Electrophysiological Probes And Treatments In Neurobehavioral Disorders

神经行为障碍的电生理学探针和治疗

• 批准号: 10688927
• 负责人: Eric M Wassermann
• 金额: $ 54.15万
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10688927
• 关键词: Affect; Anatomy; Anisotropy; Area; Attention; Back; Basal Ganglia; Behavior; Behavioral; Belief; Bilateral; Biological Markers; Brain; Brain Diseases; Cell Nucleus; Cerebellum; Clinical; Clinical effectiveness; Cognition; Corpus Callosum; Corpus striatum structure; Dopamine; Dose; Electroencephalography; Electrophysiology (science); Episodic memory; Equilibrium; Event; Functional Imaging; Functional Magnetic Resonance Imaging; Goals; Goggles; Habits; Hemispatial Neglect; Hippocampus (Brain); Home; Human; Image; Individual; Individual Differences; Inferior; Intervention Trial; Judgment; Knowledge; Laboratories; Learning; Left; Lesion; Measures; Medial; Mediating; Memory; Midbrain structure; Middle frontal gyrus structure; Motor Skills; Neural Pathways; Outcome; Parietal; Parietal Lobe; Participant; Pathway interactions; Patients; Performance; Process; Records; Rest; Rewards; Risk; Route; Seeds; Side; Site; Superior temporal gyrus; Surrogate Endpoint; Syndrome; System; Techniques; Temporal Lobe; Thalamic structure; Training; Transcranial magnetic stimulation; Uncertainty; Vision; Visual; Visual Fields; Visual attention; Visuospatial; Work; antagonist; behavior change; caudate nucleus; clinically relevant; cognitive skill; cohort; drug development; experience; experimental study; hemisphere damage; imaging study; improved; interest; learning network; neglect; neural; neurobehavioral disorder; noninvasive brain stimulation; pre-clinical; procedural memory; theories; treatment duration; visual learning; way finding; white matter

Modulation of memory networks: Human memory is composed of two, largely segregated, systems, the episodic system, which records explicit, verbalizable, records of experience, e.g., what you had for breakfast or the route from home to work, and the procedural system, which gradually builds motor and cognitive skills and habits through repetition and rewarded or punished experience. The episodic system is centered in the hippocampus and includes a network of cortical sites, while the procedural system is a system of parallel loops involving the cortex, basal ganglia, and thalamus, with important modulatory input from the midbrain dopamine nuclei. We and others have shown that transcranial magnetic stimulation (TMS) delivered to the inferior parietal cortex, an accessible node in the episodic memory network, causes a significant increase in resting state functional connectivity in the entire network and clinically relevant improvement in visual learning in healthy individuals. Stimulation is targeted to the individual subject's area with densest functional connectivity with a seed region in the hippocampus. We have reproduced this effect in two cohorts and shown that the effects on connectivity are restricted to the targeted network. In a Bayesian-adaptive trial, we have also examined the number of days of treatment required to produce a lasting effect. Because there is evidence from imaging and behavioral experiments that the episodic memory network competes with procedural learning network, we also looked for effects on regions connected with a relevant region of the striatum. We found that enhancement of connectivity in the episodic memory network also increases connectivity between the hippocampus and striatum in a way which could reduce its availability for procedural learning. Confirming this suspicion we also found an inverse correlation between episodic memory network connectivity enhancement and procedural memory performance after stimulation. This is the first direct, causal, evidence of the relationship between the two networks and is of basic and clinical interest. In work directed at revealing further details of how TMS of the episodic memory network improves memory performance, we looked at individual differences in the organization of white matter pathways from the stimulation site in the inferior parietal cortex to network sites with the greatest change in connectivity across studies. Although the target site was chosen for maximal connectivity to the hippocampus in each individual, participants with the strongest white matter connectivity from the stimulation site to the precuneus, a cortical area involved in episodic memory, had the largest effects on network connectivity and memory performance. We also used individual differences in fractional anisotropy among candidate pathways from the parietal stimulation site to the hippocampal seed to find the oligosynaptic route by which the effect propagates. Fractional anisotropy in the