Hippocampal Local Field Potentials Research Articles

Rhythms of the hippocampal network

The hippocampal local field potential (LFP) shows three major types of rhythms: theta, sharp wave-ripples and gamma. These rhythms are defined by their frequencies, they have behavioural correlates in several species including rats and humans, and they have been proposed to carry out distinct functions in hippocampal memory processing. However, recent findings have challenged traditional views on these behavioural functions. In this Review, I discuss our current understanding of the origins and the mnemonic functions of hippocampal theta, sharp wave-ripples and gamma rhythms on the basis of findings from rodent studies. In addition, I present an updated synthesis of their roles and interactions within the hippocampal network.

Coherence between Rat Sensorimotor System and Hippocampus Is Enhanced during Tactile Discrimination

Rhythms with time scales of multiple cycles per second permeate the mammalian brain, yet neuroscientists are not certain of their functional roles. One leading idea is that coherent oscillation between two brain regions facilitates the exchange of information between them. In rats, the hippocampus and the vibrissal sensorimotor system both are characterized by rhythmic oscillation in the theta range, 5–12 Hz. Previous work has been divided as to whether the two rhythms are independent or coherent. To resolve this question, we acquired three measures from rats—whisker motion, hippocampal local field potential (LFP), and barrel cortex unit firing—during a whisker-mediated texture discrimination task and during control conditions (not engaged in a whisker-mediated memory task). Compared to control conditions, the theta band of hippocampal LFP showed a marked increase in power as the rats approached and then palpated the texture. Phase synchronization between whisking and hippocampal LFP increased by almost 50% during approach and texture palpation. In addition, a greater proportion of barrel cortex neurons showed firing that was phase-locked to hippocampal theta while rats were engaged in the discrimination task. Consistent with a behavioral consequence of phase synchronization, the rats identified the texture more rapidly and with lower error likelihood on trials in which there was an increase in theta-whisking coherence at the moment of texture palpation. These results suggest that coherence between the whisking rhythm, barrel cortex firing, and hippocampal LFP is augmented selectively during epochs in which the rat collects sensory information and that such coherence enhances the efficiency of integration of stimulus information into memory and decision-making centers.

Hippocampal Sharp-Wave Ripples Influence Selective Activation of the Default Mode Network

SummaryThe default mode network (DMN) is a commonly observed resting-state network (RSN) that includes medial temporal, parietal, and prefrontal regions involved in episodic memory [1, 2, 3]. The behavioral relevance of endogenous DMN activity remains elusive, despite an emerging literature correlating resting fMRI fluctuations with memory performance [4, 5]—particularly in DMN regions [6, 7, 8]. Mechanistic support for the DMN’s role in memory consolidation might come from investigation of large deflections (sharp-waves) in the hippocampal local field potential that co-occur with high-frequency (>80 Hz) oscillations called ripples—both during sleep [9, 10] and awake deliberative periods [11, 12, 13]. Ripples are ideally suited for memory consolidation [14, 15], since the reactivation of hippocampal place cell ensembles occurs during ripples [16, 17, 18, 19]. Moreover, the number of ripples after learning predicts subsequent memory performance in rodents [20, 21, 22] and humans [23], whereas electrical stimulation of the hippocampus after learning interferes with memory consolidation [24, 25, 26]. A recent study in macaques showed diffuse fMRI neocortical activation and subcortical deactivation specifically after ripples [27]. Yet it is unclear whether ripples and other hippocampal neural events influence endogenous fluctuations in specific RSNs—like the DMN—unitarily. Here, we examine fMRI datasets from anesthetized monkeys with simultaneous hippocampal electrophysiology recordings, where we observe a dramatic increase in the DMN fMRI signal following ripples, but not following other hippocampal electrophysiological events. Crucially, we find increases in ongoing DMN activity after ripples, but not in other RSNs. Our results relate endogenous DMN fluctuations to hippocampal ripples, thereby linking network-level resting fMRI fluctuations with behaviorally relevant circuit-level neural dynamics.

Hippocampal Non-Theta-Contingent Eyeblink Classical Conditioning: A Model System for Neurobiological Dysfunction.

