Epileptic seizures are traditionally characterized as the ultimate expression of monolithic, hypersynchronous neuronal activity arising from unbalanced runaway excitation. Here we report the first examination of spike train patterns in large ensembles of single neurons during seizures in persons with epilepsy. Contrary to the traditional view, neuronal spiking activity during seizure initiation and spread was highly heterogeneous, not hypersynchronous, suggesting complex interactions among different neuronal groups even at the spatial scale of small cortical patches. In contrast to earlier stages, seizure termination is a nearly homogenous phenomenon followed by an almost complete cessation of spiking across recorded neuronal ensembles. Notably, even neurons outside the region of seizure onset showed significant changes in activity minutes before the seizure. These findings suggest a revision of current thinking about seizure mechanisms and point to the possibility of seizure prevention based on spiking activity in neocortical neurons.

The neurophysiological mechanisms by which anesthetic drugs cause loss of consciousness are poorly understood. Anesthetic actions at the molecular, cellular, and systems levels have been studied in detail at steady states of deep general anesthesia. However, little is known about how anesthetics alter neural activity during the transition into unconsciousness. We recorded simultaneous multiscale neural activity from human cortex, including ensembles of single neurons, local field potentials, and intracranial electrocorticograms, during induction of general anesthesia. We analyzed local and global neuronal network changes that occurred simultaneously with loss of consciousness. We show that propofol-induced unconsciousness occurs within seconds of the abrupt onset of a slow (<1 Hz) oscillation in the local field potential. This oscillation marks a state in which cortical neurons maintain local patterns of network activity, but this activity is fragmented across both time and space. Local (<4 mm) neuronal populations maintain the millisecond-scale connectivity patterns observed in the awake state, and spike rates fluctuate and can reach baseline levels. However, neuronal spiking occurs only within a limited slow oscillation-phase window and is silent otherwise, fragmenting the time course of neural activity. Unexpectedly, we found that these slow oscillations occur asynchronously across cortex, disrupting functional connectivity between cortical areas. We conclude that the onset of slow oscillations is a neural correlate of propofol-induced loss of consciousness, marking a shift to cortical dynamics in which local neuronal networks remain intact but become functionally isolated in time and space. electrophysiology | single units | GABA | cortical networks G eneral anesthesia is a drug-induced reversible coma commonly initiated by administering a large dose of a fast-acting drug to induce unconsciousness within seconds (1). This state can be maintained as long as needed to execute surgical and many nonsurgical procedures. One of the most widely used anesthetics is propofol, an i.v. drug that enhances GABAergic inhibitory input to neurons (2-4), with effects in cortex, thalamus, brainstem, and spinal cord (5-7). Despite the understanding of propofol's molecular actions, it is not clear how these effects at molecular targets affect single neurons and larger-scale neural circuits to produce unconsciousness.The effects on macroscopic dynamics are noticeable in the EEG, which contains several stereotyped patterns during maintenance of propofol general anesthesia. These patterns include increased delta (0.5-4 Hz) power (8, 9); increased gamma (25-40 Hz) power (9); an alpha (∼10 Hz) rhythm (10-12) that is coherent across frontal cortex; and burst suppression, an alternation between bursts of high-voltage activity and periods of flat EEG lasting for several seconds (13,14). In addition, slow oscillations (<1 Hz) have been well characterized in deeply anesthetized animals and are associated with an alternation of the neuron...

Intracranial recording is an important diagnostic method routinely used in a number of neurological monitoring scenarios. In recent years, advancements in such recordings have been extended to include unit activity of an ensemble of neurons. However, a detailed functional characterization of excitatory and inhibitory cells has not been attempted in human neocortex, particularly during the sleep state. Here, we report that such feature discrimination is possible from high-density recordings in the neocortex by using 2D multielectrode arrays. Successful separation of regular-spiking neurons (or bursting cells) from fast-spiking cells resulted in well-defined clusters that each showed unique intrinsic firing properties. The high density of the array, which allowed recording from a large number of cells (up to 90), helped us to identify apparent monosynaptic connections, confirming the excitatory and inhibitory nature of regular-spiking and fast-spiking cells, thus categorized as putative pyramidal cells and interneurons, respectively. Finally, we investigated the dynamics of correlations within each class. A marked exponential decay with distance was observed in the case of excitatory but not for inhibitory cells. Although the amplitude of that decline depended on the timescale at which the correlations were computed, the spatial constant did not. Furthermore, this spatial constant is compatible with the typical size of human columnar organization. These findings provide a detailed characterization of neuronal activity, functional connectivity at the microcircuit level, and the interplay of excitation and inhibition in the human neocortex.spontaneous activity | ensemble recordings | single unit | functional dynamics F rom columnar microcircuits (1-3) to higher-order neuronal functional units, neocortical dynamics are characterized by a large range of spatial and temporal scales (4, 5). Recent technical improvements have allowed the nature of these dynamics in the human brain to be directly explored: Single-neuron activity in conjunction with local field potentials (LFPs) can be detected from the cerebral cortex and hippocampus in the course of intense monitoring of brain activity before surgical treatment of epileptic foci (6). Modern electrode systems provide the possibility of extracellular recordings of neuronal ensembles by using either microwires (7) or high-density microelectrode arrays (8,9). Prior efforts have demonstrated excellent recordings of single-neuron activity in human cerebral cortex (10-12).Separation of units between "regular-spiking" (RS) and "fastspiking" (FS) neurons, presumably excitatory (pyramidal) and inhibitory (interneuron) cells, respectively, is commonly practiced in animal experiments. In the neocortex of various mammalian species, RS and FS cells can be reliably separated based on spike waveform, duration, and firing rates (13,14). Similar criteria were also used to successfully separate units into putative pyramidal (Pyr) cells and inhibitory interneurons (Int) in human hippocampus...