Physiology-based modeling of cortical auditory evoked potentials

Evoked potentials are the transient electrical responses caused by changes in the brain following stimuli. This work uses a physiology-based continuum model of neuronal activity in the human brain to calculate theoretical cortical auditory evoked potentials (CAEPs) from the model’s linearized response. These are fitted to experimental data, allowing the fitted parameters to be related to brain physiology. This approach yields excellent fits to CAEP data, which can then be compared to fits of EEG spectra. It is shown that the differences between resting eyes-open EEG and standard CAEPs can be explained by changes in the physiology of populations of neurons in corticothalamic pathways, with notable similarities to certain aspects of slow-wave sleep. This pilot study demonstrates the ability of our model-based fitting method to provide information on the underlying physiology of the brain that is not available using standard methods.     

Features of the stress reaction in rats with genetically-determined emotionality (from EEG indicators)]

The features of the EEG spatial organization in two rat strains, i.e., with expressed emotional reactions (Maudsley reactive, MR) and less reactive (Maudsley nonreactive, MNR) were compared in two stress situations: during exposure to the action of pain (P) (i.p. injection of 0.9% NaCl solution) and during 24-hour water deprivation (D). Multichannel EEG recording (24 derivations) and their multiparametric estimation (840 signs) made it possible to differentiate characteristic features of the EEG spatial organization in rats with initially increased emotional reactions and passive behavioral strategy during exposure to stress. In both stress-inducing conditions, an increase in crosscorrelation and coherence between cortical potentials in parallel with rise of the spectral power in the range of high-frequency theta and its drop in the range of EEG high-frequency band was observed in the MR rats. The MNR rats showed the opposite changes. Different reactivity of the ratio between the coherence and spectral power of potentials was observed in two strains of rats. This index characterizes the level of the information-energy component of the spatial organization of cortical potentials. It is suggested that different character of the EEG changes reflects the features of interhemispheric relations, information-energy processes, and cortical regulation of autonomic processes in the system of adaptive stress reactions at different levels of emotionality and behavioral strategy.     

Cortical positive potentials in the period of eye fixation prior to saccades and antisaccades

The EEG of 10 right-handed healthy subjects preceding saccade and antisaccade with mean values of latency in the eye fixations period were selected and averaged. The positive potential P2 appearing on the fixation stimuly switching on and slow positive wave following after it were more prominent before antisaccades than normal saccades. Space-temporal analyses of presaccadic potentials showed that right frontal cortex was activated more before antisaccades. These findings suggest that right cortical hemisphere dominate in spatial attention and inhibition of automatic saccades to visual stimuli in the period of antisaccades preparing. During the period of central fixations "intermediate" positivity potentials, developing in 600-400 ms prior to saccade or antisaccade onset, were find out. These potentials were predominantly recorded in the left frontal and frontosagittal cortical areas. The obtained evidence suggest that "intermediate" positive potentials a period related to the process of motor attention, anticipation and decision making in the period of eyes fixation.     

EEG coherence during unconscious visual set under conditions of increased motivation of subjects

Prestimulus EEG was recorded in the state of "operative rest" after the instruction and at the stages of formation, actualization, and extinction of unconscious visual set to perception of unequal circles. Two motivation conditions were used: (1) subjects were promised to be rewarded with a small money price for each correct response (a "general" rise of motivation) and (2) only correct assessments of stimuli of a certain kind were rewarded (a "selective" rise of motivation). In both conditions, additional motivation of subjects to the results of their performance led to an increase in EEG coherence most pronounced in the theta and alpha 1 frequency ranges in the left temporal area of the cortex. During the "general" rise of motivation the EEG coherence (as compared to the control group) was higher in a greater number of derivation pairs than during the "selective" rise. EEG coherence in "motivated" subjects was increased already at the stage of operative rest. Later on, at the set stages, no significant changes were revealed. Thus, the realized set formed by the verbal instruction, which increased motivation of subjects to the results of their performance, produced substantially more prominent changes in coherence of cortical potentials than the unconscious set formed during perception of visual stimuli.     

