Peculiarities of Formation and Reversibility of Neurogenic Stress-Related Emotional Disorders in Rats

In experiments on rats, we modeled neurogenic stress-induced emotional disorders (stress was evoked by repetitive nociceptive stimulation) and studied their peculiarities within the stressory and post-stressory periods. In these animals, drastic changes in the brain electrical activity and emotional behavior gradually developed; such changes were manifested over a long time period after cessation of the stressory influences. Our experiments demonstrated that tight and stable interrelations among brain limbic structures and negative hypothalamic emotional centers are formed under conditions of prolonged action of emotional stress. This results in the development of a protracted state of negative emotional excitation. The hippocampus is considered one of the key limbic structures responsible for the development of stable pathological stress-related reactions of the brain. Within the post-stressory period, we observed dramatic worsening of the general functional state of the animals, which developed in a parallel manner with intensification of the activity of the negative emotiogenic brain system. It is probable that the existence of periods of unstable equilibrium between oppositely directed emotional reactions in the dynamics of stress and after cessation of stressory influences is a common rule. Such periods reflect peculiarities of rearrangements in the adaptive brain mechanisms under conditions of a stable change in the mode of brain functioning in one particular situation or another.     

The development of a noisy brain

Early in life, brain development carries with it a large number of structural changes that impact the functional interactions of distributed neuronal networks. Such changes enhance information processing capacity, moving the brain from a deterministic system to one that is more stochastic. The evidence from empirical studies with EEG and functional MRI suggests that this stochastic property is a result of an increased number of possible functional network configurations for a given situation. This is captured in the variability of endogenous and evoked responses or "brain noise ". In empirical data from infants and children, brain noise increases with maturation and correlates positively with stable behavior and accuracy. The noise increase is best explained through increased noise from network level interactions with a concomitant decrease of local noise. In old adults, brain noise continues to change, although the pattern of changes is not as global as in early development. The relation between high brain noise and stable behavior is maintained, but the relationships differ by region, suggesting changes in local dynamics that then impact potential network configurations. These data, when considered in concert with our extant modeling work, suggest that maturational changes in brain noise represent the enhancement offunctional network potential--the brain's dynamic repertoire.     

The mechanism of electrically stimulated adenosine release varies by brain region

Adenosine plays an important role in neuromodulation and neuroprotection. Recent identification of transient changes in adenosine concentration suggests adenosine may have a rapid modulatory role; however, the extent of these changes throughout the brain is not well understood. In this report, transient changes in adenosine evoked by one second, 60 Hz electrical stimulation trains were compared in the caudate–putamen, nucleus accumbens, hippocampus, and cortex. The concentration of evoked adenosine varies between brain regions, but there is less variation in the duration of signaling. The highest concentration of adenosine was evoked in the dorsal caudate–putamen (0.34?±?0.08 μM), while the lowest concentration was in the secondary motor cortex (0.06?±?0.02 μM). In all brain regions, adenosine release was activity-dependent. In the nucleus accumbens, hippocampus, and prefrontal cortex, this release was partly due to extracellular ATP breakdown. However, in the caudate–putamen, release was not due to ATP metabolism but was ionotropic glutamate receptor-dependent. The results demonstrate that transient, activity-dependent adenosine can be evoked in many brain regions but that the mechanism of formation and release varies by region.     

Interweaving and overlapping of evoked potentials

The refractory effect of one stimulus upon the response to a closely following stimulus in a different modality is much less than upon the response to a stimulus in the same modality. It is therefore far more efficient to record responses to stimuli in different modalities concurrently than to record each one separately. We evaluated 2 techniques for concurrent recording. Interweaving involves recording the response to one stimulus in the intervals between recording responses to other stimuli. Overlapping occurs when two or more responses are at times being simulateneously recorded. Interweaving and overlapping reduced the time required to record auditory brain-stem responses, short-latency somatosensory evoked potentials and pattern-reversal visual evoked potentials by a factor of 3 over the time required to record each response separately. Overlapping caused no significant change in the evoked potentials. Depending upon the actual timing schedule, interweaving may distort the evoked potentials if later parts of the response to one stimulus override the evoked potential to a following stimulus. Filtering and randomization of stimulus timing may attenuate the effects of these overriding potentials.     

