Suppression of gamma EEG activity as an index of a spreading depression wave in the neocortex of a waking rabbit

A spreading depression (SD) can spontaneously develop in seizures, attacks of migraine, vascular disorders and other pathological states of the brain. However, problems in technique of recording the DC-potential in the neocortex of humans and waking animals substantially restrict the possibilities of studying functional consequences of the SD. In this article, the EEG pattern was studied in detail at the moment of the SD development. Specific features were revealed, which make it possible to detect the SD without recording shifts of the DC-potential. At the moment of the SD arrival, the interhemispheric balance drastically disturbs because of a strong decrease in the high-frequency activity. By the time indices, the course of the suppression of the gammal and gamma2 EEG frequencies is the most reliable symptom of the SD wave development. The EEG spectral power in the delta band increases with a certain delay in reference to the deep depression of the high-frequency activity and is, in essence, an SD aftereffect. The found EEG signs of an SD wave can substantially simplify the identification of this phenomenon both in experiment and clinical conditions in certain pathological states of the brain.     

Spreading depression in a waking rabbit with the spectral EEG analysis

It was shown that the manifestation of the SD phenomenon in dynamics of the cortical high-frequency gamma activity is rather prominent after bipolar interpretation of the common reference electrode derivations, i.e. when the modeling of the bipolar signal on the base of monopolar EEG recordings is used. The SD wave was accompanied by significant decrease in the power of the EEG gamma band (37-47 Hz) in all observed cortical areas. A curve of decline of gamma activity power had distinct fore and back fronts, so the time of SD appearance in different cortex areas and it's spread succession could be well determined. In the long-term experiments SD waves were characterized by normal (i.e. successive) spread through the cortex mainly in initial three-four experiments. In the subsequent tests latency of SD waves in different cortex areas changed and disturbance of propagation became obvious. Sometimes SD arose rapidly (due 0.5-2 min) on the whole dorsal neocortical surface, when the standard injection of the KCI was done. In the most of experiments the delay of the SD wave appearance was prolonged till 6-9 min or no SD wave occur at some cortical regions. Week epileptiform activity could conduct abnormalities in the SD. In many instances electrophysiological signs of the cortical excitability changes were absent. However the modified spatial SD characteristic and spontaneous occurrence of the repeated. SD waves indicated the increased functional inhomogeneities of the neighboring cortical areas. So, spectral EEG analysis in awake rabbits made it possible to characterize the SD wave both in case of its normal propagation through the cortex and in unusual forms of this reaction.     

Developmental changes in the complexity of the electrocortical activity in foetal sheep.

The foetal sheep brain develops organised sleep states from 115-120 d gestational age (dGA, term 150 dGA) alternating between REM and NREM sleep. We aimed to investigate whether maturation of REM or NREM sleep generating structures leads to the development of distinct sleep states. The electrocorticogram (ECoG) was recorded from five unanaesthetised chronically instrumented foetal sheep in utero and was analysed every 5th day between 115-130 dGA by two different non-linear methods. We calculated a non-linear prediction error which quantifies the causality of the ECoG and applied bispectral analysis which quantifies non-linear interrelations of single frequency components within the ECoG signal. The prediction error during REM sleep was significantly higher than during NREM sleep at each investigated age (P<0.0001) coincidental with poor organisation of the rhythmic pattern in the ECoG during REM sleep. At 115 dGA, organised sleep states defined behaviourally were not developed yet. The prediction error, however, showed already different states of electrocortical activity that were not detectable using power spectral analysis. The prediction error of the premature NREM sleep ECoG decreased significantly during emergence of organised sleep states between 115 and 120 dGA and continued to decrease after the emergence of distinct sleep states (P<0.05). The prediction error of the premature REM sleep ECoG did not change until 120 dGA and began to increase at 125 dGA (P<0.05). Using bispectral analysis, we showed couplings between delta waves (1.5-4 Hz) and frequencies in the range of spindle waves (4-8 and 8-12 Hz) during NREM sleep that became closer during development. The results show that maturation of ECoG synchronisation mediating structures is important for the development of organised sleep states. The further divergence of the prediction error of NREM and REM sleep after development of organised sleep states reveals continuous functional development. Thus, complementary application of non-linear ECoG analysis to power spectral analysis provide new insights in the collective behaviour of the neuronal network during the emergence of sleep states.     

