# Mid-frontal delta/theta rhythms and cognitive control in PD

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2021 · $429,127

## Abstract

Abstract
Up to 80% of patients with Parkinson's disease (PD) will suffer from cognitive symptoms, including
impaired attention, planning, reasoning and working memory as well as hallucinations, visuospatial
dysfunction, and delusions. These impairments lead to mild cognitive impairment (PD-MCI) and
dementia (PDD) in PD. Cognitive symptoms of PD are associated with enormous cost to our society.
There are no clear biomarkers and few effective treatments for PD-MCI/PDD. Because risk for PD
increases dramatically with age, this problem will surge as our population grows older. The mechanisms
contributing to PD-MCI/PDD are unknown. Our group has found that low-frequency (1-8 Hz; or
delta/theta bands) brain rhythms might be helpful in diagnosing cognitive dysfunction in PD. This
delta/theta activity originates from areas of medial frontal cortex such as the anterior cingulate, and is
detectable by mid-frontal scalp EEG electrodes. We have found that mid-frontal delta/theta brain rhythms
are engaged when healthy individuals detect novelty, errors, and conflict, or make decisions. These
rhythms are attenuated in PD patients. Our working model is that PD patients manifest diverse neuronal
and network deficits that impair mid-frontal delta/theta activity, leading to failures in engaging cognitive
control. These abnormalities contribute to PD-MCI and PDD. In this proposal we combine `big-data'
machine learning tools, intraoperative neurophysiology in humans, and new brain-stimulation paradigms
to investigate the role of mid-frontal delta/theta rhythms in PD. We will test the overall hypothesis that
mid-frontal delta/theta impairments are a mechanism of cognitive dysfunction in PD. In Aim 1 we will
determine if mid-frontal delta/theta activity predicts PD-MCI/PDD. In Aim 2 we will use unique
intraoperative recordings to determine how delta/theta activity within medial frontal cortex influences
neurons in the subthalamic nucleus, a key site of functional convergence that is targeted by current
deep-brain stimulation for PD. Notably, the subthalamic nucleus is a compact structure that receives
highly overlapping input from cognitive and motor cortical regions, making it likely that our recordings will
capture cognitive processing within this nucleus. Finally, in Aim 3 we will determine if subthalamic
nucleus deep-brain stimulation at delta/theta frequencies improves cognitive control in PD patients.
Because these experiments involve recordings across several PD patient populations (Aim 1), from
single subthalamic neurons (Aim 2), and brain stimulation (Aim 3), each of these aims will provide
independent mechanistic insight into cognitive dysfunction in PD. PD is a complex disease, but if cortical
EEG abnormalities are a consistent theme it might inspire new diagnostic tools or new brain-stimulation
therapies for cognitive dysfunction in PD. Results from this proposal could also be important for other
neurodegenerative diseases such as dementia with Lewy bodies...

## Key facts

- **NIH application ID:** 10187663
- **Project number:** 5R01NS100849-05
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Nandakumar Narayanan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $429,127
- **Award type:** 5
- **Project period:** 2017-09-25 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10187663

## Citation

> US National Institutes of Health, RePORTER application 10187663, Mid-frontal delta/theta rhythms and cognitive control in PD (5R01NS100849-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10187663. Licensed CC0.

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