Kiss, Zelma H. T.Murari, KartikeyaNoor, Muhammad Sohail2018-04-302018-04-302018-04-23http://hdl.handle.net/1880/106569Deep brain stimulation (DBS) is clinically used to treat various movement disorders and has a potential to ameliorate other conditions such as depression, epilepsy etc. However, the mechanism through which DBS alleviates symptoms is not clear which prevents its efficient application and expansion to new conditions. Modulation of motor cortex due to DBS is thought to be imperative in this therapy. Recent electrophysiology and imaging studies investigating the effects of DBS on motor cortex have reported contradictory results. One reason of this disagreement is that functional imaging techniques (functional magnetic resonance imaging and positron imaging tomography) commonly used to study DBS are neither suited for mechanistic understanding nor for chronic measurements. In this thesis, I tested a similar functional imaging technique, called intrinsic optical imaging (IOI), which can be used to better probe the functioning of DBS in animals models because it allows simultaneous imaging and electrophysiology, neurochemical manipulations, and long-term recording over months. I established that IOI can measure DBS-induced cortical perfusion consistently and using this technique I studied how various parameters of DBS, which are critical to its therapeutic effect, modulate motor cortex perfusion in rodents. The temporal and spatial dynamics of perfusion were dependent on the parameters of DBS. 'Maximum change in reflectance' and its spatial spread (two measures of hemodynamic response) increased linearly with increases in current amplitude or pulse width and had a non-linear relationship with frequency. Using simultaneous imaging and electrophysiology, I studied the relationship between DBS-induced neural and vascular response — neurovascular coupling, understanding which is necessary to interpret the data acquired with functional imaging techniques used in patients. Neurovascular coupling relationship was developed between 'maximum change in reflectance' (MCR, a measure of vascular response) and 'integrated evoked potential (IEP)' or 'multiunit broadband power' (two measures of neural response). The relationship between MCR and IEP was maintained to a stimulation frequency of 60 Hz: both increased with the frequency of stimulation. However, above 60 Hz MCR saturated while IEP increased linearly to the maximum frequency tested of 100 Hz. The relationship between MCR and multi-unit power remained coupled for the whole range of stimulation frequency applied. These relationships will help researchers in the interpretation of functional imaging studies during DBS. The technique established here and my results will further our understanding of DBS, help to improve this therapy and provide an opportunity to expand it to treat new neurologic and psychiatric conditions.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.Deep Brain StimulationNeurovascular CouplingIntrinsic Optical ImagingCortical PerfusionStimulation parametersMotor CortexThalamusExtracellular electrophysiologyNeuroscienceEngineeringEngineering--Biomedicaldoctoral thesis10.11575/PRISM/31855