for this window of plasticity.
We will study 192 10-26 year olds who do not have an Axis 1 diagnosis in themselves of a first degree relative and
will be...

## Key facts

- **NIH application ID:** 10868638
- **Project number:** 5R01MH067924-19
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** BEATRIZ LUNA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $701,047
- **Award type:** 5
- **Project period:** 2004-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10868638

## Citation

> US National Institutes of Health, RePORTER application 10868638, Refinement of Brain Mechanisms Underlying the Developmental Stabilization from Adolescent to Adult Neurocognitive Processing (5R01MH067924-19). Retrieved via AI Analytics 2026-05-30 from https://api.ai-analytics.org/grant/nih/10868638. Licensed CC0.

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