Neurophysiological analysis of the correction by nootropic substances of disorders in the bioelectric activity of the brain in animals during chronic administration of ethanol

The influence of some drugs (piracetam and 3-oxypyridine derivative) having a nootropic effect on ethanol-induced changes of bioelectrical activity was studied in experiments on freely moving rats. Discontinuation of ethanol administration (1, 2 g/kg, i.p. for 40 days) has been found to provoke destructuring of Fourier's spectral power of sensorimotor cortex and dorsal hippocamp on the EEG. Long-term administration of piracetam or 3-oxypyridine derivative (300 and 50 mg/kg, respectively, i.p. for 40 days) with ethanol has a protective effect and normalizes EEG at the cortical level. The authors discuss possible neurophysiological mechanisms of nootropic drug action in ethanol-induced pathology.     

Effect of anticholinergic drugs alone and in combination with nembutal on burst theta-neurons of the rabbit septum

Activity of neurones with rhythmic theta-bursts was recorded in the medial septum--diagonal band complex of the waking rabbits with intact and deafferented septum. Effects of anticholinergic (scopolamine, atropine) and cholinomimetic (physostigmine) drugs were investigated after i.v. injection. Cholinoblocking drugs in doses, suppressing the theta-rhythm in the hippocampal EEG, eliminated rhythmic activity in some cells with weak theta-modulation. Theta-bursts persisted in cells with stable continuous rhythmicity, though its regularity decreased in some of them. Strong reticular or sensory stimulation evoked an increase of burst frequency, involvement of additional septal cells into rhythmic activity and appearance of the theta-rhythm in the hippocampal EEG. Neither anticholinergic, nor cholinomimetic drugs influenced the frequency and basic characteristics of theta-bursts in any condition tested. The anticholinergic drugs have no selective effect upon low-frequency theta-bursts. The septohippocampal connections contain a significant non-cholinergic component. The theoretical concept of the septum as a sole source of the whole frequency band of the theta-rhythm is proposed.     

Neurophysiological indices of CNS plasticity in the course of treatment of head trauma in adolescents

Using the methods of quantitative EEG analysis and cognitive evoked potentials, we investigated delayed consequences of head trauma (HT) after nootropic therapy with cerebrolysin. The study was performed in 30 12-to 19-year-old adolescents who had had severe HT with brain contusion one to five years prior to the study and manifested asthenic symptoms. During the study, they underwent treatment with 30 daily intramuscular injections of cerebrolysin at a dose of 0.1 ml/kg body weight. A positive effect on the functional state of the brain was found in 77% of patients. It was expressed as the appearance of the occipital α rhythm in the EEGs, an increase in the EEG spectral power, normalization of frequency parameters of the α rhythm, a decrease in the power spectrum of the low-frequency θ and δ EEG activity, and shortening of the P300 peak latency. These changes were associated with an improvement of the general clinical state and the psychometric indices of attention and memory in the patients.     

Narrow-band changes in the spectral composition of the EEG under the influence of an agonist and antagonist of the cholinergic neuromediator system]

The EEG effects of intake of the mean therapeutic single dose of cholinomimetic amiridin (20 mg) or cholinolytic amizyl (2 mg) were studied in 7 healthy subjects. After the intake of the drugs with agonistic and antagonistic action, significant opposite changes in the EEG spectral density were observed in the frequency ranges of 0.6-6.7, 7.7-11.4, and 24.8-29.7 Hz. Amizyl produced an enhancement of the spectral density of the delta-, theta- and beta 2 activity and reduction of the alpha-rhythm power, while under the action of amiridin the spectral density of these rhythms changed in opposite directions. The oppositely directed changes in the alpha range were most pronounced. The peak frequency of amiridin-induced shift was equal to 9.8-10 Hz, and the same value of the spectral change induced by amizyl was 10.8-11.4 Hz. It is suggested that the spectral power density of the alpha-rhythm is an EEG index of the level of cholinergic activation.     

Dopaminergic regulation of theta activity of septohippocampal neuron in the awake rabbit

The effects of dopamine reuptake blocker nomifensine and nonselective antagonist of dopamine receptors haloperidol on the theta rhythmicity of the medial septal neurons and hippocampal EEG were investigated in the rabbit. Bilateral intracerebroventricular infusion of nomifensine (9 micrograms in each ventriculus) produced an increase in both the rate of firing and the theta modulation of medial septal neurons; the theta power of the hippocampal EEG also augmented. The degree of neuronal theta stability (time constant of damping, tao theta) significantly increased. The frequency of rhythmic bursts in the neuronal firing also substantially elevated. The amplitude, regularity and frequency of theta waves in the hippocampal EEG also increased. The antagonist haloperidol (12.5 mg) caused the opposite effect. The theta activity of medial septal neurons and the theta power of the hippocampal EEG decreased after haloperidol injection. Theta rhythmicity of septal neurons significantly diminished, the rate of rhythmic bursts in the neuronal firing also decreased, although not substantially. The theta amplitude and regularity in the hippocampal EEG also decreased. Effects of both drugs built up rapidly and then gradually attenuated. Nomifensine infusion against the background of exposure to haloperidol provoked neither increasing neuronal firing rate, nor elevating theta activity. These finding suggest that dopaminergic system produces activation of the septohippocampal system in situations that require selective attention to functionally important information.     

