Network Dysfunction and Neuromodulation following TBI
TBI 后的网络功能障碍和神经调节
基本信息
- 批准号:10655963
- 负责人:
- 金额:$ 39.19万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-04-01 至 2028-01-31
- 项目状态:未结题
- 来源:
- 关键词:AffectAnimal ModelAnimalsAreaBehavioralBrainBrain regionClinical TreatmentCodeCognitionCommunicationComplexContralateralCouplingDataElectrophysiology (science)Episodic memoryEventFunctional disorderFutureGoalsHippocampusHumanInjuryInterneuronsKnowledgeLearningMeasuresMedialMemoryMemory DisordersMemory impairmentMissionNational Institute of Neurological Disorders and StrokeNeuronsOutcome MeasurePhasePlayPopulationPrefrontal CortexPublic HealthRattusResearchRodentSeriesShort-Term MemoryStructureTranslatingTraumatic Brain Injurybehavioral outcomecognitive functiondensitydesigndisabling symptomeffective therapyexperimental studyfunctional restorationimprovedmemory consolidationmemory encodingmemory recallnetwork dysfunctionneurophysiologyneuroregulationnovelpersistent symptomrational designrestorationspatial memorytherapy designtherapy developmenttreatment strategy
项目摘要
Summary:
Although memory dysfunction is a frequent and debilitating symptom of traumatic brain injury (TBI), there are
currently no effective treatments available for this often persistent deficit. In addition, the neurophysiological
basis of this dysfunction remains unknown, hindering rational treatment design. There is mounting evidence that
precisely coordinated communications between brain regions are necessary to encode and recall information in
the neuronal ensembles that represent episodic, spatial, and working memory. The hippocampus (HC) is the
most well-studied region of memory encoding and is considered to be selectively vulnerable in both human and
animal TBI. We and others have demonstrated disruptions of oscillations in the HC following TBI, with the loss
of theta a notable finding. Rodent studies have demonstrated that restoration of theta using stimulation
(neuromodulation) can restore aspects of HC dependent memory. However, the mechanism remains unknown,
as does the complex relationship of these neuronal ensembles to oscillations and their correlation with memory
deficits after TBI. Without a deeper understanding of how ensemble coding underlying cognition and memory is
disrupted post injury, rational design of neuromodulatory and other therapies remains challenging. Therefore, a
critical need exists to determine the underlying mechanisms of the disruption of coding in networks underlying
memory formation after TBI, and how a reintroduction of theta restores cognitive function. The overall objective
of the current application is to determine how the coding of memory in the hippocampus and associated circuitry
is disrupted following TBI, and how theta neuromodulation restores function. Our central hypothesis is that TBI
disrupts communication within the larger hippocampal network which disrupts oscillatory interactions required
for encoding and recall of memory in networks of synchronized neuronal ensembles. This hypothesis is based
in part on our preliminary data demonstrating that neurons in the hippocampus synchronize improperly with
oscillations following injury, and that prominent interactions between oscillations are lost. We therefore propose
to determine whether TBI affects phase precession, theta sequences, and phase amplitude coupling in area CA1
of the hippocampus during overtrained tasks designed for these measures, as well as whether both hippocampi
are affected by a unilateral injury. In addition, we will determine the mechanism of learning and memory
dysfunction following TBI by examining neuronal ensemble activity across HC-PFC, quantifying ripple features
and replay, and correlating these measures with behavioral memory function relying on HC-PFC networks. We
will also examine the mechanism of neuromodulatory restoration of spatial/working memory in rats via
simultaneous medial septal stimulation and high-density laminar hippocampal/mPFC recordings.
Accomplishment of these goals will provide the first detailed analysis of disrupted neuronal coding and oscillatory
interactions between brain regions underlying TBI induced memory dysfunction, identify the effects of
neuromodulation on these networks, and lead to clinical treatments for this persistent sequelae of TBI.
