The candidate is pursuing a K23 career development award to conduct clinical research in the area of neuroimaging in multiple sclerosis (MS). This award will provide protected research time and training in preparation for independent R01 funding. The primary mentor for this project is Dr. Bruce Rosen, an expert in applying functional imaging tools to solve specific biological and clinical problems. Dr. Howard Weiner will serve as the secondary mentor, lending his renowned expertise in MS. Multiple sclerosis is the leading non- traumatic cause of disability in young adults. Cognitive dysfunction is common in MS and contributes to loss of employment and reduced quality of life. By exploring connectivity of brain regions, resting-state functional connectivity (fcMRI) has the potential to improve the understanding of MS pathogenesis while serving as a unique means of examining cognition. The candidate will correlate functional inter-hemispheric connectivity with measures of anatomical connectivity (diffusion tensor imaging in the corpus callosum) and corpus callosum atrophy, a common finding in MS. Correlating these measures will help evaluate the functional role of the corpus callosum in cognitive dysfunction in MS. We will also explore how cortical pathology, as demonstrated at ultra-high field (7T), affects connectivity in a locally constrained area, termed local connectivity. Both fcMRI at 3T and cortical lesion measures at 7T will be correlated with neuropsychological testing to help address how white and gray matter pathologies differentially contribute to cognitive dysfunction. In addition to mentored research activities, tailored didactic coursework and other training activities will provide formal educatio in imaging analysis and cognitive neuroscience to the candidate.

Public Health Relevance

This study aims to provide insight into the cause of cognitive dysfunction in multiple sclerosis, a leading non-traumatic cause of disability in young adults, by examining resting state functional connectivity MRI. New functional markers of the disease will be developed for future application to monitor the effectiveness of new treatments for multiple sclerosis. This study may aid in the development of future therapies specifically targeted to prevent or improve cognitive dysfunction in multiple sclerosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
4K23NS078044-05
Application #
9042436
Study Section
NST-2 Subcommittee (NST)
Program Officer
Utz, Ursula
Project Start
2012-04-01
Project End
2017-03-31
Budget Start
2016-04-01
Budget End
2017-03-31
Support Year
5
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
Tobyne, Sean M; Ochoa, Wilson B; Bireley, J Daniel et al. (2018) Cognitive impairment and the regional distribution of cerebellar lesions in multiple sclerosis. Mult Scler 24:1687-1695
Patel, Kevin R; Tobyne, Sean; Porter, Daria et al. (2018) Structural disconnection is responsible for increased functional connectivity in multiple sclerosis. Brain Struct Funct 223:2519-2526
Tobyne, Sean M; Boratyn, Daria; Johnson, Jessica A et al. (2016) A surface-based technique for mapping homotopic interhemispheric connectivity: Development, characterization, and clinical application. Hum Brain Mapp 37:2849-68
Huang, Susie Y; Tobyne, Sean M; Nummenmaa, Aapo et al. (2016) Characterization of Axonal Disease in Patients with Multiple Sclerosis Using High-Gradient-Diffusion MR Imaging. Radiology 280:244-51
Klawiter, Eric C; Ceccarelli, Antonia; Arora, Ashish et al. (2015) Corpus callosum atrophy correlates with gray matter atrophy in patients with multiple sclerosis. J Neuroimaging 25:62-7
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Klawiter, Eric C (2013) Current and new directions in MRI in multiple sclerosis. Continuum (Minneap Minn) 19:1058-73