Establishing that sleep spindle and slow wave deficits are present, are associated with cognitive dysfunction, and can be acutely manipulated in early course schizophrenia
确定睡眠纺锤波和慢波缺陷的存在,与认知功能障碍相关,并且可以在早期精神分裂症中进行急性控制
基本信息
- 批准号:10733615
- 负责人:
- 金额:$ 75.93万
- 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:2023-06-01 至 2028-03-31
- 项目状态:未结题
- 来源:
- 关键词:Acoustic StimulationAcuteAffectBrainChronicChronic SchizophreniaClinicalCognitionCognitiveCognitive deficitsCorrelative StudyCrossover DesignDataDiagnosisDiseaseDouble-Blind MethodEarly InterventionEarly treatmentElectroencephalographyGoalsHealth Care CostsImpaired cognitionImpairmentIndividualInterventionLaboratoriesLinkMeasuresMotorNappingNeurobiologyOnset of illnessParticipantPatientsPerformanceResearchRoleSchizophreniaShort-Term MemorySleepStage II SleepSystemTask PerformancesTranslatingWaxesWorkauditory stimuluscognitive changecognitive controlcognitive functioncognitive performancecomparison groupdensitydisabilityfunctional outcomesimprovedimprovement on sleepmemory consolidationnon rapid eye movementnovelsleep spindlewirelesswireless electronic
项目摘要
Project Summary. In Schizophrenia (SCZ), early interventions can make a difference, particularly for cognitive
dysfunction, a core feature of SCZ that predicts poorer clinical trajectories and functional outcomes. Cognitive
impairments in SCZ have been linked to abnormalities in sleep and sleep-specific oscillations—spindles and
slow waves— which have been established in SCZ, although mostly in chronic patients. As first steps towards
translating these observations into novel, timely interventions, we aim to establish: whether sleep oscillatory and
cognitive deficits are present in early course (EC-SCZ) patients vs. healthy controls (HC), and if these deficits
are related to each other; and 2) whether sleep manipulation with auditory stimulation can improve sleep
oscillation deficits in EC-SCZ, and if sleep oscillatory changes are related to cognitive changes in these patients.
Sleep spindles are waxing and waning, 12-16 Hz oscillations that represent the hallmark of NREM stage 2 sleep.
Slow waves are large amplitude, ~1 Hz brain oscillations that characterize NREM stage 3. We and others have
demonstrated marked deficits in sleep spindles, and to a lesser extent, slow waves in SCZ and reduced spindle
density is associated with worse memory consolidation (MC), a key cognitive function known to be altered in
SCZ. However, most of the evidence is in chronic SCZ, while the presence of altered sleep oscillations and MD
at illness onset would establish these features as robust markers of SCZ. Thus, the first goal of this proposal is
to establish whether spindle and slow wave deficits are present and are associated with reduced MC
performance in EC-SCZ patients relative to HC. We will also examine the association between sleep oscillatory
deficits and cognitive controls (CC) and working memory (WM), cognitive functions that have been linked to
spindles and slow waves in HC and are impaired in EC-SCZ patients.
To establish whether ameliorating sleep alterations may contribute to novel treatment interventions, we first need
to ascertain that sleep and sleep oscillatory deficits can be manipulated. An EEG closed-loop system, which
delivers auditory stimuli during sleep, consistently enhances slow wave and spindle activity in HC. This system,
which involves using a wireless device, can be employed with a simultaneous polysomnogram (PSG) in the
sleep laboratory to enhance feasibility and validity. However, no study has used this closed-loop approach in
SCZ. The second goal of this proposal is to demonstrate that sleep spindles and slow waves deficits can be
acutely modified with closed-loop auditory stimulation (CLAS) during sleep in EC-SCZ patients and to examine
whether CLAS-related spindle and slow wave changes are associated with cognitive changes in these patients.
We propose to perform wireless/PSG overnight sleep recordings and assess performance in the motor sequence
tapping (MST), a MC task, as the main cognitive measure and performance in the AX-CPT for CC and WM as a
secondary cognitive measure, in 70 EC-SCZ and 70 HC subjects. EC-SCZ patients will also undergo auditory
stimulation and sham nights in a double-blind, cross-over design with sleep, MST, and AX-CPT assessments.
