Neurology and Neurobehavior

The Center faculty have been involved in developing statistical methods for the practice of neurology – the field of study related to the disorders of the nervous system. Drs. Wu, Crawford, Eloyan, and Hogan collaborate closely with the faculty in the Department of Neuroscience and the Robert J. & Nancy D. Carney Institute for Brain Science developing statistical methods to understand brain function as part of a COBRE project aimed at building a center for central nervous system function. Drs. Gatsonis and Eloyan work in the area of Alzheimer’s Disease leading Biostatistics Cores of large studies (see Alzheimer’s and Dementia). Neurobehavioral disorders include behavioral impairments related to brain diseases such as multiple sclerosis and dementia. Center faculty have been working on statistical methods to understand associations of behavioral impairments and brain imaging outcomes in multiple sclerosis, as well as identify relationships of cognitive and behavioral changes in Alzheimer’s disease and imaging biomarkers.

Purposeful human behavior requires attention, decisions and action, all basic functions mediated by brain networks primarily located in the neocortex but modulated and shaped by sub-cortical processing. Behavioral and brain mechanisms of attention, including vigilance, orienting and perceptual and action selection, are key gateways into high-level function. Thus, in a general and even specific sense, attention, decision-making and the ensuing actions define human mental activities. The proposed center will investigate the mechanisms of higher brain function, with a focus on attention, decision-making, action, and disorders that modify these key systems, using a combination of genetic, behavior, and systems neuroscience approaches.

Jean Wu & Lorin Crawford Staff 1 Research Assistant i

Use of electronic cigarettes has increased dramatically in the US; recent reports suggest that rates are also increasing in pregnant women. Despite known vulnerability of the developing fetus to nicotine, the impact of maternal e-cigarette use on the developing fetus is currently unknown. The proposed study addresses an urgent and unanswered public health question regarding the impact of e-cigarettes and relative impact of e-cigarettes versus conventional cigarettes on fetal development using novel two and three-dimensional ultrasonography.

George Panpandonatos Staff 1 Research Assistant i

Despite increasing availability, use, and potency of cannabis in the US, little is known regarding effects of cannabis use during pregnancy on infant development or biological mechanisms in humans. We propose to establish a prospective prenatal cohort to discern effects of maternal cannabis use during pregnancy on infant neurobehavioral development; we will also test endocannabinoid and glucocorticoid pathways as novel mechanisms underlying effects of prenatal cannabis exposure. Results from the proposed study will provide critical data for obstetric providers and pregnant women, and will inform policy, regulations, and public health messaging regarding cannabis use by pregnant women and women of reproductive age.

George Panpandonatos Staff 1 Research Assistant i

Brain functional connectivity maps have been utilized to learn about differences of brain activation patterns between disease groups via clustering voxels based on their connectivity patters. This project develops general frameworks for estimating associations of brain connectivity maps with predictors of interest after controlling for confounders using a statistical modeling approach that allows for using the special structure of covariance outcomes for improved parameter estimation. An important contribution of this work is the extension of the model to high dimensional settings as the connectivity maps based on fMRI are often large. The proposed framework will be used to learn about functional organization of the brain during an adaptation learning task in a functional MRI study focusing on visual-motor connectivity changes during the task.

Ani Elyoan Staff 1 Research Assistant i

Despite a wealth of treatments for relapsing remitting multiple sclerosis (RRMS), developing effective treatments for progressive forms of MS remains a significant unmet need. Because the neurogenerative component of the disease often dominates over the inflammatory component in PMS, imaging outcomes commonly used in RRMS clinical trials, such as new T2 lesions and gadolinium-enhancing lesions, are insensitive outcomes in PMS. In fact, the optimal primary outcome measure for phase II and phase III PMS clinical trials is not well established. Robust outcomes to measure progression of disability would significantly aid in the rapid evaluation of treatments with potential neuroprotective effects in MS.Atrophy is considered a substrate for clinical disability and cognitive dysfunction. Advances in methodology of imaging segmentation tools allow for evaluation of specific brain regions that are preferentially affected in MS, including the thalamus, corpus callosum, and cerebellum. This proposal addresses the FY17 MSRP Focus Area of Biological Correlates of Disease Activity and Progression in MS by evaluating the ability of these regional outcome measures to assess neuroprotective therapies in MS.

Ani Elyoan Staff 1 Research Assistant i