# Neural Circuitry Resilience in Psychotic Disorders: A Multimodal Ultra-High Field Neuroimaging Study

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2020 · —

## Abstract

Abstract: Good long-term social outcome of schizophrenia (SZ) subjects is as low as 14%. Because of this,
substantial number of SZ subjects suffer from severe and protracted disability. An important contributing factor
to poor long-term outcome in schizophrenia is cognitive impairments that are resistant to current treatments.
Therefore, it is critical to examine novel mechanisms underlying cognitive impairments to design new treatments.
Recent evidence suggests that brain cortical regions and white matter pathways that connect them adapt to
pathophysiological processes. Such adaptation can mitigate impairments in selected cognitive domains offering
hopes to target selected networks for interventions to improve outcome. Using state-of-art non-invasive
neuroimaging techniques, adaptation between the cortical neuropil (synapses, dendrites and its branches,
axonal endings and interneurons) and white matter integrity measured using characteristics of water diffusion in
white matter fibers can be investigated. The goal of this project is to characterize concurrent changes in cortical
neuropil and anisotropy of water diffusion in white matter fiber tracts as a model of neural circuitry adaptability
(NCA) and its impact on cognitive performance among SZ subjects compared to healthy control subjects (HC).
We will use phosphorus magnetic resonance spectroscopy (31P MRS) at ultra-high magnetic field (7 Tesla) that
provides greater sensitivity to investigate neuropil by measuring membrane phospholipid (MPL) metabolites in
multiple anatomically well-defined regions across the entire brain. MPLs are critical ingredients of neuronal
membranes that naturally form lipid bilayers separating the intra- and extra-cellular environments. During
development and disease, imbalance between synthesis and degradation of membranes can be reliably
captured. Broadly, higher MPL precursor levels are associated with membrane expansion while higher MPL
breakdown products suggest neuropil membrane contraction. Since such dynamic changes are prominently
observed in the neuropil, 31P MRS can provide a more specific measure of neuropil than structural imaging
measures that includes neuropil as well as interneuronal space, microvasculature and neuronal soma. Neurite
Orientation Dispersion and Density Imaging (NODDI) - a state-of-the-art method to measure diffusion of water
along white matter tracts and neurite density- will be used to examine integrity of white matter pathways more
reliably than the older method of diffusion tensor imaging. Innovative nature of this proposal is highlighted by
concurrent changes in MPL metabolites and anisotropy as measures of NCA in relation to cognitive impairments
since using single modality imaging cannot measure adaptive changes in multiple tissues. Using our model of
NCA by employing multi-modal 31P MRS-NODDI data, we seek to examine association of NCA with cognitive
performance across the whole-brain (aim 1). Additionally, factors associated w...

## Key facts

- **NIH application ID:** 10013729
- **Project number:** 1I01CX001855-01A1
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Konasale M Prasad
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2021-10-01 → 2025-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10013729

## Citation

> US National Institutes of Health, RePORTER application 10013729, Neural Circuitry Resilience in Psychotic Disorders: A Multimodal Ultra-High Field Neuroimaging Study (1I01CX001855-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10013729. Licensed CC0.

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