Typical information processing is thought to depend on the integrity of neurobiological oscillations that may underlie coordination and timing of cells and assemblies within and between structures. The 3–7 Hz bandwidth of hippocampal theta rhythm is associated with cognitive processes essential to learning and depends on the integrity of cholinergic, GABAergic, and glutamatergic forebrain systems. Since several significant psychiatric disorders appear to result from dysfunction of medial temporal lobe (MTL) neurochemical systems, preclinical studies on animal models may be an important step in defining and treating such syndromes. Many studies have shown that the amount of hippocampal theta in the rabbit strongly predicts the acquisition rate of classical eyeblink conditioning and that impairment of this system substantially slows the rate of learning and attainment of asymptotic performance. Our lab has developed a brain–computer interface that makes eyeblink training trials contingent upon the explicit presence or absence of hippocampal theta. The behavioral benefit of theta-contingent training has been demonstrated in both delay and trace forms of the paradigm with a two- to fourfold increase in learning speed over non-theta states. The non-theta behavioral impairment is accompanied by disruption of the amplitude and synchrony of hippocampal local field potentials, multiple-unit excitation, and single-unit response patterns dependent on theta state. Our findings indicate a significant electrophysiological and behavioral impact of the pretrial state of the hippocampus that suggests an important role for this MTL system in associative learning and a significant deleterious impact in the absence of theta. Here, we focus on the impairments in the non-theta state, integrate them into current models of psychiatric disorders, and suggest how improvement in our understanding of neurobiological oscillations is critical for theories and treatment of psychiatric pathology.

Mild Traumatic Brain Injury Decreases Broadband Power in Area CA1.

Cognitive impairment caused by traumatic brain injury (TBI) can lead to devastating consequences for both patients and their families. The underlying neurological basis for TBI-induced cognitive dysfunction remains unknown. However, many lines of research have implicated the hippocampus in the pathophysiology of TBI. In particular, past research has found that theta oscillations, long thought to be the electrophysiological basis of learning and memory, are decreased in the hippocampus post-TBI. Here, we recorded in vivo electrophysiological activity in the hippocampi of 16 mice, 8 of which had previously undergone a TBI. Consistent with previous data, we found that theta power in the hippocampus was decreased in TBI animals compared to sham controls; however, this effect was driven by changes in broadband power and not theta oscillations. This result suggests that broadband fluctuations in the hippocampal local field potential can be used as an electrophysiological surrogate of abnormal neurological activity post-TBI.

On the photovoltaic effect in local field potential recordings.

Optogenetics allows light activation of genetically defined cell populations and the study of their link to specific brain functions. While it is a powerful method that has revolutionized neuroscience in the last decade, the shortcomings of directly stimulating electrodes and living tissue with light have been poorly characterized. Here, we assessed the photovoltaic effects in local field potential (LFP) recordings of the mouse hippocampus. We found that light leads to several artifacts that resemble genuine LFP features in animals with no opsin expression, such as stereotyped peaks at the power spectrum, phase shifts across different recording channels, coupling between low and high oscillation frequencies, and sharp signal deflections that are detected as spikes. Further, we tested how light stimulation affected hippocampal LFP recordings in mice expressing channelrhodopsin 2 in parvalbumin neurons (PV/ChR2 mice). Genuine oscillatory activity at the frequency of light stimulation could not be separated from light-induced artifacts. In addition, light stimulation in PV/ChR2 mice led to an overall decrease in LFP power. Thus, genuine LFP changes caused by the stimulation of specific cell populations may be intermingled with spurious changes caused by photovoltaic effects. Our data suggest that care should be taken in the interpretation of electrophysiology experiments involving light stimulation.

Alteration of spontaneous spectral powers and coherences of local field potential in prenatal valproic acid mouse model of autism

