David F. Tate, Ph.D. - US grants

Project Summary/Abstract Traumatic brain injury (TBI) is a major public health issue globally, and while neuroimaging has been useful in understanding disruption in brain structure and function after injury, there are a number of factors that attenuate its prognostic ability. For example, there is tremendous heterogeneity in outcome after injury which is only partially explained by injury severity. Cost frequently limits sample size in neuroimaging studies, yet given the myriad factors that have been shown to influence patient outcome (age, injury severity, socioeconomic status), small samples and mass univariate testing often result in many studies being grossly under-powered. One solution is to combine data and create novel data sharing platforms, and the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium has supported this kind of collaboration for over a decade across a range of clinical disorders. The goal of this proposal is to develop tools and data processing procedures for use in the ENIGMA Brain Injury working group. In the R61 phase, we aim to develop and test a workflow for harmonized processing of behavioral data (Aim 1) as well as structural and functional (resting-state) MRI data (Aim 2). For Aim 1 of the R61, the goal is to offer a decision tree of procedures that is data-dependent, allowing investigators to establish common cognitive endpoints across cohorts that collect a range of neuropsychological and clinical measures. This proposal will create sharable procedures, flexible tools, and generalizable guidelines for best practices for extracting common cognitive endpoints from distinct behavioral test batteries (R61 Aim 1). In Aim 2 of the R61, we develop an image processing pipeline called Harmonization and Aggregation for Functional and structural imaging data PIPEline; HAF-PIPE) that allows for aggregation of non-equivalent imaging data. A primary goal is to decentralize ComBat, an open-source data harmonization tool, so that it can be used in a virtual sharing environment. Following satisfaction of the R61 Go/No-Go criteria, which is the curation of the dataset including 13 cohorts, extraction of common cognitive endpoints, and creation of HAF- PIPE, we will move to the R33 phase. In the R33 phase, we will leverage the large, harmonized dataset and apply a machine learning technique (CorEx - Correlation Explanation) to identify patient clusters within each patient population studied. HAF-PIPE and the procedures and guidelines from the R61 phase will then be extended to additional patient populations and made available to other ENIGMA working groups. The harmonized data, along with the tools and procedures for creating them, will be accessible to researchers following proposal submission and approval as a curated dataset. With success, this proposal holds the promise of significantly advancing data curation, harmonization, and sharing in the clinical neurosciences. We anticipate that our proposal will significantly advance our understanding of factors that impact outcome after injury and will yield a tool that will be useful across the neuroimaging community.

Intimate partner violence (IPV), the physical violence, sexual violence, psychological aggression, or stalking by a current or former intimate partner, is a significant public health concern affecting approximately 10 million people in the United States annually. Approximately 33% of women exposed to IPV report physical trauma resulting in heighted risk of head injury in this population. Recent work suggests that anywhere from 40-90% of women experience head trauma due to IPV. IPV-related head trauma is caused by blunt force trauma, being pushed or violently shaken, and/or strangulation, which can result in focal trauma or contusions, acceleration and deceleration injuries, as well as hypoxia and anoxia due to strangulation, respectively. Limited research has shown that women exposed to IPV with head trauma report higher depression, anxiety, and post-traumatic stress disorder symptomatology, as well as impaired cognitive function relative to women with IPV and no exposure to head trauma. Although the clinical features of repeated exposure to head trauma identified in IPV are similar to the effects observed in military traumatic brain injury (TBI) and sports-related concussion, limited work has been done to understand IPV-related head trauma, in particular its chronic cognitive and psychological effects as well as associated brain changes. Through a multi-site research collaboration consisting of members of the Enhancing NeuroImaging and Genetics through Meta-Analysis (ENIGMA) IPV Working Group, the proposed study will characterize the cognitive, psychological, and neural profiles of IPV- related head trauma, as well as determine whether specific symptoms clusters are associated with discernable IPV subgroups. Furthermore, this proposal initiates the process of creating an IPV study cohort that will be re- assessed every 5 years to chronically assess brain and behavioral changes associated with IPV-related head trauma over the lifespan. Semi-structured interviews will be used to obtain IPV specific information such as abuse and head trauma history and frequency. A comprehensive neuropsychological battery will be used to determine cognitive and psychological status, while sophisticated neuroimaging techniques will be used to characterize neural structure, function, and brain metabolites in IPV with exposure to head trauma relative to IPV without exposure to head trauma. Finally, we will use a data-driven approach to determine whether symptom clusters differentiate subgroups of IPV. In aim 1, we will identify the cognitive and psychological profiles of subgroups of IPV. Aim 2 will examine the neuroimaging signatures in subgroups of IPV. In aim 3, we will determine whether symptom clusters are associated with discernible subgroups of IPV. The results from this study will provide critical information about the role of IPV-related head trauma in cognitive and psychological outcomes, as well as the underlying neural changes. This is important not only for understanding the chronic effects of repetitive brain trauma, but also the identification of distinct subgroups of IPV has direct implications for development of patient-centered care approaches for IPV.