The gamma band effect for episodic memory encoding is absent in epileptogenic hippocampi

https://doi.org/10.1016/j.clinph.2014.07.035Get rights and content

Highlights

  • Oscillatory patterns during episodic memory encoding in the human hippocampus are altered in epileptogenic hippocampi.

  • The gamma band effect, a robust pattern observed in non-epileptogenic hippocampi, is reversed in epileptogenic hippocampi.

  • This pattern in epileptogenic hippocampi may reflect active suppression during episodic item encoding.

Abstract

Objective

The analysis of hippocampal local field potentials in humans during the encoding of episodic memories has revealed that a robust increase in gamma band oscillatory power predicts successful item encoding, termed the gamma band subsequent memory effect (SME). No previous investigation has looked for differences in this pattern between epileptogenic and non-epileptogenic sources; we sought to examine the gamma band effect in seizure patients to address this question.

Methods

We recorded hippocampal activity in nine patients who underwent stereoelectroencephalography for seizure localization and also performed the Free Recall task, a standard test of episodic memory. We compared gamma band oscillatory activity between 15 electrodes localized to epileptogenic hippocampi and 24 electrodes in non-epileptogenic hippocampi.

Results

The epileptogenic hippocampi exhibited a significant decrease in gamma band power during successful item encoding, whereas the non-epileptogenic group exhibited the expected positive gamma band effect (t(37) = 4.69, p<0.0001).

Conclusions

The typical gamma band effect is reversed for epileptogenic hippocampi.

Significance

This is the first study to demonstrate a difference for epileptogenic hippocampi for an important oscillatory pattern that normally predicts successful item encoding. Patients with epilepsy suffer selective impairment of episodic memory ability, so our findings are especially relevant for clinicians and memory researchers alike.

Introduction

Episodic memory, in which specific memory items are placed within temporal context during encoding and retrieval, strongly depends on the contribution of the hippocampus (Burgess et al., 2002, Tulving, 2002). Correspondingly, episodic memory shows selective and marked degradation in patients with temporal lobe epilepsy (Dupont et al., 2000). The implantation of electrodes in human patients to localize seizures has provided memory researchers with the opportunity to explore patterns of brain activity that occur during episodic memory encoding with high spatial and temporal resolution (Jacobs and Kahana, 2010). By comparing features of brain activity during successful versus unsuccessful item encoding, researchers can identify oscillatory patterns that uniquely predict memory formation (Sederberg et al., 2003, Sederberg et al., 2007). These patterns are termed subsequent memory effects (SME).

In the human hippocampus, the most robust and consistent SME is an increase in gamma band (40–200 Hz) oscillatory power during successful item encoding (Sederberg et al., 2007). This gamma band effect is considered a positive SME because power is relatively higher when memories are formed versus when they are not. At other frequency bands by contrast, changes in power often show the opposite pattern, with decreased power during successful encoding (a negative SME). Using invasive recordings, a hippocampal gamma band effect has also been observed during working memory tasks, spatial navigation, and autobiographical memory in human participants (Ekstrom et al., 2005, Fell et al., 2001, van Vugt et al., 2010, Axmacher et al., 2007). These studies have generally excluded abnormal hippocampi, especially epileptogenic hippocampi, because these investigations typically seek to establish generalizable human patterns analogous to animal data. There is evidence of diminished BOLD responsiveness in abnormal hippocampi in epilepsy patients during episodic memory; this effect may predict memory decline after surgery (Jokeit et al., 2001). An analysis of recognition memory in epilepsy patients identified differences in interictal spiking throughout the brain for recognized memory items, suggesting that memory processes interact with epileptic networks at the neurophysiological level (Matsumoto et al., 2013). However, no direct comparison of the gamma band SME between epileptogenic and non-epileptogenic hippocampi has been undertaken.

To examine the gamma band SME in epilepsy, we analyzed a set of nine patients (ten hippocampal implantations, age 18–62, seven female) who underwent stereoelectroencephalography (sEEG) for seizure localization and then performed an episodic memory task. We compared activity during the encoding of episodic memories between epileptogenic and non-epileptogenic hippocampi, hypothesizing that the gamma band SME would be absent or diminished in the epileptogenic hippocampi. We demonstrate that gamma band activity is significantly different between the two groups: in epileptogenic hippocampi gamma power decreases during successful item encoding, while non-epileptogenic hippocampi exhibit the expected + SME. We discuss some theoretical underpinnings and implications for this finding.

Section snippets

Methods

Electrode implantation was performed using the ROSA stereotactic robot after a double-contrast high resolution volume acquisition MRI (Gonzalez-Martinez et al., 2013). Patients were tested from 48 h after implantation when clinical obligations permitted and when they had not suffered seizure activity for at least four hours while awake and fully able to participate. Sessions were not initiated if patients were drowsy or otherwise unwilling to engage in the task. Sessions in which a patient

Results

To directly compare the gamma band subsequent memory effect between epileptogenic and non-epileptogenic hippocampi, we recorded hippocampal activity from nine patients undergoing pre-operative sEEG for seizure localization (eight unilateral, one bilateral implantation). The patients received an average of 10.6 implanted arrays, all inserted with millimeter accuracy using the ROSA stereotactic robot (Gonzalez-Martinez et al., 2013). The ictal onset location and pattern of spread were determined

Discussion

Our data show for the first time that a robust pattern of oscillatory activity seen during human memory formation, the hippocampal gamma band SME, is absent in epileptogenic hippocampi. In humans, a negative gamma band effect has been observed only rarely for the lowest edge of the gamma frequency range (Fell et al., 2001, Sederberg et al., 2007); gamma frequencies above 40 Hz exhibit a reliable positive effect in the non-epileptogenic hippocampi that comprise the dataset for existing analyses (

Conflict of interest

None of the authors have potential conflicts of interest to be disclosed.

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