Focal thalamocortical circuit dysfunction mediates motor and cognitive deficits in developmental epilepsy
局灶性丘脑皮质回路功能障碍介导发育性癫痫的运动和认知缺陷
基本信息
- 批准号:10158524
- 负责人:
- 金额:$ 68.93万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-05-15 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:Absence EpilepsyAcoustic StimulationAddressAttentionBenignCerebrumCharacteristicsChildChildhoodClinicalCognitiveCognitive deficitsDataDevelopmentDiagnosticDiazepamDiseaseElectrophysiology (science)EpilepsyFocal SeizureFunctional disorderGeneralized seizuresGoalsImpaired cognitionImpairmentInterventionKnowledgeLearningLinkMediatingMotorNeurobehavioral ManifestationsNeuropsychologyPerformancePharmaceutical PreparationsPhysiologySchoolsSeizuresSensorySeveritiesSleepSleep DeprivationSleep disturbancesStructureSymptomsSyndromeTestingWorkchildhood epilepsycognitive functioncognitive performancecommon treatmentcomputerized toolsdensitydevelopmental diseaseepileptic encephalopathiesfunctional outcomesimprovedindexingmemory consolidationmotor deficitmotor impairmentmotor learningmotor symptommultimodal datanon rapid eye movementsensory gatingsleep abnormalitiessleep spindletreatment strategy
项目摘要
Project Summary / Abstract
Benign epilepsy with centrotemporal spikes (BECTS) is the most common focal childhood epilepsy syndrome,
characterized by a transient period of seizures and abundant epileptiform spikes arising from the sensorimotor
cortex during non-REM (NREM) sleep. Recent findings indicate that BECTS is a developmental disorder with a
wider range of severity than previously appreciated. In addition to seizures, children have deficits in attention
and motor coordination. The motor and cognitive symptoms in BECTS exist on a spectrum of severity, clinically
and genetically overlapping with severe epileptic encephalopathies, which are characterized by permanent and
progressive declines in cerebral function coincident with sleep activated spikes. There are currently no proven
treatment strategies to address the neuropsychological deficits in BECTS or other epileptic encephalopathies.
Several lines of evidence, including our preliminary findings, suggest a dysfunction in thalamocortical circuitry
drives the motor and cognitive abnormalities in BECTS. First, thalamocortical structural circuits are abnormal in
BECTS. Second, children with BECTS have reduced sleep spindles, oscillations that are critical for memory
consolidation during NREM sleep and generated and propagated by thalamocortical circuitry. Third,
thalamocortical sensory gating is impaired in children with centrotemporal spikes, like those observed in
BECTS. Effective dampening or “gating” of irrelevant sensory information prior to reaching the cortex, mediates
performance on attentional tasks. Despite this evidence, the relationship between thalamocortical
electrophysiology, connectivity, and cognitive symptoms in BECTS has not been investigated. The long term
goal of this project is to test the hypothesis that focal thalamocortical circuit dysfunction mediates the
motor and cognitive symptoms in BECTS. Our interdisciplinary team - consisting of a pediatric
epileptologist, a neuropsychologist, and a computational neuroscientist – will use validated experimental
paradigms and computational tools to collect and analyze multimodal data to link thalamocortical circuit
abnormalities to cognitive deficits in children with BECTS. First, we will determine whether children with
BECTS show abnormal sleep spindle activity that relates to impaired sleep-dependent memory consolidation.
Second, we will determine whether impaired sensory gating and thalamocortical connectivity relate to impaired
attention in BECTS. Third, we will test the impact of medication and closed loop auditory stimulation on
thalamocortical spindles, gating, and cognitive function in BECTS. Completion of the proposal goals will
represent significant progress towards understanding the pathophysiological mechanisms underlying cognitive
dysfunction in BECTS, and the identification of new targets and approaches for treating cognitive deficits in
BECTS and related epileptic encephalopathies.
.
项目总结/摘要
良性癫痫伴中央颞区棘波(BECTS)是最常见的儿童局灶性癫痫综合征,
其特征在于短暂的癫痫发作和由感觉运动神经引起的大量癫痫样棘波
非快速眼动睡眠(NREM)最近的研究结果表明,BECTS是一种发育障碍,
比以前认识到的更广泛的严重程度。除了癫痫发作,孩子们的注意力也有缺陷
和运动协调。临床上,BECTS的运动和认知症状存在严重程度谱
并且在遗传上与严重的癫痫性脑病重叠,其特征是永久性的,
大脑功能的进行性下降与睡眠激活的尖峰一致。目前还没有证据表明
治疗策略,以解决BECTS或其他癫痫性脑病的神经心理缺陷。
包括我们的初步发现在内的几条证据都表明,
导致BECTS中的运动和认知异常。首先,丘脑皮质结构回路异常,
谢谢第二,患有BECTS的儿童睡眠纺锤波减少,这是对记忆至关重要的振荡
在NREM睡眠期间巩固,并由丘脑皮层回路产生和传播。第三、
中央颞区棘波儿童的丘脑皮质感觉门控受损,如
谢谢在到达皮层之前,有效地抑制或“门控”无关的感觉信息,
注意力任务的表现。尽管有这些证据,
BECTS的电生理学、连通性和认知症状尚未研究。长期
本项目的目的是检验局灶性丘脑皮质回路功能障碍介导
BECTS中的运动和认知症状。我们的跨学科团队-由儿科
癫痫学家,神经心理学家和计算神经科学家-将使用经过验证的实验
范例和计算工具来收集和分析多模态数据,以连接丘脑皮层回路
BECTS儿童的认知缺陷异常。首先,我们将确定是否有儿童
BECTS显示与受损的睡眠依赖性记忆巩固相关的异常睡眠纺锤体活动。
其次,我们将确定受损的感觉门控和丘脑皮层连接是否与受损的
注意BECTS。第三,我们将测试药物治疗和闭环听觉刺激对
BECTS中的丘脑皮质纺锤体、门控和认知功能。提案目标的完成将
代表着对认知障碍的病理生理机制的理解的重大进展。
BECTS的功能障碍,并确定新的目标和方法来治疗认知缺陷,
BECTS和相关癫痫性脑病。
.