Changes in the functional parameters of the brain structures under the influence of enkephalin-like tetrapeptidamide

In complex neurophysiological and cytobiochemical study single injections of tetrapeptide amide (TPA) caused a short-term analgetic effect which manifested itself in the absence of motor reactions and EEG changes of cortical and subcortical brain structures after painful stimulation of extremities. This effect was accompanied by changes of some indices of transmitter (monoamine oxidase) and protein metabolism in the cerebral hemispheres at cellular and subcellular levels. In 30-40 min after a TPA injection, EEG suppression and absence of EPs to light flashes were observed in cortical and subcortical structures. Simultaneously motor disorders developed. The observed EEG changes had an undulatory character: on the second day EEGs were restored and on the third day--suppressed once again. This period of TPA action was accompanied by varied changes of the investigated types of metabolism. The question of the necessity of systemic approach to the study of TPA action is discussed, as such an approach allows to reveal complex neurophysiological and fine biochemical relations in the reactions of brain structures and in animal behaviour.     

Positive potentials of the human brain at different stages of preparation of a visually triggered saccade

The EEG of 10 right-handed subjects preceding saccades with mean values of latent periods were selected and averaged. Two standard paradigms of presentation of visual stimuli (central fixation stimulus-peripheral target succession): with a 200-ms inerstimulus interval (GAP) and successive single step (SS). During the period of central fixation, two kinds of positive potentials were observed: fast potentials of "inermediate" positivity (IP) developing 600-400 ms prior to saccade onset and fast potentials of "leading" positivity (LP), which immediately preceded the offset of the central fixation stimulus. Peak latency of the LP potentials was 300 ms prior to saccade onset in the SS paradigm and 400 ms in the GAP paradigm. These potentials were predominantly recorded in the frontal and frontosagittal cortical areas. Decrease in the latency by 30-50 ms in the GAP paradigm was associated with more pronounced positive potentials during the fixation period and absence of the initiation potential P-1' (or decrease in its amplitude). The obtained evidence suggest that the fast positive presaccadic potentials are of a complex nature related to attention, anticipation, motor preparation, decision making, saccadic initiation, and backward afferentation.     

Electroencephalographic study of iron-induced chronic focal cortical epilepsy in rat: propagation of cortical epileptic activity to substantia nigra and thalamus.

Cortical epileptic focus was produced by an intracortical injection of FeCl3 in rat cerebral cortex using standard techniques. How after its onset in the cortical focus, the epileptiform activity evolved with time in the thalamus and substantia nigra has been determined. To study the propagation of the epileptiform activity, the local EEG and multiple unit action potentials were recorded from these structures simultaneously with the cortical epileptiform EEG. The results showed that in thalamus and substantia nigra epileptiform activity appeared simultaneously with that in the cortical focus. Intensity of epileptic activity in thalamus and substantia nigra on the whole increased in parallel with that in the cortical focus. The results suggest that the thalamic and nigral epileptiform activity may reinforce the cortical epileptiform activity.     

Loss of cortical function in mice after decapitation, cervical dislocation, potassium chloride injection, and CO2 inhalation

