# Microstructural Neuroimaging of Synaptic Pruning and Myelination in Adolescent Psychosis

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $234,000

## Abstract

Project Summary
A number of neuropsychiatric disorders, including psychotic spectrum disorders (PSD), have been associated
with developmental changes in brain structure and function. Adolescence is a period of special importance,
with alterations of synaptic pruning and myelination trajectories proposed as neural mechanisms underlying
PSD. There is also a growing interest in ways that neurodevelopmental changes may be leveraged as
treatment targets. Unfortunately, such efforts are limited by the technology currently available for monitoring
microstructural change. Neuroimaging is ideal for investigating in-vivo developmental changes, due to its non-
invasive nature. However, the measures used are often indirect, and the extent to which they are sensitive to
neural microstructure is not always clear. Accordingly, the imaging methods community continues to develop
increasingly sophisticated techniques to improve our estimation of tissue characteristics, but there is often
substantial delay in translating new methodologies to clinical populations. One modality that has the potential
to improve our understanding of brain microstructure is multishell diffusion weighted imaging (mDWI). One
emerging mDWI method is neurite orientation dispersion and density imaging (NODDI), which can yield
sophisticated estimates of microstructural architecture. In particular, NODDI allows estimation of three factors
relevant to development: neurite orientation, reflecting dendritic density and the complexity of dendritic
branching, neurite density, which is correlated with myelination, and cellular density. Although these measures
are relevant to many neuropsychiatric disorders, this technique has not been broadly adopted, with little
existing work using NODDI in PSD and no work in adolescent or young adult patients. This project will employ
NODDI as well as standard structural grey and white matter imaging measures in a sample of healthy
adolescents and adolescents with PSD (age 12-18), in order to establish the utility of NODDI as a measure of
synaptic pruning and myelination. First, the degree to which NODDI measures are similar or different to
standard measures of grey matter thickness and white matter integrity will be assessed. Secondly, whether
NODDI measures are sensitive to differences in pruning across adolescence by comparing cross sectional age
related differences between groups. And the final assessment will be whether NODDI is more or differently
sensitive than standard measures by testing if it is more predictive of chronological age, functional connectivity,
and patient status. If successful, this project would establish evidence that NODDI provides unique information
that may be valuable for investigating neuropsychiatric disorders, and further, that the measure can detect
maturational differences between diagnostic groups, which could impact how clinical researchers perform
diffusion imaging moving forward. In addition to the impact on the larger clini...

## Key facts

- **NIH application ID:** 9822187
- **Project number:** 5R21MH116433-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** KATHERINE Helen KARLSGODT
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $234,000
- **Award type:** 5
- **Project period:** 2018-11-14 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9822187

## Citation

> US National Institutes of Health, RePORTER application 9822187, Microstructural Neuroimaging of Synaptic Pruning and Myelination in Adolescent Psychosis (5R21MH116433-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9822187. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*