Identify abnormal neurocognitive circuits in temporal lobe epilepsy

识别颞叶癫痫的异常神经认知回路

• 批准号: 7491452
• 负责人: Joseph I. Tracy
• 金额: $ 16.95万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7491452
• 关键词: Adult; Affect; Area; Bilateral; Binding; Brain; Brain Mapping; Brain imaging; Brain region; Cells; Cognitive; Cognitive deficits; Contralateral; Data; Development; Digit structure; Disease; Epilepsy; Epileptogenesis; Episodic memory; Excision; Fire - disasters; Focus Groups; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Hippocampus (Brain); Image; Informed Consent; Learning; Left; Location; Magnetic Resonance Imaging; Medial; Memory; Methods; Modality; Morbidity - disease rate; Neural Pathways; Neurocognitive; Operative Surgical Procedures; Partial Epilepsies; Patients; Performance; Process; Range; Recording of previous events; Recruitment Activity; Risk; Seizures; Signal Transduction; Site; Specific qualifier value; Staging; Task Performances; Temporal Lobe; Temporal Lobe Epilepsy; Testing; behavior measurement; cost; gray matter; improved; interest; model development; neural circuit; neuropsychological; relating to nervous system; response; skills; stem; theories

DESCRIPTION (provided by applicant): The goal of the study is to detect Magnetic Resonance Imaging (MRI) evidence of correlated neural signalling in medial temporal lobe epilepsy (mTLE) patients consistent with epiletogenesis and then test for the cognitive effects of this potential brain circuit. The development of epileptiform activity remote from the epileptogenic region may facilitate correlated neural signalling between the affected brain regions. The location of new neural connections built up by epileptogenesis, while not completely random, are not constrained to make neuropsychological sense in terms of laying the neural groundwork for effective cognitive skill. This abnormal, correlated signal should create favored neural pathways that can be recruited by neurocognitive networks to cause maladaptive activation that reduces cognitive performance. When cells of the primary focus fire, activation in the newly built neural circuit should be potentiated. Therefore, it becomes possible to observe these aberrant connections not just during clinically observable seizure activity, but also during cognitive stimulation of the primary epileptogenic zone. MTLE patients with Unilateral (n=15) versus Bilateral (n=15) epileptic activity will be studied along with matched, healthy contols (n=15). The goals of the study are to: (1) test for functional connectivity between gray matter regions consistent with epileptogenesis, (2) provide evidence for the development of epilepsy- driven neural circuits and determine their impact on memory performance, (3) provide evidence that flawed task performance can emerge from the activation of disease-driven neural circuits. Two imaging modalities will be utilized. Functional Connectivity MR Analysis will be used to verify the functional connections, respectively, between the regions of interests (left and right medial temporal lobes in patients with mTLE). Functional MRI will be used to determine the presence of anomalous activation involving these mTL regions during the cognitive tasks that is consistent with epileptogenesis. The project offers the possibility of providing indirect evidence for epileptogenesis, specifying its cognitive effects, and offering a potential model for the development of cognitively ineffective and aberrant neural circuitry in adults as a result of neural disease. The data will have implications for theories of learning by demonstrating how disease-driven correlated neural signals can form maladaptive neurocognitive networks that detrimentally influence performance. Summary Developing multimodal brain imaging methods for confirming the presence or impact of additional epileptiform activity outside the primary seizure focus will help with accurate selection of candidates for focal epilepsy surgery, aid in the planning of potential staged surgeries, and influence informed consent regarding surgical risks such as potential cognitive deficits and the expected degree of seizure control. Evidence suggesting that the lesional epileptic zone initiated a circuit of maladaptive cognitive responses will increase the cognitive "cost" of the epilepsy and likely increase the need for surgical control of the seizures. Multimodal mapping of brain regional connectivity will improve localization of functionally intact cognitive networks, increase our ability to tailor the surgical resection to avoid these areas, and open up the benefits of epilepsy surgery to a wider range of patients who might have been excluded because of concerns over cognitive morbidity.