项目摘要。在精神分裂症(SCZ)中,早期干预可以发挥作用,特别是在认知方面。
功能障碍,SCZ的核心特征,预测较差的临床轨迹和功能结果。认知
SCZ的损伤与睡眠异常和睡眠特异性振荡-纺锤波有关,
慢波-已经在SCZ中建立,尽管主要是在慢性患者中。作为迈向
将这些观察转化为新颖的,及时的干预措施,我们的目标是建立:睡眠是否振荡,
与健康对照(HC)相比,早期(EC-SCZ)患者存在认知缺陷,如果这些缺陷
听觉刺激的睡眠操作是否能改善睡眠
EC-SCZ的振荡缺陷,以及睡眠振荡变化是否与这些患者的认知变化有关。
睡眠纺锤波有增有减,12-16 Hz的振荡代表了NREM第2阶段睡眠的标志。
慢波是表征NREM阶段3的大振幅、~ 1Hz脑振荡。我们和其他人已经
在睡眠纺锤波中表现出明显的缺陷,在较小程度上,SCZ中的慢波和减少的纺锤波
密度与更差的记忆巩固(MC)有关,MC是一种已知会改变的关键认知功能,
SCZ。然而,大多数证据是在慢性SCZ,而存在改变睡眠振荡和MD
将这些特征确定为SCZ的可靠标志物。因此,本提案的第一个目标是
确定是否存在纺锤波和慢波缺陷,以及是否与MC减少相关
EC-SCZ患者相对于HC的性能。我们还将研究睡眠振荡与睡眠质量之间的关系。
缺陷和认知控制(CC)和工作记忆(WM),认知功能已被链接到
在HC中的纺锤波和慢波,在EC-SCZ患者中受损。
为了确定改善睡眠改变是否有助于新的治疗干预,我们首先需要
以确定睡眠和睡眠振荡缺陷可以被操纵。一种脑电闭环系统,
在睡眠期间提供听觉刺激,持续增强HC中的慢波和纺锤波活动。这个系统,
包括使用无线设备,可以与同步多导睡眠图(PSG)一起使用,
睡眠实验室,以提高可行性和有效性。然而,没有研究使用这种闭环方法,
SCZ。该提案的第二个目标是证明睡眠纺锤波和慢波缺陷可以被
在EC-SCZ患者睡眠期间用闭环听觉刺激(CLAS)进行急性修改,并检查
CLAS相关的纺锤波和慢波改变是否与这些患者的认知改变相关。
我们建议进行无线/PSG夜间睡眠记录,并评估运动序列中的表现
敲击(MST),一个MC任务,作为主要的认知测量和表现,在AX-CPT CC和WM作为一个
在70例EC-SCZ和70例HC受试者中进行了次要认知测量。EC-SCZ患者还将接受听觉
刺激和假夜,采用双盲、交叉设计,进行睡眠、MST和AX-CPT评估。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Fabio Ferrarelli其他文献
Fabio Ferrarelli的其他文献
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{{ truncateString('Fabio Ferrarelli', 18)}}的其他基金
Enhancing prefrontal oscillatory activity and working memory performance with noninvasive brain stimulation in early-course schizophrenia
通过无创脑刺激治疗早期精神分裂症,增强前额叶振荡活动和工作记忆表现
- 批准号:
10364064 - 财政年份:2021
- 资助金额:
$ 75.93万 - 项目类别:
Enhancing prefrontal oscillatory activity and working memory performance with noninvasive brain stimulation in early-course schizophrenia
通过无创脑刺激治疗早期精神分裂症,增强前额叶振荡活动和工作记忆表现
- 批准号:
10483147 - 财政年份:2021
- 资助金额:
$ 75.93万 - 项目类别:
Enhancing prefrontal oscillatory activity and working memory performance with noninvasive brain stimulation in early-course schizophrenia
通过无创脑刺激治疗早期精神分裂症,增强前额叶振荡活动和工作记忆表现
- 批准号:
10668480 - 财政年份:2021
- 资助金额:
$ 75.93万 - 项目类别:
Elucidating neural mechanisms of hypo/mania using theta burst stimulation
使用θ爆发刺激阐明低/躁狂的神经机制
- 批准号:
10513817 - 财政年份:2020
- 资助金额:
$ 75.93万 - 项目类别:
Elucidating neural mechanisms of hypo/mania using theta burst stimulation
使用θ爆发刺激阐明低/躁狂的神经机制
- 批准号:
10308023 - 财政年份:2020
- 资助金额:
$ 75.93万 - 项目类别:
Characterize differences in sleep spindles between Clinical High Risk and healthy controls longitudinally.
纵向描述临床高风险组和健康对照组之间睡眠纺锤波的差异。
- 批准号:
9376357 - 财政年份:2017
- 资助金额:
$ 75.93万 - 项目类别:
Characterize differences in sleep spindles between Clinical High Risk and healthy controls longitudinally.
纵向描述临床高风险组和健康对照组之间睡眠纺锤波的差异。
- 批准号:
9750107 - 财政年份:2017
- 资助金额:
$ 75.93万 - 项目类别:
Characterize differences in sleep spindles between Clinical High Risk and healthy controls longitudinally.
纵向描述临床高风险组和健康对照组之间睡眠纺锤波的差异。
- 批准号:
10160958 - 财政年份:2017
- 资助金额:
$ 75.93万 - 项目类别:
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