The electrophysiological characteristics and behavioral manifestations of hippocampal and thalamic spreading depression]

Behavioral manifestations of spreading depression (SD) were compared with SD electrophysiological characteristics in these structures. Carbon electrodes were suitable for recording DC slow potential changes in freely moving animal. It was shown that short (0.1 s) high-frequency (200 Hz) electrical stimulation of thalamus and hippocampus with intensity 50-300 microA easily triggered SD wave in these structures in narcotized and awake rats. The threshold of SD occurrence in dorsal hippocampus was the same or sometimes lower than that of the primary afterdischarge. Penetrating SD into ventral hippocampus provoked long latency seizure discharge and wet-dog shakings in awake rats. Intensity of locomotor activity accompanying bilateral hippocampal SD exceeded orienting response significantly. Contrary to hippocampus, thalamic SD was usually subseizure and unilateral phenomenon and had a clear tranquil effect on the rat locomotor activity. It was found that the rats didn't change the compartment preference after 20-45 SD waves in the thalamus or in the hippocampus.     

The effect of scopolamine on the spatial organization of rat cortical potentials

The influence of scopolamine (1 mg/kg, i.p.) on the spatial organization of the neocortical electrical activity was studied in rats. A decrease in the spectral power and coherence of brain potentials in the range of the dominant theta-rhythm peak (6.00-7.25 Hz) and their increase in the adjacent low-frequency band were observed. Both indices were decreased in the wide beta band (19.00-30.00 Hz). The described changes took place over the whole areas of the right hemisphere and parieto-temporal region of the left hemisphere. The obtained results are discussed with respect to the role of the cholinergic brain system in the higher nervous activity.     

Emotionality and spatio-temporal organization of momentary EEG potentials

With the aim to reveal features of the neocortical spatiotemporal organization of potentials characteristic of different genetically predetermined emotional levels, momentary values of EEG potentials were analyzed in inbred rats of MR and MNRA strains. A topogram was described by a basic parameter such as its general level (the mean of momentary values of potentials derived from 24 symmetrical electrodes bilaterally implanted into the brain cortex) and a similarity coefficient (correlation between the set of its momentary values and that of a standard topogram). The general level and similarity coefficient values were calculated for a series of successive topograms individually for the right and left hemisphere. Also, right- and left-side power spectra of these series were calculated. In rats of MR strain, significant (p < 0.05) peaks in the general level and similarity coefficient spectra were observed in the delta (2.0 Hz), teta (6.5 Hz) and alpha (9 Hz) frequency bands. In this strain, the general level power was higher at the right side, and the similarity coefficient power displayed the left-side dominance. In rats of MNRA strain, peaks in the delta(2.0 Hz) band coinsided in the general level and similarity coefficient spectra, whereas, independently, the general level spectra had peaks in the theta band (7.0 Hz), and similarity coefficient had peaks at frequencies 3.0, 4.5, and 6.0 Hz. The left-side general level spectral power was higher than the right-side general level spectral power in the delta and lower in the high-frequency theta bands. The similarity coefficient power displayed the left-side dominance for the peaks in the delta (2.0 Hz) and theta (3.0 Hz) bands, and it displayed the right-side dominance for the peaks in the theta (4.5 Hz) band. The specific features of the cortical spatiotemporal organization of potentials revealed in rats of MR and MNRA strains suggest different modes of functioning of at least two systems, reticulo-thalamo-corticaland hippocampo-cortical.     

