Mathematical Biology Seminar Chuck Dorval University of Utah Wednesday November 30, 2011 3:05pm in LCB 225 "Unraveling the Paradox of Parkinsonian Symptom Relief via Deep Brain Stimulation" Abstract: Deep brain stimulation (DBS) can reduce motor-symptom severity in persons with moderate to severe Parkinson's Disease (PD), but the mechanisms of DBS remain unclear. We hypothesize that effective DBS regularizes neuronal activity in the surrounding tissue, enabling downstream brain regions to function unimpeded by pathological information generated by PD. With a Hodgkin-Huxley style network model, we demonstrate that regularization of neuronal activity in deep brain regions enables proper information transmission downstream. We validate these results by measuring symptom severity in human participants with PD in response to DBS that can increase or decrease the regularity of neuronal activity. From that work, we construct a theoretical model in which neuronal firing pattern entropy drives symptoms: more entropy equals more severe symptoms. We develop a novel method of firing-pattern-entropy and mutual-information estimation that is uniquely appropriate for the exponential decays of neuronal time constants. From electrophysiological recordings in two animal models of PD, we find that indeed, firing pattern entropy in the relevant regions increases with disease severity, and decreases with symptom alleviating DBS. However, despite entropy increases, the mutual information between neuron pairs actually decreases with symptom severity, and increases with effective DBS. Thus during DBS, in addition to downstream regions operating unimpeded by PD pathological activity, deep brain regions adjacent to stimulation are able to communicate more effectively amongst themselves. Although this result seems counter-intuitive from an information theory perspective ? the high entropy states (i.e., large information capacity) convey less information than the low entropy states (i.e., small information capacity) ? it supports the hypothesis that neuronal firing irregularity drives symptom severity.