parietal-parahippocampal pathway and several pathways via other regions of the medial temporal lobe predicted the changes in hippocampal functional connectivity produced by parietal TMS. Fractional anisotropy in these pathways was also related to changes in episodic, but not procedural, memory. In other work, we found that enhancement of hippocampal connectivity by TMS increases the connectivity of the hippocampal network and caudate nucleus and that this effect is likely mediated via the precuneus and/or the ventrolateral thalamus. Moreover, this increase in connectivity between the episodic memory network and nodes of the procedural memory network was associated with a proportional decrease in procedural memory performance after parietal TMS. This mechanism could account for the classical observation of functional antagonism between memory systems under laboratory conditions. We are in the process of using event-related electroencephalography (EEG) to study how individual TMS trains, delivered to the posterior parietal cortex, online, during a memory task, affect brain activity associated with the encoding and recall of information. Modulation of the visual attentional network: There are simple and reliable ways of inducing quantifiable changes in behavior, including adaptation to prism goggles that shift vision a few degrees to either side. We are studying the basis of this phenomenon with functional MRI and using TMS to intervene in the same neural pathways and attempt to produce the same imaging and behavior changes. This work is aimed at a getting a better understanding and developing new treatments for the syndrome of hemispatial neglect after right hemisphere damage. Adaptation to vision-shifting prisms (PA) alters spatial cognition according to the direction of visual displacement by temporarily modifying sensorimotor mapping. Right-shifting prisms (right PA) improve neglect of left visual field in patients, possibly by decreasing activity in the left hemisphere and increasing it in the right. Left PA shifts attention rightward in healthy individuals by an opposite mechanism. However, functional imaging studies of PA are inconsistent, perhaps because of differing activation tasks. Recently, we measured resting-state functional connectivity in healthy individuals before and after PA. When contrasted, right versus left PA decreased RSFC in the spatial navigation network defined by the right posterior parietal cortex (PPC), hippocampus, and cerebellum. Within-PA-direction comparisons showed that right PA increased resting state functional connectivity in subregions of the PPCs and between the PPCs and the right middle frontal gyrus and left PA decreased RSFC between these regions. Both right and left PA decreased RSFC between the PPCs and bilateral temporal areas. In summary, right PA increases connectivity in the right frontoparietal network and left PA produces essentially opposite effects. Furthermore, right, compared with left, PA modulates resting state functional connectivity in the right hemisphere navigation network. Hemispatial neglect is thought to result from disruption of interhemispheric equilibrium. Right hemisphere lesions deactivate the right frontoparietal network and hyperactivate the left via release from interhemispheric inhibition. Support for this theory comes from TMS studies in healthy subjects, in whom right PPC inhibition causes neglect-like, rightward, visuospatial bias. Concurrent TMS and fMRI after right PPC TMS show task-dependent changes but may have failed to identify effects of stimulation in areas not directly activated by the specific task, providing an incomplete picture. We used resting-state functional connectivity after inhibitory TMS over the right PPC to look for changes in the networks underlying visuospatial attention. In a crossover experiment in healthy individuals, we delivered continuous theta burst TMS to the right PPC and vertex (control). We hypothesized that PPC stimulation would cause a rightward visuospatial bias, decrease PPC connectivity with frontal areas, and increase PPC connectivity with the attentional network in the left hemisphere. We also expected that individual differences in fractional anisotropy (FA) in white matter connections between the PPCs would account for variability in TMS-induced RSFC changes. As expected, TMS over the right PPC caused a rightward shift in line bisection judgment and increased RSFC between the right PPC and the left superior temporal gyrus. This effect was inversely related to fractional anisotropy, a measure of white matter organization, in the posterior corpus callosum. Local inhibition of the right PPC reshapes connectivity in the attentional network and depends on interhemispheric connections.

