The visual cortex alpha-scanning: EEG and magnetic resonance tomography data

Exact localization of equivalent current dipoles (ECD) was obtained by combining the EEG and the MRI mapping allowing to trace the ECG displacement over the cortex. The data obtained corroborate localization of the alpha-rhythm ECD in the Gyrus Calcarina: the human primary visual cortex. Successive shifts of the ECD over this area during generation of each alpha-wave, were revealed. The data are discussed in the light of the "scanning hypothesis" that predicted a certain functional meaning of the alpha-wave spreading for cortical processing of sensory information.     

Rhythmic photostimulation and a number of alpha-rhythm dipoles in the human brain

Dynamic study of the equivalent current dipoles (ECDs) of alpha rhythm in the human brain was performed in a one-dipole model. The number of ECDs was shown to be dependent on the time course of visual stimulation, on the phase shift of triggering of flickers with alpha-rhythm frequency from alpha-wave, as well as on the type of visual illusions produced in subjects by this stimulation. The data are discussed in accordance with the "scanning hypothesis" that predict a certain functional meaning of the spreading alpha-wave for cortical processing of sensory information in the human brain.     

Trajectories of shifting of dipole sources of visual evoked potentials over the human brain

Dynamic study of 3D localization of the equivalent current dipole (ECD) sources of visual evoked potentials (EP) in the human brain was performed in 18 healthy subjects using a two-dipole model. Dipole tracing was performed for relatively early EP components (N1, P1, and N2) with 1-ms step. The analysis confirmed localization of these ECDs mainly in the right occipital cortex and revealed their successive shift over this area in the anterior-medial direction and then backwards in all subjects during generation of the EP components. Typically, some successive arch-like trajectories of the shift were revealed (75.8%); their duration was relatively standard (about 25 ms) and did not depend on the stimulus shape and EP phase. Between the 1st and the 2nd trajectories (110-120 ms after the stimulus onset) a jump in ECD coordinates in the medial direction was found in 85% of cases. Possible significance of the findings for the insight into dynamic topography of the visual feature processing in the human brain is discussed.     

Spontaneous Slow Fluctuation of EEG Alpha Rhythm Reflects Activity in Deep-Brain Structures: A Simultaneous EEG-fMRI Study

The emergence of the occipital alpha rhythm on brain electroencephalogram (EEG) is associated with brain activity in the cerebral neocortex and deep brain structures. To further understand the mechanisms of alpha rhythm power fluctuation, we performed simultaneous EEGs and functional magnetic resonance imaging recordings in human subjects during a resting state and explored the dynamic relationship between alpha power fluctuation and blood oxygenation level-dependent (BOLD) signals of the brain. Based on the frequency characteristics of the alpha power time series (APTS) during 20-minute EEG recordings, we divided the APTS into two components: fast fluctuation (0.04–0.167 Hz) and slow fluctuation (0–0.04 Hz). Analysis of the correlation between the MRI signal and each component revealed that the slow fluctuation component of alpha power was positively correlated with BOLD signal changes in the brain stem and the medial part of the thalamus and anterior cingulate cortex, while the fast fluctuation component was correlated with the lateral part of the thalamus and the anterior cingulate cortex, but not the brain stem. In summary, these data suggest that different subcortical structures contribute to slow and fast modulations of alpha spectra on brain EEG.     

Dipole tracing of visual evoked potentials in human brain

3D tracing of equivalent current dipoles (ECDs) of averaged human visual evoked potentials (VEP) by their distribution across a 34-electrode array was obtained under short presentation of pattern-onset stimuli (sets of 45 horizontal, vertical bars or crosses). Using a 2-dipole spherical three-layer model, we dynamically (step of 1 ms) localized dipoles in four healthy subjects. Dipole locations were matched to anatomical brain regions visualized in structural MRI. Best-fitting source parameters were superimposed on MR images of each subject to identify the anatomical structures giving rise to the surface patterns. It was found that during 50-300 ms following the onset of the stimuli, the ECDs in all subjects were localized in the occipital cortex and demonstrated reliable systematic shift in localization. Two local (1-2 cm3) zones of the preferable dipole attendance were found at 5-6 cm behind zero line: the first one was localized near the midline of the brain, whereas the other zone was situated in the right hemisphere at a distance of 6-7 cm from the first zone. Their localization and strength of activation were reliably different for crosses and lines and changed during VEP generation. Zones of relatively rare dipole attendance were found also. The data are discussed in relation to localization of initial and endpoint of ECDs trajectories, as well as with sensitivity of the visual cortex to line crossing and branching.     

