# Cross-frequency coupling: its role in brain function and dysfunction

> **NIH NIH RF1** · GEORGETOWN UNIVERSITY · 2020 · $839,700

## Abstract

Abstract
 One of the high priority research areas listed in the BRAIN 2025 Report is a better understanding of the
brain network dynamics across time and space from human electrophysiological recordings. The RFA-MH-20-
120 “BRAIN Initiative: Secondary Analysis and Archiving of BRAIN Initiative Data” specifically focuses on the
use of large volumes of existing data stored in open access public databases. In the proposed studies, we will
perform an innovative secondary analysis of existing intracranial EEG records from patients with medicine-
resistant epilepsy collected during their presurgical evaluation. These records from public repositories would
allow us to study dynamic interactions between hippocampal and neocortical structures during the development
of pathological activity as well as during verbal memory tasks. We will use a novel and rapidly developing
approach from the realm of machine learning algorithms namely, deep learning neural networks. Physiological
mechanisms of memory formation and consolidation as well as pathophysiological mechanisms of epilepsy are
poorly understood. The main hypothesis of this proposal is that physiological function and dysfunction of the
hippocampal-neocortical system may have a common mechanism that depends on the dynamic interaction of
electrophysiological oscillations in the system. Brain oscillations have been suggested to be involved in
information transfer within and between brain networks by modulating neural excitability at different spatial and
temporal scales. The interaction of oscillations across different time scales is referred to as ‘cross-frequency
coupling’ and it represents a high-order structure in the functional organization of brain rhythms. Aberrant
patterns of cross-frequency coupling may lead to memory dysfunction as well as facilitate the propagation of
pathological activity. At present, the field does not have a mechanistically justified criterion to distinguish between
physiological and pathological oscillations especially regarding their high-order interactions. We will study cross-
frequency coupling during the interictal-ictal transition (Aim 1) and during successful and unsuccessful verbal
memory performance (Aim 2) using Deep Learning algorithms. One of the study goals is to create a neural
network capable of recognizing patterns of cross-frequency coupling as biomarkers of different physiological and
pathological functional states of the brain. A comprehensive characterization of cross-frequency coupling would
allow us to distinguish between physiological and aberrant forms of interaction between brain networks at
different time scales. The study results will deepen our knowledge about the functional organization of brain
rhythms and will provide a new method to recognize functional states from electrophysiological records of brain
activity. This method will be applicable for a more accurate monitoring, diagnosis and treatment of memory
impairments in neurological and ment...

## Key facts

- **NIH application ID:** 10008042
- **Project number:** 1RF1MH123192-01
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** ANDREI V MEDVEDEV
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $839,700
- **Award type:** 1
- **Project period:** 2020-08-12 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10008042

## Citation

> US National Institutes of Health, RePORTER application 10008042, Cross-frequency coupling: its role in brain function and dysfunction (1RF1MH123192-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10008042. Licensed CC0.

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