Simulating human sleep spindle MEG and EEG from ion channel and circuit level dynamics

Although they form a unitary phenomenon, the relationship between extracranial M/EEG and transmembrane ion flows is understood only as a general principle rather than as a well-articulated and quantified causal chain.We present an integrated multiscale model, consisting of a neural simulation of thalamus and cortex during stage N2 sleep and a biophysical model projecting cortical current densities to M/EEG fields. Sleep spindles were generated through the interactions of local and distant network connections and intrinsic currents within thalamocortical circuits. 32,652 cortical neurons were mapped onto the cortical surface reconstructed from subjects' MRI, interconnected based on geodesic distances, and scaled-up to current dipole densities based on laminar recordings in humans. MRIs were used to generate a quasi-static electromagnetic model enabling simulated cortical activity to be projected to the M/EEG sensors.The simulated M/EEG spindles were similar in amplitude and topography to empirical examples in the same subjects. Simulated spindles with more core-dominant activity were more MEG weighted.Previous models lacked either spindle-generating thalamic neural dynamics or whole head biophysical modeling; the framework presented here is the first to simultaneously capture these disparate scales.This multiscale model provides a platform for the principled quantitative integration of existing information relevant to the generation of sleep spindles, and allows the implications of future findings to be explored. It provides a proof of principle for a methodological framework allowing large-scale integrative brain oscillations to be understood in terms of their underlying channels and synapses

Intracranial neuronal ensemble recordings and analysis in epilepsy

Pathological neuronal firing was demonstrated 50 years ago as the hallmark of epileptically transformed cortex with the use of implanted microelectrodes. Since then, microelectrodes remained only experimental tools in humans to detect unitary neuronal activity to reveal physiological and pathological brain functions. This recording technique has evolved substantially in the past few decades; however, based on recent human data implying their usefulness as diagnostic tools, we expect a substantial increase in the development of microelectrodes in the near future. Here, we review the technological background and history of microelectrode array development for human examinations in epilepsy, including discussions on of wire-based and microelectrode arrays fabricated using micro-electro-mechanical system (MEMS) techniques and novel future techniques to record neuronal ensemble. We give an overview of clinical and surgical considerations, and try to provide a list of probes on the market with their availability for human recording. Then finally, we briefly review the literature on modulation of single neuron for the treatment of epilepsy, and highlight the current topics under examination that can be background for the future development

Invazív neuromoduláció a gyógyszerrezisztens epilepsziák kezelésében

Absztrakt A neuromoduláció az orvostudománynak egy új, igen dinamikusan fejlődő területe, ami azt vizsgálja, hogy az elektromos, kémiai vagy mechanikai behatások mi módon változtatják meg a központi és a perifériás idegrendszer működését. Ugyanakkor egy reverzibilis terápiás módszer, aminek segítségével a gyógyszeresen már nem befolyásolható mozgászavarok, neuropathiás fájdalmak, epilepsziák, bizonyos pszichiátriai kórképek vagy akár a súlyos spasticitas, hólyag- és székletürítési zavarok, ischaemiás szívbetegség okozta panaszok és tünetek jelentősen javulnak és ezzel szignifikánsan javítható a betegek életminősége. A neuromodulációnak két nagy területe a noninvazív és az invazív neuromoduláció. A noninvazív neuromodulációhoz tartozik a repetitív transcranialis mágneses ingerlés, az egyenáramú stimuláció (direct current stimulation) és a transcutan elektromos neurostimuláció. Az invazív neuromodulációhoz sorolandó módszerek a mély agyi stimuláció, a motorosagykéreg-stimuláció, a gerincvelő-stimuláció, a perifériásideg-stimuláció, a sacralisideg-ingerlés és a subcutan stimuláció. A cikkben áttekintjük az epilepszia-sebészetben napjainkban alkalmazott neuralis interface technológiákat. Orv. Hetil., 2015, 156(52), 2103–2109

Roles Played by the Na+/Ca2+ Exchanger and Hypothermia in the Prevention of Ischemia-Induced Carrier-Mediated Efflux of Catecholamines into the Extracellular Space: Implications for Stroke Therapy

