# Investigation of silent mesial temporal lobe hyperexcitability in Alzheimer's disease

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $183,712

## Abstract

PROJECT SUMMARY / ABSTRACT
There have been no new treatments approved for Alzheimer’s disease (AD) over the past 15 years. It is
estimated that by the year 2050, AD will affect 14 million Americans and cost the nation over $1 trillion
annually. A fresh perspective on AD is needed, to uncover new disease mechanisms that drive cognitive
decline in AD, and to identify new treatment targets for more successful drug development. This pilot study will
investigate a novel brain electrical abnormality that was recently discovered in two AD patients who underwent
intracranial recordings with foramen ovale electrodes (FOEs). FOEs are a safe and minimally invasive means
to obtain high fidelity recordings of electrical activity from the mesial temporal lobes (mTL), one of the first brain
regions affected by AD pathology. FOE recordings from these AD patients revealed abundant mTL epileptiform
discharges and frequent seizures occurring during sleep. The vast majority of this epileptiform activity was
silent, occurring without any overt clinical symptoms and without any visible signs on scalp EEG. Whether
silent mTL epileptiform activity is common in early stages of AD, and whether this activity contributes to
memory impairment in AD is unknown, because AD patients almost never undergo the intracranial recordings
needed to detect this activity. The goal of this proposal is to further investigate the role of silent mTL
epileptiform activity in early stages of AD. The over-arching hypothesis is that there exists a subset of AD
patients in whom silent mTL epileptiform activity is a potent and modifiable contributor to cognitive decline. If
true, reduction of this activity could comprise a new treatment target for symptomatic relief or disease
modification in AD. This study will be performed at the Massachusetts General Hospital (Boston, MA) and
Baylor Medical Center / St. Luke’s Hospital (Houston, TX). Eight participants with amnestic mild cognitive
impairment or mild dementia due to AD will be recruited to undergo insertion of FOEs, followed by 3 days of
continuous recordings with FOEs and scalp EEG. Recordings will be analyzed to characterize any silent mTL
epileptiform abnormalities present and to correlate these findings with clinical and scalp EEG features. The
specific aims of this study are: 1) Identify and characterize the spectrum of clinically silent mTL activity that
occurs in early stages of AD; 2) Demonstrate the feasibility of recruiting and recording AD participants with
FOEs, and determine the relationship between the duration and yield of these recordings; and 3) Assess
clinical and scalp EEG features common to AD patients with silent mTL epileptiform activity. In the long term,
this research has the potential to reveal a novel and potentially treatable neurophysiologic mechanism by
which memory function becomes disrupted in early stages of AD. The data obtained here will be used to guide
the design of larger studies using intracranial recordings...

## Key facts

- **NIH application ID:** 9977778
- **Project number:** 5R21AG064413-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Alice D Lam
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $183,712
- **Award type:** 5
- **Project period:** 2019-07-15 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977778

## Citation

> US National Institutes of Health, RePORTER application 9977778, Investigation of silent mesial temporal lobe hyperexcitability in Alzheimer's disease (5R21AG064413-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9977778. Licensed CC0.

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