The adult brain is capable of considerable functional reorganization often manifest as long term modification of synaptic strength (strengthening as long-term potentiation or LTP, and weakening as long term depression or LTD). This plasticity is increasingly targeted in rehabilitative therapeutic interventions in attempts to restore brain function after mild traumatic brain injury (mTBI). In particular, recovery of function after brain injury has involved training regimens thought to work by repetitively activating and thus enhancing synaptic efficacy or the passive and active stimulation of afferent pathways and their synaptic targets by noninvasive or chronically implanted stimulating apparatus. However, the stimulation protocols generally used in clinical rehabilitation strategies are based on those used in classic in vitro animal studies, often focusing on the frequency of conditioning synaptic stimulation but with little attention paid to the pattern of stimulation. Most stimulation protocols for inducing LTP and LTD have relied on regular stimulation patterns where interstimulus intervals (ISIs) are all equal (coefficient of variation, CV=0). However, some recent studies have incorporated more physiologically salient stimulation patterns (e.g. Poisson-distributed ISIs, CV=1). The major goal of my research is to determine the stimulation patterns that are most effective at facilitating the functional reorganization of synapses after mTBI. My pre-clinical laboratory animal based experiments will systematically test how patterns of synaptic stimulation activate calcium signaling and trigger plasticity (LTD and LTP) under normal conditions and after mTBI. These results will provide baseline data in the normal brain and insights into how mTBI modulates sensitivity to potentially restorative therapeutic post-injury neural stimulation interventions. These results should provide quantitative characterization of the interactions of stimulation pattern and frequency, indicating where appropriate intersections of these two features of stimulation of surviving cortical pathways can be defined, enabling the design of optimal stimulus sets to facilitate the selective strengthening and weakening of appropriate cortical pathways in injured cerebral cortex. This knowledge should guide the future application of stimulus based neurorehabilitation therapies that use emerging clinical in vivo stimulation technologies such as magnetic stimulation, optical stimulation, or multielectrode array stimulation in the injured human brain.
- Baylor College of Medicine
Instructor, Department of Neuroscience