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Note: thesis: Thesis (Ph. D.)--Brown University, 2019
Genre (aat): theses
Abstract: The need to arrest ongoing or planned actions is a hallmark of adaptive control that is crucial for goal-directed behaviors and survival. When the brain is subjected to competing signals that try to express conflicting behaviors, it needs to halt to evaluate the consequences under volitional control, or to avoid aversive situations through reflexive suppression. The cortico-Basal Ganglia system is responsible for mediating response inhibition to buy the cognitive system time to implement the appropriate action. A subcortical brain area whose dysfunctions result in pathology such as Parkinson's, the Subthalamic Nucleus (STN) is responsible for braking behavioral expression. Experiments have shown that under response conflict conditions, STN spiking and theta power are elevated. Unfortunately, the electrophysiological mechanisms underlying these neural signatures remain poorly understood. To address this, we have built a novel biophysically principled large-scale model of the subthalamopallidal network, including prototypic and arkypallidal units, that is sparsely and probabilistically connected. Conflict was simulated by driving cortical input to STN and varying the level of co-activation across cortical feeds. We test how biophysical, cortical dynamics, and architectural constraints impact the relationship among cortical conflict, STN theta power, and spiking. Our simulations show that the STN-GPe network does not resonate at theta on its own, but can do so in response to cortical theta or to cortical burst-events representing action selection dynamics. Rhythmic burst-events, representing a state of conflict when cortical motor plans vacillate in the theta range, led to prolonged theta and increased spiking, consistent with empirical literature. Analysis of underlying mechanisms revealed that NMDA, but not AMPA, currents were necessary and sufficient for theta power expression and for an empirically observed STN triphasic response characterized by spiking, silence and bursting periods. Finally, theta band resonance was also strongly modulated by architectural constraints, with maximal theta with increased presence of STN "coincidence-detector" units that receive input from multiple cortical populations, due to an NMDA-dependent supralinear response. Our results are insightful in connecting biophysical principles with dynamic and architectural constraints to understand the nature of STN processing in response conflict, the disruption of which can lead to impulsivity and compulsivity.
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Subject (fast) (authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/01763130")
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Subject (fast) (authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/01149959")
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Type of Resource (primo): dissertations