Student Theses and Dissertations

Date of Award

2013

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

RU Laboratory

Pfaff Laboratory

Keywords

Deep Brain Stimulation, central thalamus, generalized arousal, traumatic brain injury, motor activity, temporal pattern

Abstract

Deep Brain Stimulation (DBS) is a promising neurosurgical technique that may be useful in promoting emergence to consciousness in minimally conscious state (MCS) patients. In this context, DBS of the central thalamus (CT/DBS) is intended to act as a surrogate input from the ascending arousal systems to support cortical recruitment for cognitive tasks. To test the effectiveness of CT/DBS, intact mice and a mouse model of traumatic brain injury (TBI) have been stimulated under the hypothesis that CT/DBS increases generalized arousal. Two of the three dimensions of the operational definition of generalized arousal are presented here: motor activity and sensory (specifically olfactory) responsiveness. In addition to the question of the effectiveness of CT/DBS to increase generalized arousal, this thesis explores the efficiency of a small set of parameters of stimulation. The data presented in this thesis show that 1) CT/DBS can increase generalized arousal as measured by motor activity in intact mice; 2) that a previously unexplored parameter of DBS, temporal pattern, can modulate its effectiveness; 3) a novel mouse model of TBI, multiple TBI, can produce motor activity and neurological deficits that last 10-14 days; 4) CT/DBS can increase generalized arousal as measured by motor activity in this mouse model of traumatic brain injury; and finally, 5) there is no evidence that DBS can potentiate an olfactory response in intact mice or in a mouse model of traumatic brain injury. To summarize, these data show that CT/DBS can increase generalized arousal as measured by motor activity in intact and brain injured mice and add further experimental evidence from the laboratory to support the idea that CT/DBS can be therapeutic for MCS patients. The data presented here also show that temporal pattern is important in one context of DBS, but it would not be surprising if temporal pattern turns out to be important in many other contexts of DBS. The brain does not usually work in monotonic pulses. Why should neuromodulation in the service of CNS arousal be any different? Exploring the effects of temporal patterns in DBS is certainly a promising new field of research and could ultimately benefit patients by fine-tuning the exact amount of electricity necessary to produce clinical results and thereby optimizing efficacy and reducing side effects of DBS.

Comments

A thesis presented to the faculty of The Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy

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