Extent of Single-Neuron Activity Modulation by Hippocampal Interictal Discharges Predicts Declarative Memory Disruption in Humans
Extent of Single-Neuron Activity Modulation by Hippocampal Interictal Discharges Predicts Declarative Memory Disruption in Humans
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DOI：
10.1523/jneurosci.1380-19.2019
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发表时间：
2020-01-15
影响因子：
5.3
通讯作者：
Rutishauser, Ueli
中科院分区：
文献类型：
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作者：
Reed, Chrystal M.;Mosher, Clayton P.;Rutishauser, Ueli
癫痫患者的记忆力减退很常见。在这些患者中，发作间期EEG通常显示发作间期癫痫样放电（IED）。虽然简易爆炸装置与短暂的认知障碍有关，但人们对这一点的原因仍然知之甚少。我们研究了人类（男性和女性）海马IED对接受深度电极监测的难治性癫痫患者记忆任务期间单神经元活动的影响。我们量化了海马IED对单个神经元活动的影响，以及这种调制对主观宣称的记忆强度的影响。在所有记录的神经元中，728个神经元中有50个神经元的活动受到IED的显著调制，其中内侧颞叶（416个中的33个）和特别是右侧海马（58个中的12个）的调制最强。推定的抑制性神经元，确定其细胞外的签名，更有可能被调制的简易爆炸装置比推定的兴奋性神经元（19 157对31 571）。行为上，海马IED的发生是伴随着一个熟悉的图像识别中断，只有当他们发生了2秒前刺激发作。相反，简易爆炸装置并没有损害编码或识别新的图像，表明高的时间和任务的简易爆炸装置的影响特异性。IED对单个神经元的调制程度与检索试验的声明置信度相关，较高的放电率表示置信度降低。总之，这些数据链接的瞬时调制个别神经元的简易爆炸装置在特定的细胞类型的特定陈述性记忆缺陷，从而揭示了一种机制，简易爆炸装置破坏内侧颞叶依赖的陈述性记忆提取过程。
Memory deficits are common in epilepsy patients. In these patients, the interictal EEG commonly shows interictal epileptiform discharges (IEDs). While IEDs are associated with transient cognitive impairments, it remains poorly understood why this is. We investigated the effects of human (male and female) hippocampal IEDs on single-neuron activity during a memory task in patients with medically refractory epilepsy undergoing depth electrode monitoring. We quantified the effects of hippocampal IEDs on single-neuron activity and the impact of this modulation on subjectively declared memory strength. Across all recorded neurons, the activity of 50 of 728 neurons were significantly modulated by IEDs, with the strongest modulation in the medial temporal lobe (33 of 416) and in particular the right hippocampus (12 of 58). Putative inhibitory neurons, as identified by their extracellular signature, were more likely to be modulated by IEDs than putative excitatory neurons (19 of 157 vs 31 of 571). Behaviorally, the occurrence of hippocampal IEDs was accompanied by a disruption of recognition of familiar images only if they occurred up to 2 s before stimulus onset. In contrast, IEDs did not impair encoding or recognition of novel images, indicating high temporal and task specificity of the effects of IEDs. The degree of modulation of individual neurons by an IED correlated with the declared confidence of a retrieval trial, with higher firing rates indicative of reduced confidence. Together, these data link the transient modulation of individual neurons by IEDs to specific declarative memory deficits in specific cell types, thereby revealing a mechanism by which IEDs disrupt medial temporal lobe-dependent declarative memory retrieval processes.