Electrographic registration of metabolic changes in the cerebral cortex evoked by sensory stimuli]

In chronic experiments on rabbits, sensory stimuli from platinum electrodes, located on pia mater in different parts of the cerebral cortex, may produce negative changes of the electrode potential or bioelectrochemical potential (BEChP) lasting from one to dozens of seconds with an amplitude from tenths of millivolts to several millivolts. Sometimes the amplitude of BEChP changes amounted to dozens of millivolts. When recorded from dura mater the changes were much smaller, and in the bone they could not be detected. The evoked BEChP changes appeared only against the background of high initial negative values of the electrode potential (2-3 mv and more) and when the electrodes were not polarized by the amplifier input. A low resistance at the amplifier input contributed to the appearance of evoked BEChP changes. The BEChP change is a complex phenomenon. On one hand, it involves a change of the electrode potential proper which proceeds from shifts in the redox systems (it is recorded both on platinum and golden electrodes) and from changes in the metabolites' content (to which platinum electrodes alone are selectively sensitive). On the other hand, the participation of polarographic processes is also probable. The BEChP changes differ by their latency and by their pattern from the shifts of the DC potential level; this possibly shows that the two kinds of nervous activity manifestaions are related to different aspects of brain tissue activity.     

Optical recording of the odor-evoked responses in olfactory structures of the brain of the terrestrial mollusk Helix

Regular oscillations were recorded in olfactory part of the brain (procerebrum) of gastropod mollusk Helix both electrographically and optically. In general, oscillations resembled those in slugs reported earlier. Odor application caused a transient change in the procerebral oscillations followed by appearance of a special pattern. For the first time the evoked potential was recorded in procerebrum and mapped in reference to the area of oscillations. The area of spreading of evoked potential roughly corresponded to the neuropil projection, while the oscillations were recorded in the projection of the cell body layer of procerebrum. The wave of the evoked potential emerged near the place of the olfactory nerve entrance into the procerebrum and propagated via the procerebrum neuropil towards the cell body layer. The evoked potential did not produce a phase-independent wave in rhythmical oscillations.     

The background and evoked neuronal impulse activity of embryonic neurotransplant of somatosensory brain cortex in rats

The investigation was intended for studying the character of the background and evoked impulse activity of embryonic neurotransplant neurons 4 months after homotopical allotransplantation into the barrel field of somatosensory recipient's brain cortex of the rat. It is established, that the current average frequency of background impulse activity of transplant neurons is reduced in comparison with one of the control rats. It is shown that the evoked impulse activity of neurotransplant develops with the long latency than in somatosensory cortex of the control animals. Thus in patterns of the evoked activity of neurotransplant cells reactions, characteristic for the neurons of barrel field somatosensory recipient's cortex of control rats are registered: an increase of frequency of pulses' generating, or alternating of the activation and reduction periods of impulse frequency with its subsequent regeneration up to a pristine level.     

Modification of radiation injury by ramipril, inhibitor of angiotensin-converting enzyme, on optic neuropathy in the rat

Inhibitors of angiotensin-converting enzyme (ACE) have been used to reduce radiation-induced normal tissue injury. The present study was carried out to determine whether ramipril, one of the inhibitors of ACE, would ameliorate radiation-induced brain damage, using a well-characterized optic neuropathy model in the rat, one of the most critical and radiosensitive structures in the brain. The brains of adult Fischer rats were irradiated stereotactically with 30 Gy using a single collimated beam. Six months after irradiation and 1.5 mg/kg day(-1) ramipril (started 2 weeks after irradiation), rats were assessed for optic nerve damage functionally, using visual evoked potential, and histologically. Results show that ramipril conferred significant modification of radiation injury, since rats receiving radiation alone showed a threefold lengthening in the mean peak latency in the visual evoked potential, whereas 75% of rats receiving radiation followed by ramipril had evoked potentials that resembled those of normal untreated control rats. The histology of irradiated and ramipril-treated optic nerves appeared nearly normal, while there was significant demyelination in both optic nerves of irradiated rats. The study represents the first demonstration of prophylaxis of radiation injury by a carboxyl-containing ACE inhibitor, providing a pharmacological strategy designed to reduce radiation-induced normal tissue damage.     

