The goal of the proposed studies is to develop two complementary animal models to advance deep brain stimulation (DBS) of the central thalamus (CT) as a therapeutic strategy for the treatment of acquired cognitive disabilities resulting from traumatic brain injury (TBI). Each day of the year approximately 4,000 Americans suffer a traumatic brain injury (TBI), leaving as many as 100,000 persons/year with long-term cognitive disabilities. We will form a multidisciplinary research program utilizing systems neuroscience and bioengineering methods to improve the efficacy of central thalamic brain stimulation (CT/DBS). The research team will be lead by investigators at Weill- Cornell Medical in partnership with researchers at The Rockefeller University and Medical College of Wisconsin. Dr. Nicholas Schiff (Weill-Cornell), a leading neurologist/neuroscientist in the fields of CT/DBS and human brain injury studies, will act as P.I. of the R01 along with Dr. Keith Purpura (Weill-Cornell), an expert systems neurophysiologist, to carry out a series of experimental studies in intact alert, behaving monkeys. The work with monkeys will examine the influence of different patterns of electrical stimulation on rostral central thalamic neurons. These neurons link the brain stem centers that control arousal with the cerebral cortex, and play a crucial role in integrating cortex, striatum and thalamus. Behavioral effects of continuous stimulation and of brief pulses applied at specific times will be evaluated during the performance of two elementary cognitive tasks. Neural activity in the monkey's frontal lobe during and following stimulation will also be examined. Dr. Donald Pfaff (Rockefeller), a world- renowned expert on the cellular basis of behavior, will adapt a vetted set of arousal assays he developed for the mouse to studies of CT/DBS. Preliminary results in his laboratory have shown that CT/DBS in the mouse can facilitate behavioral performance following induced traumatic brain injury. Dr. Christopher Butson (Medical College of Wisconsin), a bioengineer and expert in computational modeling of brain electrical stimulation will develop detailed models of the volume of tissue activated in the animal experiments at Weill-Cornell and Rockefeller. He will also supervise the development and analysis of a probabilistic atlas to identify the sites of optimal application of CT/DBS. This atlas will assist in the construction of a human atlas that could be used in the treatment of non-progressive brain injuries. Thus, the long-range goal of this work is to optimize neuromodulation strategies employing electrical stimulation of the central thalamus to treat cognitive impairment following TBI.
Acquired cognitive impairment following severe brain injury leave as many as 100,000 Americans each year with devastating disabilities. The studies proposed here will help to advance the necessary knowledge to advance and further develop a novel application of electrical brain stimulation aimed at improving the lives of patients suffering with these lifelong challenges.
|Baker, Jonathan L; Ryou, Jae-Wook; Wei, Xuefeng F et al. (2016) Robust modulation of arousal regulation, performance, and frontostriatal activity through central thalamic deep brain stimulation in healthy nonhuman primates. J Neurophysiol 116:2383-2404|
|Tabansky, Inna; Quinkert, Amy Wells; Rahman, Nadera et al. (2014) Temporally-patterned deep brain stimulation in a mouse model of multiple traumatic brain injury. Behav Brain Res 273:123-32|
|Schiff, N D; Shah, S A; Hudson, A E et al. (2013) Gating of attentional effort through the central thalamus. J Neurophysiol 109:1152-63|
|Schiff, Nicholas D (2012) Moving toward a generalizable application of central thalamic deep brain stimulation for support of forebrain arousal regulation in the severely injured brain. Ann N Y Acad Sci 1265:56-68|
|Quinkert, A W; Pfaff, D W (2012) Temporal patterns of deep brain stimulation generated with a true random number generator and the logistic equation: effects on CNS arousal in mice. Behav Brain Res 229:349-58|
|Goldfine, Andrew M; Schiff, Nicholas D (2011) What is the role of brain mechanisms underlying arousal in recovery of motor function after structural brain injuries? Curr Opin Neurol 24:564-9|
|Quinkert, Amy Wells; Vimal, Vivek; Weil, Zachary M et al. (2011) Quantitative descriptions of generalized arousal, an elementary function of the vertebrate brain. Proc Natl Acad Sci U S A 108 Suppl 3:15617-23|
|Shah, Sudhin A; Schiff, Nicholas D (2010) Central thalamic deep brain stimulation for cognitive neuromodulation - a review of proposed mechanisms and investigational studies. Eur J Neurosci 32:1135-44|
|Schiff, Nicholas D (2010) Recovery of consciousness after brain injury: a mesocircuit hypothesis. Trends Neurosci 33:1-9|
|Quinkert, Amy Wells; Schiff, Nicholas D; Pfaff, Donald W (2010) Temporal patterning of pulses during deep brain stimulation affects central nervous system arousal. Behav Brain Res 214:377-85|
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