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: 10915959
• 负责人: Eric M Wassermann
• 金额: $ 48.33万
• 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/10915959
• 关键词: Affect; Anatomy; Anisotropy; Area; Back; Basal Ganglia; Behavior; Behavioral; Belief; Biological Markers; Brain; Brain Diseases; Brain region; Cell Nucleus; Cephalic; Chronic Fatigue Syndrome; Clinical; Clinical effectiveness; Dimensions; Disease; Dopamine; Dose; Electrodes; Electroencephalography; Electrophysiology (science); Environment; Episodic memory; Event; Fatigue; Functional Magnetic Resonance Imaging; Goals; Habits; Hippocampus; Home; Human; Impairment; Individual; Individual Differences; Inferior; Intervention Trial; Investigation; Knowledge; Learning; Maps; Measures; Medial; Memory; Midbrain structure; Motor Skills; Outcome; Pain; Parietal Lobe; Parkinson Disease; Pathway interactions; Performance; Physical Efforts; Predisposition; Prefrontal Cortex; Production; Psyche structure; Punishment; Records; Regulation; Rest; Retrieval; Rewards; Risk; Role; Route; Site; Stimulus; Structure; Surrogate Endpoint; System; Techniques; Temporal Lobe; Thalamic structure; Training; Transcranial magnetic stimulation; Uncertainty; Ventral Striatum; Work; behavioral outcome; clinically relevant; cognitive skill; cohort; drug development; experience; experimental study; grasp; improved; interest; member; memory encoding; neural; neurobehavioral disorder; neuroregulation; noninvasive brain stimulation; pre-clinical; response; segregation; synchronous delivery; theories; visual learning; white matter; willingness

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 reproduced this effect in two cohorts and shown that the effects on connectivity are restricted to the targeted network. Using the effects of TMS, we have also explored effects of episodic memory activation on the procedural network, explaining previously described aspects of their interaction. We have also used individual differences in white matter fractional anisotropy to find the pathways by which the activity responsible for these effects reaches medial temporal lobe structures from the parietal cortex. This year, we began analysis of a study using event-related and resting state electroencephalography (EEG) to see how single TMS trains, delivered to the posterior parietal cortex, online, during a memory task, affect brain activity and performance associated with the encoding and recall of information. The control condition was identical TMS, delivered to the vertex. One aim of the study was to investigate how TMS modulates EEG neural measures of successful memory and the association of this modulation with behavioral performance. During encoding, TMS delivered to the posterior parietal lobe and targeted to the episodic memory network increased the late positive posterior ERP (400-600ms in posteromedial electrodes) and significantly decreased the stimulus-evoked theta/alpha (4-13Hz) power for stimuli that were later remembered. Both of these EEG signatures were associated with successful recall of encoded information in previous work. During during rest after encoding and TMS, network-targeted stimulation significantly decreased the stimulus-evoked theta/alpha (4-13Hz) power. During retrieval of previously presented stimuli, network-targeted TMS, increased the late positive posterior ERP (400-600ms in posteromedial electrodes) for correctly recalled stimuli, relative to incorrect trials. The other main aim of this study was to examine how memory task state influences susceptibility to TMS effects on the network and determine the optimal neural state for improving memory. Network-targeted TMS, delivered synchronously with encoding of information, relative to delivery prior to trial onset, improved memory for encoded stimuli. TMS under these conditions also increased the late positive posterior ERP (400-600ms in the posteromedial electrodes). Investigation of the unpleasantness of physical effort I have a long-standing interest in role of the reward system, not just in learning, where we have done several studies, but in the regulation of behavior. In particular, I am interested in the theory that the valuation placed on action governs the willingness to exert mental and physical effort. Distortions in the estimation of the rewarding or punishing value of goals and actions may play a role in disorders of impaired effort production and excessive fatigue, e.g., Parkinson disease, where the reward system is known to be affected, and chronic fatigue syndrome/myalgic encephalomyelitis, where the mechanism is unknown. Another question of interest is whether neuromodulation targeted to the subjective valuation system (SVN), which assigns rewarding and punishing values to actions, goals, and objects in the environment, might affect willingness to exert effort. Our first study in this project is a fMRI experiment to compare activation of the SVN (ventromedial prefrontal cortex, ventral striatum, posterior cingulate), related to the rated unpleasantness of painful thermal stimulation (an established paradigm) effort (grip force). Our hypothesis is that the SVN will be activated proportionally to the rated unpleasantness of both pain and effort. If this hypothesis is borne out, we will proceed to a TMS experiment targeting the subjective valuation network and looking for changes in functional connectivity and activation in response to effort, as well as an exploratory behavioral outcome.