Previously, autism spectrum disorder (ASD) has been identified mainly by social communication deficits and behavioral symptoms. However, a link between behaviors and learning process in the brain of animal model of autism remained largely unexplored. Particularly, spontaneous neural signaling in learning-related brain areas has not been studied. This study investigated local field potential (LFP) of the hippocampus (HP), the olfactory bulb (OB) and the medial prefrontal cortex (mPFC) in mice prenatally exposed to valproic acid (VPA) on gestational day 13. Adult male Swiss albino mouse offspring implanted with intracranial electrodes were used. VPA-exposed mice exhibited ASD-associated behaviors. Hippocampal LFP analysis revealed that VPA group significantly increased low gamma activity (25–45 Hz) during awake immobility. Regression analyses confirmed positive correlations between locomotor speed and hippocampal theta oscillations in control but not VPA group. VPA group exhibited increases in delta (1–4 Hz) and beta (25–35 Hz) activities in OB during awake immobility and active exploring, respectively. Moreover, significantly increased and decreased coherences between HP and OB of VPA animals were seen within gamma (active exploration) and theta (awake immobility) ranges, respectively. In addition, significant increase in coherence between HP and mPFC was seen within delta range during active exploration. In addition to three ASD symptoms, VPA animals also exhibited differential patterns of olfacto-hippocampal LFP, altered locomotor speed-related hippocampal theta activities and distinct interplays between HP and learning-related brain areas. The altered olfacto-hippocampal and medial prefrontal cortex-hippocampal networks may underlie impairments in autism mouse model.

Diversity of sharp-wave–ripple LFP signatures reveals differentiated brain-wide dynamical events

Sharp-wave-ripple (SPW-R) complexes are believed to mediate memory reactivation, transfer, and consolidation. However, their underlying neuronal dynamics at multiple scales remains poorly understood. Using concurrent hippocampal local field potential (LFP) recordings and functional MRI (fMRI), we study local changes in neuronal activity during SPW-R episodes and their brain-wide correlates. Analysis of the temporal alignment between SPW and ripple components reveals well-differentiated SPW-R subtypes in the CA1 LFP. SPW-R-triggered fMRI maps show that ripples aligned to the positive peak of their SPWs have enhanced neocortical metabolic up-regulation. In contrast, ripples occurring at the trough of their SPWs relate to weaker neocortical up-regulation and absent subcortical down-regulation, indicating differentiated involvement of neuromodulatory pathways in the ripple phenomenon mediated by long-range interactions. To our knowledge, this study provides the first evidence for the existence of SPW-R subtypes with differentiated CA1 activity and metabolic correlates in related brain areas, possibly serving different memory functions.

Role of brain glycogen in the response to hypoxia and in susceptibility to epilepsy.

Although glycogen is the only carbohydrate reserve of the brain, its overall contribution to brain functions remains unclear. It has been proposed that glycogen participates in the preservation of such functions during hypoxia. Several reports also describe a relationship between brain glycogen and susceptibility to epilepsy. To address these issues, we used our brain-specific Glycogen Synthase knockout (GYS1Nestin-KO) mouse to study the functional consequences of glycogen depletion in the brain under hypoxic conditions and susceptibility to epilepsy. GYS1Nestin-KO mice presented significantly different power spectra of hippocampal local field potentials (LFPs) than controls under hypoxic conditions. In addition, they showed greater excitability than controls for paired-pulse facilitation evoked at the hippocampal CA3–CA1 synapse during experimentally induced hypoxia, thereby suggesting a compensatory switch to presynaptic mechanisms. Furthermore, GYS1Nestin-KO mice showed greater susceptibility to hippocampal seizures and myoclonus following the administration of kainate and/or a brief train stimulation of Schaffer collaterals. We conclude that brain glycogen could play a protective role both in hypoxic situations and in the prevention of brain seizures.

Effects of memantine on hippocampal long-term potentiation, gamma activity, and sensorimotor gating in freely moving rats

Memantine, an uncompetitive N-methyl-D-aspartate receptor antagonist, is used for treatment of patients with Alzheimer's disease. The mechanisms of memantine in relieving cognitive and behavioral symptoms are unclear, and this study attempts to elucidate its action on network and synaptic functions of the hippocampus. The effects of memantine on electrographic activity and hippocampal long-term potentiation (LTP) were investigated in freely moving rats. Basal dendritic excitation on hippocampal CA1 pyramidal cells showed a robust LTP after theta-frequency primed bursts, and the LTP was higher after 5–10 mg/kg intraperitoneal (ip) memantine pretreatment, as compared with saline pretreatment. Injection of scopolamine (5 mg/kg ip) before memantine failed to block the LTP-enhancing effect of memantine. Memantine as compared with saline pretreatment did not affect the LTP after an afterdischarge induced by high-frequency (200-Hz) train stimulation. Memantine (5 or 10 mg/kg ip) significantly enhanced gamma oscillations in the hippocampal local field potentials of 40–100 Hz during walking and awake immobility. Memantine at 10 mg/kg ip, but not at 5 mg/kg ip, increased prepulse inhibition of the acoustic startle response, while both 5 and 10 mg/kg ip memantine enhanced the acoustic startle response as compared with saline-injected rats. These electrophysiological and behavioral effects of memantine are unique among N-methyl-D-aspartate receptor antagonists but are consistent with memantine's effects in improving cognitive and sensorimotor functions of Alzheimer's patients.