Electroencephalograms (EEG) and visual evoked potentials (VEP) in mice were recorded to evaluate loss of cortical function during the first 30 s after euthanasia by various methods. Tracheal cannulae (for positive-pressure ventilation, PPV) and cortical surface electrodes were placed in mice anesthetized with inhaled halothane. Succinylcholine was used to block spontaneous breathing in the mice, which then underwent continuous EEG recording. Photic stimuli (1 Hz) were presented to produce VEPs superimposed on the EEG. Anesthesia was discontinued immediately before euthanasia. Compared with that obtained before euthanasia, EEG activity during the 30-s study period immediately after euthanasia was significantly decreased after cervical dislocation (at 5 to 10 s), 100% PPV-CO2 (at 10 to 15 s), decapitation (at 15 to 20 s), and cardiac arrest due to KCl injection (at 20 to 25 s) but not after administration of 70% PPV-CO2. Similarly, these euthanasia methods also reduced VEP amplitude, although 100% PPV-CO2 treatment affected VEP amplitude more than it did EEG activity. Thus, 100% PPV-CO2 treatment significantly decreased VEP beginning 5 to 10 s after administration, with near abolition of VEP by 30 s. VEP amplitude was significantly reduced at 5 to 10 s after cervical dislocation and at 10 to 15 s after decapitation but not after either KCl or 70% PPV-CO2 administration. The data demonstrate that 100% PPV-CO2, decapitation, and cervical dislocation lead to rapid disruption of cortical function as measured by 2 different methods. In comparison, 70% PPV-CO2 and cardiac arrest due to intracardiac KCl injection had less rapid effects on cortical function.     

Reticular activation and the dynamics of neuronal networks

It is postulated that during arousal the cortical system is driven by a spatially and temporally noisy signal arising from non-specific reticulo-cortical pathways. An elementary unit of cortical neuroanatomy is assumed, which permits non-linear dynamics to be represented by stochastic linear equations. Under these assumptions the resonant modes of the system of cortical dendrites approach thermodynamic equilibrium. Specific sensory signals perturb the dendritic system about equilibrium, generate low frequency, linear, non-dispersive waves corresponding to the EEG, which in turn regulate action potential sequences, and instantiate internal inputs to the dendritic field. A large and distributed memory capacity in axo-synaptic couplings, resistance to interference between functionally separate logical operations, and a very large next-state function set emerge as properties of the network. The model is able to explain the close association of the EEG with cognition, the channel of low capacity corresponding to the field of immediate attention, the low overall correlation of action potentials with EEG, and specificity of action potentials in some neurons during particular cognitive activity. Predictions made from hypothesis include features of thermal equilibrium in EEG (determinable by autoregression) and expectation that the cortical evoked response can be accounted for as the response to a sensory impulse of specific time characteristics.     

Electrical activity of the visual cortex under conditions of altered monoamine levels in the brain of animals

In experiments on 8 rabbits and 12 rats changes in electrograms of the visual cortex of alert animals were studied under photic stimulation in conditions of pharmacological action on monoamine (MA) brain systems. After injection of MA precursors (5-oxitriptophane and d, 1-dioxiphenylalanine) following phenomena were observed: a) decrease of the amplitude of the averaged evoked potentials to rhythmic photic stimuli (1-20 imp. sec.-1); b) an enhancement of fast (15-25 Hz) oscillations in the cortical spontaneous electrical activity and weakening and modification of the effects of the blockader of synthesis of MA-alpha-methyl-dioxiphenylalanine. Under light stimulation potentiation of MA precursors effects was observed in the frequency spectra of electrocorticograms. In the same conditions the specificity of action of cathecholamines precursor was revealed in the form of an increase of power of rhythms of 5-7 Hz and it; decrease in 2-3 Hz. Possible mechanisms of the revealed phenomena are discussed.     

Changes in EEG power, acoustic evoked potentials and heart rate after mildly arousing non-acoustic priming stimuli in carp (Cyprinus carpio).

1. Changes in EEG power spectrum of carp to a priming non-acoustic stimulus followed by acoustic clicks were compared to those due to acoustic clicks delivered alone. Recordings were made from the telencephalon, midbrain and medulla. Acoustic evoked potentials (AEPs) to the clicks were also recorded. 2. EEG power changes to non-acoustic stimuli occurred over the whole 1-40 Hz frequency range and were regionally specific and consistent. 3. The changes in the EEG midfrequency 12-24 Hz power spectrum to non-acoustic stimuli were significantly correlated with changes in the AEP to subsequent clicks. An elevated medullary AEP amplitude and reduced duration were correlated with increased medullary EEG power and increased midbrain AEP duration. 4. Telencephalic EEG power changes were inversely related to changes in medullary and midbrain AEP amplitude.     