Post-radiation effect on the interhemispheric asymmetry in EEG and thermography characteristics

Complex analysis of EEG and thermographic parameters carried out in 10 healthy subjects and 34 patients, Chernobyl clean-up participants revealed a correlation between EEG and brain temperature changes in the baseline state and during mental arithmetic. During cognitive activity the maximal increase in the average EEG coherence and temperature shifts in healthy subjects were observed in the left frontotemporal and right parietotemporal areas. In patients changes in both parameters under study were most pronounced, the interhemispheric relations were impaired. The visual analysis revealed "flat" and "hypersynchronous" EEG types in patients. The dominant pathologic activity in the betal range indicative of mediobasal and oral brainstem lesions was characteristic of the flat EEG. This type of activity was observed in 60% of patients. In these cases, a general decrease in EEG coherence and temperature was most pronounced in the left hemisphere. The hypersynchronou EEG type (40% patients) was characterized by paroxysmal activity in the theta and alpha ranges suggesting diencephalic brain lesions. In these cases, EEG coherence and temperature were more variable; changes in the right hemisphere were significant, be it increase or decrease. Our complex approach to investigation of brain activity in different aspects seems to be promising in estimation of the brain functional state both in healthy persons and patients in remote terms after exposure to radiation. The specific hemispheric temperature changes revealed in Chernobyl patients especially during cognitive activity can be the sequels of postradiation disorders of vascular neuro-circulation. The EEG findings suggest subcortical disorders at different levels (diencephalic or brainstem) and functional failure of the right or left hemispheres in remote terms after exposure to radiation.     

The physical basis of alpha waves in the electroencephalogram and the origin of the “Berger effect”

Synchronised activity, differing in phase in different populations of neurons, plays an important role in existing theories on the function of brain oscillations (e.g., temporal correlation hypothesis). A prerequisite for this synchronisation is that stimuli are capable of affecting (resetting) the phase of brain oscillations. Such a change in the phase of brain waves is also assumed to underlie the Berger effect: when observers open their eyes, the amplitude of EEG oscillations in the alpha band (8–13 Hz) decreases significantly. This finding is usually thought to involve a desynchronisation of activity in different neurons. For functional interpretations of brain oscillations in the visual system, it therefore seems to be crucial to find out whether or not the phase of brain oscillations can be affected by visual stimuli. To answer this question, we investigated whether alpha waves are generated by a linear or a nonlinear mechanism. If the mechanism is linear – in contrast to nonlinear ones – phases cannot be reset by a stimulus. It is shown that alpha-wave activity in the EEG comprises both linear and nonlinear components. The generation of alpha waves basically is a linear process and flash-evoked potentials are superimposed on ongoing alpha waves without resetting their phase. One nonlinear component is due to light adaptation, which contributes to the Berger effect. The results call into question theories about brain-wave function based on temporal correlation or event-related desynchronisation.Electronic Supplementary Material: Supplementary material is available for this article at     

Electron microscopic evidence for the assembly of soluble pentameric extracellular domains of the nicotinic acetylcholine receptor

