Objective

To characterize local field potentials, high frequency oscillations, and single unit firing patterns in microelectrode recordings of human limbic onset seizures.

Methods

Wide bandwidth local field potential recordings were acquired from microelectrodes implanted in mesial temporal structures during spontaneous seizures from six patients with mesial temporal lobe epilepsy.

Results

In the seizure onset zone, distinct epileptiform discharges were evident in the local field potential prior to the time of seizure onset in the intracranial EEG. In all three seizures with hypersynchronous (HYP) seizure onset, fast ripples with incrementally increasing power accompanied epileptiform discharges during the transition to the ictal state (p < 0.01). In a single low voltage fast (LVF) onset seizure a triad of evolving HYP LFP discharges, increased single unit activity, and fast ripples of incrementally increasing power were identified ~20 s prior to seizure onset (p < 0.01). In addition, incrementally increasing fast ripples occurred after seizure onset just prior to the transition to LVF activity (p < 0.01). HYP onset was associated with an increase in fast ripple and ripple rate (p < 0.05) and commonly each HYP discharge had a superimposed ripple followed by a fast ripple. Putative excitatory and inhibitory single units could be distinguished during limbic seizure onset, and heterogeneous shifts in firing rate were observed during LVF activity.

Significance

Epileptiform activity is detected by microelectrodes before it is detected by depth macroelectrodes, and the one clinically identified LVF ictal onset was a HYP onset at the local level. Patterns of incrementally increasing fast ripple power are consistent with observations in rats with experimental hippocampal epilepsy, suggesting that limbic seizures arise when small clusters of synchronously bursting neurons increase in size, coalesce, and reach a critical mass for propagation.

The theta rhythm-a slow (6-12 Hz) oscillatory component of the local field potential-plays a critical role in spatial navigation and memory by coordinating the activity of neuronal ensembles within the medial temporal lobe (MTL). Although theta has been extensively studied in freely moving rodents, its presence in humans has been elusive and primarily investigated in stationary subjects. Here we used a unique clinical opportunity to examine theta within the human MTL during untethered, real-world ambulatory movement. We recorded intracranial electroencephalographic activity from participants chronically implanted with the wireless NeuroPace responsive neurostimulator (RNS) and tracked their motion with sub-millimeter precision. Our data revealed that movement-related theta oscillations indeed exist in humans, such that theta power is significantly higher during movement than immobility. Unlike in rodents, however, theta occurs in short bouts, with average durations of ∼400 ms, which are more prevalent during fast versus slow movements. In a rare opportunity to study a congenitally blind participant, we found that both the prevalence and duration of theta bouts were increased relative to the sighted participants. These results provide critical support for conserved neurobiological characteristics of theta oscillations during ambulatory spatial navigation, while highlighting some fundamental differences across species in these oscillations between humans and rodents.

Uncovering the neural mechanisms underlying human natural ambulatory behavior is a major challenge for neuroscience. Current commercially available implantable devices that allow for recording and stimulation of deep brain activity in humans can provide invaluable intrinsic brain signals but are not inherently designed for research and thus lack flexible control and integration with wearable sensors. We developed a mobile deep brain recording and stimulation (Mo-DBRS) platform that enables wireless and programmable intracranial electroencephalographic recording and electrical stimulation integrated and synchronized with virtual reality/augmented reality (VR/AR) and wearables capable of external measurements (e.g., motion capture, heart rate, skin conductance, respiration, eye tracking, and scalp EEG). When used in freely moving humans with implanted neural devices, this platform is adaptable to ecologically valid environments conducive to elucidating the neural mechanisms underlying naturalistic behaviors and to the development of viable therapies for neurologic and psychiatric disorders.