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.
Essential Tremor and dystonic tremor are clinically difficult to differentiate. The pathophysiology of these tremor disorders is thought to be related to abnormal brain networks but is not completely understood. We plan to examine the brain networks in essential tremor and dystonic tremor with advanced imaging techniques to enhance the current pathophysiological understanding. We will use task based functional MRI protocol to examine the brain activity in cerebellum-motor cortex network and basal ganglia-motor cortex network. We will examine the connectivity patterns in these networks with task based functional MRI and diffusion weighted structural imaging techniques. We will also correlate these brain activity patterns with clinical and physiological analysis of tremors. We believe these insights will facilitate development of a reliable algorithm for improved distinction of essential tremor and dystonic tremor impacting the diagnostics of tremors and delivery of accurate treatment in clinical practice.
| Wagle Shukla, Aparna; Deeb, Wissam; Patel, Bhavana et al. (2018) Is deep brain stimulation therapy underutilized for movement disorders? Expert Rev Neurother 18:899-901 |
| Wagle Shukla, Aparna; Fox, Susan H (2018) Th17 lymphocyte spearheads the immune attack in Parkinson's disease: New evidence for neuronal death. Mov Disord 33:1560 |
| Wagle Shukla, Aparna; Hu, Wei; Jabarkheel, Zakia et al. (2018) Globus Pallidum DBS for Task-Specific Dystonia in a Professional Golfer. Tremor Other Hyperkinet Mov (N Y) 8:487 |
| Archer, Derek B; Coombes, Stephen A; Chu, Winston T et al. (2018) A widespread visually-sensitive functional network relates to symptoms in essential tremor. Brain 141:472-485 |
| Wagle Shukla, Aparna; Hu, Wei; Legacy, Joseph et al. (2018) Combined effects of rTMS and botulinum toxin therapy in benign essential blepharospasm. Brain Stimul 11:645-647 |
| Wagle Shukla, Aparna; De Jesus, Sol; Meng, Fan-Gang et al. (2017) Focal cervical dystonia presents in the setting of acute cerebellar hemorrhage. J Neurol Sci 375:307-308 |
| Wagle Shukla, Aparna; Malaty, Irene A (2017) Botulinum Toxin Therapy for Parkinson's Disease. Semin Neurol 37:193-204 |
| Wagle Shukla, Aparna; Zeilman, Pam; Fernandez, Hubert et al. (2017) DBS Programming: An Evolving Approach for Patients with Parkinson's Disease. Parkinsons Dis 2017:8492619 |
| Wagle Shukla, Aparna; Fox, Susan (2017) Complex genetics of Tourette's Syndrome: Piecing the puzzle. Mov Disord 32:1685 |
| Wagle Shukla, Aparna; Okun, Michael; Vaillancourt, David et al. (2017) The ice test to differentiate essential tremor from Parkinson's disease tremor. Clin Neurophysiol 128:2181-2183 |
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