EEG power spectrum analysis for monitoring depth of anaesthesia during experimental surgery

The first attempts to introduce computerized power spectrum analysis of the electroencephalogram (EEG) as an intraoperative anaesthesia monitoring device started approximately 30 years ago. Since that time, the effects of various anaesthetic agents, sedative and analgesic drugs on the EEG pattern have been addressed in numerous studies in human patients and different animal species. These studies revealed dose-dependent changes in the EEG power spectrum for many intravenous and volatile anaesthetics. Moreover, EEG responses evoked by surgical stimuli during relative light levels of surgical anaesthesia have been classified as 'arousal' and 'paradoxical arousal' reaction, previously referred to as 'desynchronization' and 'synchronization', respectively. Contrasting reports on the correlation between quantitative EEG (QEEG) variables derived from power spectrum analysis (i.e. spectral edge frequency, median frequency) and simultaneously recorded clinical signs such as movement and haemodynamic responses, however, limited the routine use of intraoperative EEG monitoring. In addition, the appearance of EEG burst suppression pattern and isoelectricity at clinically relevant concentrations/doses of newer general anaesthetics (i.e. isoflurane, sevoflurane, propofol) may have weakened the dose-related EEG changes previously reported. Despite these findings, the EEG power spectrum analysis may still provide valuable information during intraoperative monitoring in the individual subject. The information obtained from EEG power spectrum analysis may be further supplemented by newer EEG indices such as bispectral index and approximate entropy or other neurophysiological monitors including auditory evoked potentials or somatosensory evoked potentials.     

Neurophysiological effects of recombinant interferon-gamma and -alpha in man

Treatment of malignant tumors with interferon (IFN) is in some patients accompanied by serious neurological side effects. The present study assessed neurophysiological changes in spontaneous EEG activity, visual-evoked cortical potentials (VEPs), and brainstem auditory-evoked potentials (BAEPs) during IFN-gamma or IFN-alpha therapy in 9 patients. In addition, blood pressure, heart rate and body temperature were monitored. In all sessions under IFN, the latency of the P100 component of the VEP was shortened as compared to baseline conditions. IFN also reduced latencies of BAEP components, and diminished amplitudes of the spontaneous EEG activity within the alpha and beta frequency band. These latter effects were somewhat less consistent than those on VEPs. The major neurophysiological changes appeared to be similar for IFN-gamma and IFN-alpha. The results are in accord with an excitatory effect of IFN on central nervous activity. The magnitude of changes excludes a neurotoxicity of IFN-gamma or IFN-alpha at the doses used in this study.     

Electroencephalographic brain dynamics following manually responded visual targets

Scalp-recorded electroencephalographic (EEG) signals produced by partial synchronization of cortical field activity mix locally synchronous electrical activities of many cortical areas. Analysis of event-related EEG signals typically assumes that poststimulus potentials emerge out of a flat baseline. Signals associated with a particular type of cognitive event are then assessed by averaging data from each scalp channel across trials, producing averaged event-related potentials (ERPs). ERP averaging, however, filters out much of the information about cortical dynamics available in the unaveraged data trials. Here, we studied the dynamics of cortical electrical activity while subjects detected and manually responded to visual targets, viewing signals retained in ERP averages not as responses of an otherwise silent system but as resulting from event-related alterations in ongoing EEG processes. We applied infomax independent component analysis to parse the dynamics of the unaveraged 31-channel EEG signals into maximally independent processes, then clustered the resulting processes across subjects by similarities in their scalp maps and activity power spectra, identifying nine classes of EEG processes with distinct spatial distributions and event-related dynamics. Coupled two-cycle postmotor theta bursts followed button presses in frontal midline and somatomotor clusters, while the broad postmotor "P300" positivity summed distinct contributions from several classes of frontal, parietal, and occipital processes. The observed event-related changes in local field activities, within and between cortical areas, may serve to modulate the strength of spike-based communication between cortical areas to update attention, expectancy, memory, and motor preparation during and after target recognition and speeded responding.     

