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（由申请方提供）：本研究的目的是检测与癫痫发生一致的内侧颞叶癫痫（mTLE）患者中相关神经信号的磁共振成像（MRI）证据，然后测试该潜在脑回路的认知效应。远离致痫区域的癫痫样活动的发展可能促进受影响脑区域之间的相关神经信号传导。癫痫形成所建立的新神经连接的位置虽然不是完全随机的，但在为有效的认知技能奠定神经基础方面，并不局限于神经心理学意义。这种异常的、相关的信号应该会产生有利的神经通路，这些通路可以被神经认知网络招募，导致适应不良的激活，从而降低认知能力。当主要焦点的细胞被激活时，新建立的神经回路的激活应该被加强。因此，不仅在临床上可观察到的癫痫发作活动期间，而且在原发性癫痫区的认知刺激期间，都可以观察到这些异常连接。将对单侧（n=15）与双侧（n=15）癫痫活动的MTLE患者与匹配的健康对照组（n=15）一起进行沿着研究。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接性，（2）为癫痫驱动的神经回路的发展提供证据，并确定其对记忆表现的影响，（3）提供证据表明，有缺陷的任务表现可能来自疾病驱动的神经回路的激活。将使用两种成像模式。功能连接MR分析将分别用于验证感兴趣区域（mTLE患者的左内侧颞叶和右内侧颞叶）之间的功能连接。功能性MRI将用于确定在认知任务期间是否存在与癫痫发生一致的涉及这些mTL区域的异常激活。该项目提供了提供癫痫发生的间接证据的可能性，具体说明其认知影响，并提供了一个潜在的模型，在成人中的认知无效和异常的神经回路的发展，作为神经疾病的结果。这些数据将通过展示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来影响学习理论。总结开发多模态脑成像方法来确认原发性癫痫发作病灶以外的其他癫痫样活动的存在或影响，将有助于准确选择局灶性癫痫手术的候选人，帮助规划潜在的分期手术，并影响有关手术风险（如潜在的认知缺陷和癫痫发作控制的预期程度）的知情同意。有证据表明，病灶癫痫区启动了一个适应不良的认知反应回路，这将增加癫痫的认知“成本”，并可能增加癫痫发作的手术控制需求。大脑区域连接的多模式映射将改善功能完整的认知网络的定位，提高我们定制手术切除以避免这些区域的能力，并为更广泛的患者开放癫痫手术的益处，这些患者可能因认知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.

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

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

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.