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Catherine J Chu其他文献
Catherine J Chu的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Catherine J Chu', 18)}}的其他基金
Targeting pathologic spike-ripples to isolate and disrupt epileptic dynamics
针对病理性尖峰波纹来隔离和破坏癫痫动力学
- 批准号:
10322163 - 财政年份:2021
- 资助金额:
$ 68.93万 - 项目类别:
Targeting pathologic spike-ripples to isolate and disrupt epileptic dynamics
针对病理性尖峰波纹来隔离和破坏癫痫动力学
- 批准号:
10096727 - 财政年份:2021
- 资助金额:
$ 68.93万 - 项目类别:
Targeting Pathologic Spike-Ripples to Isolate and Disrupt Epileptic Dynamics
针对病理性尖峰波纹来隔离和破坏癫痫动力学
- 批准号:
10526434 - 财政年份:2021
- 资助金额:
$ 68.93万 - 项目类别:
Focal thalamocortical circuit dysfunction mediates motor and cognitive deficits in developmental epilepsy
局灶性丘脑皮质回路功能障碍介导发育性癫痫的运动和认知缺陷
- 批准号:
10359112 - 财政年份:2020
- 资助金额:
$ 68.93万 - 项目类别:
Focal Thalamocortical Circuit Dysfunction Mediates Motor and Cognitive Deficits in Developmental Epilepsy
局灶性丘脑皮质回路功能障碍介导发育性癫痫的运动和认知缺陷
- 批准号:
10570912 - 财政年份:2020
- 资助金额:
$ 68.93万 - 项目类别:
Identification of Cortical Biomarkers for Seizure Risk in Childhood Epilepsy
儿童癫痫发作风险的皮质生物标志物的鉴定
- 批准号:
9034013 - 财政年份:2015
- 资助金额:
$ 68.93万 - 项目类别:
Identification of Cortical Biomarkers for Seizure Risk in Childhood Epilepsy
儿童癫痫发作风险的皮质生物标志物的鉴定
- 批准号:
9487038 - 财政年份:2015
- 资助金额:
$ 68.93万 - 项目类别:
Identification of Cortical Biomarkers for Seizure Risk in Childhood Epilepsy
儿童癫痫发作风险的皮质生物标志物的鉴定
- 批准号:
9133481 - 财政年份:2015
- 资助金额:
$ 68.93万 - 项目类别:
相似海外基金
Binaural cue sensitivity in children and adults with combined electric and acoustic stimulation
电和声相结合刺激儿童和成人的双耳提示敏感性
- 批准号:
10585556 - 财政年份:2022
- 资助金额:
$ 68.93万 - 项目类别:
Place-Based Mapping in Electric-Acoustic Stimulation Listeners
电声刺激听众中的基于位置的映射
- 批准号:
10320457 - 财政年份:2021
- 资助金额:
$ 68.93万 - 项目类别:
Electro-acoustic stimulation assisted nano-abrasive blasting system
电声刺激辅助纳米磨料喷砂系统
- 批准号:
20K04192 - 财政年份:2020
- 资助金额:
$ 68.93万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
id-ear: biometric recognition based on response to acoustic stimulation
id-ear:基于对声刺激的响应的生物识别
- 批准号:
505807-2016 - 财政年份:2018
- 资助金额:
$ 68.93万 - 项目类别:
Collaborative Research and Development Grants
Characterization and Modelling of the Electrode-Nerve Interface for Electro-Acoustic Stimulation in Cochlear Implant Users
用于人工耳蜗用户电声刺激的电极-神经接口的表征和建模
- 批准号:
396932747 - 财政年份:2018
- 资助金额:
$ 68.93万 - 项目类别:
Research Grants
Bubbles for bone: acoustic stimulation for drug delivery in fracture repair.
骨气泡:骨折修复中用于药物输送的声刺激。
- 批准号:
1960951 - 财政年份:2017
- 资助金额:
$ 68.93万 - 项目类别:
Studentship
Bubbles for bone: acoustic stimulation for drug delivery in fracture repair.
骨气泡:骨折修复中用于药物输送的声刺激。
- 批准号:
1946034 - 财政年份:2017
- 资助金额:
$ 68.93万 - 项目类别:
Studentship
id-ear: biometric recognition based on response to acoustic stimulation
id-ear:基于对声刺激的响应的生物识别
- 批准号:
505807-2016 - 财政年份:2017
- 资助金额:
$ 68.93万 - 项目类别:
Collaborative Research and Development Grants
Bubbles for bone: acoustic stimulation for drug delivery in fracture repair
骨气泡:骨折修复中用于药物输送的声刺激
- 批准号:
1938424 - 财政年份:2017
- 资助金额:
$ 68.93万 - 项目类别:
Studentship
Bubbles for biofilm: acoustic stimulation for drug delivery in fracture repair
生物膜气泡:骨折修复中药物输送的声刺激
- 批准号:
1938469 - 财政年份:2017
- 资助金额:
$ 68.93万 - 项目类别:
Studentship