New perspectives in brain information processing

Brain cortex activity, as variously recorded by scalp or cortical electrodes in the electroencephalography (EEG) frequency range, probably reflects the basic strategy of brain information processing. Various hypotheses have been advanced to interpret this phenomenon, the most popular of which is that suitable combinations of excitatory and inhibitory neurons behave as assemblies of oscillators susceptible to synchronization and desynchronization. Implicit in this view is the assumption that EEG potentials are epiphenomena of action potentials, which is consistent with the argument that voltage variations in dendritic membranes reproduce the postsynaptic effects of targeting neurons. However, this classic argument does not really fit the discovery that firing synchronization over extended brain areas often appears to be established in about 1 ms, which is a small fraction of any EEG frequency component period. This is in contrast with the fact that all computational models of dynamic systems formed by more or less weakly interacting oscillators of near frequencies take more than one period to reach synchronization. The discovery that the somatodendritic membranes of specialized populations of neurons exhibit intrinsic subthreshold oscillations (ISOs) in the EEG frequency range, together with experimental evidence that short inhibitory stimuli are capable of resetting ISO phases, radically changes the scheme described above and paves the way to a novel view. This paper aims to elucidate the nature of ISO generation mechanisms, to explain the reasons for their reliability in starting and stopping synchronized firing, and to indicate their potential in brain information processing. The need for a repertoire of extraneuronal regulation mechanisms, putatively mediated by astrocytes, is also inferred. Lastly, the importance of ISOs for the brain as a parallel recursive machine is briefly discussed.     

The phases of visual cortex and hippocampal evoked potentials in rabbit reflect the orienting reaction in case of visual stimuli intensity changes

The oddball paradigm was applied in experiments with waking rabbits using rare (deviant) and frequent (standard) stimuli, which were similar in color but different in intensity, deviant ones being of lower intensity. In addition, the VEPs to the single deviants were averaged. Such single deviants (without standard stimuli) were given at the beginning and at the end of the stimulation. The positivity of cortical and hippocampal visual evoked potentials to deviant stimuli increased in comparison to responses to standards and single deviants. The VEP-peaks P1 and P2 in the visual cortex and the VEP P1, N1 and P2 peaks in hippocampus increased. The most prominent significant changes were demonstrated for cortical VEP P2 (P130) peak. It is suggested that the increase of positivity to oddball deviants is due to the orienting reflex arising in response to rare stimuli. The increase of P2-peak can be connected with the transfer of information signaling changes of light intensity. It was demonstrated that the most clear and contrast differences in the VEPs to deviants and standards took place for the case of minimal distinction in their intensities. This fact may reflect the orienting reactionto threshold stimuli.     

Complex, multifocal, individual-specific attention-related cortical functional circuits

Recent studies focusing on the analysis of individual patterns of non-sensory-motor CNS activity may significantly alter our view of CNS functional mapping. We have recently provided evidence for highly variable attention-related Slow Potential (SP) generating cortical areas across individuals (Basile et al., 2003, 2006). In this work, we present new evidence, searching for other physiological indexes of attention by a new use of a well established method, for individual-specific sets of cortical areas active during expecting attention. We applied latency corrected peak averaging to oscillatory bursts, from 124-channel EEG recordings, and modeled their generators by current density reconstruction. We first computed event-related total power, and averaging was based on individual patterns of narrow task-induced band-power. This method is sensitive to activity out of synchrony with stimuli, and may detect task-related changes missed by regular Event-Related Potential (ERP) averaging. We additionally analyzed overall inter-electrode phase-coherence. The main results were (1) the detection of two bands of attention-induced beta range oscillations (around 25 and 21 Hz), whose scalp topography and current density cortical distribution were complex multi-focal, and highly variable across subjects, including prefrontal and posterior cortical areas. Most important, however, was the observation that (2) the generators of task-induced oscillations are largely the same individual-specific sets of cortical areas active during the resting, baseline state. We concluded that attention-related electrical cortical activity is highly individual-specific (significantly different from sensory-related visual evoked potentials or delta and theta induced band-power), and to a great extent already established during mere wakefulness. We discuss the critical implications of those results, in combination with other studies presenting individual data, to functional mapping: the need to abandon group averaging of task-related cortical activity and to revise studies on group averaged data, since the assumption of universal function to each cortical area appears deeply challenged. Clinical implications regard the interpretation of focal lesion consequences, functional reorganization, and neurosurgical planning.     

