# Developing electrophysiological markers for clinical trials in autistic adults

> **NIH NIH R01** · CHILDREN'S HOSP OF PHILADELPHIA · 2024 · $756,283

## Abstract

Project Summary
Brain electrophysiological phenotyping holds promise for parsing heterogeneity in ASD and enabling testing of
proposed treatments more reliably in biologically-based subgroups of ASD. There have been considerable
advances in the non-invasive imaging and electrophysiologic correlates of phenotypes in ASD, in children,
including 1) delayed auditory evoked response components (M50, M100 latency); 2) delayed magnetic
mismatch fields (MMF) elicited by vowel contrasts as well as atypical rightward lateralization; 3) atypical
development of gamma-band oscillatory phase synchrony, coupled to atypical levels of inhibitory
neurotransmitter, GABA; and 4) atypical motor oscillatory activity, particularly the post-movement beta rebound
(PMBR). We have suggested that such electrophysiological signatures might serve as biomarkers in stratifying
patients for inclusion in clinical trials according to biology, rather than behavior alone. However, little is known
about how these candidate biomarkers mature into adulthood. This is important because there are millions of
adults on the autism spectrum, presenting in clinic in need of treatment. Our preliminary studies suggest that
there might be persistence of childhood electrophysiological phenotypes into adulthood (in particular, auditory
M50/M100 and MMF delays), while differences in auditory gamma band phase synchrony and motor PMBR
oscillatory responses may in fact emerge during adolescence. If indeed childhood biological differences persist
into adulthood and/or some biological differences emerge in late adolescence/ early adulthood, then the
opportunity and target for remediation may also persist in adulthood. This would indicate the need for a
quantitative biomarker for both stratification (inclusion/exclusion) purposes but also for monitoring treatment
target engagement, as well as longer term evidence of brain response. We will recruit 72 autistic adolescents/
adults (14-45yrs, 48M, 24F) and 72 age-/sex-matched typically developing (TD) peers into a multimodal
imaging study with a 12-week longitudinal design to mimic a typical pharmaceutical trial and establish precision
estimates for each metric to define the resolution of interval change in subsequent trials. We will carry out the
following Aims. In Aim 1, we will evaluate, in a sample of adults, the group level ASD vs TD discrimination of
each of a battery of MEG metrics and assess intra- and inter-subject variability over three scan sessions
(baseline, 4weeks, 12weeks). This will establish the effect size required of any putative pharmaceutical. In
Aim 2, we will use multimodal imaging to address heterogeneity and probe the biological
underpinnings of M50 latency prolongation in adults. In Aim 3, we will use simultaneously-acquired MEG and
EEG, to determine the efficacy of EEG analogs of the proposed MEG measures to achieve similar group-
level discrimination of individuals with ASD vs TD. EEG is lower-cost, simpler to perform and has wid...

## Key facts

- **NIH application ID:** 10875646
- **Project number:** 5R01MH129594-03
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** EDWARD S BRODKIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $756,283
- **Award type:** 5
- **Project period:** 2022-09-05 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10875646

## Citation

> US National Institutes of Health, RePORTER application 10875646, Developing electrophysiological markers for clinical trials in autistic adults (5R01MH129594-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10875646. Licensed CC0.

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