A common ankyrin-G-based mechanism retains KCNQ and NaV channels at electrically active domains of the axon.

KCNQ (KV7) potassium channels underlie subthreshold M-currents that stabilize the neuronal resting potential and prevent repetitive firing of action potentials. Here, antibodies against four different KCNQ2 and KCNQ3 polypeptide epitopes show these subunits concentrated at the axonal initial segment (AIS) and node of Ranvier. AIS concentration of KCNQ2 and KCNQ3, like that of voltage-gated sodium (NaV) channels, is abolished in ankyrin-G knock-out mice. A short motif, common to KCNQ2 and KCNQ3, mediates both in vivo ankyrin-G interaction and retention of the subunits at the AIS. This KCNQ2/KCNQ3 motif is nearly identical to the sequence on NaV alpha subunits that serves these functions. All identified NaV and KCNQ genes of worms, insects, and molluscs lack the ankyrin-G binding motif. In contrast, vertebrate orthologs of NaV alpha subunits, KCNQ2, and KCNQ3 (including from bony fish, birds, and mammals) all possess the motif. Thus, concerted ankyrin-G interaction with KCNQ and NaV channels appears to have arisen through convergent molecular evolution, after the division between invertebrate and vertebrate lineages, but before the appearance of the last common jawed vertebrate ancestor. This includes the historical period when myelin also evolved.

High-frequency oscillations and seizure generation in neocortical epilepsy.

Neocortical seizures are often poorly localized, explosive and widespread at onset, making them poorly amenable to epilepsy surgery in the absence of associated focal brain lesions. We describe, for the first time in an unselected group of patients with neocortical epilepsy, the finding that high-frequency (60-100 Hz) epileptiform oscillations are highly localized in the seizure onset zone, both before and temporally removed from seizure onset. These findings were observed in all six patients with neocortical epilepsy out of 23 consecutive patients implanted with intracranial electrodes for pre-surgical evaluation during the study period. The majority of seizures (62%) in these patients were anticipated by an increase in high-frequency activity in the 20 min prior to neocortical seizure onset. Contrary to observations in normal brain, high-frequency activity was strongly modulated by behavioural state, and was maximal during slow-wave sleep, which may explain the propensity for neocortical onset seizures to begin during sleep. These findings point to an important role for neuromodulatory circuits, probably involving the thalamus, in mechanisms underlying seizure generation in neocortical epilepsy. These findings demonstrate that high-frequency epileptiform oscillations may prove clinically useful in localizing the seizure onset zone in neocortical epilepsy, for identifying periods of increased probability of seizure onset, and in elucidating mechanisms underlying neocortical ictogenesis. Confirmation that prolonged bursts of high-frequency activity may predict focal onset neocortical seizures will require prospective validation on continuous, prolonged recordings in a larger number of patients. Importantly, the results show that the dynamic range utilized in current clinical practice for localization of epileptogenic brain largely ignores fundamental oscillations that are signatures of an epileptogenic brain. It may prove that many currently available clinical EEG systems and EEG analysis methods utilize a dynamic range that discards clinically important information.

Blood pO2 and blood flow at the optic disc.

A fundus camera-based phosphorometer to noninvasively and quasicontinuously measure the blood partial pressure of oxygen (pO(2,blood)) in the microvasculature of the pig optic nerve using the principle of the phosphorescence quenching by O(2) is described. A porphyrin dye is injected into the venous circulation and the decay of its phosphorescence emission is detected locally in the eye, after excitation with a flash of light. Combined with blood flow measurements by means of a laser Doppler flowmeter mounted on the phosphorometer, we demonstrate the capability of the instrument to determine the time course of optic nerve blood flow and pO(2,blood) in response to various physiological stimuli, such as hyperoxia and hypercapnia. This instrument appears to be a useful tool for the investigation of the oxygenation of the optic nerve.

Evidence for self-organized criticality in human epileptic hippocampus.

Self-organized criticality (SOC) is a property of complex dynamic systems that evolve to a critical state, capable of producing scale-free energy fluctuations. A characteristic feature of dynamical systems exhibiting SOC is the power-law probability distributions that describe the dynamics of energy release. We show experimental evidence for SOC in the epileptic focus of seven patients with medication-resistant temporal lobe epilepsy. In the epileptic focus the probability density of pathological energy fluctuations and the time between these energy fluctuations scale as (energy) and (time), respectively. The power-laws characterizing the probability distributions from these patients are consistent with computer simulations of integrate-and-fire oscillator networks that have been reported recently. These findings provide insight into the neuronal dynamics of epileptic hippocampus and suggest a mechanism for interictal epileptiform fluctuations. The presence of SOC in human epileptic hippocampus may provide a method for identifying the network involved in seizure generation.

Time-frequency spectral estimation of multichannel EEG using the Auto-SLEX method.

In this paper, we apply a new time-frequency spectral estimation method for multichannel data to epileptiform electroencephalography (EEG). The method is based on the smooth localized complex exponentials (SLEX) functions which are time-frequency localized versions of the Fourier functions and, hence, are ideal for analyzing nonstationary signals whose spectral properties evolve over time. The SLEX functions are simultaneously orthogonal and localized in time and frequency because they are obtained by applying a projection operator rather than a window or taper. In this paper, we present the Auto-SLEX method which is a statistical method that 1) computes the periodogram using the SLEX transform, 2) automatically segments the signal into approximately stationary segments using an objective criterion that is based on log energy, and 3) automatically selects the optimal bandwidth of the spectral smoothing window. The method is applied to the intracranial EEG from a patient with temporal lobe epilepsy. This analysis reveals a reduction in average duration of stationarity in preseizure epochs of data compared to baseline. These changes begin up to hours prior to electrical seizure onset in this patient.