Quantitative Electrophysiology to Link Neuroplasticity, Brain State, and Behavioral Change in Human Visual Cortex

定量电生理学将神经可塑性、大脑状态和人类视觉皮层的行为变化联系起来

• 批准号: 10643593
• 负责人: Ryan Thomas Ash
• 金额: $ 27.71万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10643593
• 关键词: Address; Affect; Amblyopia; Animal Model; Animals; Area; Arousal; Attention; Attention Deficit Disorder; Authorization documentation; Bayesian Modeling; Behavior; Behavior Therapy; Behavioral; Biology; Blindness; Brain; Cerebrum; Clinic; Clinical; Computer Models; Contrast Sensitivity; Data; Data Set; Development; Discrimination; Disease; Electroencephalography; Electrophysiology (science); Emotions; Environment; Feedback; Felis catus; Future; Goals; Human; Impairment; Knowledge; Lead; Learning; Left; Link; Magnetic Resonance Imaging; Measures; Mediating; Mental Depression; Mentors; Methods; Modeling; Motor Cortex; Neuronal Plasticity; Neurons; Neurosciences; Noise; Optics; Patients; Perception; Physiology; Process; Psychophysics; Recovery; Regulation; Rehabilitation therapy; Research; Research Personnel; Research Proposals; Role; Scotoma; Sensory; Signal Transduction; Source; Strabismus; Stress; Stroke; Study models; Synapses; Synaptic plasticity; Syndrome; Techniques; Testing; Time; Training; Traumatic Brain Injury; Treatment Efficacy; Vision; Vision Disorders; Visual Cortex; Visual Fields; Visual attention; Visual evoked cortical potential; Visual impairment; Visuospatial; Work; addiction; area striata; attentional modulation; authority; autism spectrum disorder; chronic pain; cortical visual impairment; experience; experimental study; frontal eye fields; in vivo; inattention; insight; mind control; mouse model; neural; neural correlate; neurophysiology; neuropsychiatric disorder; neuropsychiatry; neuroregulation; novel; preconditioning; programs; repetitive transcranial magnetic stimulation; response; retinotopic; visual control; visual plasticity; visual processing

PROJECT SUMMARY / ABSTRACT Rehabilitation of central visual disorders like amblyopia and cortical visual impairment depends on synaptic plasticity, the changes in synaptic connections between neurons in the brain. A major regulator of synaptic plas- ticity is brain state - the moment-to-moment fluctuations in attention, arousal, emotions and other factors sep- arate from the actual content of experience - but brain states are generally left uncontrolled in treatment. Con- trolling brain state may be particularly important for brain stimulation therapies like repetitive transcranial mag- netic stimulation (rTMS), which mediate their effect through induction of neuroplasticity. The goal of this re- search proposal is to explore how attentional state - an experimentally tractable, well-understood, and disease- relevant brain state mechanism - regulates rTMS-induced neuroplasticity to the human visual cortex (Aim 1) and frontal eye fields (FEF, Aim 2). Changes in the steady-state visual evoked potential (ssVEP) contrast-response function following rTMS provide a high signal-to-noise neural readout of visual cortical neuroplasticity, while changes in psychophysical contrast discrimination sensitivity provides a perceptual readout of plasticity. During rTMS, subjects will orient attention to either the same or opposite retinotopic visual field to which rTMS is tar- geted, to determine how attentional state affects the propensity of rTMS to induce neuroplasticity. Powerful quantitative linking models will then be used to link rTMS-induced neural changes to perceptual changes, and to determine which neural changes most contribute to behavioral change (Aim 3). These experiments will pro- vide novel evidence that attentional state controls the neuroplasticity effects of brain stimulation. Moreover, they will help identify the cortical circuit mechanisms that are affected by rTMS and which of these mechanisms are most determinative of behavioral change following rTMS. Together this provides fundamental knowledge in hu- man visual cortical plasticity addressing NEI’s Area of Emphasis Biology and Neuroscience of Vision, and will inform the development of brain state control paradigms to augment the efficacy of rehabilitative neuromodula- tion therapies for visual disorders including hemineglect, cerebral scotoma, and amblyopia, in line with NEI’s core programs on Strabismus/Amblyopia/Visual Processing and Low Vision/Blindness Rehabilitation. In the process, the candidate will expand upon his background in in vivo synaptic plasticity and optical physiology in autism animal models to gain expertise in core methods of human neuroscience including rTMS, MRI, EEG, visual spatial attention paradigms, and computational modeling, learning from Stanford mentors who are au- thorities in these techniques (Dr. Nolan Williams, Dr. Tony Norcia, and Dr. Justin Gardner). He will take full advantage of Stanford’s vibrant intellectual environment, interacting with clinicians and researchers to bridge the gap between basic neuroscience bench and the clinic bedside. This training will allow the candidate to estab- lish a unique research niche at the interface of neuromodulation, neuroplasticity, and brain states and eventually lead a translational program to implement neuromodulation-assisted behavioral and rehabilitation therapies.

