Mid-frontal Delta/Theta and Cognitive Control

Summary

Abstract Cognitive symptoms of Parkinson's disease (PD) include deficits in attention, working memory, and reasoning. These deficits affect up to 80% of PD patients and lead to mild cognitive impairment (PD-MCI) and dementia in PD (PDD). There is a critical need to better understand cognitive impairment in PD to develop new targeted treatments. The long-term goal is to define the mechanisms of PD-related cognitive impairment. PD involves diverse processes such as dopamine and acetylcholine dysfunction, synuclein aggregation, and genetic factors. During the past funding period, the investigators linked PD-related cognitive impairment to dysfunction in frontal midline delta (1-4 Hz) and theta (5-7 Hz) rhythms, which the work has established as a marker of cognitive control. However, it is unknown why PD patients have deficits in these low-frequency brain rhythms. The preliminary magnetic resonance imaging (MEG) and magnetoencephalography (MRI) implicate the anterior midcingulate cortex (aMCC) as a potential source of frontal midline delta/theta rhythms. In the next funding period, the objective is to determine the mechanisms and predictive power of delta/theta rhythms in PD, which will help to better understand the pathophysiology of PD-related cognitive impairment. Collaboration between the University of New Mexico (UNM) and University of Iowa (UI) that will bring together MEG, MRI, longitudinal EEG, and adaptive subthalamic (STN) deep-brain stimulation (DBS). The investigators will test the overall hypothesis that frontal midline delta/theta dysfunction contributes to cognitive impairments in PD. In Aim 1, the investigators will determine the structural basis for delta/theta rhythm deficits in PD. In Aim 2, the investigators will determine the predictive power of delta/theta rhythm deficits in PD. In Aim 3, the investigators will determine how tuned low-frequency STN DBS impacts cortical activity and cognition. The results will have relevance for basic-science knowledge of the fundamental pathophysiology of cognitive impairment in PD and related dementias. Because this proposal will study patients with PDD, the findings are directly relevant to Alzheimer's-related dementias (ADRD).

Conditions

• Parkinson&Amp;Amp;#39;s Disease (PD)

Interventions

DEVICE

Deep-brain Stimulation

a neurosurgical procedure that uses implanted electrodes and electrical stimulation to treat movement disorders and certain neuropsychiatric conditions when medications are ineffective or cause significant side effects.

DEVICE

Transcranial Magnetic Stimulation

Transcranial magnetic stimulation (TMS) is a non-invasive treatment that uses magnetic fields to stimulate specific areas of the brain.

DEVICE

Transcranial Alternating Current Stimulation

Transcranial Alternating Current Stimulation (tACS) is a non-invasive brain stimulation technique that uses weak, alternating electrical currents applied to the scalp to modulate brain activity and potentially influence cognitive processes by entraining brain oscillations.

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS)

  collaborator NIH

• Nandakumar Narayanan

  lead OTHER

Study Design

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Model

FACTORIAL

Eligibility

Min Age

18 Years

Max Age

99 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2017-09-25

Primary Completion

2029-12-31

Completion

2029-12-31

FDA Device

Yes

Countries

• United States

Study Locations