Current Projects

Identification of individuals at risk for epilepsy after traumatic brain injury

Epilepsy is a chronic, debilitating neurological disorder that affects millions of people across the globe. Epilepsy due to head injury, known as post-traumatic epilepsy (PTE), represents an opportunity to understand the changes in the brain (epileptogenesis) that lead to epilepsy. We use human MRI to help understand the unique structural and functional changes in the brain leading to PTE and develop tools for epilepsy risk stratification after head injury—a prerequisite for feasible clinical trials of therapies for the prevention of epilepsy. 

The neurobiological phenotype of traumatic brain injury (TBI) involves both focal (e.g., contusions) and diffuse (e.g., axonal injury) injury mechanisms. Both animal and human data implicate damage to the limbic system in those with epilepsy after head injury. We use MRI to determine the effects of focal and diffuse injury mechanisms on the limbic network in patients with TBI who develop epilepsy. We use neuroimaging data from a large, well-characterized cohort of participants with TBI and uninjured controls, the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI).

Characterization of post-traumatic epilepsy phenotypes

Considerable effort has focused on identifying blood, imaging, electrophysiologic, and molecular biomarkers of epileptogenesis to facilitate clinical trials of antiepileptogenic therapy. Despite these investments, no biomarker has achieved sufficient accuracy and validation for clinical implementation. A major limitation is that PTE has largely been treated as a single disease, whereas increasing evidence suggests that it comprises heterogeneous epileptic phenotypes with distinct structural and network characteristics. We are focused on defining clinically meaningful phenotypes of human post-traumatic epileptogenesis to accelerate biomarker discovery. To achieve this goal, we leverage structural neuroimaging and neurophysiologic data to characterize the phenotypic diversity of the epilepsies occurring after brain injury. Our broader goal is to use quantitative neuroimaging to define neurobiologically grounded phenotypes of neurological disorders, which will improve our understanding of disorders such as epilepsy and TBI and ultimately improve care.

Characterization of epilepsy phenotypes

This project is focused on developing brain imaging biomarkers capable of detecting epileptogenic lesions in patients with drug resistant focal epilepsy. Such biomarkers are needed to increase the number of patients eligible for potentially curative epilepsy surgery. We use a form of quantitative MRI known as MRI fingerprinting (MRF) to identify epileptogenic lesions. We use two innovative and clinically translatable approaches, spatial normative modeling and brain asymmetry analysis, to generate quantitative patient-specific deviation maps inferred from MRF images in patients with drug resistant focal epilepsy. Our goal is to build upon prior work using mainly group level analyses of qualitative MRI to develop a framework for patient level inference and move the field forward, towards neuroimaging-based biomarkers of epileptogenic brain lesions and better surgical outcomes.