Characterization of in utero valproic acid mouse model of autism by local field potential in the hippocampus and the olfactory bulb

Valproic acid (VPA) mouse model of autism spectrum disorder (ASD) has been characterized mostly by impaired ultrasonic vocalization, poor sociability and increased repetitive self-grooming behavior. However, its neural signaling remained unknown. This study investigated the local field potentials (LFPs) in the dorsal hippocampal CA1 and the olfactory bulb while animals exploring a novel open field. VPA was administered at gestational day 13. The results demonstrated three core features of ASD in male offspring. However, there was no difference in Y-maze performance and locomotor activity. Analysis of hippocampal LFP power revealed significantly increased slow wave (1–4Hz) and high gamma (80–140Hz) oscillations and decreased theta (4–12Hz) activity in VPA mice. In the olfactory bulb, VPA animals showed greater slow wave (1–4Hz) and beta (25–40Hz) activity and lower activity of low gamma (55–80Hz) wave. Regression analysis revealed positive correlations between hippocampal theta power and locomotor speed for both control and VPA-exposed mice. There was no significant difference between groups for modulation index of theta (4–12Hz) phase modulated gamma (30–200Hz) amplitude. These findings characterized VPA mouse model with LFP oscillations that might provide better understanding of neural processing in ASD.

Disordered Ripples Are a Common Feature of Genetically Distinct Mouse Models Relevant to Schizophrenia

We present results from a novel comparative approach to the study of the mechanisms of psychiatric disease. Previous work has examined neural activity patterns in the hippocampus of a freely behaving mouse model associated with schizophrenia, the calcineurin knockout mouse. Here, we examined a genetically distinct mouse model that exhibits a similar set of behavioral phenotypes associated with schizophrenia, a transgenic model expressing a putative dominant-negative DISC1 (DN-DISC1). Strikingly, the principal finding of the earlier work is replicated in the DN-DISC1 mice, that is, a selective increase in the numbers of sharp-wave ripple (SWR) events in the hippocampal local field potential (LFP), while at the same time other LFP patterns such as theta and gamma are unaffected. SWRs are thought to arise from hippocampal circuits and reflect the coordinated activity of the principal excitatory cells of the hippocampus in specific patterns that represent reactivated memories of previous experiences and imagined future experiences that predict behavior. These findings suggest that multiple genetic alterations could converge on distinct patterns of aberrant neurophysiological function to give rise to common behavioral phenotypes in psychiatric disease.

Auditory cortical and hippocampal local-field potentials to frequency deviant tones in urethane-anesthetized rats: An unexpected role of the sound frequencies themselves

The human brain can automatically detect auditory changes, as indexed by the mismatch negativity of event-related potentials. The mechanisms that underlie this response are poorly understood. We recorded primary auditory cortical and hippocampal (dentate gyrus, CA1) local-field potentials to serial tones in urethane-anesthetized rats. In an oddball condition, a rare (deviant) tone (p=0.11) randomly replaced a repeated (standard) tone. The deviant tone was either lower (2200, 2700, 3200, 3700Hz) or higher (4300, 4800, 5300, 5800Hz) in frequency than the standard tone (4000Hz). In an equiprobability control condition, all nine tones were presented at random (p=0.11). Differential responses to deviant tones relative to the standard tone were found in the auditory cortex and the dentate gyrus but not in CA1. Only in the dentate gyrus, the responses were found to be standard- (i.e., oddball condition-) specific. In the auditory cortex, the sound frequencies themselves sufficed to explain their generation. These findings tentatively suggest dissociation among non-contextual afferent, contextual afferent and auditory change detection processes. Most importantly, they remind us about the importance of strict control of physical sound features in mismatch negativity studies in animals.

Conceptualization and validation of an open-source closed-loop deep brain stimulation system in rat.