Unique spectral peak in phrenic nerve activity characterizes gasps in decerebrate cats

The respiratory pattern of gasping has been characterized on the phrenic nerve as rapidonset, rapid-rise, large-amplitude bursts of neural activity. Furthermore, medullary sites critical for the neurogenesis of gasping have been identified and are not the sites of identified respiratory neurons, such as the dorsal and ventral respiratory groups. I classified envelopes of phrenic nerve activity as eupneic breaths, or gasps based on the time-domain features of duration, shape, and amplitude. Gasps were elicited by hypoxia and low blood pressure in 9 of 12 decerebrate cats. Inspiratory times were 1.15 +/- 0.43 (SD) for eupneic breaths and 0.55 +/- 0.18s for gasps. The high-frequency peaks in the power spectra of phrenic nerve activity were at 80 +/- 13 Hz for eupneic breaths and at 120 +/- 21 Hz for gasps. Three of the 12 cats developed a breathing pattern that began as a normal breath and terminated in a gasp. Power spectra of the normal portion had eupneic spectral peaks (75 +/- 24 Hz); power spectra of the gasp portion had the high peaks at 110 +/- 23 Hz, a value 1.5 times higher than that for the normal peaks. Although this analysis of peripheral nerve activity cannot distinguish between two central pattern generators at two distinct anatomical sites or one pattern generator operating in two distinct modes, the fact that gasps were much shorter in duration and had markedly higher spectral peaks than control breaths supports the idea that the central pattern generator for gasping is not the central pattern generator for eupnea.     

Force fluctuations are modulated by alternate muscle activity of knee extensor synergists during low-level sustained contraction.

The study examined the hypothesis that altered synergistic activation of the knee extensors leads to cyclic modulation of the force fluctuations. To test this hypothesis, the force fluctuations were investigated during sustained knee extension at 2.5% of maximal voluntary contraction force for 60 min in 11 men. Surface electromyograms (EMG) were recorded from the rectus femoris (RF), vastus lateralis (VL), and vastus medialis (VM) muscles. The SD of force and average EMG (AEMG) of each muscle were calculated for 30-s periods during alternate muscle activity. Power spectrum of force was calculated for the low- (< or =3 Hz), middle- (4-6 Hz), and high-frequency (8-12 Hz) components. Alternate muscle activity was observed between RF and the set of VL and VM muscles. The SD of force was not constant but variable due to the alternate muscle activity. The SD was significantly greater during high RF activity compared with high VL and VM activity (P < 0.05), and the correlation coefficient between the SD and AEMG was significantly greater in RF [0.736 (SD 0.095), P < 0.05] compared with VL and VM. Large changes were found in the high-frequency component. During high RF activity, the correlation coefficient between the SD and high-frequency component [0.832 (SD 0.087)] was significantly (P < 0.05) greater compared with other frequency components. It is suggested that modulations in knee extension force fluctuations are caused by the unique muscle activity in RF during the alternate muscle activity, which augments the high-frequency component of the fluctuations.     

Regional features of the electrical activity of the neocortex in the dog over a wide range of frequencies

Autospectral characteristics (ASC) of potentials of different neocortical areas of dogs in a state of quiet wakefulness were studied in a wide frequency band (1-100 Hz) by means of correlation-spectral analysis. A transition from evaluation of the mean power tendencies to a construction of distributions of different power levels for each of five arbitrarily chosen frequency bands permitted to reveal regional differences in ASC of each animal as well as interindividual EEG distinctions. The regional differences observed in all frequency bands (though not equally expressed) including the higher ones indicate not only the informativity of high-frequency components of electrical neocortical activity but also their neuronal origin.     

