The Knowles Lab
Check out our recent publication in Nature Neuroscience
Epilepsy affects ~1% of all children and is defined by recurrent, unprovoked seizures, impaired cognitive abilities, and diminished quality of life. The predisposition for seizures is thought to result from abnormal plasticity and excessive synchrony in affected neural networks. Myelin plasticity is a newly recognized mode of activity-dependent neural network adaptation. The potential for dysregulated myelin plasticity in disease states such as epilepsy is unexplored. Myelination of axons increases conduction velocity and promotes coordinated network function including oscillatory synchrony. During and after age-dependent developmental myelination, increases in myelin occur when humans and rodents acquire new skills. While adaptive myelin plasticity modulates networks to support function in the healthy state, it is unknown whether this process also contributes to network dysfunction in neurological disease.
The Knowles lab conducts basic, translational and clinical research to study how seizures shape white matter, and how changes in white matter shape the course of epilepsy and its comorbidities. We discovered that generalized (absence) seizures induce aberrant myelination that promotes seizure progression. Thus, maladaptive myelination may be a novel pathogenic mechanism in epilepsy and other neurological diseases. Using innovative imaging, electrophysiological, histological and molecular biology techniques, we are studying multiple questions.
- How does white matter structure change throughout the brain over the course of epilepsy?
- How does white matter structure impact network synchronization, seizures and cognition?
- What signaling pathways underlie aberrant white matter plasticity in different forms of epilepsy?
- What can we learn from white matter changes found with various imaging modalities in humans with epilepsy?
Our overarching goals are to better understand how epilepsy occurs and to develop treatments that improve the lives of children with epilepsy.