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 using systems neuroscience and computational approaches to understand the underlying mechanisms of traumatic brain injury and cognitive disorders involving the limbic system. These two areas of focus overlap in both substrates (dysfunctional interacting networks) and outcomes (cognitive disruption).

Traumatic Brain Injury (TBI)

TBI affects over 3 million people in the US per year. Diffuse brain injury can occur during many types of TBI, and has effects predominantly on the white matter connections (axons) between brain areas. 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 the lab is addressing. Disconnection between these networks means that ensembles of cells that are normally connected via these axonal tracts may be disrupted and have difficulty communicating.

Post–Traumatic Epilepsy (PTE)

One of the most prominent disorders associated with TBI is post–traumatic epilepsy. We are focusing our efforts on the effects of diffuse brain on the hippocampus, one of the most excitable structures in the brain. Our results so far indicate that axonal disruption of pathways leading into the hippocampus and within it may be disrupted post injury. In addition, the circuitry has become hyper–excitable, even after one week post injury. We are investigating the mechanisms of this phenomena, and whether there is a time frame for recovery of this phenomena, and whether over the long term these injuries can induce seizure disorders or sub–clinical phenomena.

Limbic System Dysfunction

The limbic system is a highly interconnected set of cortical and sub–cortical structures that are involved in many disorders. We have previously focused our efforts on the integration of inputs in the striatum (Tourette's, OCD, Schizophrenia) and how these are propagated to the rest of the brain. Disruptions in the interactions between the "Emotional Triad" of the prefrontal cortex, the hippocampus, and the amygdala likely underlie other disorders such as anxiety and PTSD. We are currently beginning to investigate the interaction between TBI and the limbic system, as well as whether structures like the amygdala are affected by diffuse TBI. This may give us insight into the correlation of PTSD and TBI, and whether there are substrates in the limbic system that are dysfunctional post TBI.