The release of [3H]dopamine ([3H]DA) and [3H]noradrenaline ([3H]NA) in acutely perfused rat striatal and cortical slice preparations was measured at 37 °C and 17 °C under ischemic conditions. The ischemia was simulated by the removal of oxygen and glucose from the Krebs solution. At 37 °C, resting release rates in response to ischemia were increased; in contrast, at 17 °C, resting release rates were significantly reduced, or resting release was completely prevented. The removal of extracellular Ca2+ further increased the release rates of [3H]DA and [3H]NA induced by ischemic conditions. This finding indicated that the Na+/Ca2+ exchanger (NCX), working in reverse in the absence of extracellular Ca2+, fails to trigger the influx of Ca2+ in exchange for Na+ and fails to counteract ischemia by further increasing the intracellular Na+ concentration ([Na+]i). KB-R7943, an inhibitor of NCX, significantly reduced the cytoplasmic resting release rate of catecholamines under ischemic conditions and under conditions where Ca2+ was removed. Hypothermia inhibited the excessive release of [3H]DA in response to ischemia, even in the absence of Ca2+. These findings further indicate that the NCX plays an important role in maintaining a high [Na+]i, a condition that may lead to the reversal of monoamine transporter functions; this effect consequently leads to the excessive cytoplasmic tonic release of monoamines and the reversal of the NCX. Using HPLC combined with scintillation spectrometry, hypothermia, which enhances the stimulation-evoked release of DA, was found to inhibit the efflux of toxic DA metabolites, such as 3,4-dihydroxyphenylacetaldehyde (DOPAL). In slices prepared from human cortical brain tissue removed during elective neurosurgery, the uptake and release values for [3H]NA did not differ from those measured at 37 °C in slices that were previously maintained under hypoxic conditions at 8 °C for 20 h. This result indicates that hypothermia preserves the functions of the transport and release mechanisms, even under hypoxic conditions. Oxidative stress (H2O2), a mediator of ischemic brain injury enhanced the striatal resting release of [3H]DA and its toxic metabolites (DOPAL, quinone). The study supports our earlier findings that during ischemia transmitters are released from the cytoplasm. In addition, the major findings of this study that hypothermia of brain slice preparations prevents the extracellular calcium concentration ([Ca2+]o)-independent non-vesicular transmitter release induced by ischemic insults, inhibiting Na+/Cl--dependent membrane transport of monoamines and their toxic metabolites into the extracellular space, where they can exert toxic effects

Complete Inference of Causal Relations between Dynamical Systems

From philosophers of ancient times to modern economists, biologists and other researchers are engaged in revealing causal relations. The most challenging problem is inferring the type of the causal relationship: whether it is uni- or bi-directional or only apparent - implied by a hidden common cause only. Modern technology provides us tools to record data from complex systems such as the ecosystem of our planet or the human brain, but understanding their functioning needs detection and distinction of causal relationships of the system components without interventions. Here we present a new method, which distinguishes and assigns probabilities to the presence of all the possible causal relations between two or more time series from dynamical systems. The new method is validated on synthetic datasets and applied to EEG (electroencephalographic) data recorded in epileptic patients. Given the universality of our method, it may find application in many fields of science

Superficial Slow Rhythms Integrate Cortical Processing in Humans

The neocortex is composed of six anatomically and physiologically specialized layers. It has been proposed that integration of activity across cortical areas is mediated anatomically by associative connections terminating in superficial layers, and physiologically by slow cortical rhythms. However, the means through which neocortical anatomy and physiology interact to coordinate neural activity remains obscure. Using laminar microelectrode arrays in 19 human participants, we found that most EEG activity is below 10-Hz (delta/theta) and generated by superficial cortical layers during both wakefulness and sleep. Cortical surface grid, grid-laminar, and dual-laminar recordings demonstrate that these slow rhythms are synchronous within upper layers across broad cortical areas. The phase of this superficial slow activity is reset by infrequent stimuli and coupled to the amplitude of faster oscillations and neuronal firing across all layers. These findings support a primary role of superficial slow rhythms in generating the EEG and integrating cortical activity

A neokortikális és hippocampális epilepsziák komplex elektrofiziológiai rétegelvezetéses és szövettani vizsgálata emberben = Complex laminar electrophysiological and histological examination of the human neocortical and hippocampal epilepsies

Az OITI és a MTA PKI együttműködésében részletesen kidolgoztuk az intraoperatív és krónikus multielektróda beültetés technikai feltételeit és a vizsgálatok forgatókönyvét. Létrehoztunk egy kombinált multielektródás és konvencionális klinikai grid-sztrip elektródos elvezető rendszert, mely segítségével az operáció alatt, illetve krónikusan tudunk elvezetni intrahippokampális, intrakortikális, valamint szubdurális potenciálokat. Kimutattuk a szubikulumban generált különféle epilepsziás kisülések és a laterális temporális kéreg aktivitásának kapcsolatait, kimutattuk továbbá az alvásban és epilepsziában fontos K-komplexum generátorainak kérgi eredetét. Vizsgáltuk az alvási oszcilláció és az epilepsziás események kapcsolatát, kimutattuk, hogy epilepsziás emberben a felszínhez közeli kérgi rétegek igen erős szinaptikus és tüzelési aktivitást mutatnak az alvási oszcilláció aktív fázisában. Kimutattuk továbbá, hogy az aktív fázis csoportosítja az epilepsziás kisüléseket. A kérgi elektromos ingerlés hatását vizsgálva epilepsziás betegeken megállapítottuk, hogy a rövid elektromos ingerek inaktiválják a kérget, amit későbbiekben terápiás céllal lehet hasznosítani. | In collaboration with the OITI and MTA PKI we have worked out in details the intraoperative and chronic multielectrode implantation technique and the schedule of the investigation. We have established a combined system composed of the conventional clinical grid and strip based electrophysiology apparatus and the novel investigational multielectrode system to measure intrahippocampal, intracortical and subdural potentials chronically and intraoperatively. We have shown the relationship of the subicular and lateral temporal lobe epileptic discharges, we have also shown the cortical origin of the K-complex, an important brain wave in sleep and epilepsy. We have investigated the slow sleep oscillation and its relationship to epilepsy. The slow waves were originated in the superficial layers of the cortex and the epileptiform discharges were grouped by the up-states of the slow oscillation. Investigating the effect of electrical stimulation, we have shown that brief current pulses can inactivate the cortex, which effect can also be exploited in the therapy of epilepsy