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。 我们在两个队列中重现了这种效果，并表明对连通性的影响仅限于目标网络。使用TMS的影响，我们还探索了情节记忆激活对程序网络的影响，并解释了先前描述的相互作用方面。我们还使用了白质分数各向异性方面的个体差异来找到负责这些作用的活动的途径，从而从顶叶皮层达到内侧颞叶结构。 今年，我们开始使用与事件相关和静止状态脑电图（EEG）进行研究的分析，以查看单个TMS训练如何在记忆任务期间在线交付给在线的顶叶皮层，影响大脑活动，并影响与信息编码和回忆相关的大脑活动和性能。控制条件是相同的TMS，输送到顶点。 该研究的一个目的是研究TMS如何调节成功记忆的脑电图神经测量以及该调制与行为性能的关联。在编码过程中，将TMS输送到后顶叶并靶向发作性记忆网络增加了后期ERP的晚期阳性（400-600ms的后体电极），并显着降低了刺激诱发的Theta/Alpha（4-13Hz）的刺激功率，以期被记住。这两个EEG签名都与以前的工作中成功召回编码信息有关。在编码和TMS后休息期间，靶向网络的刺激显着降低了刺激引起的theta/alpha（4-13Hz）功率。在检索先前提出的刺激时，靶向网络的TMS，与不正确的试验相对于不正确的试验增加了后期的阳性后ERP（后部电极中的400-600ms），以正确召回刺激。 这项研究的另一个主要目的是检查记忆任务状态如何影响TMS对网络影响的敏感性，并确定改善记忆的最佳神经状态。与信息的编码同步交付的网络靶向TMS相对于试验开始之前的交付，改进了编码刺激的记忆。在这些条件下的TMS还增加了后阳后ERP晚期（后体电极中的400-600ms）。 调查身体努力的不愉快 我对奖励系统的角色有持续的兴趣，不仅在学习中，我们在哪里进行了几项研究，而且对行为的调节进行了兴趣。特别是，我对以行动为基础的理论感兴趣。估计目标和行动的奖励或惩罚价值的扭曲可能在​​努力产生和过度疲劳的疾病中起作用，例如帕金森病，帕金森病，奖励系统受到影响，以及慢性疲劳综合征/肌肌性脑脊髓炎，在该机构中，该机制未知。感兴趣的另一个问题是，针对主观估值系统（SVN）的神经调节是否会影响环境中的行动，目标和对象的价值观，可能会影响努力的意愿。我们在该项目中的首次研究是FMRI实验，以比较SVN的激活（腹侧前额叶皮层，腹侧纹状体，后扣带回），与疼痛的热刺激（已建立范式）的额定不愉快的不愉快性有关（Grip Force）。我们的假设是，SVN将与疼痛和努力的额定不愉快性相称地激活。如果该假设得到证实，我们将继续进行针对主观估值网络的TMS实验，并寻找响应努力以及探索性行为结果的功能连通性和激活的变化。

项目成果

Association Between Traumatic Brain Injury-Related Brain Lesions and Long-term Caregiver Burden.

• DOI: 10.1097/htr.0000000000000151
• 发表时间: 2016-03
• 期刊: The Journal of head trauma rehabilitation
• 作者: Guevara AB;Demonet JF;Polejaeva E;Knutson KM;Wassermann EM;Grafman J;Krueger F
• 通讯作者: Krueger F

Multiple parietal pathways are associated with rTMS-induced hippocampal network enhancement and episodic memory changes.

• DOI: 10.1016/j.neuroimage.2021.118199
• 发表时间: 2021-08-15
• 期刊: NeuroImage
• 影响因子: 5.7
• 作者: Freedberg M;Cunningham CA;Fioriti CM;Murillo J;Reeves JA;Taylor PA;Sarlls JE;Wassermann EM
• 通讯作者: Wassermann EM

Predictors of Neurocognitive Syndromes in Combat Veterans.

退伍军人神经认知综合症的预测因素。

• DOI: 10.7759/cureus.293
• 发表时间: 2015
• 期刊: Cureus
• 作者: Roy,MichaelJ;Costanzo,Michelle;Gill,Jessica;Leaman,Suzanne;Law,Wendy;Ndiongue,Rochelle;Taylor,Patricia;Kim,Hyung-Suk;Bieler,GayleS;Garge,Nikhil;Rapp,PaulE;Keyser,David;Nathan,Dominic;Xydakis,Michael;Pham,Dzung;Wassermann,
• 通讯作者: Wassermann,

Tolerability of transcranial direct current stimulation in childhood-onset schizophrenia.

儿童期精神分裂症经颅直流电刺激的耐受性。

• DOI: 10.1016/j.brs.2011.01.001
• 发表时间: 2011-10
• 期刊: BRAIN STIMULATION
• 影响因子: 7.7
• 作者: Mattai, Anand;Miller, Rachel;Weisinger, Brian;Greenstein, Deanna;Bakalar, Jennifer;Tossell, Julia;David, Christopher;Wassermann, Eric M.;Rapoport, Judith;Gogtay, Nitin
• 通讯作者: Gogtay, Nitin

Reward improves long-term retention of a motor memory through induction of offline memory gains.

• DOI: 10.1016/j.cub.2011.02.030
• 发表时间: 2011-04-12
• 期刊: CURRENT BIOLOGY
• 影响因子: 9.2
• 作者: Abe, Mitsunari;Schambra, Heidi;Wassermann, Eric M.;Luckenbaugh, Dave;Schweighofer, Nicolas;Cohen, Leonardo G.
• 通讯作者: Cohen, Leonardo G.