# The Progressive Elevation of Spontaneous Cortical Activity in HAND (PESCAH) Project

> **NIH NIH R01** · FATHER FLANAGAN'S BOYS' HOME · 2022 · $405,100

## Abstract

Project Summary/Abstract
It is well known that human cortical neurons exhibit spontaneous firing in the absence of incoming exogenous
and endogenous input. Across a neuronal population, these discharges summate with local dendritic currents
and synaptic potentials to produce cortical rhythmic activity, which is often referred to as “spontaneous activity.”
Such spontaneous rhythms are ubiquitous throughout the human brain, but their role in modulating cognition is
only beginning to be understood. Recently, we used magnetoencephalography (MEG) to show that the strength
of spontaneous activity directly affects neural oscillatory activity in the same cortical area, and in-turn modulates
real time task performance in controls and person with HIV (PWH). Additionally, we have shown that spontaneous
activity in multiple brain regions is accentuated and inextricably linked to oscillatory activity in patients with HIV-
related cognitive impairment. In fact, our preliminary data suggests that the level of spontaneous activity in
specific brain regions, as well as the dynamic interplay between these spontaneous rhythms and cortical
oscillations, may be vital in identifying the degree of cognitive impairment in HIV-infected adults. The goals of
the parent project are to quantify the trajectory of age-related elevations in spontaneous cortical activity in a large
group of PWH and demographically-matched controls, and evaluate how the strength of such spontaneous
activity affects neural oscillations and real time cognitive performance. In 2019-2020, we used an administrative
supplement to extend our framework to include beta-amyloid positive patients with amnestic mild cognitive
impairment (MCI) and mild-to-moderate Alzheimer’s disease (AD). This work has been broadly successful and
resulted in groundbreaking publications in leading journals, with multiple other papers pending revision. With the
proposed second administrative supplement, we will extend this work by adding tau-PET imaging to the overall
cohort. Specifically, we will identify the role of aberrant spontaneous neuronal activity in AD, MCI, and PWH, and
examine the spatial covariance between tau, beta-amyloid, and increased spontaneous neural activity in these
patients. In line with our findings to date, spontaneous activity will be uniquely elevated in PWH, especially
cognitively impaired PWH, and systematically decreased in patients with AD/MCI relative to cognitively normal
controls. Further, amyloid burden will spatially covary with the strength of altered neural oscillations in those with
AD/MCI, but not PWH who exhibit amyloid negativity like controls. Finally, we hypothesize that tau deposition
will be significantly higher in those with AD/MCI relative to PWH, and that tau deposition will predict cognitive
performance in those with AD/MCI but not PWH. Beyond providing a novel conceptual framework based on
known neurophysiological principles to the study of AD/MCI, this supplement will provide...

## Key facts

- **NIH application ID:** 10496019
- **Project number:** 3R01MH116782-05S1
- **Recipient organization:** FATHER FLANAGAN'S BOYS' HOME
- **Principal Investigator:** Tony W. Wilson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $405,100
- **Award type:** 3
- **Project period:** 2021-01-15 → 2024-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10496019

## Citation

> US National Institutes of Health, RePORTER application 10496019, The Progressive Elevation of Spontaneous Cortical Activity in HAND (PESCAH) Project (3R01MH116782-05S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10496019. Licensed CC0.

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