描述（由申请人提供）：该研究的目的是检测磁共振成像（MRI）在颞叶癫痫中内侧癫痫（MTLE）患者中相关神经信号传导的证据，然后与癫痫发生一致，然后测试该潜在脑电路的认知作用。与癫痫病区域远离癫痫样活动的发展可能有助于受影响的大脑区域之间的神经信号传导。通过癫痫发生建立的新神经联系的位置并非完全随机，但并不是在为有效的认知技能奠定神经基础方面的神经心理学意义。这种异常，相关的信号应产生受青睐的神经途径，神经认知网络可以募集，以引起适应不良的激活，从而降低认知性能。当主要重点射击的细胞时，应增强新建造的神经回路中的激活。因此，不仅可以在临床上可观察到的癫痫发作活性期间，而且在原发性癫痫发射区的认知刺激期间观察到这些异常连接。将研究单侧（n = 15）与双侧（n = 15）的MTLE患者以及匹配，健康的抑制（n = 15）的癫痫活性。该研究的目标是：（1）测试与癫痫发生一致的灰质区域之间的功能连通性，（2）为发展癫痫发电的神经回路提供了证据，并确定其对记忆性能的影响，（3）提供了有缺陷的任务表现，表明有缺陷的疾病驱动神经通用神经通用的神经环流的激活。将使用两种成像方式。功能连通性MR分析将分别用于验证利益区域之间（MTLE患者的左侧和右侧颞叶）之间的功能连接。功能性MRI将用于确定与癫痫发生一致的认知任务期间涉及这些MTL区域的异常激活的存在。该项目提供了提供间接证据的癫痫生成，指定其认知作用的可能性，并为成人因神经疾病而在成年人中的认知无效和异常神经回路的发展提供了潜在的模型。数据将通过证明疾病驱动的相关神经信号如何形成适应不良的神经认知网络，从而对学习的理论产生影响。摘要开发了多模式脑成像方法，以证实主要癫痫发作之外的其他癫痫病活动的存在或影响将有助于准确选择候选者进行局灶性癫痫手术，有助于计划潜在的分期手术，并影响有关手术风险的知情同意，例如潜在的认知缺陷和预期的静脉控制程度。证据表明，病变的癫痫区引发了不良适应性认知反应的回路将增加癫痫的认知“成本”，并可能增加对癫痫发作的手术控制的需求。大脑区域连通性的多模式映射将改善功能完整的认知网络的定位，提高我们调整手术切除以避免这些区域的能力，并为可能被排除在外的患者中，使癫痫手术的益处为认知性发病率而被排除在外。

项目成果

Increased microstructural white matter correlations in left, but not right, temporal lobe epilepsy.

• DOI: 10.1002/hbm.22614
• 发表时间: 2015-01
• 期刊: HUMAN BRAIN MAPPING
• 影响因子: 4.8
• 作者: Pustina, Dorian;Doucet, Gaelle;Sperling, Michael;Sharan, Ashwini;Tracy, Joseph
• 通讯作者: Tracy, Joseph

Early and late age of seizure onset have a differential impact on brain resting-state organization in temporal lobe epilepsy.

• DOI: 10.1007/s10548-014-0366-6
• 发表时间: 2015-01
• 期刊: BRAIN TOPOGRAPHY
• 影响因子: 2.7
• 作者: Doucet, Gaelle E.;Sharan, Ashwini;Pustina, Dorian;Skidmore, Christopher;Sperling, Michael R.;Tracy, Joseph I.
• 通讯作者: Tracy, Joseph I.

Functional connectivity abnormalities vary by amygdala subdivision and are associated with psychiatric symptoms in unilateral temporal epilepsy.

• DOI: 10.1016/j.bandc.2013.08.001
• 发表时间: 2013-11
• 期刊: BRAIN AND COGNITION
• 影响因子: 2.5
• 作者: Doucet, Gaelle E.;Skidmore, Christopher;Sharan, Ashwini D.;Sperling, Michael R.;Tracy, Joseph I.
• 通讯作者: Tracy, Joseph I.

Contralateral interictal spikes are related to tapetum damage in left temporal lobe epilepsy.

• DOI: 10.1111/epi.12721
• 发表时间: 2014-09
• 期刊: Epilepsia
• 影响因子: 5.6
• 作者: Pustina D;Doucet G;Skidmore C;Sperling M;Tracy J
• 通讯作者: Tracy J

Predicting the laterality of temporal lobe epilepsy from PET, MRI, and DTI: A multimodal study.

• DOI: 10.1016/j.nicl.2015.07.010
• 发表时间: 2015
• 期刊: NeuroImage. Clinical
• 作者: Pustina D;Avants B;Sperling M;Gorniak R;He X;Doucet G;Barnett P;Mintzer S;Sharan A;Tracy J
• 通讯作者: Tracy J