Conventional deep brain stimulation (DBS) applies constant electrical stimulation to specific brain regions to treat neurological disorders. Closed-loop DBS with real-time feedback is gaining attention in recent years, after proved more effective than conventional DBS in terms of pathological symptom control clinically. Here we demonstrate the conceptualization and validation of a closed-loop DBS system using open-source hardware. We used hippocampal theta oscillations as system input, and electrical stimulation in the mesencephalic reticular formation (mRt) as controller output. It is well documented that hippocampal theta oscillations are highly related to locomotion, while electrical stimulation in the mRt induces freezing. We used an Arduino open-source microcontroller between input and output sources. This allowed us to use hippocampal local field potentials (LFPs) to steer electrical stimulation in the mRt. Our results showed that closed-loop DBS significantly suppressed locomotion compared to no stimulation, and required on average only 56% of the stimulation used in open-loop DBS to reach similar effects. The main advantages of open-source hardware include wide selection and availability, high customizability, and affordability. Our open-source closed-loop DBS system is effective, and warrants further research using open-source hardware for closed-loop neuromodulation.

HCN channels enhance spike phase coherence and regulate the phase of spikes and LFPs in the theta-frequency range

What are the implications for the existence of subthreshold ion channels, their localization profiles, and plasticity on local field potentials (LFPs)? Here, we assessed the role of hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels in altering hippocampal theta-frequency LFPs and the associated spike phase. We presented spatiotemporally randomized, balanced theta-modulated excitatory and inhibitory inputs to somatically aligned, morphologically realistic pyramidal neuron models spread across a cylindrical neuropil. We computed LFPs from seven electrode sites and found that the insertion of an experimentally constrained HCN-conductance gradient into these neurons introduced a location-dependent lead in the LFP phase without significantly altering its amplitude. Further, neurons fired action potentials at a specific theta phase of the LFP, and the insertion of HCN channels introduced large lags in this spike phase and a striking enhancement in neuronal spike-phase coherence. Importantly, graded changes in either HCN conductance or its half-maximal activation voltage resulted in graded changes in LFP and spike phases. Our conclusions on the impact of HCN channels on LFPs and spike phase were invariant to changes in neuropil size, to morphological heterogeneity, to excitatory or inhibitory synaptic scaling, and to shifts in the onset phase of inhibitory inputs. Finally, we selectively abolished the inductive lead in the impedance phase introduced by HCN channels without altering neuronal excitability and found that this inductive phase lead contributed significantly to changes in LFP and spike phase. Our results uncover specific roles for HCN channels and their plasticity in phase-coding schemas and in the formation and dynamic reconfiguration of neuronal cell assemblies.

Harnessing the power of theta: natural manipulations of cognitive performance during hippocampal theta-contingent eyeblink conditioning.

Neurobiological oscillations are regarded as essential to normal information processing, including coordination and timing of cells and assemblies within structures as well as in long feedback loops of distributed neural systems. The hippocampal theta rhythm is a 3–12 Hz oscillatory potential observed during cognitive processes ranging from spatial navigation to associative learning. The lower range, 3–7 Hz, can occur during immobility and depends upon the integrity of cholinergic forebrain systems. Several studies have shown that the amount of pre-training theta in the rabbit strongly predicts the acquisition rate of classical eyeblink conditioning and that impairment of this system substantially slows the rate of learning. Our lab has used a brain-computer interface (BCI) that delivers eyeblink conditioning trials contingent upon the explicit presence or absence of hippocampal theta. A behavioral benefit of theta-contingent training has been demonstrated in both delay and trace forms of the paradigm with a two- to four-fold increase in learning speed. This behavioral effect is accompanied by enhanced amplitude and synchrony of hippocampal local field potential (LFP)s, multi-unit excitation, and single-unit response patterns that depend on theta state. Additionally, training in the presence of hippocampal theta has led to increases in the salience of tone-induced unit firing patterns in the medial prefrontal cortex, followed by persistent multi-unit activity during the trace interval. In cerebellum, rhythmicity and precise synchrony of stimulus time-locked LFPs with those of hippocampus occur preferentially under the theta condition. Here we review these findings, integrate them into current models of hippocampal-dependent learning and suggest how improvement in our understanding of neurobiological oscillations is critical for theories of medial temporal lobe processes underlying intact and pathological learning.

