Identify abnormal neurocognitive circuits in temporal lobe epilepsy

描述（由申请人提供）：本研究的目的是检测与癫痫发生一致的内侧颞叶癫痫（mTLE）患者的相关神经信号的磁共振成像（MRI）证据，然后测试这一潜在脑回路的认知影响。远离癫痫发生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。癫痫发生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，并不局限于具有神经心理学意义。这种异常的、相关的信号应该会创造出有利的神经通路，这些神经通路可以被神经认知网络吸收，导致适应性不良的激活，从而降低认知表现。当初级焦点的细胞被激活时，新建立的神经回路的激活应该被增强。因此，不仅可以在临床观察到的癫痫发作活动中观察到这些异常连接，而且可以在原发性癫痫发病区的认知刺激期间观察到这些异常连接。单侧（n=15）与双侧（n=15）癫痫活动的MTLE患者将与匹配的健康对照（n=15）一起研究。这项研究的目的是：(1)测试与癫痫发生一致的灰质区域之间的功能连接，(2)为癫痫驱动的神经回路的发展提供证据，并确定它们对记忆表现的影响，(3)提供证据，证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。将采用两种成像方式。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将用于确定认知任务期间涉及这些mTL区域的异常激活的存在，这与癫痫发生一致。该项目提供了为癫痫发生提供间接证据的可能性，明确了其认知影响，并为神经疾病导致成人认知无效和异常神经回路的发展提供了一个潜在的模型。这些数据将通过展示疾病驱动的相关神经信号如何形成不利影响表现的适应性不良神经认知网络，对学习理论产生影响。发展多模式脑成像方法来确认主要癫痫病灶外额外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，有助于计划潜在的分阶段手术，并影响对手术风险的知情同意，如潜在的认知缺陷和预期的癫痫控制程度。有证据表明，病变癫痫区启动了一个适应性不良的认知反应回路，这将增加癫痫的认知“成本”，并可能增加手术控制癫痫发作的必要性。大脑区域连接的多模态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，并为更广泛的可能因担心认知发病率而被排除在外的患者开放癫痫手术的好处。

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.