Hippocampal oscillations, interictal discharges, and memory formation

 描述(由申请人提供)： 目的：本研究旨在探讨癫痫患者的记忆障碍与脑电异常之间的关系。颞叶癫痫(TLE)患者通常在智力正常的情况下表现出记忆障碍。这一发现与建立新记忆在很大程度上依赖于海马体和其他内侧颞叶结构的功能的理论是一致的，海马体和其他内侧颞叶结构是TLE中已知功能失调的网络。先前的研究发现，认知任务表现的中断与发作间期癫痫样放电(IED)的存在之间存在关联。IED是间歇性的尖峰或尖锐的波，反映了神经元的异常放电，但不会形成癫痫。IED中嵌入的可能是病理性高频伽马振荡(HFO)，与正常的高频活动不同，正常高频活动被认为是记忆形成的基础。在临床实践中，IED仅被认为是癫痫的标志，并不被药物抑制。然而，关于对认知功能构成最大风险的IED的特性或IED导致认知缺陷的机制，人们知之甚少。本研究考察了在编码过程中IED对刺激项目后续记忆的影响。这项研究的第一个目的是确定海马区IED的空间和时间特征，这些特征将预测较差的延迟回忆和再认，以及确定嵌入的病理性HFO的影响。第二个目标是确定IED中断内存编码的机制。假设是IED扰乱了构成记忆形成基础的正常脑电节律。更具体地说，预测是IED将导致在记忆编码过程中诱导的正常高频伽马活动量减少。此外，有人提出，IED及其相关的病理性HFO将扰乱整个海马区正常伽马振荡的同步计时或“一致性”。研究计划/方法：为了验证这些假设，患有TLE的受试者将在脑电记录期间完成记忆任务。测试将包括语言和非语言编码、工作记忆以及延迟回忆和识别任务。这些电极将被植入海马体内或海马体旁，以在可能的癫痫切除手术之前进行临床评估。简易爆炸装置将通过人工审查进行识别，时间和空间属性将使用神经扫描软件进行量化。HFO的功率和相干性将使用光谱分析进行评估。临床相关性：IED对正常脑电振荡的干扰将有助于解释该患者群体中的短暂性和长期记忆障碍。这项拟议的研究还将确定简易爆炸装置内的病理性HFO是否会导致其不利的认知影响。有证据表明，IED干扰了记忆编码所需的电活动，这可能表明有必要抑制放电，或者为记忆功能障碍的新治疗指明了方向。这些发现可能会指导未来旨在通过改变异常振荡活动来改善癫痫患者认知的治疗方法的研究。

 DESCRIPTION (provided by applicant): Objective: The proposed study will investigate the relationship between memory deficits and abnormal electrical activity seen on electroencephalography (EEG) in patients with seizures. Patients with temporal lobe epilepsy (TLE) often demonstrate memory dysfunction in the setting of otherwise normal intelligence. This finding is consistent with the theory that establishing new memories is dependent to a large extent on the function of the hippocampus and other mesial temporal lobe structures, a network known to be dysfunctional in TLE. Prior studies found an association between disruptions of cognitive task performance and the presence of interictal epileptiform discharges (IEDs). IEDs are intermittent spikes or sharp waves that reflect abnormal neuronal firing, but do not organize into a seizure. Embedded within the IEDs may be pathological high frequency gamma oscillations (HFOs), distinct from the normal high frequency activity that is thought to underlie memory formation. In clinical practice, IEDs are considered only to be markers of epilepsy and are not suppressed with medications. Little is known, however, regarding the properties of IEDs that pose the greatest risk to cognitive function or the mechanism by which IEDs cause cognitive deficits. The present study examines the effects of IEDs during encoding on subsequent memory for the stimulus items. The first aim of the study is to determine the spatial and temporal characteristics of IEDs within the hippocampus that will predict poorer delayed recall and recognition, as well as identify the effect of embedded pathological HFOs. The second aim is to identify the mechanism by which IEDs interrupt memory encoding. The hypothesis is that IEDs disrupt the normal EEG rhythms that underlie memory formation. More specifically, the prediction is that IEDs will cause a decrease in the amount of normal high frequency gamma activity induced during memory encoding. Furthermore, it is proposed that IEDs and their associated pathological HFOs will disrupt the synchronous timing, or "coherence," of normal gamma oscillations throughout the hippocampus. Research Plan/Methods: To test these hypotheses, subjects with TLE will complete memory tasks during intracranial EEG recordings. Testing will include verbal and non-verbal encoding, working memory, and delayed recall and recognition tasks. The electrodes will be implanted within or alongside the hippocampus for clinical evaluations prior to possible resective epilepsy surgery. IEDs will be identified by manual review, with temporal and spatial properties quantified using Neuroscan software. HFO power and coherence will be assessed using spectral analysis. Clinical Relevance: The interruption of normal EEG oscillations by IEDs would help to explain both transient and long-term memory dysfunction in this patient population. The proposed study will also determine if pathological HFOs within the IEDs contribute to their adverse cognitive effects. Evidence that IEDs disrupt electrical activity necessary for memory encoding may indicate the need for suppression of discharges or point the way to new treatments for memory dysfunction. These findings could direct future investigations aimed at therapeutic approaches to improve cognition in epilepsy patients by alteration of abnormal oscillatory activity.