# The Effects of Injury Timing on Neural Microstructural Complexity and Motor Impairments in Cerebral Palsy

> **NIH NIH R03** · NORTHWESTERN UNIVERSITY · 2020 · $158,000

## Abstract

PROJECT SUMMARY
Cerebral palsy is the most common physical disability of childhood. Pediatric hemiplegia represents a third of
this population and is often due to a unilateral brain injury that occurs in the prenatal or perinatal periods. Our
recent work provides evidence that the timing of the injury has a significant effect on severity and type of motor
impairment. If the brain injury occurs before birth, in which pruning of the ipsilateral corticospinal projections has
not yet occurred, there is a relative preservation of these projections and strength in the paretic limb, however,
this comes at the cost of abnormal mirror limb movements that are simultaneously driven from the contralesional
hemisphere. Conversely, a later injury, in which pruning of the contralesional ipsilateral corticospinal projections
is already occurring, there is a better likelihood for independent limb control, but this comes at the cost of
increased expression of weakness in the paretic limb. Since time-varying interruptions can occur during
developmental synaptic pruning, it is likely that white and gray matter complexity are concurrently altered to
ultimately drive the expression of these specific motor impairments. The proposed project will provide unique
insight into the plastic and degenerative neural microstructural mechanisms as a function of time in disrupted
development as it relates to typical childhood development. There have been many diffusion tensor imaging
studies of cerebral palsy, but there is no clear consensus on the neuropathophysiology primarily due to the
inherent limitations in modeling capabilities, data acquisition, and heterogeneity of motor impairment expression
in cerebral palsy. As an alternative, our laboratory specializes in practical techniques that go beyond the
capabilities of diffusion tensor imaging to characterize white and gray matter neural complexity with advanced
diffusion methods and modeling. Furthermore, as we are able to recruit individuals with heterogeneous sub-
types of cerebral palsy through an extensive research registry, the proposed project offers, for the first time, to
characterize the effects of injury timing on neural microstructural complexity and motor impairments in pediatric
hemiplegia. Our central hypothesis is that timing of unilateral ischemic brain injury impacts neural tissue
microstructural complexity in both hemispheres to cascade to motor impairments of hand weakness and
stereotypic losses of independent upper limb control. Aim 1 is designed to provide novel imaging biomarker
candidates of white and gray matter as a function of injury timing in neural development. Aim 2 is set up to
quantify upper limb mirror movement and weakness using practical, yet novel, quantitative bedside device
measures and clinical assessments. Preliminary findings of the proposed work will provide novel baseline
biomarkers to guide future large scale (R01) basic science studies which are able to detect and study white and
gr...

## Key facts

- **NIH application ID:** 9873976
- **Project number:** 5R03HD094615-02
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Carson J Ingo
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $158,000
- **Award type:** 5
- **Project period:** 2019-02-14 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9873976

## Citation

> US National Institutes of Health, RePORTER application 9873976, The Effects of Injury Timing on Neural Microstructural Complexity and Motor Impairments in Cerebral Palsy (5R03HD094615-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9873976. Licensed CC0.

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