Exploitation of soluble extracellular domains (ECDs) of the nicotinic acetylcholine receptor may provide a route to crystallographic studies aimed at exploring the structure and function of the intact receptor. The first step towards this goal is to manufacture and isolate soluble fragments that fold and assemble to form a functionally relevant complex. The baculovirus insect cell expression system was used to co-express soluble ECDs of all four muscle-type nicotinic acetylcholine receptor subunits (alpha, beta, gamma & delta-ECD) from Torpedo. Protein complexes were purified using either the conformationally sensitive monoclonal antibody mAb35, specific for a folded alpha subunit, or a NiNTA affinity resin, specific for a polyhistidine tag engineered on the delta-ECD. Western blotting with subunit specific antibodies confirmed the co-expression of each ECD and furthermore, indicated that the alpha, beta and gamma-ECDs were being co-purified with the polyhistidine-tagged delta-ECD. Chemical cross-linking was used to show that these co-purified proteins had indeed interacted specifically to form soluble oligomeric complexes. A low-resolution, three-dimensional image of these purified complexes, composed only of ECDs, was obtained by electron microscopy. They were shown to resemble the extracellular vestibule of the native receptor, having the same pseudo-pentameric symmetry, size and shape. Expression of incomplete sets of the four nicotinic acetylcholine receptor ECDs did not yield detectable complexes.     

Cortical potential imaging using L-curve and GCV method to choose the regularisation parameter

Background

The electroencephalography (EEG) is an attractive and a simple technique to measure the brain activity. It is attractive due its excellent temporal resolution and simple due to its non-invasiveness and sensor design. However, the spatial resolution of EEG is reduced due to the low conducting skull. In this paper, we compute the potential distribution over the closed surface covering the brain (cortex) from the EEG scalp potential. We compare two methods – L-curve and generalised cross validation (GCV) used to obtain the regularisation parameter and also investigate the feasibility in applying such techniques to N170 component of the visually evoked potential (VEP) data.

Methods

Using the image data set of the visible human man (VHM), a finite difference method (FDM) model of the head was constructed. The EEG dataset (256-channel) used was the N170 component of the VEP. A forward transfer matrix relating the cortical potential to the scalp potential was obtained. Using Tikhonov regularisation, the potential distribution over the cortex was obtained.

Results

The cortical potential distribution for three subjects was solved using both L-curve and GCV method. A total of 18 cortical potential distributions were obtained (3 subjects with three stimuli each – fearful face, neutral face, control objects).

Conclusions

The GCV method is a more robust method compared to L-curve to find the optimal regularisation parameter. Cortical potential imaging is a reliable method to obtain the potential distribution over cortex for VEP data.

     

Multiple parameter comparative EEG analysis in alcoholism and narcotic dependence

Multiparametric comparative analysis of spatial organization of EEG was carried out in 137 alcoholics and 131 heroin addicts. Common and different deviations from normal EEG (105 control subjects) were found. Global alterations of EEG spatial organization were observed in drug addicts (as compared to alcoholics). Such changes characterized increasing synchronizing effects of mesolimbic and brainstem structures on the brain cortex. The ethanol effects were more specific and asymmetric. Changes in EEG spectral-coherence characteristics were revealed in all frequency band, however, maximal changes took place in the high-frequency theta in drug addicts and in narrow-frequency alpha subranges in alcoholics. Different effects on the high-frequency EEG component (19.00-21.25 Hz) and information-energy index (coherence-to-spectral power ratio) suggest the difference influence of ethanol and heroin on emotional-motivational and cognitive processes as well as the level of consciousness. The obtained data on EEG discrimination of alcoholism and drug addiction (the inverse problem solution) on the basis of "specific" EEG patterns appear to have considerable promise in development of systems of occupational selection.     

Changes in the oxygen tension level in different brain structures of rats in the waking-sleep cycle

Changes of oxygen tension level (pO2) in the visual cortex, dorsal hippocampus, lateral hypothalamus and central grey substance were studied during wake-sleep cycle in rats. The dependence was established of pO2 level changes on the character of behavioural reactions and on the accompanying hippocampal EEG activity: during orienting-investigatory and active defensive behaviour and also during paradoxical sleep, accompanied by hippocampal theta rhythm, pO2 level increased; during passive-defensive behaviour "freezing" reaction accompanied by desynchronization of the hippocampal rhythmic, the level of pO2 decreased. The obtained data confirm Routtenberg hypothesis about two relatively independent systems of ascending activation with different types of hippocampal EEG activity and supplement it with a thesis that the activity of these systems is accompanied by different shifts of brain oxidative metabolism.     

