# Simultaneous EEG/fMRI to disentangle neural and vascular mechanisms of Alzheimer's disease pathology

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $586,437

## Abstract

Abstract. Alzheimer’s disease (AD) is presently an untreatable neurodegenerative disorder with a massive
public health burden. With invention of biomarker technologies for imaging β-amyloid (Aβ) plaques and
neurofibrillary tangles in the living human brain, it became clear that these pathologies that define AD begin
decades prior to overt dementia symptoms resulting from this disease. This prolonged pre-dementia period
offers opportunities for early interventions. However, much is currently unknown about the complex AD
pathophysiology in these early stages. One intriguing observation is that the early Aβ pathology is often
localized to highly metabolic regions of the brain. These regions, also known as ‘cortical hubs’ due to their high
functional interconnectivity with other brain areas, may display activity related susceptibility. Animal models
show that, in functionally active brain regions, disrupted rapid temporal structure of intrinsic neural activity and
neurovascular dysregulation can influence Aβ homeostasis. It is possible that these pathophysiological
mechanisms hold true in the aging human brain. However, precise measurement of rapid neural activity and
neurovascular regulation in the higher-order brain areas most vulnerable to AD has been challenging.
Currently available imaging techniques, when used alone, have severe limitations. The signal measured by
functional magnetic resonance imaging (fMRI) reflects coupling between metabolic demand of active brain
cells and a nutritive increase in cerebral blood flow and cannot differentiate between dysfunctions in neural
activity itself and this neurovascular coupling (NVC). Techniques, such as electroencephalography (EEG),
cannot unambiguously localize the recorded neurophysiological signal to specific neural networks. To
overcome this critical barrier, we developed a cutting-edge scanning and analysis paradigm that [1]
simultaneously records EEG and fMRI data, [2] detects and quantifies short timescale structure of transient
events of intrinsic neurophysiological activity in cortical networks, and [3] uses these neural network events to
anchor assessment of capacity to adjust vascular energy delivery in response to activity demands. Such
selective measurements in unique neural networks will be used in the current project to test if disrupted rapid
neural function and NVC in the active ‘cortical hubs’ are associated and show temporal precedence to Aβ
pathology and the linked deficits in higher-order cognitive domains in a longitudinal cohort of older adults
without clinical dementia. We will quantify Aβ pathology by leveraging novel ultra-sensitive blood biomarkers.
Successful implementation of this approach would suggest that, in the aging human brain, abnormal fast
neural dynamics and NVC in specific cortical regions are disease states predisposing to Aβ pathological
changes. If such disease states are an upstream process to Aβ pathology, then in future studies, it may be
possible to regu...

## Key facts

- **NIH application ID:** 10888372
- **Project number:** 5R01AG075753-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Tatiana Sitnikova
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $586,437
- **Award type:** 5
- **Project period:** 2022-08-15 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10888372

## Citation

> US National Institutes of Health, RePORTER application 10888372, Simultaneous EEG/fMRI to disentangle neural and vascular mechanisms of Alzheimer's disease pathology (5R01AG075753-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10888372. Licensed CC0.

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