Neural Dynamics Underlying Initiation and Control of Pathological Thalamocortical Oscillations PDF Download

Author: Jordan Michael Sorokin
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Languages : en
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Book Description
Neural oscillations -- or, "brain waves" -- are a ubiquitous feature in a wide variety of cognitive processes. Underlying many of these oscillations are strong recurrent connections between the cortex and the thalamus, known as the cortico-thalamo-cortical (CTC) network. This network plays an important role in synchronizing sensory information, transitioning the brain into sleep, facilitating memory consolidation, modulating attention, and many other processes. However, under certain conditions the CTC network becomes hyper-synchronized and produces pathological oscillations termed absence seizures, which can hinder normal brain function and negatively impact learning and development. While the genetic mutations and single-cell physiology of absence seizures have been well characterized, there are conflicting hypotheses regarding the roles of the thalamus and cortex in the initiation and maintenance of absence seizures, and little understanding of network-wide dynamics during transitions into and out of seizures. This is partially due to the difficulty in selectively targeting the cortex or thalamus (given their recurrent connections), as well as the challenge of simultaneously recording neural activity from these regions. In this dissertation, I examine thalamic and cortical neural dynamics involved in seizure control, with the aim to improve our ability to treat patients with absence epilepsy and provide a more complete picture of how CTC oscillations can go awry. In chapter 1 I provide an overview of the current knowledge and working hypotheses in the field, and summarize the work contained in subsequent chapters. In chapter 2 I investigate the ability of the thalamus to control seizures in real-time by manipulating the firing mode of a large population of thalamic neurons. Phasic thalamic output to the cortex can induce seizures, while tonic thalamic output can interrupt them. In chapter 3 I describe efforts to understand the relationship between pre-seizure neural activity and subsequent seizure strength. Individual absence seizures can vary in their duration, hinting that the recruitment and/or synchronization of the CTC network may be heterogeneous and possibly dependent on pre-seizure brain activity. In chapter 4 I expand on this work by simultaneously recording individual neurons from both the cortex and thalamus to gain a more detailed description of pre-seizure neural dynamics. Lastly in chapter 5 I evaluate the ability to track individual neurons during seizures and demonstrate how inferences of neural activity become corrupted due to poor single-cell resolution during synchronous events.