Persistence of Cortical Sensory Processing during Absence Seizures in Human and an Animal Model: Evidence from EEG and Intracellular Recordings

Absence seizures are caused by brief periods of abnormal synchronized oscillations in the thalamocortical loops, resulting in widespread spike-and-wave discharges (SWDs) in the electroencephalogram (EEG). SWDs are concomitant with a complete or partial impairment of consciousness, notably expressed by an interruption of ongoing behaviour together with a lack of conscious perception of external stimuli. It is largely considered that the paroxysmal synchronizations during the epileptic episode transiently render the thalamocortical system incapable of transmitting primary sensory information to the cortex. Here, we examined in young patients and in the Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a well-established genetic model of absence epilepsy, how sensory inputs are processed in the related cortical areas during SWDs. In epileptic patients, visual event-related potentials (ERPs) were still present in the occipital EEG when the stimuli were delivered during seizures, with a significant increase in amplitude compared to interictal periods and a decrease in latency compared to that measured from non-epileptic subjects. Using simultaneous in vivo EEG and intracellular recordings from the primary somatosensory cortex of GAERS and non-epileptic rats, we found that ERPs and firing responses of related pyramidal neurons to whisker deflection were not significantly modified during SWDs. However, the intracellular subthreshold synaptic responses in somatosensory cortical neurons during seizures had larger amplitude compared to quiescent situations. These convergent findings from human patients and a rodent genetic model show the persistence of cortical responses to sensory stimulations during SWDs, indicating that the brain can still process external stimuli during absence seizures. They also demonstrate that the disruption of conscious perception during absences is not due to an obliteration of information transfer in the thalamocortical system. The possible mechanisms rendering the cortical operation ineffective for conscious perception are discussed, but their definite elucidation will require further investigations.     

Significance of presetting an analyzer system in discriminating light intensity in the cat

EEG and behavioural reactions were studied at the action of signal and nonsignal light flashes. The minimal time of stimulus exposition necessary for preserving differences in EEG activation reactions to nonreinforced stimuli of different intensity (in a diapason from 3.5 to 250 lk) was shown to exceed 1 s. After giving the signal meaning to the flashes the minimal time of stimulus exposition when the animals were capable to discriminate intensity of the flashes (in a diapason from 3.5 to 30 lk) just at the first presentation, was equal to 0.1 s. Decrease of the minimal time of stimulus exposition necessary for discrimination of the light signals was supposed to be stipulated by their biological significance and presetting of the analyzing system being organized by preliminary learning a crude analysis of stimuli. Discrimination of the light stimuli of short duration was impossible without such presetting.     

The mechanism of action of a reinforcing stimulus]

Experiments on alert non-immobilized rabbits revealed that electrical cutaneous stimulation of a limb, used as a reinforcing agent in elaboration of a conditioned reflex to photic flashes, weakened slow polyrhythmic oscillations of background EEG and late components of evoked potentials in the visual cortex to photic flashes. Against this background, the connection between slow potentials and spike activity in both the visual and sensorimotor cortical areas considerably diminished. During EEG activation, induced by the reinforcing stimulus, inhibitory pauses and post-inhibitory activation in the firing of the neocortical units weakened and protracted, ordered spike activity appeared. The data obtained are in agreement with the hypothesis that weakening of the recurrent inhibition system is one of the basic mechanisms in the action of the reinforcing stimulus in conditioning.