内存网络的调制： 人类的记忆由两个，很大程度上隔离的系统组成，即情节系统，它们记录了明确的，可说的，可说的，例如，您在早餐或从家到工作的路线以及过程系统的经验记录，以及逐渐通过重复和奖励和奖励或惩罚或惩罚或惩罚或惩罚的经验来逐渐建立运动和认知技能和习惯。情节系统以海马为中心，包括皮质位点网络，而程序系统是涉及皮质，基底神经节和丘脑的平行环系统，并具有中脑多巴胺核的重要调节性输入。 我们和其他人已经表明，传递到下颅皮层（TMS）是情节记忆网络中的可访问节点，导致整个网络中的静止状态功能连通性显着提高，并且在健康个体中的视觉学习方面与临床相关。 刺激针对个人受试者的区域，其功能连接与海马中的种子区域最密集。 我们已经在两个队列中重现了这种效果，并表明对连接性的影响仅限于目标网络。在一项贝叶斯自适应试验中，我们还检查了产生持久作用所需的治疗天数。 由于来自成像和行为实验的证据表明，情节记忆网络与程序学习网络竞争，因此我们还寻找对与纹状体相关区域相关的区域的影响。我们发现，情节记忆网络中连通性的提高还可以以一种可以降低其程序学习的可用性的方式提高海马和纹状体之间的连通性。确认了这种怀疑，我们还发现刺激后的情节内存网络连接增强与程序记忆性能之间存在逆相关性。 这是两个网络之间关系的第一个直接，因果关系，具有基本和临床感兴趣。 在旨在揭示情节内存网络TM的进一步细节的工作中，我们研究了白质途径组织中的个体差异，从刺激位点的刺激位点到跨研究的连通性最大变化的网络站点的刺激位点。 尽管选择了目标位点，以最大程度地连接到每个人的海马，但从刺激位点到precuneus的参与者最强的参与者是参与情节记忆的皮质区域，对网络连接性和记忆性能的影响最大。 我们还使用了从顶刺激部位到海马种子的候选途径中分数各向异性的个体差异，以找到效果传播的寡突触途径。 顶叶 - 帕拉皮省途径的分数各向异性和通过内侧颞叶的其他区域的多个途径预测了顶叶TMS产生的海马功能连通性的变化。这些途径中的分数各向异性也与情节性（但程序性记忆）的变化有关。 在其他工作中，我们发现通过TMS提高海马连通性会增加海马网络和尾状核的连通性，并且这种效应可能是通过前后节和/或腹侧丘脑介导的。 此外，情节内存网络与程序记忆网络节点之间的连通性增加与顶叶TMS后的程序记忆性能的比例下降相关联。 这种机制可以解释实验室条件下记忆系统之间功能拮抗作用的经典观察。 我们正在使用与事件相关的脑电图（EEG）来研究单个TMS在记忆任务期间在线运送到后顶层皮层的单个TMS训练如何影响与信息编码和回忆有关的大脑活动。 视觉注意网络的调制： 有一些简单可靠的方法可以引起可量化的行为变化，包括对将视觉转移几个程度转移到两侧的棱镜护目镜的适应。 我们正在研究使用功能性MRI的这种现象的基础，并使用TMS干预相同的神经途径，并试图产生相同的成像和行为变化。 这项工作的目的是在右半球损害后，以更好地理解并开发新的治疗方法。 适应视力转移棱镜（PA）通过暂时修改感觉运动映射来根据视觉位移的方向来改变空间认知。右移动棱镜（右PA）改善了患者对左视野的忽视，可能是通过减少左半球的活动并在右侧增加活动。左PA通过一种相反的机制向健康个体中的注意力转移。但是，PA的功能成像研究是不一致的，这可能是由于激活任务的不同。最近，我们测量了PA之前和之后健康个体中静止状态的功能连通性。当形成鲜明对比时，右PA与左PA在空间导航网络中降低了RSFC，该空间导航网络由右后顶皮层（PPC），海马和小脑定义。 PA内方面的比较表明，右PA增加了PPC子区域以及PPC之间的静息状态功能连接性，右中间额回和左PA降低了这些区域之间的RSFC。左右PA都降低了PPC和双侧时间区域之间的RSFC。总而言之，右PA增加了右额叶网络中的连通性，左PA产生基本相反的效果。此外，与左侧相比，右侧PA调节右半球导航网络中的静止状态功能连接。 半疏松被认为是由于半球间平衡的破坏而造成的。右半球病变停用了右额叶网络，并通过半球间抑制作用通过释放来使左活化。对该理论的支持来自健康受试者的TMS研究，其中正确的PPC抑制作用会导致忽视，向右，视觉空间偏见。右PPC TMS之后的并发TMS和fMRI显示了任务依赖性的变化，但可能无法识别未直接由特定任务直接激活的区域的刺激效果，从而提供了不完整的图片。我们在右PPC上使用抑制性TMS后使用静止状态功能连接，以寻找视觉空间关注的网络的变化。在健康个体的跨界实验中，我们将连续的theta爆发TMS传递到右PPC和顶点（对照）。我们假设PPC刺激会导致右视觉空间偏差，降低与额叶区域的PPC连接，并增加左半球注意力网络的PPC连接性。我们还期望PPC之间的白质连接中分数各向异性（FA）的个体差异将解释TMS诱导的RSFC变化的变化。正如预期的那样，右PPC上的TMS导致线双分配判断的向右移动，并增加了右PPC和左上颞回之间的RSFC。这种效应与后call体中的白质组织分数各向异性成反比。对右PPC的局部抑制会重塑注意网络中的连通性，并取决于半球间连接。