Identify abnormal neurocognitive circuits in temporal lobe epilepsy

描述(申请人提供)：这项研究的目标是检测内侧颞叶癫痫(MTLE)患者与癫痫发生相一致的相关神经信号的磁共振成像(MRI)证据，然后测试这一潜在大脑回路的认知效应。远离致痫区域的癫痫样活动的发展可能促进受影响的脑区之间的相关神经信号传递。癫痫发生所建立的新的神经连接的位置，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，并不受限制地使神经心理学具有意义。这种异常的、相关的信号应该会产生有利的神经通路，神经认知网络可以招募这些通路来导致适应不良的激活，从而降低认知能力。当主灶的细胞激发时，新建立的神经回路中的激活应该得到加强。因此，不仅可以在临床可观察到的癫痫发作活动中观察到这些异常联系，而且在初级致痫区的认知刺激过程中也可以观察到这些异常联系。单侧(n=15)或双侧(n=15)癫痫发作的MTLE患者将与匹配的健康对照组(n=15)一起进行研究。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通性；(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，表明疾病驱动的神经回路的激活可能会出现任务表现缺陷。将使用两种成像方式。功能连接磁共振分析将分别用于验证感兴趣区域(MTLE患者的左侧和右侧内侧颞叶)之间的功能连接。功能磁共振成像将被用来确定在与癫痫发生相一致的认知任务中涉及这些MTL区域的异常激活的存在。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，并为成人由于神经疾病而导致的认知无效和异常神经回路的发展提供了一个潜在的模型。这些数据将对学习理论产生影响，因为它展示了疾病驱动的相关神经信号如何形成不适应的神经认知网络，从而有害地影响学习成绩。开发多模式脑成像方法以确认主要癫痫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者，帮助规划潜在的分期手术，并影响对手术风险的知情同意，例如潜在的认知缺陷和预期的癫痫控制程度。有证据表明，癫痫区启动了一系列不适应的认知反应，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式映射将改善功能完整的认知网络的定位，增加我们为避免这些区域而量身定做手术切除的能力，并使癫痫手术的好处惠及更广泛的患者，这些患者可能因为担心认知发病率而被排除在外。

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.