Changes in the EEG Spectrum and Subjective Characteristics of the General State after Stimulation with Variable Frequency Photic Stimuli with Two Types of Organization

Two sinusoidal signals, one with a constant frequency of 13 Hz and the other with a frequency continuously changing from 1 to 6 Hz and back, were presented simultaneously to subjects through spectacles with light-emitting diodes either to both eyes as a product (amplitude modulation of a constant frequency by a variable one) or to each eye separately. Both kinds of variable frequency exposure revealed a rhomboid pattern of the resonance activation of the EEG spectrum, similar to the spectral dynamics of a signal subject to amplitude modulation. This testifies to the key role of EEG amplitude modulation in the responses of the nervous system to variable frequency rhythmic stimuli. Both types of photic stimulation led to a substantial increase in EEG spectral density and improved the subjects' self-rating of the overall state of well-being, activity, and mood. In addition, separate stimulation of each eye led to an improvement in the anxiety and exercise performance indices (the Luscher color test) and a significant correlation between the intensity of EEG responses and changes in the general state. These differences are explained in terms of the involvement of the interhemispheric interaction mechanisms in the processing of complex rhythmic signals by the brain.     

Human attention as a specific linkage of EEG rhythms with the wave modulators of the cardiac rhythm

Two types of attention (active and passive) were described as specific correlations between central and peripheral oscillatory processes. The active attention was characterized by an enhance of the activity of the high-frequency respiratory heart rate modulator positively correlated with an increase in the EEG gamma-rhythm power. At the same time, the activity of the low-frequency heart-rate modulator was positively correlated with the depression of the low-frequency EEG and with phasic gamma-rhythm reactions (300 ms after stimulus presentation). During the passive attention, the power of the metabolic hear rate modulator increased, its positive correlation with the spectral power of the low-frequency EEG rhythms was observed. The sensory component of the gamma-rhythm was shown to increase with attention attraction.     

Dynamic characteristics of the human resonance EEG responses to rhythmic photostimulation

The development of the resonance EEG responses of the left and right occipital areas was studied in right-handed men during prolonged (12 or 120 s) rhythmic, photostimulation with the intensity of 0.7 J and frequencies of 6, 10, and 16 Hz. Analysis of the EEG fine spectral structure was applied to compare the accumulated baseline EEG spectra and EEG spectra during photostimulation, to observe the dynamics of the short-term spectra and to detect power changes in the EEG narrow spectral band sharply coincident with the stimulation frequency. The more pronounced EEG responses to photostimulation were observed in subjects with the initially low EEG baseline, α-rhythm. Two-minute flash trains produced a substantial increase in the EEG power within the stimulation frequency with superposed oscillatory processes with different periods. These fluctuations are considered a reflection of intricate interaction between the adaptive and resonance EEG responses to the presented intermittent stimulation. Under 12-s stimulation the resonance EEG responses are steadily recorded within the first 3 s of stimulation and immediately after the flash cessation EEG power at the stimulation frequency returns to the initial level. The resonance EEG responses were more pronounced in the right hemisphere than in the left one, especially, at the stimulation frequencies of 6 and 16 Hz. With increasing the stimulation frequency, the maximum of resonance EEG responses was reached earlier. Under the stimulation frequency of 6 Hz, the maximal response was recorded 9–12 s after the beginning of flashes, at the frequencies of 10 and 16 Hz, it was recorded within 3–6 and 3 s, respectively.     

Changes in electrical brain activity in patients with panic disorders

Brain electrical activity was recorded in 38 patients with typical and in 42 patients with atypical panic disorders, also in 30 normal controls. Compared to controls, patients both with typical and with atypical panic disorders differed significantly in reduced spectral power of the EEG alpha band in the right hemisphere. Moreover, in patients with typical panic disorders, the spectral power of the EEG beta1 band was increased in the frontal, temporal, central, and parietal areas of the right hemisphere. In patients with atypical panic disorders, the spectral power of the theta band was increased in the temporal areas of the right hemisphere. The changes in the EEG activity in patients with typical panic disorders are supposed to reflect an increase in activity of non-specific systems of the mesencephalic reticular formation, and the EEG changes in patients with atypical panic attacks may be associated with increased activity of the temporolimbic brain structures.     

