Mid-frontal Delta/Theta and Cognitive Control

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 knowl