概括:
尽管记忆功能障碍是创伤性脑损伤 (TBI) 的常见且令人衰弱的症状,但
目前还没有有效的治疗方法来治疗这种经常持续存在的缺陷。此外,神经生理学
这种功能障碍的基础仍然未知,阻碍了合理的治疗设计。越来越多的证据表明
大脑区域之间精确协调的通信对于编码和回忆信息是必要的
代表情景记忆、空间记忆和工作记忆的神经元集合。海马体 (HC) 是
记忆编码中研究最深入的区域,被认为在人类和人类中都有选择性地脆弱
动物创伤性脑损伤。我们和其他人已经证明了 TBI 后 HC 振荡的中断,损失
θ 是一个值得注意的发现。啮齿动物研究表明,使用刺激可以恢复 θ
(神经调节)可以恢复 HC 依赖性记忆的各个方面。但具体机制仍不清楚,
这些神经元群与振荡的复杂关系及其与记忆的相关性也是如此
TBI 后的赤字。如果没有更深入地了解底层认知和记忆的集成编码是如何进行的
损伤后,神经调节和其他疗法的合理设计仍然具有挑战性。因此,一个
迫切需要确定底层网络编码中断的根本机制
TBI 后的记忆形成,以及重新引入 θ 如何恢复认知功能。总体目标
当前应用的目的是确定海马体和相关电路中的记忆编码如何
TBI 后神经调节被破坏,以及 θ 神经调节如何恢复功能。我们的中心假设是 TBI
破坏更大的海马网络内的通信,从而破坏所需的振荡相互作用
用于同步神经元网络中记忆的编码和回忆。这个假设是基于
部分基于我们的初步数据,表明海马体中的神经元与
损伤后的振荡,并且振荡之间的显着相互作用消失。因此我们建议
确定 TBI 是否影响 CA1 区域中的相位进动、θ 序列和相位幅度耦合
在为这些措施设计的过度训练任务中海马体的变化,以及海马体是否
受到单侧伤害的影响。此外,我们还将确定学习和记忆的机制
通过检查 HC-PFC 的神经元集合活动,量化纹波特征来检测 TBI 后的功能障碍
和重播,并将这些测量与依赖于 HC-PFC 网络的行为记忆功能相关联。我们
还将通过以下方式检查大鼠空间/工作记忆的神经调节恢复机制
同时进行内侧间隔刺激和高密度层状海马/mPFC 记录。
这些目标的实现将为破坏的神经元编码和振荡提供首次详细分析。
TBI 引起的记忆功能障碍的大脑区域之间的相互作用,确定
这些网络上的神经调节,并导致针对 TBI 这种持续后遗症的临床治疗。
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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John Allen Wolf其他文献
John Allen Wolf的其他文献
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{{ truncateString('John Allen Wolf', 18)}}的其他基金
Chronic Focal and Diffuse Traumatic Brain Injury: Mechanisms Underlying Epileptogenesis and Progressive Dysfunction
慢性局灶性和弥漫性创伤性脑损伤:癫痫发生和进行性功能障碍的机制
- 批准号:
10225986 - 财政年份:2020
- 资助金额:
$ 39.19万 - 项目类别:
Chronic Focal and Diffuse Traumatic Brain Injury: Mechanisms Underlying Epileptogenesis and Progressive Dysfunction
慢性局灶性和弥漫性创伤性脑损伤:癫痫发生和进行性功能障碍的机制
- 批准号:
10490256 - 财政年份:2020
- 资助金额:
$ 39.19万 - 项目类别:
Chronic Focal and Diffuse Traumatic Brain Injury: Mechanisms Underlying Epileptogenesis and Progressive Dysfunction
慢性局灶性和弥漫性创伤性脑损伤:癫痫发生和进行性功能障碍的机制
- 批准号:
10710035 - 财政年份:2020
- 资助金额:
$ 39.19万 - 项目类别:
Neuromodulation as a Therapy for PTSD following Chronic TBI
神经调节作为慢性 TBI 后 PTSD 的治疗方法
- 批准号:
10454756 - 财政年份:2018
- 资助金额:
$ 39.19万 - 项目类别:
Neuromodulation as a Therapy for PTSD following Chronic TBI
神经调节作为慢性 TBI 后 PTSD 的治疗方法
- 批准号:
10116979 - 财政年份:2018
- 资助金额:
$ 39.19万 - 项目类别:
Network Dysfunction and Neuromodulation following TBI
TBI 后的网络功能障碍和神经调节
- 批准号:
9903464 - 财政年份:2017
- 资助金额:
$ 39.19万 - 项目类别:
Mechanisms of Cortico-Limbic Network Dysfunction Underlying PTSD after TBI
TBI 后导致 PTSD 的皮质边缘网络功能障碍的机制
- 批准号:
8856874 - 财政年份:2015
- 资助金额:
$ 39.19万 - 项目类别:
Mechanisms of Cortico-Limbic Network Dysfunction Underlying PTSD after TBI
TBI 后导致 PTSD 的皮质边缘网络功能障碍的机制
- 批准号:
9007890 - 财政年份:2015
- 资助金额:
$ 39.19万 - 项目类别:
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