Balazs Dombovari

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.

Two-Dimensional Multi-Channel Neural Probes With Electronic Depth Control

This paper presents multi-electrode arrays for in vivo neural recording applications incorporating the principle of electronic depth control (EDC), i.e., the electronic selection of recording sites along slender probe shafts independently for multiple channels. Two-dimensional (2D) arrays were realized using a commercial 0.5- μm complementary-metal-oxide-semiconductor (CMOS) process for the EDC circuits combined with post-CMOS micromachining to pattern the comb-like probes and the corresponding electrode metallization. A dedicated CMOS integrated front-end circuit was developed for pre-amplification and multiplexing of the neural signals recorded using these probes.

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.

Two-dimensional multi-channel neural probes with electronic depth control

Multi-electrode arrays for in vivo neural recording are presented incorporating the principle of electronic depth control, i.e. an electronic selection of electrode locations along the probe shaft independently for multiple channels. Two-dimensional (2D) arrays are realized using a commercial CMOS process for the electronic circuits combined with post-CMOS micromachining for shaping the probes and electrode metallization. These 2D arrays can be further assembled into 3D arrays. Two-dimensional arrays with IrO x metal finish show electrode impedances between 100 KΩ and 1 MΩ. In vivo tests demonstrate the capability to simultaneously record multi-unit activity in addition to local field potentials on all 32 available output channels of the probe combs. Electronic steering enabled some of the electrodes to record from cortical and others to record from thalamic sites in the rat. This new device significantly increases the amount of useful information that can be obtained from a single experiment.

In vivo validation of the electronic depth control probes

Abstract In this article, we evaluated the electrophysiological performance of a novel, high-complexity silicon probe array. This brain-implantable probe implements a dynamically reconfigurable voltage-recording device, coordinating large numbers of electronically switchable recording sites, referred to as electronic depth control (EDC). Our results show the potential of the EDC devices to record good-quality local field potentials, and single- and multiple-unit activities in cortical regions during pharmacologically induced cortical slow wave activity in an animal model.

High channel count electrode system to investigate thalamocortical interactions

Abstract A novel silicon-based microelectrode array with one- and two-dimensional variants was developed in the framework of the EU-funded research project NeuroProbes. The electrode array comprises complementary-metal-oxide-semiconductor based integrated circuitry to implement the concept of electronic depth control which is used to select up to 32 recording sites from more than 1000 possible electrode channels integrated on four slender probe shafts. The electrode array was tested in acute experiments performed simultaneously in cortex and thalamus of the rat brain. In both brain regions good quality local field potential and multiunit activity was recorded during the tests.