Segmental inhibition of laser-evoked brain potentials by ipsi- and contralaterally applied cold pressor pain.

An experiment was designed to quantify the inhibitory effect of cold pressor pain (ice water immersion) on brain potentials evoked by acute laser-induced pain. One hand (including the C7 dermatome) was immersed into ice water and simultaneously the laser-evoked brain potentials were elicited consecutively from the right and left lower forearms within the C7 dermatomes. The cold pressor pain was continuously rated on a visual analogue scale (VAS). The size of the averaged brain potentials evoked from the ipsi- and contralateral C7 dermatomes were reduced significantly during cold pressor pain. The largest decrease was obtained for the potentials evoked within the C7 dermatome ipsilateral to the cold pressor pain. The size (power) of the brain potentials to individual stimuli could be measured and was correlated to the intensity of the cold pressor pain (VAS score). During the onset phase of cold pressor pain, there was a decrease in power of the individual brain potentials evoked from the C7 dermatome contralateral to the cold pressor pain but the potentials, evoked from the C7 dermatome ipsilateral to cold pressor pain, were decreased more. The overall rating of the laser-induced pain intensity showed that the perceived intensity was lowest when evoked from the dermatome concurrently exposed to cold pressor pain.     

Dynamics of acoustical evoked potentials on a background of habituation to verbal stimulus in persons with different individual anxiety levels

Changes in the amplitude and the latencies of peak P300 of acoustical evoked potential on a background of the verbal stimulus novelty loss were used for determination of the brain activity specifity in individuals with various anxiety levels. The increase of the peak P300 latency of acoustical evoked potential on a background of trace processes arising after habituation was determined. This parameter did not depend on an anxiety level. However, the latency change depended on the attentional level to a submitted signal. The peak P300 amplitude in the right temporal cortex field was connected with the anxiety level--there was a growth of amplitude on a habituation background with the low anxious subjects, and with the highly anxious people the changes of this parameter were not observed. The anxiety level has rendered influence to dehabituation reaction. Dehabituation is observed with the low-anxiety subjects.     

Effect of lamotrigine on a novel model of epilepsy

The effect of lamotrigine (LTG) on evoked and spontaneous seizure-like activity induced by veratridine, was investigated. Rat brain slices were examined using conventional electrophysiological intracellular techniques. Alteration of sodium channel function by veratridine (0.3 microM) induced spontaneous seizure-like activity in the hippocampal CA1 pyramidal neurons. Therapeutic concentrations of LTG (5-10 microM) inhibited both evoked and spontaneous bursting induced by veratridine. This inhibition was voltage-dependent indicating possible interaction between the drug and the inactivated state of sodium channels. There was an increase in the firing threshold of the bursting but no change in the resting membrane potential (RMP) and membrane input resistance. Results from this work suggest that the veratridine model of epilepsy is very sensitive to drugs which act on sodium channels. These data make the veratridine model a suitable tool for screening potential sodium channel-dependent antiepileptic drugs.     

The dynamics of somatosensory and visual evoked potentials as a correlate of reversible states of altered consciousness]

Somatosensory and visual evoked potentials (EPs) of the brain of 17 sensitive subjects (extrasenses) and 12 ordinary healthy subjects were studied. It was found that during extrasensory activity (direct impact, meditation) in comparison to rest values, the amplitude of intermediate and late components of visual and somatosensory EPs of both hemispheres and early components of somatosensory EPs of ipsilateral in relation to stimulation hemisphere diminished 2-4--fold. There was a recovery of these components after discontinuation of extrasensory activity. It is shown that ordinary subjects could not change their EPs when they tried their best to decrease EPs. It is shown that ordinary subjects could not change their EPs when they tried their best to decrease EPs. It is suggested that the ability of extrasenses for reversible changes of their mind by direct adjustment of the activity of the ascending nonspecific systems of the brain and by alterations of interhemispheric relations forms the basis of extrasensory activity.     

