# CRCNS: US-Spain Research Proposal: Interpreting MEG Biomarkers of Alzheimer's Progression with Human Neocortical Neurosolver

> **NIH NIH R01** · BROWN UNIVERSITY · 2022 · $236,511

## Abstract

Over the last decade, there has been a growing interest in understanding the brain mechanisms
 underlying the loss of the brain homeostasis in the continuum of Alzheimer's Disease (AD). Animal
 models suggest that the substrate for this phenomenon is the loss of the excitatory/inhibitory (E/I) balance
 due to the toxic effects of amyloid oligomers and plaques on inhibitory terminals. This hyperexcitability is
 presumed to underlie the observed increases in power and interarea synchronization of alpha/beta
 frequency oscillations measured in humans with electro- and magneto-encephalography (M/EEG).
 Amnesic mild cognitively impaired (aMCI) patients present increased resting-state MEG power in (7-14Hz)
 alpha and (15-29Hz) beta bands in brain regions with higher amyloid deposition. Additionally, aMCI
 patients who later converted to AD (CONV), compared to non-converters (NOCONV), showed increased
 synchrony between anterior and posterior brain regions. While animal and human studies are highly
 synergistic, it is unknown if the hyperexcitability found in animal models is the origin of the
 hypersynchronization found in human neurophysiology. To bridge this gap, the current proposal will apply
 a recently developed a computational neural modeling framework uniquely designed to link human
 macroscale M/EEG signals to the underlying cellular and circuit level dynamics that can be interrogated
 with invasive animal recordings or other imaging modalities (e.g., MR spectroscopy, tractography), namely
 Human Neocortical Neurosolver (HNN). We will apply new analysis methods to previously collected
 longitudinal MEG, tractography, volumetry, and MR GABA spectroscopy data in CONV- and NOCONV-
 aMCI patients and controls (Aims 1 and 3) and integrate the results with the HNN framework (Aim 2) to
 establish new early diagnostic AD biomarkers and to interpret the detailed neural mechanisms underlying
 these biomarkers.
RELEVANCE (See instructions):
 There is a growing public health need to understanding the brain mechanisms underlying the loss of the
 brain homeostasis in the continuum of Alzheimer's Disease (AD). This project aims to define new early
 diagnostic measures for AD and targeted treatment strategies for early intervention based on identified
 neural circuit abnormalities. The project has the potential to open a completely new window to counteract
 and delay cognitive decline with aging, ultimately reducing the cost for caregivers and improving the

## Key facts

- **NIH application ID:** 10474580
- **Project number:** 5R01AG076227-02
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** STEPHANIE Ruggiano JONES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $236,511
- **Award type:** 5
- **Project period:** 2021-09-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10474580

## Citation

> US National Institutes of Health, RePORTER application 10474580, CRCNS: US-Spain Research Proposal: Interpreting MEG Biomarkers of Alzheimer's Progression with Human Neocortical Neurosolver (5R01AG076227-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10474580. Licensed CC0.

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