Effect of thyrotropin-releasing hormone (TRH) on EEG topography

EEG topography by a microcomputer system (ATAC-3700 Nihon-Kohden) was performed in the rabbit in order to investigate the mechanism of TRH action on the brain wave. Power spectral analysis was carried out using a fast Fourier transform algorithm. The square root of the power spectra was defined as the equivalent potential over each frequency band by Ueno & Matsuoka's method. Potential fields of EEG frequency band were printed out on the topographic maps. The potentials of the electrocortical delta and theta waves were high, while the potentials of the alpha, beta 1 and beta 2 waves were low. Stimulation of the nucleus ventralis anterior (VA) by 3 Hz and 8 Hz resulted in a decrease in these potentials, especially, those of the alpha, beta 1 and beta 2 waves. The potentials of the alpha and fast waves were increased following unilateral destruction of VA. In the rabbit, in which TRH 0.5 mg/kg had been administered beforehand, there was no decrease in the potential of each wave induced by stimulation of VA with frequencies of 3 Hz and 8 Hz. The findings suggest involvement of the diffuse thalamocortical projection system in the activation of EEG by TRH.     

Neurophysiological and Psychophysiological Effects of Sulpiride in the Norm and in Patients with Opiate Addiction

We studied characteristics of the EEG activity and psychophysiological indices in healthy persons and patients with opiate addiction (in the states of abstinence and remission) before and after peroral introduction of 200 mg sulpiride. In the initial state, spectral characteristics of EEG in patients with opiate addiction differed from those in the control (in healthy tested subjects) by higher relative powers of low- and high-frequency components (delta and beta waves) and a considerable depression of the alpha rhythm. Treatment with sulpiride evoked changes in the spectral characteristics of EEG, which showed a significant intergroup specificity; intensification of alpha oscillations was a general effect in all groups. We conclude that the effects of sulpiride on the EEG activity comprised components typical of both neuroleptics and antidepressants; in the group of patients in the abstinence state, the pattern of effects of sulpiride was close in its profile to the effect of anxiolytics. Dynamics of the indices of psychophysiological testing after sulpiride treatment demonstrated that the drug exerts mostly positive regulating effects on the state of higher nervous functions in patients with opiate addiction.     

Human motor cortical activity is selectively phase-entrained on underlying rhythms

The functional significance of electrical rhythms in the mammalian brain remains uncertain. In the motor cortex, the 12-20 Hz beta rhythm is known to transiently decrease in amplitude during movement, and to be altered in many motor diseases. Here we show that the activity of neuronal populations is phase-coupled with the beta rhythm on rapid timescales, and describe how the strength of this relation changes with movement. To investigate the relationship of the beta rhythm to neuronal dynamics, we measured local cortical activity using arrays of subdural electrocorticographic (ECoG) electrodes in human patients performing simple movement tasks. In addition to rhythmic brain processes, ECoG potentials also reveal a spectrally broadband motif that reflects the aggregate neural population activity beneath each electrode. During movement, the amplitude of this broadband motif follows the dynamics of individual fingers, with somatotopically specific responses for different fingers at different sites on the pre-central gyrus. The 12-20 Hz beta rhythm, in contrast, is widespread as well as spatially coherent within sulcal boundaries and decreases in amplitude across the pre- and post-central gyri in a diffuse manner that is not finger-specific. We find that the amplitude of this broadband motif is entrained on the phase of the beta rhythm, as well as rhythms at other frequencies, in peri-central cortex during fixation. During finger movement, the beta phase-entrainment is diminished or eliminated. We suggest that the beta rhythm may be more than a resting rhythm, and that this entrainment may reflect a suppressive mechanism for actively gating motor function.     

31P NMR of Mg-ATP in dilute solutions: complexation and exchange.