Power and phase properties of oscillatory neural responses in the presence of background activity

Natural sensory inputs, such as speech and music, are often rhythmic. Recent studies have consistently demonstrated that these rhythmic stimuli cause the phase of oscillatory, i.e. rhythmic, neural activity, recorded as local field potential (LFP), electroencephalography (EEG) or magnetoencephalography (MEG), to synchronize with the stimulus. This phase synchronization, when not accompanied by any increase of response power, has been hypothesized to be the result of phase resetting of ongoing, spontaneous, neural oscillations measurable by LFP, EEG, or MEG. In this article, however, we argue that this same phenomenon can be easily explained without any phase resetting, and where the stimulus-synchronized activity is generated independently of background neural oscillations. It is demonstrated with a simple (but general) stochastic model that, purely due to statistical properties, phase synchronization, as measured by ‘inter-trial phase coherence’, is much more sensitive to stimulus-synchronized neural activity than is power. These results question the usefulness of analyzing the power and phase of stimulus-synchronized activity as separate and complementary measures; particularly in the case of attempting to demonstrate whether stimulus-synchronized neural activity is generated by phase resetting of ongoing neural oscillations.     

Formation of the functional organization of the cerebral cortex at rest in young schoolchildren varying in the maturity of cerebral regulatory systems: I. Analysis of EEG spectral characteristics in the state of rest

Spectral correlation analysis of the EEG was used to study the organization of the rhythmic electrical activity (EA) of the cerebral cortex in normal children aged seven to eight and nine to ten years and children with the two types of functional immaturity of cerebral regulatory systems most common at this age, namely, fronto-thalamic regulatory system immaturity (IFTS) and brainstem nonspecific activation system immaturity (deficiency) (DNA). Statistical comparison (ANOVA) of these groups of children with respect to the absolute and relative α-and ?-band spectral powers of the background EEGs of 12 cortical areas showed the specific features of the effects of functional immaturity of regulatory systems at different levels on the cortical rhythmic EA pattern at rest. DNA led to a significant increase in the absolute spectral power of α and ? waves recorded in all derivations in both age groups, which indicated a generalized decrease in cortex activation in these children. IFTS caused a significant decrease in the relative strength of α waves and an increase in the strength of ? waves. Taking into account the results of ontogenetic studies, this may be regarded as evidence for a relative underdevelopment of cortical rhythm-generating networks. The absolute spectral powers of both α and ? waves were decreased in all groups of children by nine to ten years of age, which indicated that nonspecific activation was enhanced in the age interval studied. Significant changes were observed in children with functional immaturity of regulatory systems. In children with DNA, the age-related increase in cortex activation was expressed as a significant increase in the α-rhythm peak frequency. In children with IFTS, by nine to ten years of age, both the absolute and relative strengths of ? waves were decreased in most cortical areas studied, which may be regarded as the progressive formation of cortical rhythm-generating mechanisms.     

Effect of nootropic drugs on the dopamine release and dopamine uptake in structures of the rat striatum

Nootropics increase the overflow of dopamine from rat striatum slices in a concentration dependent manner, but without relation to their clinical effectiveness. The influence of a nootropic drugs and of amphetamine on the stimulus induced dopamine release points to a relationship between nootropic and nooanaleptic activity, on the one hand, and transmitter release, on the other. Dopamine re-uptake is not altered by nootropics like piracetam.     

The effect of newly synthesized psychotropic preparations on the "open field" behavior of rats]

The results of effect of some new synthesized psychotropic drugs of nootropic series on rats' behavior in "open field" are given. The increase of locomotive activity and decrease of emotional tension correlated with the rise of rats' ability to learning during working-out of avoidance reaction in shuttle-box, e.i. conditionally reflectory memory. It has been concluded that the study of dynamics of behavioral reactions in "open field" may be used for testing of new synthesized psychotropic drugs of nootropic series.     

Electroencephalographic effects of the intracentral administration of antibodies to brain-specific antigen S-100]

The EEG method with the assessment of the rhythm power on analogue computers was used to examine the effects of intracentral administration of antibodies to the brain-specific antigen S-100 (S-100 protein). Intracerebral injections of antibodies to S-100 protein caused an increase of the EEG basic rhythm power in the hippocampus, caudate nucleus and the mesenphalic reticular formation, with the subsequent development of epileptiform activity in these structures.     

