Document text
Principal Investigator: Katherine Louise Bottenhorn
Organization: UNIVERSITY OF SOUTHERN CALIFORNIA
Fiscal Year: 2024
Award: $124,169
Funding agency: National Institute of Mental Health
PROJECT SUMMARY
This proposal aims to address the BRAIN Initiative goals of developing and applying technologies for
innovative study of the relationships between biological processes, neural structure, and brain function, to
further our understanding of how sex hormones (e.g., estradiol, testosterone, progesterone) exert organizing
effects on brain development during puberty. Animal and postmortem human research has revealed that these
effects include cytoarchitectonic changes, including apoptosis and changes to dendrite structure, but
technology has limited in vivo study in humans. While neuroimaging has provided insight into associations
between sex hormone levels during puberty and the brain’s macro-scale and functional architecture, this
literature overlooks potential neurobiological mechanisms (e.g., cytoarchitecture changes) and the impact of
phasic versus tonic (i.e., annual versus weekly) hormone changes on brain development. The proposed
human neuroimaging project addresses these gaps by integrating estimates of cytoarchitecture from advanced
biophysical modeling of diffusion-weighted imaging, to complement commonly used macro-scale and
functional architecture measures, and by assessing both sparsely and densely sampled hormone levels using
three independent studies of youth at various stages of pubertal maturation. Furthermore, the proposed
research applies machine learning to facilitate multi-dataset integration and investigation of how hormone
levels are related to correspondence between the brain’s structural and functional architectures. The candidate
has a background in magnetic resonance imaging, including with developmental populations, is experienced in
developing and applying data-driven tools for studying large-scale brain networks, and seeks further training in
neuroendocrinology, machine learning, and diffusion-weighted imaging to become an independent researcher
in this field. During the mentored phase, she will (1) develop and train a model that predicts sex hormone
levels from functional connectomics in a large adolescent dataset, test its accuracy predicting the same and
novel hormones in an independent adolescent dataset, and share the pre-trained model for use by the broader
research community and (2) assess roles of sex hormone levels during puberty in developing structure-
function associations using multivariate, cross-decomposition approaches. Training from leaders in adolescent
neuroendocrinology, machine learning, multi-dataset analysis, and diffusion-weighted imaging will aid in this
work and prepare her for the independent phase, when she will (3) apply the pretrained model to predict (a)
average hormone levels, to further assess the generalizability of identified sex hormone-related brain networks,
and (b) weekly sex hormone levels, to assess the role of phasic hormone changes on the identification of tonic
neurobiological associations. Then, she will (4) apply further cross-decomposition approaches to model the
role of hormones in associations between the brain’s functional architecture and each macro- and
cytoarchitecture across pubertal development in three independent datasets.
Terms: <12-20 years old><Address><Adolescence><Adolescent><Adolescent Youth><Androgenic Agents><Androgenic Compounds><Androgens><Androstenolone><Animals><Apoptosis><Apoptosis Pathway><Aquadiol><Architecture><Area><Autopsy><BRAIN initiative><Behavior><Biological Function><Biological Process><Brain><Brain Diseases><Brain Disorders><Brain Nervous System><Brain Research through Advancing Innovative Neurotechnologies initiative><CNS plasticity><Communities><Complement><Complement Proteins><Contraceptive Usage><Corlutina><Corluvite><Corpus Luteum Hormone><Coupling><Cyclogest><DHEA><DWI (diffusion weighted imaging)><DWI-MRI><Data><Data Collection><Data Set><Dehydroisoandrosterone><Delta4-pregnene-3,20-dione><Dendrites><Development><Differences between sexes><Differs between sexes><Diffusion MRI><Diffusion Magnetic Resonance Imaging><Diffusion Weighted MRI><Diffusion weighted imaging><Diffusion-weighted Magnetic Resonance Imaging><Dimenformon><Diogyn><Diogynets><Encephalon><Encephalon Diseases><Endocrine><Endocrine Gland Secretion><Engineering / Architecture><Error Sources><Estrace><Estradiol><Estradiol-17 beta><Estradiol-17beta><Estraldine><Estrogens><Exhibits><Female Adolescents><Functional MRI><Functional Magnetic Resonance Imaging><Funding><Gestagenic Agents><Gestagens><Gestiron><Gestone><Goals><Gonadal Steroid Hormones><Hormone Receptor><Hormones><Human><Image><Individual Differences><Intracranial CNS Disorders><Intracranial Central Nervous System Disorders><Investigation><Investigators><Least Squares><Least-Squares Analyses><Least-Squares Analysis><Link><Lipo-Lutin><Literature><Luteohormone><Lutocyclin><Lutocylin M><Lutogyl><Lutromone><MR Imaging><MR Tomography><MRI><MRIs><Machine Learning><Magnetic Resonance Imaging><Measures><Mediating><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Mentors><Modeling><Modern Man><Morphology><NMR Imaging><NMR Tomography><Neural Development><Neuranatomies><Neuranatomy><Neuroanatomies><Neuroanatomy><Neurobiology><Neuroendocrine><Neuroendocrine System><Neuroendocrinology><Neuronal Plasticity><Neurosecretory Systems><Nuclear Magnetic Resonance Imaging><Ovocyclin><Ovocylin><Participant><Phase><Population><Prasterone><Pregn-4-ene-3,20-dione><Pregnenedione><Prevalence><Progestagenic Agents><Progestasert><Progestational Agents><Progestational Compounds><Progestational Hormones><Progesterone><Progesterone Agents><Progestins><Progestogel><Progestogens><Progestol><Progeston><Programmed Cell Death><Progynon><Prolidon><Proluton><Psychopathology><Puberty><Research><Research Personnel><Research Resources><Researchers><Resources><Role><Sampling><Sex Differences><Sex Hormones><Sex Steroid Hormones><Sexual differences><Staging><Structure><Syngesterone><Technology><Testing><Testosterone><Therapeutic Androgen><Therapeutic Dehydroepiandrosterone><Therapeutic Estradiol><Therapeutic Estrogen><Therapeutic Hormone><Therapeutic Progesterone><Therapeutic Progestin><Therapeutic Testosterone><Thick><Thickness><Time><Training><Trans-Testosterone><Utrogestan><Work><Youth><Youth 10-21><Zeugmatography><abnormal psychology><adolescence (12-20)><adolescent girl><biophysical model><central nervous system plasticity><cognitive development><complementation><computer based prediction><connectome><contraceptive use><critical period><dMRI><data integration><dehydroepiandrosterone><design><designing><developmental><diffusion tensor imaging><experience><fMRI><girls><gonadal steroids><imaging><in vivo><innovate><innovation><innovative><innovative technologies><insight><juvenile><juvenile human><machine based learning><model generalizability><necropsy><neural><neural imaging><neural mechanism><neural plasticity><neuro-imaging><neurobiological><neurobiological mechanism><neurodevelopment><neuroimaging><neurological imaging><neuromechanism><neuroplastic><neuroplasticity><novel><postmortem><pre-trained model><precision medicine><precision-based medicine><predictive modeling><receptor expression><role model><sex><sex based differences><sex steroid><sex-dependent differences><sex-related differences><sex-specific differences><social role><substantia alba><tool><white matter>