1. Monovalent-cation [(CH3)4N+, K(I), Na(I)] ATP, 1 mM in nucleotide, in aqueous solutions at pH 7.2, 24 degrees C, generates 2 different 31P NMR spectra, depending upon the salt content of the solution. At salt concentrations below 10 mM, the 31P NMR signals are chemically-shifted upfield (Na salt: alpha, -11.44 delta; beta, -22.91 delta; gamma, -8.36 delta) and the beta- and gamma-groups are broadened (at half-height: alpha, 3.5 Hz; beta, 9.6 Hz; gamma, 69 Hz). Above 10 mM salt, the signals are shifted downfield and are narrow (Na salt: alpha, -11.09 delta, 1.9 Hz; beta, -21.75 delta, 3.3 Hz; gamma, -6.30 delta, 3.9 Hz). 2. The Na-Mg-ATP complex, corresponding to the composition Na6Mg1ATP2, yields a single set of 31P resonances at concentrations of nucleotide of 100 mM, that upon dilution to 0.2 mM, resolve into 2 sets of ATP resonances characterized by low-field and high-field beta- and gamma-group resonance pairs. This set of ATP resonances, in contrast to the resonance set at 100 mM ATP, are broad (100 mM in ATP: alpha, -10.7 delta, 3.7 Hz; beta, -20.1 delta, 15 Hz; gamma, -5.7 delta, 7.3 Hz. 0.2 mM in ATP: alpha, -10.7 delta, 47 Hz; beta, -18.8 and -21.6 delta, 316 and 274 Hz; gamma, -5.5 and -8.7 delta, 460 and 374 Hz). 3. This new data, in combination with data derived from a survey of metal-ion-ATP studies, are interpreted in terms of ATP dimers, incorporating 2 molecules of ATP and 2 metal cations, that exist in water under the physiological conditions of neutral pH, high salt content [135 mM K(I)] and ATP concentrations in the range of 3 mM. 4. A compilation of 31P in vivo and ex vivo data compared to a reference Mg-ATP chemical shift vs Mg/ATP ratio plot indicates that ATP is not fully Mg-saturated in living systems and that 41% exists as the Mg(ATP)2 complex.     

Spectral characteristics of skin sympathetic nerve activity in heat-stressed humans

Skin sympathetic nerve activity (SSNA) exhibits low- and high-frequency spectral components in normothermic subjects. However, spectral characteristics of SSNA in heat-stressed subjects are unknown. Because the main components of the integrated SSNA during heat stress (sudomotor/vasodilator activities) are different from those during normothermia and cooling (vasoconstrictor activity), we hypothesize that spectral characteristics of SSNA in heat-stressed subjects will be different from those in subjects subjected to normothermia or cooling. In 17 healthy subjects, SSNA, electrocardiogram, arterial blood pressure (via Finapres), respiratory activity, and skin blood flow were recorded during normothermia and heat stress. In 7 of the 17 subjects, these variables were also recorded during cooling. Spectral characteristics of integrated SSNA, R-R interval, beat-by-beat mean blood pressure, skin blood flow variability, and respiratory excursions were assessed. Heat stress and cooling significantly increased total SSNA. SSNA spectral power in the low-frequency (0.03-0.15 Hz), high-frequency (0.15-0.45 Hz), and very-high-frequency (0.45-2.5 Hz) regions was significantly elevated by heat stress and cooling. Interestingly, heat stress caused a greater relative increase of SSNA spectral power within the 0.45- to 2.5-Hz region than in the other spectral ranges; cooling did not show this effect. Differences in the SSNA spectral distribution between normothermia/cooling and heat stress may reflect different characteristics of central modulation of vasoconstrictor and sudomotor/vasodilator activities.     

Spectral and coherence EEG analysis of rats differing in the level of seizure readiness

The resting EEGs of several brain structures (motor and visual cortex, caudate nucleus and intralaminar thalamic nuclei) were submitted to spectral and coherence computer analyses in two rat strains. Genetically predisposed to convulsive state KM rats were shown to differ from nonpredisposed Wistar rats in EEG spectral properties. KM rats EEG pattern was characterized by increase of low frequencies (1-2 Hz) power and decrease of faster activity (5-12 Hz) power in cortical spectrograms as well as by decrease of caudate nucleus EEG absolute power. The coherence value between cortical or subcortical structures at below 4 Hz was intensified in KM rats. Reinforcement of cortical auto-oscillating properties manifested by ECoG synchronization in cortical-thalamic resonance interaction as well as weakening of striatal inhibitory system may constitute neurophysiological mechanisms of enhanced convulsive readiness. The probable role of mediator imbalance in these mechanisms is discussed.     

