# Multimodal dMRI, MRS and MEG studies of language impairment in low-verbal ASD

> **NIH NIH R01** · CHILDREN'S HOSP OF PHILADELPHIA · 2024 · $694,551

## Abstract

PROJECT SUMMARY
In the prior work we have extended our multimodal magnetoencephalography (MEG) and magnetic resonance
imaging (MRI) approaches and have shown that it is possible to model, or predict, the latency of the auditory
evoked neuromagnetic field component, the M50, occurring approximately 50-100ms post stimulus in children,
but delayed in ASD, and measured by magnetoencephalography (MEG), by using diffusion magnetic
resonance imaging (dMRI) to quantify the microstructure of the auditory pathway white matter (in particular the
thalamocortical acoustic radiations). While this approach accounted for more than 50% of the variance in
typically developing controls, it was confounded by heterogeneity in a cohort of ~100children with autism
spectrum disorder (ASD). However, this actually allowed identification of a sub-population of children with ASD
whose M50 responses appeared as “outliers” to the TD model (i.e. “unpredictably long M50’s); interestingly,
these children showed significantly lower levels of gamma-aminobutyric acid (GABA) estimated by advance
magnetic resonance spectroscopy (MRS) than their ASD peers whose latencies were consistent with the TD
model. Identification of this group has significant implications for treatment/intervention by identifying a
biological basis for stratification (sub-population definition) and thus a putative biological target for intervention
(as well as a means of defining an inclusion criterion for selecting that therapy). The present proposal extends
this work to the scientifically and societally critical group of children with ASD with severe language and
cognitive impairments, who are under-included in imaging research, but whose vital participation is made
possible by a combined behavioral and technical protocol we have recently developed, called MEG-PLAN, and
its MRI analog: MRI-PLAN. To ascertain the clinical and behavioral implications of delayed M50 brain
responses, we also recruit children with mixed etiology intellectual and developmental disability (IDD), but not
autism, and seek to identify the relative associations of language impairment, cognitive impairment and ASD
diagnosis to the M50 latency delay and to investigate the biophysical underpinnings of these association with
multimodal MEG, MRI and MRS. We also extend beyond examination of auditory response timing to probes of
auditory and language neuronal circuitry via. oscillatory responses also detected by MEG and examine their
relation to GABA levels as well as to clinical language assessment. Taken together, this proposal focuses on
several levels of stratification to combat the formidable heterogeneity observed in ASD and, critically, employs
state of the art multimodal methodologies, made feasible by the MEG-PLAN and MRI-PLAN protocols, in
severely-impaired children with ASD (conventionally not included in such research) to assess generalization of
observations across the broad autism spectrum.

## Key facts

- **NIH application ID:** 10914003
- **Project number:** 5R01DC021051-02
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Timothy P Roberts
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $694,551
- **Award type:** 5
- **Project period:** 2023-09-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10914003

## Citation

> US National Institutes of Health, RePORTER application 10914003, Multimodal dMRI, MRS and MEG studies of language impairment in low-verbal ASD (5R01DC021051-02). Retrieved via AI Analytics 2026-06-04 from https://api.ai-analytics.org/grant/nih/10914003. Licensed CC0.

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