Dissertation
Genetic Markers of Inter-Individual and Task-Dependent Differences in Neurobehavioral Impairment During Total Sleep Deprivation
Doctor of Philosophy (PhD), Washington State University
01/2017
Handle:
https://hdl.handle.net/2376/112040
Abstract
Until recently, cognitive impairment associated with sleep loss was thought to involve a global decrement in overall neurobehavioral functioning driven by reduced vigilant attention. However, it has been demonstrated that there are task-dependent differences in neurobehavioral performance impairment and that sleep loss impacts specific components of cognition differentially. Additionally, there are robust, systematic inter-individual differences in cognitive impairment during sleep loss. which are also task-specific. This suggests that performance deficits are multi-faceted and involve compromised functioning in multiple neural pathways. However, the mechanisms subserving inter-individual and task-dependent differences are poorly understood. The stable and repeatable, phenotypic nature of these differences in performance impairment due to sleep loss suggests that genetic differences may be involved. The purpose of this dissertation is to utilize genetic variants as a tool to investigate neural mechanisms underlying inter-individual and task-dependent differences associated with resilience or vulnerability to neurobehavioral impairment during total sleep deprivation (TSD).
In Chapter 2, we investigated how genetic variants are associated with resilience or vulnerability to impairment on the psychomotor vigilance test (PVT) during TSD. We found that a variant of the tumor necrosis factor alpha (TNFα) gene is associated with resilience to performance impairment, specifically attentional lapses. The results implicate TNFα in attentional pathways affected by TSD, and suggest a role for TNFα in promoting local sleep. In Chapter 3, we investigated how genetic variants of the dopaminergic system, as well as TNFα, impact time-on-task decrements on the PVT during TSD. We showed that a variant of the dopamine transporter 1 (DAT1) gene provides protection against the amplification of the time-on-task effect during TSD, implicating striatal dopamine in performance impairment due to the interaction between TSD and the time-on-task effect. In Chapter 4, we investigated how genetic variants of the dopaminergic system impact dynamic decision making during TSD. We showed that a variant of the catechol-O-methyltransferase (COMT) gene confers substantial vulnerability to performance impairment. This finding implicates fronto-striatal dopamine circuitry in impaired dynamic decision making during TSD. Taken together, these findings provide specific evidence of distinct neural pathways involved in inter-individual and task-dependent differences in cognitive impairment during TSD.
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Details
- Title
- Genetic Markers of Inter-Individual and Task-Dependent Differences in Neurobehavioral Impairment During Total Sleep Deprivation
- Creators
- Brieann Satterfield
- Contributors
- Hans PA Van Dongen (Advisor)Jonathan P Wisor (Committee Member)Ilia N Karatsoreos (Committee Member)Matthew E Layton (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Program in Neuroscience
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Number of pages
- 156
- Identifiers
- 99900581827101842
- Language
- English
- Resource Type
- Dissertation