Regional features of electrical reactions (in the frequency band of 1-225 Hz) in the cerebral cortex to conditioned stimuli in the course of instrumental conditioning

Power spectra of short-term (less than 1 s) EEG-reactions (in the frequency band of 1-225 Hz) were studied in dogs in the course of instrumental food conditioning. These reactions were observed in different areas of the cortex in response to positive and differentiated conditioned stimuli. Regional features between the spectra were found both in the power level and frequency structure. The power of the reactions in the visual and parietal areas of the left hemisphere was higher than in the motor areas. Power spectra of reactions to differentiated stimuli were significantly lower than the spectra of reactions to positive stimuli mainly owing to the high-frequency components (80-225 Hz). In these both cases, prestimulus power spectra did not differ. The frequency structure of corresponding EEG-reactions consisted of individual spectral peaks, mainly both gamma (30-80 Hz) and higher-frequency (80-225 Hz) bands.     

Selective attention in dogs from energy characteristics of neocortical potentials in the 1-220 Hz band

The state of selective attention was studied in dogs in the course of instrumental conditioning. During interstimuli intervals, this state was manifested in the state of strained waiting for conditioned stimuli. Electrical activity of different areas in both hemispheres was analyzed using the Fast Fourier Transformation. It was shown that in the process of development of selective attention, the high-frequency EEG components (40-200 Hz) in the motor area of the right hemisphere and the visual and parietal areas of the left hemisphere had a predominant significance over the traditional EEG frequencies of 1-30 Hz. The state of selective attention was characterized by another functional mosaic organization of the neocortical potentials.     

Subclinical exposure to low-dose endotoxin impairs EEG maturation in preterm fetal sheep

Exposure to chorioamnionitis is strongly associated with neurodevelopmental disability after premature birth; however, it remains unclear whether subclinical infection affects functional EEG maturation. Chronically instrumented 103-104-day-old (0.7 gestational age: term 147 days) fetal sheep in utero were randomized to receive either gram-negative LPS by continuous low-dose infusion (100 ng iv over 24 h, followed by 250 ng/24 h for 4 days; n = 6) or the same volume of normal saline (n = 9). Arterial plasma cortisol, ACTH, and IL-6 were measured. The delta (0-3.9 Hz), theta (4-7.9 Hz), alpha (8-12.9 Hz), and beta (13-22 Hz) components of the EEG were determined by power spectral analysis. Brains were taken after 10 days for histopathology. There were no changes in blood gases, cardiovascular variables, or EEG power during LPS infusion, but a transient rise in plasma cortisol and IL-6 (P < 0.05). LPS infusion was associated with loss of the maturational increase to higher frequency activity, with reduced alpha and beta power, and greater delta power than saline controls from 6 to 10 days (P < 0.05). Histologically, LPS was associated with increased numbers of microglia and TNF-α-positive cells in the periventricular white matter and frontoparietal cortex, increased caspase-3-positive cells in white matter, but no loss of CNPase-positive oligodendrocytes, Nurr-1 subplate cells, or gyral complexity. These data suggest that low-dose endotoxin exposure can impair EEG maturation in preterm fetal sheep in association with neural inflammation but without hemodynamic disturbances or cortical injury.     

Groups of passive and active control state in longitudinal experiments: an electrophysiological study

Long-term electrophysiological experiments were carried out with rats with chronically implanted electrodes into dopaminergic brain structures. Within 4 weeks after surgery, the relative spectral power of electrical activity in the delta1 and delta2 frequency bands decreased, while the relative spectral power in the alpha, beta1 and beta2 bands increased. A delayed (to the 4-5th week after surgery) increase in the total amount of sleep and REM sleep percent was observed in the sleep architecture of these animals. Multiple (during 2 weeks daily) intraperitoneal saline injections altered the dynamic of electrophysiological indices on the 2nd-3rd postsurgery weeks. The total sleep amount being not increased, the total and mean REM sleep durations increased, and the dynamic of the relative spectral power of electrical activity in the dopaminergic brain structures in the delta1, alpha and beta2 bands was found to be changed.