Projects

Introduction/Background: The function and organization of the brain primary motor cortex (M1) circuits -- crucial for motor control -- has not yet been resolved. Most brain-machine interfaces used by spinal cord injury patients decode their motor information from M1, predominantly from large layer 5 corticospinal cells. As part of our NIH-funded project we have developed the most realistic and detailed computational model of M1 circuits and corticospinal neurons up to date, based on novel data provided by experimentalist collaborators.

We use multiscale modeling to look at brain diseases, treated by neurology, psychiatry, neurosurgery, physiatry (rehab) and other specialties.  Particular focuses have been on stroke, epilepsy and schizophrenia.  We have also modeled Alzheimer disease, Parkinson disease, dystonia and others.  As one example, our recent studies of schizophrenia have emphasized the need for multiple scale analysis for evaluating the connections between molecular and synaptic alterations at the lower scales with the transmission of information leading to disruptions of thought at the higher scales.

Multiscale modeling using computer simulation is increasingly recognized as a major method, along with data-mining, for assimilating the vast and ever-growing knowledge base in systems biology. This will improve understanding of the links between molecules and disease manifestation for translational research to the clinic. The bridging of chemophysiology (chemical signaling in neurons and astrocytes) with electrophysiology provides a fundamental connection that will necessarily underpin higher organizational scales.