The hippocampus plays a vital role in various aspects of cognition including both memory and spatial navigation. To understand electrophysiologically how the hippocampus supports these processes, we recorded intracranial electroencephalographic activity from 46 neurosurgical patients as they performed a spatial memory task. We measure signals from multiple brain regions, including both left and right hippocampi, and we use spectral analysis to identify oscillatory patterns related to memory encoding and navigation. We show that in the left but not right hippocampus, the amplitude of oscillations in the 1–3-Hz “low theta” band increases when viewing subsequently remembered object–location pairs. In contrast, in the right but not left hippocampus, low-theta activity increases during periods of navigation. The frequencies of these hippocampal signals are slower than task-related signals in the neocortex. These results suggest that the human brain includes multiple lateralized oscillatory networks that support different aspects of cognition.

Summary Objectives Interictal epileptiform discharges (IEDs) have been linked to memory impairment, but the spatial and temporal dynamics of this relationship remain elusive. In the present study, we aim to systematically characterize the brain areas and times at which IEDs affect memory. Methods Eighty epilepsy patients participated in a delayed free recall task while undergoing intracranial EEG monitoring. We analyzed the locations and timing of IEDs relative to the behavioral data in order to measure their effects on memory. Results Overall IED rates did not correlate with task performance across subjects (r = 0.03, p = 0.8). However, at a finer temporal scale, within-subject memory was negatively affected by IEDs during the encoding and recall periods of the task but not during the rest and distractor periods (p < 0.01, p < 0.001, p = 0.3, and p = 0.8 respectively). The effects of IEDs during encoding and recall were stronger in the left hemisphere than in the right (p < 0.05). Out of six brain areas analyzed, IEDs in the inferior temporal, medial temporal, and parietal areas significantly affected memory (false discovery rate < 0.05). Significance These findings reveal a network of brain areas sensitive to IEDs with key nodes in temporal as well as parietal lobes. They also demonstrate the time-dependent effects of IEDs in this network on memory.

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Background Electrocorticography studies are typically conducted in patients undergoing video EEG monitoring, but these studies are subject to confounds such as the effects of pain, recent anesthesia, analgesics, drug changes, antibiotics, and implant effects. New Method Techniques were developed to obtain electrocorticographic (ECoG) data from freely moving subjects performing navigational tasks using the RNS® System (NeuroPace, Inc., Mountain View, CA), a brain-responsive neurostimulation medical device used to treat focal onset epilepsy, and to align data from the RNS System with cognitive task events with high precision. These subjects had not had recent surgery, and were therefore not confounded by the perioperative variables that affect video EEG studies. Results Task synchronization using the synchronization marker technique provides a quantitative measure of clock uncertainty, and can align data to task events with less than 4ms of uncertainty. Hippocampal ECoG activity was found to change immediately before an incorrect response to a math problem compared to hippocampal activity before a correct response. In addition, subjects were found to have variable but significant changes in theta band power in the hippocampus during navigation compared to when subjects were not navigating. We found that there is theta-gamma phase-amplitude coupling in the right hippocampus while subjects stand still during a navigation task. Comparison with Existing Methods An alignment technique described in this study improves the upper bound on task-ECoG alignment uncertainty from approximately 30ms to under 4ms. The RNS System is one of the first platforms capable of providing untethered ambulatory ECoG recording in humans, allowing for the study of real world instead of virtual navigation. Compared to intracranial video EEG studies, studies using the RNS System platform are not subject to confounds caused by the drugs and recent surgery inherent to the perioperative environment. Furthermore, these subjects provide the opportunity to record from the same electrodes over the course of many years. Conclusions The RNS System enables us to study human navigation with unprecedented clarity. While RNS System patients have fewer electrodes implanted than video EEG patients, the lack of external artifact and confounds from recent surgery make this system a useful tool to further human electrophysiology research.

The factors that control the occurrence of interictal epileptiform discharges (IEDs) are not well understood. We suspected that this phenomenon reflects an attention-dependent suppression of interictal epileptiform activity. We hypothesized that IEDs would occur less frequently when a subject viewed a task-relevant stimulus compared to viewing a blank screen. Furthermore, IEDs have been shown to impair memory when they occur in certain regions during the encoding or recall phases of a memory task. Although these discharges have a short duration, their impact on memory suggests that they have longer lasting electrophysiological effects. We found that IEDs were associated with an increase in low frequency power and a change in the balance between low and high frequency oscillations for several seconds. We found that the occurrence of IEDs is modified by whether a subject is attending to a word displayed on screen or is observing a blank screen. Additionally, we found that discharges in brain regions in every lobe impair memory. These findings elucidate the relationship between IEDs and memory impairment and reveal the task dependence of the occurrence of IEDs.

Objective This study was undertaken to evaluate the influence that subject‐specific factors have on intracranial interictal epileptiform discharge (IED) rates in persons with refractory epilepsy. Methods One hundred fifty subjects with intracranial electrodes performed multiple sessions of a free recall memory task; this standardized task controlled for subject attention levels. We utilized a dominance analysis to rank the importance of subject‐specific factors based on their relative influence on IED rates. Linear mixed‐effects models were employed to comprehensively examine factors with highly ranked importance. Results Antiseizure medication (ASM) status, time of testing, and seizure onset zone (SOZ) location were the highest‐ranking factors in terms of their impact on IED rates. The average IED rate of electrodes in SOZs was 34% higher than the average IED rate of electrodes outside of SOZs (non‐SOZ; p < .001). However, non‐SOZ electrodes had similar IED rates regardless of the subject's SOZ location (p = .99). Subjects on older generation (p < .001) and combined generation (p < .001) ASM regimens had significantly lower IED rates relative to the group taking no ASMs; newer generation ASM regimens demonstrated a nonsignificant association with IED rates (p = .13). Of the ASMs included in this study, the following ASMs were associated with significant reductions in IED rates: levetiracetam (p < .001), carbamazepine (p < .001), lacosamide (p = .03), zonisamide (p = .01), lamotrigine (p = .03), phenytoin (p = .03), and topiramate (p = .01). We observed a nonsignificant association between time of testing and IED rates (morning–afternoon p = .15, morning–evening p = .85, afternoon–evening p = .26). Significance The current study ranks the relative influence that subject‐specific factors have on IED rates and highlights the importance of considering certain factors, such as SOZ location and ASM status, when analyzing IEDs for clinical or research purposes.

Existing literature suggests that transcranial direct current stimulation (tDCS) produces a small enhancement in memory in neuropsychological patients, but transcranial alternating current stimulation (tACS) and transcranial random noise stimulation (tRNS) have not been found to have an effect on memory. Most studies of transcranial magnetic stimulation (TMS) have found that TMS has no positive effect on memory. Vagus nerve stimulation can acutely enhance memory, while chronic therapy does not appear to alter memory performance. We found that there is the most evidence for significant memory enhancement using intracranial stimulation techniques, especially chronic stimulation of the fornix and task-responsive stimulation of the lateral temporal lobe. Presently, there are no existing therapeutic options for directly treating epilepy-related memory deficits. While neurostimulation technologies for memory enhancement are largely still in the experimental phase, neurostimulation appears promising as a future technique for treating epilepsy-related memory deficits.