Expression and characterization of soluble forms of the extracellular domains of the beta, gamma and epsilon subunits of the human muscle acetylcholine receptor

The nicotinic acetylcholine receptor (AChR) is a ligand-gated ion channel found in muscles and neurons. Muscle AChR, formed by five homologous subunits (alpha2 beta gamma delta or alpha2 beta gamma epsilon), is the major antigen in the autoimmune disease, myasthenia gravis (MG), in which pathogenic autoantibodies bind to, and inactivate, the AChR. The extracellular domain (ECD) of the human muscle alpha subunit has been heterologously expressed and extensively studied. Our aim was to obtain satisfactory amounts of the ECDs of the non-alpha subunits of human muscle AChR for use as starting material for the determination of the 3D structure of the receptor ECDs and for the characterization of the specificities of antibodies in sera from patients with MG. We expressed the N-terminal ECDs of the beta (amino acids 1-221; beta1-221), gamma (amino acids 1-218; gamma1-218), and epsilon (amino acids 1-219; epsilon1-219) subunits of human muscle AChR in the yeast, Pichia pastoris. beta1-221 was expressed at approximately 2 mg.L(-1) culture, whereas gamma1-218 and epsilon1-219 were expressed at 0.3-0.8 mg.L(-1) culture. All three recombinant polypeptides were glycosylated and soluble; beta1-221 was mainly in an apparently dimeric form, whereas gamma1-218 and epsilon1-219 formed soluble oligomers. CD studies of beta1-221 suggested that it has considerable beta-sheet secondary structure with a proportion of alpha-helix. Conformation-dependent mAbs against the ECDs of the beta or gamma subunits specifically recognized beta1-221 or gamma1-218, respectively, and polyclonal rabbit antiserum raised against purified beta1-221 bound to (125)I-labeled alpha-bungarotoxin-labeled human AChR. Moreover, immobilization of each ECD on Sepharose beads and incubation of the ECD-Sepharose matrices with MG sera caused a significant reduction in the concentrations of autoantibodies in the sera, showing specific binding to the recombinant ECDs. These results suggest that the expressed proteins present some near-native conformational features and are thus suitable for our purposes.     

Influence of the extracellular domain size on the dynamic behavior of membrane proteins

The dynamic behavior of plasma membrane proteins mediates various cellular processes such as cellular motility, communication, and signaling. It is widely accepted that the dynamics of the membrane proteins is determined either by the interactions of the transmembrane domain with the surrounding lipids or by the interactions of the intracellular domain with cytosolic components such as cortical actin. Although initiation of different cellular signaling events at the plasma membrane has been attributed to the extracellular domain (ECD) properties recently, the impact of ECDs on the dynamic behavior of membrane proteins is rather unexplored. Here, we investigate how ECD properties influence protein dynamics in the lipid bilayer by reconstituting ECDs of different sizes or glycosylation in model membrane systems and analyzing ECD-driven protein sorting in lipid domains as well as protein mobility. Our data show that increasing the ECD mass or glycosylation leads to a decrease in ordered domain partitioning and diffusivity. Our data reconcile different mechanisms proposed for the initiation of cellular signaling by linking the ECD size of membrane proteins with their localization and diffusion dynamics in the plasma membrane.     

Autologous biological response modification of the gonadotropin receptor

It is generally held with respect to heterotrimeric guanine nucleotide binding protein-coupled receptors that binding of ligand stabilizes a conformation of receptor that activates adenylyl cyclase. It is not formally appreciated if, in the case of G-protein-coupled receptors with large extracellular domains (ECDs), ECDs directly participate in the activation process. The large ECD of the glycoprotein hormone receptors (GPHRs) is 350 amino acids in length, composed of seven leucine-rich repeat domains, and necessary and sufficient for high affinity binding of the glycoprotein hormones. Peptide challenge experiments to identify regions in the follicle-stimulating hormone (FSH) receptor (FSHR) ECD that could bind its cognate ligand identified only a single synthetic peptide corresponding to residues 221-252, which replicated a leucine-rich repeat domain of the FSHR ECD and which had intrinsic activity. This peptide inhibited human FSH binding to the human FSHR (hFSHR) and also inhibited human FSH-induced signal transduction in Y-1 cells expressing recombinant hFSHR. The hFSHR-(221-252) domain was not accessible to anti-peptide antibody probes, suggesting that this domain resides at an interface between the hFSHR ECD and transmembrane domains. CD spectroscopy of the peptide in dodecyl phosphocholine micelles showed an increase in the ordered structure of the peptide. CD and NMR spectroscopies of the peptide in trifluoroethanol confirmed that hFSHR-(221-252) has the propensity to form ordered secondary structure. Importantly and consistent with the foregoing results, dodecyl phosphocholine induced a significant increase in the ordered secondary structure of the purified hFSHR ECD as well. These data provide biophysical evidence of the influence of environment on GPHR ECD subdomain secondary structure and identify a specific activation domain that can autologously modify GPHR activity.     

