Functional Brain Networks in Essential Tremor and Dystonic Tremor

University Of Florida, Gainesville FL

Investigators

Linked publications & trials

Abstract

? DESCRIPTION (provided by applicant): Essential tremor (ET) is regarded as the most common movement disorder with an estimated prevalence of around 4% after the age of 40 years. Diagnosis of ET is ascertained on the basis of defined clinical criteria however there are concerns among movement disorder specialists that ET is over diagnosed in the community. ET is frequently confused with other neurological disorders associated with tremors for example Parkinson's disease. Since the FDA approved dopamine transporter SPECT (the DAT scan) imaging, differentiation of ET from Parkinson's disease has become easier and reliable. The other major differential diagnosis of ET is tremors associated with dystonia (dystonic tremor). Differentiation of ET from dystonic tremor based on the existing clinical methods is a major challenge. Although imaging methods may allow a better differentiation of ET and dystonic tremor, these methods cannot develop without a complete understanding on the pathophysiology of these two disorders. The pathophysiology of ET and dystonic tremor is broadly considered to have relation to abnormal brain networks. ET is primarily related to abnormal functioning of the cerebellum-motor cortex network and dystonic tremor traditionally is related to abnormal basal ganglia-motor cortex network. However recent studies suggest the cerebellum-motor cortex network may be important even in dystonic tremor. The primary goal of this K23 study is to characterize and compare these brain networks related to ET and dystonic tremor and advance our pathophysiological understanding. We will examine ET and dystonic tremor with a task based functional MRI protocol and diffusion weighted imaging. We will use a reliable grip force task to identify the amplitude of blood oxygenation level dependent (BOLD) activity and connectivity in these networks. We will use diffusion tractography to examine the connectivity patterns in these networks. Our central hypothesis is that the BOLD activity and the functional and structural connectivity in basal ganglia- motor cortex and cerebellum-motor cortex networks will reveal distinct patterns of abnormalities in ET and dystonic tremor. These critical insights into pathophysiological brain networks that underlie ET and dystonic tremor will be used to develop imaging based markers for differentiation of tremors in the clinical settings The candidate's long-term goal is to develop an independent and successful research program focused on the characterization of movement disorders physiology which can lay guidelines for better diagnosis and improve treatment opportunities for these disorders. To achieve this goal, the candidate has organized a training program involving advanced coursework in functional and structural imaging techniques, tremor physiology methods, biostatistics and clinical research methods. The primary mentor, Dr. David Vaillancourt is a well- established NIH funded researcher in functional and structural imaging techniques. He is an experienced mentor with a reputation for fostering the development of many young trainees into independent, NIH funded, investigators. In this application, he has assembled a team of renowned clinicians, biostatistician and experts in essential tremor, dystonia and imaging to serve as co-mentors and members on the advisory committee. University of Florida provides numerous training activities and resources, including regular seminars, lectures and journal clubs on clinical research, physiological techniques and relevant data analysis techniques. In summary, the candidate has chosen the right setting and environment to conduct a mentor guided research with advanced imaging techniques important for differentiation of ET and dystonic tremor and improved therapeutics in future.