Sex Differences in Alcohol Use Disorder Neurodegeneration using Multimodal PET and DTI Neuroimaging - Project Summary/Abstract
The program of research and training described in this K01 application will provide the candidate with the
requisite skills to become an independent investigator understanding sex differences in neurodegeneration
(i.e., microglia and white matter tracts) and neurocognition in alcohol use disorder (AUD) to identify novel
treatment targets that address sex differences. The research component of this 5-year plan involves the
application of: (1) positron emission tomography (PET) imaging to examine sex differences in neurocognitive
function that underlie sex differences in microglia levels in AUD; (2) diffusion tensor magnetic resonance
imaging (DTI) to examine sex differences in white matter tract integrity in AUD and; (3) PET and DTI
multimodal integration analysis to determine the relationship between microglia levels, white matter tract
integrity, and neurocognitive function in women and men with AUD. Sixty (15 male and 15 female) individuals
with AUD and 30 age-, sex-, and smoking-matched healthy controls will participate in both PET and DTI
scanning to facilitate PET, DTI, and PET/DTI integration analysis. To systematically identify sex differences in
patterns of white matter tract integrity, the candidate will also examine data from a large, archived,
neuroimaging DTI dataset (The Human Connectome Project), to generate publications and productivity during
data collection. This combination of novel data collection and secondary data analyses is designed to
maximize the candidate's training via provision of hands-on experience in both: (1) the theory and conduct of
her own combined multimodal neuroimaging study under guided supervision of recognized experts; and, (2)
the analysis and interpretation of large-scale neuroimaging datasets. In pursuit of these goals, the candidate
proposes to undertake further training in four primary areas: (1) the neurobiology of AUD, (2) treatment
outcomes research and clinical corelates of AUD, (3) DTI and multimodal neuroimaging, and (4) biostatistical
approaches. The opportunities afforded by the K01 mechanism would enable the candidate to embark on a
rigorous, structured 5-year program of training and research, designed to provide her with the necessary skills
in the four areas highlighted above. This program of study will combine formal didactic courses, directed
readings, one-on-one tutorials, specialized workshops, attendance of scientific research conferences, and
mentored research experience. The research and training proposed in this K01 provides an ideal
interdisciplinary opportunity to achieve the candidate's long-term career goal of becoming an independent
scientist with a particular focus on sex as a biological variable in the neurobiology of AUD. The team of
mentors and collaborators are leaders in these fields and, together with the stimulating and collaborative
environment of the Yale School of Medicine, will facilitate the candidate's growth and prepare her for an
independent career at the interface of AUD neuroscience and neuroimaging research.