Factor analysis of interrelations between EEG waves with various frequency ranges in adults and 5-6 year old children]

Statistical interrelations among different amplitude-temporal features of the EEG waves of different frequency bands in adults and 5-6-year old children are determined mainly by two factors. The first one is related to the alpha-wave index and amplitude and the beta-wave index, the second one--to the alpha-wave average period. Adults revealed a higher level of negative correlation between the EEG wave amplitude and index and the theta-wave index than the 5-6-year old children.     

Graph Theoretical Analysis of BOLD Functional Connectivity during Human Sleep without EEG Monitoring

Background

Functional brain networks of human have been revealed to have small-world properties by both analyzing electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) time series.

Methods & Results

In our study, by using graph theoretical analysis, we attempted to investigate the changes of paralimbic-limbic cortex between wake and sleep states. Ten healthy young people were recruited to our experiment. Data from 2 subjects were excluded for the reason that they had not fallen asleep during the experiment. For each subject, blood oxygen level dependency (BOLD) images were acquired to analyze brain network, and peripheral pulse signals were obtained continuously to identify if the subject was in sleep periods. Results of fMRI showed that brain networks exhibited stronger small-world characteristics during sleep state as compared to wake state, which was in consistent with previous studies using EEG synchronization. Moreover, we observed that compared with wake state, paralimbic-limbic cortex had less connectivity with neocortical system and centrencephalic structure in sleep.

Conclusions

In conclusion, this is the first study, to our knowledge, has observed that small-world properties of brain functional networks altered when human sleeps without EEG synchronization. Moreover, we speculate that paralimbic-limbic cortex organization owns an efficient defense mechanism responsible for suppressing the external environment interference when humans sleep, which is consistent with the hypothesis that the paralimbic-limbic cortex may be functionally disconnected from brain regions which directly mediate their interactions with the external environment. Our findings also provide a reasonable explanation why stable sleep exhibits homeostasis which is far less susceptible to outside world.     

Refolding of the Escherichia coli expressed extracellular domain of alpha 7 nicotinic acetylcholine receptor.

Heterologous expression of the extracellular domains (ECDs) of the nicotinic acetylcholine receptor (AChR) subunits may give large amounts of proteins for studying the functional and spatial characteristics of their ligand-binding sites. The ECD of the alpha 7 subunit of the homo-oligomeric alpha 7 neuronal AChR appears to be a more suitable object than the ECDs of other heteromeric neuronal or muscle-type AChRs. The rat alpha 7 ECDs (amino-acid residues approximately 1-210) were recently expressed in Escherichia coli as fusion proteins with maltose-binding protein [Fischer, M., Corringer, P., Schott, K., Bacher, A. & Changeux, J. (2001) Proc. Natl Acad. Sci. USA 98, 3567-3570] and glutathione S-transferase (GST) [Utkin, Y., Kukhtina, V., Kryukova, E., Chiodini, F., Bertrand, D., Methfessel, C. & Tsetlin, V. (2001) J. Biol. Chem. 276, 15810-15815]. However, these proteins exist in solution mostly as high-molecular mass aggregates rather than monomers or oligomers. In the present work it is found that refolding of GST-alpha 7-(1-208) protein in the presence of 0.1% SDS considerably decreases the formation of high-molecular mass aggregates. The C116S mutation in the alpha 7 moiety was found to further decrease the aggregation and to increase the stability of protein solutions. This mutation slightly increased the affinity of the protein for alpha-bungarotoxin (from Kd approximately 300 to 150 nm). Gel-permeation HPLC was used to isolate the monomeric form of the GST-alpha 7-(1-208) protein and its mutant almost devoid of SDS. CD spectra revealed that the C116S mutation considerably increased the content of beta structure and made it more stable under different conditions. The monomeric C116S mutant appears promising both for further structural studies and as a starting material for preparing the alpha 7 ECD in an oligomeric form.     