Age-related decrease in theta and gamma coherence across dorsal ca1 pyramidale and radiatum layers.

In both humans and rodents, aging is linked to impairments in hippocampus dependent learning. Given such deficits, one would expect corresponding changes in hippocampal local field potentials, which represent the integration of multiple inputs onto a given dendritic field within the hippocampus. The current experiment examined coherence of theta and gamma in young and aged rats at sub-millimeter and millimeter distant locations both within and across layers in CA1 of the dorsal hippocampus. The degree to which different dendritic layers show coherent oscillations indicates the uniformity of the inputs and local circuitry, and may form an important element for processing information. Aged rats had lower coherence in all frequency ranges; this was most marked within a layer as the distance between electrodes increased. Notably, unlike younger rats, in the aged rats coherence was not affected by running on the maze. Furthermore, despite the previously reported effects of cholinergic activation on theta frequency and power, there was no effect of the cholinomimetic physostigmine on coherence. These data indicate an age related fragmentation in hippocampal processing that may underlie some of the observed learning and memory deficits.

Optogenetic activation of CA1 pyramidal neurons at the dorsal and ventral hippocampus evokes distinct brain-wide responses revealed by mouse fMRI.

The dorsal and ventral hippocampal regions (dHP and vHP) are proposed to have distinct functions. Electrophysiological studies have revealed intra-hippocampal variances along the dorsoventral axis. Nevertheless, the extra-hippocampal influences of dHP and vHP activities remain unclear. In this study, we compared the spatial distribution of brain-wide responses upon dHP or vHP activation and further estimate connection strengths between the dHP and the vHP with corresponding extra-hippocampal areas. To achieve this, we first investigated responses of local field potential (LFP) and multi unit activities (MUA) upon light stimulation in the hippocampus of an anesthetized transgenic mouse, whose CA1 pyramidal neurons expressed a step-function opsin variant of channelrhodopsin-2 (ChR2). Optogenetic stimulation increased hippocampal LFP power at theta, gamma, and ultra-fast frequency bands, and augmented MUA, indicating light-induced activation of CA1 pyramidal neurons. Brain-wide responses examined using fMRI revealed that optogenetic activation at the dHP or vHP caused blood oxygenation level-dependent (BOLD) fMRI signals in situ. Although activation at the dHP induced BOLD responses at the vHP, the opposite was not observed. Outside the hippocampal formation, activation at the dHP, but not the vHP, evoked BOLD responses at the retrosplenial cortex (RSP), which is in line with anatomical evidence. In contrast, BOLD responses at the lateral septum (LS) were induced only upon vHP activation, even though both dHP and vHP send axonal fibers to the LS. Our findings suggest that the primary targets of dHP and vHP activation are distinct, which concurs with attributed functions of the dHP and RSP in spatial memory, as well as of the vHP and LS in emotional responses.

Hippocampal theta rhythm after local administration of procaine or amphetamine into the ventral tegmental area in fear conditioned rats

The ventral tegmental area (VTA) is thought to be an important component in the mesocorticolimbic system involved in the regulation of theta rhythm in the hippocampus. In this study we investigate the effect of pharmacological inactivation (local procaine infusion) or activation (local amphetamine infusion) of the VTA on theta rhythm parameters during task specific behavior in fear conditioned, freely moving rats. Animals were implanted with bilateral recording electrodes into the dorsal hippocampus (CA1) and bilateral injection cannulas into the VTA. Behavioral activities and hippocampal local field potentials (LFP) were recorded throughout the experiment, in pre- and post-injection conditions. We found that intra-VTA injection of procaine temporarily suppressed fear conditioned avoidance response (escape from the foot-shock arena) and also influenced hippocampal theta rhythm parameters during immobility linked with arousal and/or attention. Procaine infusion decreased the signal power (Pmax) of theta rhythm during immobility behavior, in comparison to the control group (water infusion), whereas administration of amphetamine had no effect on the behavior and hippocampal LFP. Our results indicate that temporal inactivation of neuronal activity in the VTA affects hippocampal theta rhythm linked with attentional immobility and suppresses avoidance response in fear conditioned animals.

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

ObjectiveThe 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. MethodsWe 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. ResultsThe 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). ConclusionsThe typical gamma band effect is reversed for epileptogenic hippocampi. SignificanceThis 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.