Investigation of non-invasive brain stimulation for the treatment of apathy

Candidate and training: Dr. Sklerov, MD MS, is a movement disorders trained neurologist who has been
involved in patient-oriented research throughout her training and early career. Dr. Sklerov holds a tenure track
position of Assistant Professor of Neurology at the University of North Carolina, where she is pursuing her
research and clinical interests in non-motor symptoms of Parkinson’s disease (PD). Dr. Sklerov’s long-term
career goal is to become a leading independent clinical researcher in developing novel treatments for
neuropsychiatric symptoms of neurologic and psychiatric diseases. The training plan, created in conjunction with
her mentors and advisors, will allow the applicant to achieve her goals: 1) To obtain training in the use of
electroencephalography (EEG) in brain stimulation research, 2) To gain experience in the use and applications
of transcranial magnetic stimulation (TMS), 3) To expand her knowledge and experience in clinical trial design,
and 4) To develop grantsmanship and professional development skills for supporting an independent research
career. Her mentorship team includes Drs. Flavio Frohlich, Ph.D, and Dr. David Rubinow, MD.
Research: Apathy, or lack of enthusiasm or concern for things that were previously interesting, is a common
and debilitating motivational disturbance in neurologic and psychiatric diseases. Apathy is linked to higher levels
of cognitive impairment, depression, care partner stress levels, and more severe psychiatric and neurologic
disease, and is often refractory to treatment. Transcranial magnetic stimulation (TMS), a form non-invasive brain
stimulation, is effective in treating depression when targeting the dorsolateral prefrontal cortex (DLPFC) but has
had limited study in apathy. Disruption in medial brain structures, such as the medial prefrontal cortex (mPFC)
and anterior cingulate cortex (ACC), is a common finding in motivational disorders, regardless of underlying
disease. Medial brain structures are preferentially affected in Parkinson’s disease (PD) on pathologic
examination, while other brain regions, such as the DLPFC, are spared. The overarching goal of the proposed
research is to develop apathy TMS targets. Aim 1 will investigate change in performance of an incentivized
motivational task (a measure of apathy) in response to TMS targeting the mPFC. Aim 2 will investigate the use
of electroencephalography (EEG) as a surrogate measure of target engagement. Developing a brain stimulation
target for apathy has the potential to improve quality of life and disease course for millions of Americans
struggling with psychiatric and neurologic illness. Completing the research and training proposed here will allow
the applicant to obtain the preliminary data and expertise necessary to build her innovative research program
and apply for R01 level funding. We expect that this research will improve our understanding of refractory apathy,
and promote development of a widely-available and safe therapeutic option for apathy.