Molecular and neural mechanisms associated with injury and recovery from traumatic brain injury

与创伤性脑损伤的损伤和恢复相关的分子和神经机制

基本信息

项目摘要

Optimal reward-guided behavior relies on intact connections between prefrontal cortex and striatum: circuitry that is disrupted by frontal brain injury1,2. Sustaining a brain injury increases risk for developing depression, anxiety, attention deficits, mood disorders and problems with impulse control3,4. The symptoms of frontal traumatic brain injury (TBI) strongly resemble psychiatric disorders with regards to disruptions in reward-guided behavior, and therefore may share common mechanisms driving behavioral impairments. Mechanisms may include a combination of inflammatory, molecular, and cellular changes that are triggered by injury. Determining which factors mediate persistent effects of behavior is necessary to understand chronic impacts of TBI and develop treatments addressing the often debilitating symptoms enduring after injury. The proposed research will examine how severe and mild frontal TBI impacts neural communication with its distributed striatal network to influence reward-guided behavior. Identifying a neurophysiology signature associated with reward deficits would provide a new target for brain-based treatment options. Neuromodulation, altering the electrical potentials of the brain, may serve as a potential intervention to remediate behavioral deficits by restoring rhythmic brain patterns and structural integrity of their underlying connections following injury. Preclinical testing in translational animal models is critical to better understand the structural and functional mechanisms driving behavioral impairments, and to test repetitive brain stimulation as a method to remediate effects of injury. The first goal of this proposal is to quantify behavioral consequences of severe and mild frontal TBI made using a controlled cortical impact (CCI) in rodents. TBI causes axonal shearing of white matter tracts and chronic inflammation resulting in long-term changes to the brain’s microstructure. Abnormalities in corticostriatal connectivity is being implicated in the onset of psychiatric-like symptoms, yet the relationship with TBI-induced impairments remains unclear. As one of the most widely used injury models in animals, CCI produces focal damage in rats that mirrors concussion, contusion, and hemorrhage in humans by driving an impactor directly into the brain through a surgical opening in the skull30. The injury severity and location are controlled by the experimenter and highly reproducible across animals. After injury, rats will perform a probabilistic reversal learning task which requires reward-guided decision making, behavioral inhibition, flexible behavior, and conditional discrimination: cognitive functions that all depend on intact prefrontal cortex. Reward-related behavioral impairments on the reversal learning task will be related to microstructural changes. To capture disturbances in the cortico-striatal network after TBI, brain activity will be recorded as rats run the probabilistic reversal learning task. Neural activity is not random, it oscillates at periodic frequencies to coordinate communication within and between distributed brain areas. Each of these frequency bands are predicted to coordinate different aspects of behavior through long-range coupling in functional networks. Large-scale local field potential probes will be used to record from 32 brain areas simultaneously capturing these oscillatory dynamics during reward-guided behavior. Identifying frequency-specific activity that is disrupted by TBI, would offer insight into the neural mechanisms of reward-guided behavior and point to a new therapeutic target. Lastly, brain stimulation targeting the cortico-striatal network will be used to assess its effectiveness at inducing neuroplasticity changes to remediate effects of TBI. We will follow neuromodulation procedures known to be successful in humans with the goal of studying the structural and functional mechanisms associated with restored reward-guided behavior. The proposal will examine if stimulation to lateral orbitofrontal cortex can improve reward-guided behavior, restore cortico-striatal network activity, and induce long-term structural changes. This research is critical to identify mechanisms of TBI and remediate reward-related impairments.
最佳的奖励引导行为依赖于前额皮质和纹状体之间完整的连接

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 }}

Miranda Francoeur Koloski其他文献

20. On-Demand Beta Frequency Stimulation Modulates Temporal Discounting Choice
  • DOI:
    10.1016/j.biopsych.2024.02.198
  • 发表时间:
    2024-05-15
  • 期刊:
  • 影响因子:
  • 作者:
    Miranda Francoeur Koloski;Morteza Salimi;Jonathan Mishler;Dhakshin Ramanathan
  • 通讯作者:
    Dhakshin Ramanathan
P7. Beta Oscillatory Activity Reflects Value Representation in Cortico-Striatal Reward Networks
  • DOI:
    10.1016/j.biopsych.2022.02.242
  • 发表时间:
    2022-05-01
  • 期刊:
  • 影响因子:
  • 作者:
    Miranda Francoeur Koloski;Sidharth Hulyalkar;Jessica Cramer;Dhakshin Ramanathan
  • 通讯作者:
    Dhakshin Ramanathan

Miranda Francoeur Koloski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 }}

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了