Comparative influence of nootropic preparations on the emetic effect of morphine

The effect of electroshock (ECS) and piracetam, oxiracetam or N-acetylglycinamide on the passive avoidance conditioned response in rats was studied. The antiemetic effect of the compounds was examined in cats as well. The results obtained allowed us to distinct the nootropic and antiemetic action of the drugs. The substances possessed a similar ability to prevent ECS-induced amnesia. On the contrary, oxiracetam completely prevented the emetic response to morphine at doses 100 times lower and piracetam at doses 10 times higher then those of the opioid. N-Acetylglycinamide had no antiemetic activity. The results obtained show that oxiracetam is 100 times more active in antiemetic test than piracetam. These data comprise the novel properties of nootropic drugs.     

The structure of the background EEG of the rabbit in the high-frequency portion of the spectrum]

With the purpose of studying the character and structure of high frequency bioelectric activity of rabbits cerebral cortex in the state of calm alertness, the EEG ensembles of different areas of the cortex (sensorimotor, visual, acoustic) and dorsal hippocampus were studied with FFT method. A supposition was made about the presence of systemic organization of the background EEG in rabbits cerebral cortex, reflected, in particular, in the presence of determined components both of chaotic and rhythmic character having different degrees of manifestation. Heterogeneity was revealed in distribution of energies of spectral EEG components in the studied frequency ranges from 14.7 to 100 Hz with predominance of total specific energy value in the band of 14.7-60 Hz. In coherence functions of all the studied pairs of EEG leads rhythmic component, stable in time, was absent. Functions of the mean EEG coherence in the band of 61-100 Hz had significantly greater values in comparison with the values in the band of 14.7-40 Hz.     

EEG correlates and possible predictors of the efficacy of the treatment of endogenous depression

Analysis of EEG spectral power values and quantitative clinical scores of depressive conditions has been carried out in the dynamics of the treatment of 40 patients with endogenous depression, with the main goal to study the neurophysiological correlates and to search for possible predictors of therapeutic outcome. The reduction of depressive symptoms by the end of the treatment course was associated with EEG signs of improvement of the brain’s functional state. Significant correlations have been revealed between the EEG narrow-band spectral power values and clinical scores. As well, significant correlations have been revealed between some initial (before the beginning of the treatment) EEG parameters and quantitative clinical scores at the initial stage of remission. The values of EEG β₁ and β₂ spectral power appeared to be predictors, while initially larger values of EEG spectral power were associated with the high manifestation of residual depressive symptoms after the treatment. The results support the basic views on the brain’s mechanisms of various aspects of depressive disorders and reveal the possible neurophysiological predictors of the efficacy of the treatment of endogenous depression.     

Effects of tranquilizing agents on bioelectrical activity of the rat brain]

The action of diazepam, meprobamate, trioxazine and mexidol on bioelectrical activity of sensorimotor cortex and dorsal hippocamp of the left and right hemisphere of the brain in conscious rat in free behavior has been studied. All the drugs produced a decline in the frequency of the dominant peak of EEG power spectra. Diazepam and meprobamate increased beta-activity. It is concluded that the decreased frequency may be due to an anxiolytic effect of the tranquilizers, whereas high beta-activity is related to muscle relaxant effect of some drugs.     

Rhythmic modulation of theta oscillations supports encoding of spatial and behavioral information in the rat hippocampus

Oscillatory patterns of activity in various frequency ranges are ubiquitously expressed in cortical circuits. While recent studies in humans emphasized rhythmic modulations of neuronal oscillations ("second-order" rhythms), their potential involvement in information coding remains an open question. Here, we show that a rhythmic (～0.7?Hz) modulation of hippocampal theta power, unraveled by second-order spectral analysis, supports encoding of spatial and behavioral information. The phase preference of neuronal discharge within this slow rhythm significantly increases the amount of information carried by action potentials in various motor/cognitive behaviors by (1) distinguishing between the spikes fired within versus outside the place field of hippocampal place cells, (2) disambiguating place firing of neurons having multiple place fields, and (3) predicting between alternative future spatial trajectories. This finding demonstrates the relevance of second-order spectral components of brain rhythms for decoding neuronal information.     

Specificity of the action of piracetam, encephabol and Cleregil on the transcallosal evoked potential

The influence of some drugs having nootropic effect on transcallosal evoked potential was studied in the experiments on non-anesthetized rabbits. Pyracetam, pyritinol and cleregil have been established to increase the amplitude of transcallosal evoked potential. Each of these drugs was found to exert specific effects on this neurophysiological phenomenon. The authors suggest that transcallosal evoked potential can prove helpful in the detection of new drugs with possible nootropic effect.