Sounds reset rhythms of visual cortex and corresponding human visual perception

An event in one sensory modality can phase reset brain oscillations concerning another modality. In principle, this may result in stimulus-locked periodicity in behavioral performance. Here we considered this possible cross-modal impact of a sound for one of the best-characterized rhythms arising from the visual system, namely occipital alpha-oscillations (8-14 Hz). We presented brief sounds and concurrently recorded electroencephalography (EEG) and/or probed visual cortex excitability (phosphene perception) through occipital transcranial magnetic stimulation (TMS). In a first, TMS-only experiment, phosphene perception rate against time postsound showed a periodic pattern cycling at ~10 Hz phase-aligned to the sound. In a second, combined TMS-EEG experiment, TMS-trials reproduced the cyclical phosphene pattern and revealed a ~10 Hz pattern also for EEG-derived measures of occipital cortex reactivity to the TMS pulses. Crucially, EEG-data from intermingled trials without TMS established cross-modal phase-locking of occipitoparietal alpha oscillations. These independently recorded variables, i.e., occipital cortex excitability and reactivity and EEG phase dynamics, were significantly correlated. This shows that cross-modal phase locking of oscillatory visual cortex activity can arise in the human brain to affect perceptual and EEG measures of visual processing in a cyclical manner, consistent with occipital alpha oscillations underlying a rapid cycling of neural excitability in visual areas.     

Relating Alpha Power and Phase to Population Firing and Hemodynamic Activity Using a Thalamo-cortical Neural Mass Model

Oscillations are ubiquitous phenomena in the animal and human brain. Among them, the alpha rhythm in human EEG is one of the most prominent examples. However, its precise mechanisms of generation are still poorly understood. It was mainly this lack of knowledge that motivated a number of simultaneous electroencephalography (EEG) – functional magnetic resonance imaging (fMRI) studies. This approach revealed how oscillatory neuronal signatures such as the alpha rhythm are paralleled by changes of the blood oxygenation level dependent (BOLD) signal. Several such studies revealed a negative correlation between the alpha rhythm and the hemodynamic BOLD signal in visual cortex and a positive correlation in the thalamus. In this study we explore the potential generative mechanisms that lead to those observations. We use a bursting capable Stefanescu-Jirsa 3D (SJ3D) neural-mass model that reproduces a wide repertoire of prominent features of local neuronal-population dynamics. We construct a thalamo-cortical network of coupled SJ3D nodes considering excitatory and inhibitory directed connections. The model suggests that an inverse correlation between cortical multi-unit activity, i.e. the firing of neuronal populations, and narrow band local field potential oscillations in the alpha band underlies the empirically observed negative correlation between alpha-rhythm power and fMRI signal in visual cortex. Furthermore the model suggests that the interplay between tonic and bursting mode in thalamus and cortex is critical for this relation. This demonstrates how biophysically meaningful modelling can generate precise and testable hypotheses about the underpinnings of large-scale neuroimaging signals.     

Variability of the EEG autocorrelation structure in adolescents with schizophrenia spectrum disorders

Quantitative analysis of changes in the autocorrelation structure of EEG short segments (in the range of several seconds) was performed in healthy adolescents (n = 39) and adolescents with schizophrenia spectrum disorders (n = 39). The variability of the EEG autocorrelation structure was shown to be higher in patients with the greatest trend in the frontal leads. It is suggested that psychopathology of the schizophrenia spectrum is accompanied by a break in the mutual determination of cortical neural networks with predominant localization of this process in the frontal areas of the brain cortex.