Frontal midline delta/theta rhythms and cognitive control in PD

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. Our 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, we linked PD-related cognitive impairment to dysfunction in frontal midline delta (1–4 Hz) and theta (5–7 Hz) rhythms, which our work has established as a marker of cognitive control. However, it is unknown why PD patients have deficits in these low-frequency brain rhythms. Our 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, our 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). We will test the overall hypothesis that frontal midline delta/theta dysfunction contributes to cognitive impairments in PD. In Aim 1, we will determine the structural basis for delta/theta rhythm deficits in PD. In Aim 2, we will determine the predictive power of delta/theta rhythm deficits in PD. In Aim 3, we will determine how tuned low-frequency STN DBS impacts cortical activity and cognition. Our 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, our findings are directly relevant to Alzheimer’s-related dementias (ADRD).