Project Summary: The overall goal of this project is to provide applicant J. Nicole Bentley, MD appropriate
resources and mentorship to develop skills allowing a path to research independence in the field of
neuromodulation for cognitive disorders. This proposal focuses on the role of dorsolateral prefrontal cortex
(DLPFC) in altered cognition in Parkinson’s disease (PD) patients with simultaneous intracranial cortical and
subcortical recordings during awake deep brain stimulation (DBS) surgery. Cognitive impairment is a common
non-motor symptom of Parkinson’s disease (PD), affecting one-quarter of newly diagnosed patients, and more
than 80% of patients over the course of the disease. Despite its prevalence, very few treatment options exist.
Unfortunately, mainstay treatments for motor symptoms of PD such as dopaminergic medications and high-
frequency deep brain stimulation (DBS) do not improve and in some instances can even worsen cognitive
symptoms. Recent evidence in PD patients suggests that reduced prefrontal theta frequency oscillatory activity
is associated with impaired cognition, specifically evident in the domain of inhibitory control. Given its dense
connections to basal ganglia and pre-motor areas, neuromodulation of the DLPFC-basal ganglia network could
enhance elements of cognitive dysfunction in PD. Our novel preliminary data shows DLPFC and subcortical
power modulation and phase-amplitude coupling during an intraoperative Simon task measuring inhibitory
control, and that bursting theta-frequency DBS modulates DLPFC theta power. Here we propose studies to (1)
simultaneously record DLPFC and globus pallidus interna (GPi) local field potentials (LFPs) in awake PD patients
during the Simon task, and (2) contrast continuous and intermittent theta stimulation from the DBS electrode at
the GPi to determine the effect on behavioral and electrophysiologic measures. Given the increasing prevalence
of cognitive impairment and the dearth of available treatments, there is an urgent need to foster the development
of clinician-neuroscientists with this interest. As a neurosurgeon with specialization in neuromodulation, Dr.
Bentley is an ideal candidate to serve in this role. She has assembled a multi-disciplinary and multi-institutional
team of expert mentors who will provide guidance and support towards the scientific and career development
aims of this proposal. She and her mentors have designed a career development plan consisting of cognitive
neuroscience, computational neuroscience, and signal processing techniques. These training aims will be
combined with the high volume of a tertiary movement disorders functional neurosurgery practice at the
University of Alabama, Birmingham. With the institution’s robust resources in research computing, biostatistics,
engineering, and neurophysiology, this proposal will ensure that Dr. Bentley is well-prepared for progressing to
research independence by the completion of this award.