Characterizing Sleep Signatures and its effects on Cognition in New-Onset Temporal Lobe Epilepsy
新发颞叶癫痫的睡眠特征及其对认知的影响
基本信息
- 批准号:10644795
- 负责人:
- 金额:$ 19.26万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-07-01 至 2028-06-30
- 项目状态:未结题
- 来源:
- 关键词:AcademyAcoustic StimulationAddressAdultAnticonvulsantsAttentionAttentional deficitAwardBehaviorBiological MarkersChildhoodChronicClinical Trials DesignCognitionCognitiveCognitive deficitsCoupledCouplingCrossover DesignDataDevelopmentDiseaseElderlyElectroencephalographyEpilepsyExhibitsFunctional Magnetic Resonance ImagingGoalsImpairmentIndividualInterruptionInterventionIntervention TrialKnowledgeLearningLinkMeasuresMedicineMemoryMemory impairmentMentored Patient-Oriented Research Career Development AwardMentorsMonitorNational Institute of Neurological Disorders and StrokeNewly DiagnosedParticipantPatientsPatternPerformancePersonsPharmaceutical PreparationsPhasePhysiciansPolysomnographyPublic HealthQuality of lifeRandomizedResearchResearch PriorityScalp structureSchoolsScientistSeizuresSleepSleep ArchitectureSleep DisordersSleep FragmentationsSleep disturbancesTechniquesTemporal LobeTemporal Lobe EpilepsyTestingTherapeutic InterventionTimeTrainingUnderemploymentUnited Statescognitive developmentcognitive enhancementcognitive functioncognitive performancecomorbiditycomparison controldensityepileptiformexperiencehigh riskimprovedlow socioeconomic statusmemory consolidationmemory recallneural networknon rapid eye movementnovelpoor sleepskillssleep abnormalitiessleep patternsleep physiologysleep spindlesustained attentionyoung adult
项目摘要
Project Summary/Abstract
Temporal Lobe Epilepsy (TLE) is characterized by disordered neural network activity and temporal lobe seizures.
As many as 3 million individuals with TLE in the United States also experience cognitive and sleep problems,
resulting in poor school performance in childhood, with high risk of underemployment in adulthood, and
consequent lower socioeconomic status. Individuals with TLE frequently experience sleep fragmentation, which
disrupts memory consolidation and sustained attention, both of which are impaired in this disorder. While these
comorbidities can be long-term consequences of repeated seizures and medications, it is now known that they
also often present prior to the first recognized seizure and worsen over time even with successful seizure
treatment. This suggests that an early neural network abnormality may underlie seizure development while
simultaneously impairing sleep and cognitive development, even prior to the added effects of disorder chronicity.
In spite of this, there has been limited research addressing mechanisms underlying these sleep and cognitive
problems in TLE. This represents a critical unmet public health need and both the National Academy of
Medicine and NINDS have identified this notable gap as a research priority. I will begin to address this gap with
the my K23 proposal by investigating abnormal sleep architecture patterns in TLE that directly contribute to
cognitive deficits using both an observational (Aim 1) and a mechanistic interventional (Aim 2) approach. In
typical NREM sleep, electroencephalogram (EEG) slow wave oscillations are phase-locked and coupled with
sleep spindle oscillations (SW-SSO), which facilitates memory consolidation and potentially improves attention.
In TLE, disordered networks that result in interictal epileptic discharges and seizures may also contribute to
altered SW-SSO coupling during sleep, resulting in memory and attention deficits. A single night of acoustic
stimulation (AS) has been proven effective in enhancing SW-SSO coupling and improving cognitive performance
in healthy older adults but has not been studied in TLE. My central hypothesis is that disordered networks in
newly diagnosed TLE patients result in altered sleep architecture, which disrupt memory consolidation and
attention capability. I will test this hypothesis by: (1) characterizing TLE sleep architecture using computational
EEG – sleep spindle density, slow wave power, interictal epileptiform discharges, and SW-SSO coupling (Aim
1a), (2) linking these specific TLE-related sleep architecture patterns to cognitive processing (Aim 1b); (3)
determining if AS enhances SW-SSO coupling in young adults with TLE (Aim 2a) and (4) determining if enhanced
SW-SSO coupling improves memory and attention in TLE (Aim 2b). This training award will provide me the
opportunity to extend my research expertise into computational sleep EEG acquisition and analysis, acoustic
stimulation techniques, and clinical trial design. My long-term goal is to leverage connections between sleep,
behavior and neural network activity to develop and implement tailored cognitive and sleep interventions for
individuals with epilepsy.
项目总结/文摘
项目成果
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