项目摘要 /摘要 弱视和皮质视觉障碍等中枢视觉疾病的康复取决于突触 可塑性，大脑神经元之间突触连接的变化。突触塑料的主要调节剂 技巧是大脑状态 - 注意力，唤醒，情绪和其他因素的瞬间波动 - 从经验的实际内容中进行的 - 但在治疗中通常无法控制。 con 拖钓大脑状态对于重复经颅杂志等大脑刺激疗法可能尤其重要 网络刺激（RTMS），通过诱导神经塑性来介导其作用。这个重新的目标 搜索建议是探讨注意力状态的方式 - 实验性的，可充分理解和疾病 - 相关的大脑状态机制 - 调节RTMS诱导的人类视觉皮层的神经可塑性（AIM 1）和 额眼场（FEF，AIM 2）。稳态视觉诱发电位（SSVEP）对比反应的变化 RTMS之后的功能提供了视觉皮质神经可塑性的高信噪神经元读数，而 心理物理对比歧视敏感性的变化提供了可塑性的感知读数。期间 RTMS，受试者将注意相同或相反的视网膜视野，RTMS为TAR- 抓住，确定注意力状态如何影响RTM诱导神经可塑性的承诺。强大的 然后，定量链接模型将用于将RTMS诱导的神经变化与感知变化联系起来，并将其链接 确定哪些神经变化最大程度促进行为改变（AIM 3）。这些实验将对 VIDE NOMED SICED COATIONAL状态控制着脑刺激的神经可塑性作用。而且，他们 将有助于确定受RTM影响的皮质电路机制，这些机制中的哪些是 RTMS之后的行为变化大多数决定。这共同提供了Hu-的基本知识 人类视觉皮质可塑性针对Nei的强调生物学和视觉神经科学的领域，并将 告知大脑状态控制范例的发展，以提高康复性神经瘤的效率 视觉疾病的疗法，包括Hemineglect，大脑Scotoma和amblyopia，符合Nei的 关于斜视/弱视/视觉处理以及低视力/失明康复的核心计划。在 过程，候选人将在其体内突触可塑性和光学生理学的背景下扩展 自闭症动物模型以获得人类神经科学核心方法的专业知识，包括RTMS，MRI，EEG， 视觉空间关注范例和计算建模，从斯坦福大学的导师那里学习 这些技术中的胸部（诺兰·威廉姆斯博士，托尼·诺西亚博士和贾斯汀·加德纳博士）。他会满足 斯坦福大学充满活力的智力环境的优势，与临床医生和研究人员互动以桥接 基本神经科学台和诊所床边之间的差距。这项培训将使候选人能够证明 在神经调节，神经塑性和大脑状态以及最终 领导一项转化计划来实施神经调节辅助行为和康复疗法。