Laminar analysis of slow wave activity in humans.

Brain electrical activity is largely composed of oscillations at characteristic frequencies. These rhythms are hierarchically organized and are thought to perform important pathological and physiological functions. The slow wave is a fundamental cortical rhythm that emerges in deep non-rapid eye movement sleep. In animals, the slow wave modulates delta, theta, spindle, alpha, beta, gamma and ripple oscillations, thus orchestrating brain electrical rhythms in sleep. While slow wave activity can enhance epileptic manifestations, it is also thought to underlie essential restorative processes and facilitate the consolidation of declarative memories. Animal studies show that slow wave activity is composed of rhythmically recurring phases of widespread, increased cortical cellular and synaptic activity, referred to as active- or up-state, followed by cellular and synaptic inactivation, referred to as silent- or down-state. However, its neural mechanisms in humans are poorly understood, since the traditional intracellular techniques used in animals are inappropriate for investigating the cellular and synaptic/transmembrane events in humans. To elucidate the intracortical neuronal mechanisms of slow wave activity in humans, novel, laminar multichannel microelectrodes were chronically implanted into the cortex of patients with drug-resistant focal epilepsy undergoing cortical mapping for seizure focus localization. Intracortical laminar local field potential gradient, multiple-unit and single-unit activities were recorded during slow wave sleep, related to simultaneous electrocorticography, and analysed with current source density and spectral methods. We found that slow wave activity in humans reflects a rhythmic oscillation between widespread cortical activation and silence. Cortical activation was demonstrated as increased wideband (0.3-200 Hz) spectral power including virtually all bands of cortical oscillations, increased multiple- and single-unit activity and powerful inward transmembrane currents, mainly localized to the supragranular layers. Neuronal firing in the up-state was sparse and the average discharge rate of single cells was less than expected from animal studies. Action potentials at up-state onset were synchronized within +/-10 ms across all cortical layers, suggesting that any layer could initiate firing at up-state onset. These findings provide strong direct experimental evidence that slow wave activity in humans is characterized by hyperpolarizing currents associated with suppressed cell firing, alternating with high levels of oscillatory synaptic/transmembrane activity associated with increased cell firing. Our results emphasize the major involvement of supragranular layers in the genesis of slow wave activity.

Properties of in vivo interictal spike generation in the human subiculum.

A large proportion of hippocampal afferents and efferents are relayed through the subiculum. It is also thought to be a key structure in the generation and maintenance of epileptic activity; rhythmic interictal-like discharges were recorded in previous studies of subicular slices excised from temporal lobe epilepsy patients. In order to investigate if and how the subiculum is involved in the generation of epileptic discharges in vivo, subicular and lateral temporal lobe electrical activity were recorded under anesthesia in 11 drug-resistant epilepsy patients undergoing temporal lobectomy. Based on laminar field potential gradient, current source density, multiple unit activity (MUA) and spectral analyses, two types of interictal spikes were distinguished in the subiculum. The more frequently occurring spike started with an initial excitatory current (current source density sink) in the pyramidal cell layer associated with increased MUA in the same location, followed by later inhibitory currents (current source density source) and decreased MUA. In the other spike type, the initial excitation was confined to the apical dendritic region and it was associated with a less-prominent increase in MUA. Interictal spikes were highly synchronized at spatially distinct locations of the subiculum. Laminar data showed that the peak of the initial excitation occurred within 0-4 ms at subicular sites separated by 6 mm at the anterior-posterior axis. In addition, initial spike peak amplitudes were highly correlated in most recordings. A subset of subicular and temporal lobe spikes were also highly synchronous, in one case the subicular spikes reliably preceded the temporal lobe discharges. Our results indicate that multiple spike generator mechanisms exist in the human epileptic subiculum suggesting a complex network interplay between medial and lateral temporal structures during interictal epileptic activity. The observed widespread intra-subicular synchrony may reflect both of its intrinsic and extrinsically triggered activity supporting the hypothesis that subiculum may also play an active role in the distribution of epileptiform activity to other brain regions. Limited data suggest that subiculum might even play a pacemaker role in the generation of paroxysmal discharges.

