Perelman School of Medicine at the University of Pennsylvania

Wolf Lab

Welcome to the Wolf Lab

The Wolf Lab in the Department of Neurosurgery is dedicated to understanding the underlying mechanisms of how traumatic brain injury can lead to persistent learning and memory dysfunction, post-traumatic stress disorder, and post-traumatic epilepsy.  Our unique systems neuroscience and computational approaches are uncovering changes in how regions of the brain communicate and encode information following injury.  These alterations in the limbic system, a group of brain regions dedicated to memory and emotional processing, potentially underlie the cognitive and emotional disorders that persist following injury.  In addition, hyperexcitability in this circuitry following TBI may lead to post-traumatic epilepsy.  Using the knowledge of these circuitry alterations, we are developing neuromodulation strategies for the treatment of these disorders following TBI.

Traumatic Brain Injury (TBI)

TBI affects over 3 million people in the U.S. per year, and many more worldwide. During many types of TBI including concussion, inertial forces have effects predominantly on the white matter connections (axons) within and between brain regions. The brain is a series of interconnected networks, including connections between the cortex and sub–cortical structures. How these networks interact, and how the communication between them is disrupted post injury is one of the major questions our lab is addressing. Disconnection or timing disruptions between these networks means that groups of neurons that are normally connected via these axonal tracts may be disrupted and have difficulty communicating following injury.

Cognitive and Emotional Dysfunction

The limbic system is a highly interconnected set of cortical and sub–cortical structures that are the substrate for memory and emotional regulation. Disruptions in the interactions between the "emotional triad" of the prefrontal cortex, the hippocampus, and the amygdala likely underlie disorders such as anxiety and PTSD following TBI. We are currently investigating the effects of TBI on the limbic system, including communication between and encoding/processing of information in these regions. This may give us insight into the mechanisms of memory disorders, the contribution of TBI to PTSD, and which substrates in the limbic system are dysfunctional following TBI.

Post–Traumatic Epilepsy (PTE)

One of the most prevalent disorders associated with TBI is post–traumatic epilepsy. We are working to understand the contributions of various injury components such as inertial injury or contusion of the brain to the development of PTE.  One focus of this research is on the effects of diffuse brain injury on the hippocampus, one of the most excitable structures in the brain. Our results so far indicate that disruption of axonal pathways leading into the hippocampus (and within it) may be disrupted post injury. In addition, the circuitry has become hyperexcitable. We have also developed a new PTE model utilizing a more focal contusion injury, which we hope will allow us to understand mechanisms of epileptogenesis and develop therapies to block this progression.

Technology Development for Neurophysiology

In order to develop better tools for examining circuitry changes in the above disease models, we have been collaborating with a number of electrode and hardware developers for many years to develop better tools for small and large animal recordings, particularly high-density laminar recordings in awake behaving animals using wireless technology.