Transient cortical excitation at the onset of visual fixation.

Primates actively examine the visual world by rapidly shifting gaze (fixation) over the elements in a scene. Despite this fact, we typically study vision by presenting stimuli with gaze held constant. To better understand the dynamics of natural vision, we examined how the onset of visual fixation affects ongoing neuronal activity in the absence of visual stimulation. We used multiunit activity and current source density measurements to index neuronal firing patterns and underlying synaptic processes in macaque V1. Initial averaging of neural activity synchronized to the onset of fixation suggested that a brief period of cortical excitation follows each fixation. Subsequent single-trial analyses revealed that 1) neuronal oscillation phase transits from random to a highly organized state just after the fixation onset, 2) this phase concentration is accompanied by increased spectral power in several frequency bands, and 3) visual response amplitude is enhanced at the specific oscillatory phase associated with fixation. We hypothesize that nonvisual inputs are used by the brain to increase cortical excitability at fixation onset, thus "priming" the system for new visual inputs generated at fixation. Despite remaining mechanistic questions, it appears that analysis of fixation-related responses may be useful in studying natural vision.

Attention and arousal related modulation of spontaneous gamma-activity in the auditory cortex of the cat.

Sensory information processing in neocortex is associated with rhythmic synchronized gamma frequency firing of sensory cortical units and similar frequency oscillations of the field potentials. Different aspects of the gamma activity (20-80 Hz) have been suggested as correlates of attention, arousal and sensory binding. It is clear that attention has a modality selective influence, while arousal has a more general effect on the sensory systems. We used an experimental conditioning paradigm to separate these differential effects of attention and arousal on spontaneous neocortical gamma activity. We recorded field potentials with epidural electrodes placed above the auditory cortical areas of cats. The animals performed a simple instrumental alimentary conditioning task with different modality (visual and auditory) conditioned stimuli. When they attended to the auditory conditioned stimulus, both frequency and power increase of spontaneous gamma activity were detected. However when they attended visual, we found no power increase of gamma activity recorded above auditory areas, while the frequency increase was the same as in the "attend auditory" condition. We conclude that the power modulation of gamma activity is modality specific and thus can be attributed to selective attention, whereas the frequency modulation of gamma activity shows no modality specificity, it is influenced by the arousal level.

Short and long term biocompatibility of NeuroProbes silicon probes.

Brain implants provide exceptional tools to understand and restore cerebral functions. The utility of these devices depends crucially on their biocompatibility and long term viability. We addressed these points by implanting non-functional, NeuroProbes silicon probes, without or with hyaluronic acid (Hya), dextran (Dex), dexamethasone (DexM), Hya+DexM coating, into rat neocortex. Light and transmission electron microscopy were used to investigate neuronal survival and glial response. The surface of explanted probes was examined in the scanning electron microscope. We show that blood vessel disruption during implantation could induce considerable tissue damage. If, however, probes could be inserted without major bleeding, light microscopical evidence of damage to surrounding neocortical tissue was much reduced. At distances less than 100 microm from the probe track a considerable neuron loss ( approximately 40%) occurred at short survival times, while the neuronal numbers recovered close to control levels at longer survival. Slight gliosis was observed at both short and long term survivals. Electron microscopy showed neuronal cell bodies and synapses close (<10 microm) to the probe track when bleeding could be avoided. The explanted probes were usually partly covered by tissue residue containing cells with different morphology. Our data suggest that NeuroProbes silicon probes are highly biocompatible. If major blood vessel disruption can be avoided, the low neuronal cell loss and gliosis should provide good recording and stimulating results with future functional probes. We found that different bioactive molecule coatings had small differential effects on neural cell numbers and gliosis, with optimal results achieved using the DexM coated probes.