Serotonin and histamine receptor-mediated inhibition of serotonin and noradrenaline release in rat brain cortex under nimodipine treatment

Rat brain cortex slices preincubated with [³H]serotonin or [³H]noradrenaline (25 100 nmol/l each) were superfused and the effects of serotonin and histamine on the electrically (0.3 or 3 Hz) evoked tritium overflow were studied.

In slices preincubated with [³H]serotonin the extent of inhibition of the electrically (3 Hz) evoked tritium overflow produced by histamine was increased when the concentration of [³H]serotonin used for incubation was decreased. The evoked overflow tended to be lower in slices from 2-year-old rats than in slices from 6-month-old animals whereas the inhibitory effect of histamine on the evoked overflow did not differ. Treatment of rats with nimodipine for at least 6 weeks did not significantly affect the evoked overflow in slices from 6-month and 2-year-old rats nor did it significantly alter the serotonin- and histamine-mediated inhibition of the evoked overflow in slices from young adult rats. The extent of histamine-mediated inhibition of the electrically evoked tritium overflow from slices (of young adult rats) preincubated with [³H]noradrenaline did not change when the concentration of [³H]noradrenaline used for incubation was decreased; the degree of inhibition markedly increased when the frequency of stimulation was lowered from 3 to 0.3 Hz. The inhibitory effect of histamine on the electrically (0.3 Hz) evoked overflow was mimicked by the H₃ receptor agonist R-(−)--methylhistamine and antagonized by the H₃ receptor antagonist thioperamide. The electrically evoked overflow and its inhibition by histamine were not affected by nimodipine, irrespective of whether the Ca²⁺ antagonist was administered in vivo (for at least 6 weeks) or added to the superfusion medium in vitro.

It is concluded that (1) the extent of the H₃ receptor-mediated effect in rat brain cortex slices can be markedly increased by lowering the concentration of the tracer in slices preincubated with [³H]serotonin and by lowering the stimulation frequency in slices preincubated with [³H]noradrenaline; (2) the H₃ receptor-mediated inhibition of serotonin release is not changed during aging and (3) nimodipine does not significantly influence serotonin release and noradrenaline release and their serotonin and/or histamine receptor-mediated modulation.     

The reconstruction of the perceptual spaces of brightness and color on the basis of visual evoked potentials and their comparison with the data from behavioral trials

The visual evoked potentials to a change in color stimuli were studied. The amplitude of the N85 component was correlated with color discrimination. In cases when the brightness of one color was fixed and that of the other one changed, the amplitude dynamics of N85 was V-shaped with the minimum corresponding to the point of equal brightness of both colors. The N85 amplitude in this point serves as a measure of discrimination between stimuli chromaticity. The perceptual color space in rabbit (possessing two cone pigments) was constructed in accordance with the amplitudes of N85 to color change. This space represented a hypersphere in the four-dimensional Euclidean space. The perceptual spaces for brightness and color reconstructed on the basis of conditioning probabilities and N85 amplitudes evoked by replacement of colored and achromatic stimuli were shown to coincide. This suggests the common mechanism of the vector color coding.     

睡眠剥夺对脑电活动相位相干性的影响研究

将小波变换和相位相干分析应用到事件相关电位实验的脑电信号中。在正常状态和一夜睡眠剥夺状态下提取12名受试者的视觉ERP,进行30～60Hz的小波变换,以此计算前额叶区域的导联内相位相干,以及枕叶和前额叶之间的相位相干性。发现睡眠剥夺引起前额叶的导联内相位相干活动减少和延迟,表明大脑维持完成任务的能力下降;枕叶与前额叶之间的gamma波段相位相干活动减少,表明功能区域之间的电活动传递效应减弱。基于小波变换的相位相干分析可以得到脑电的同步活动,为更好地理解睡眠的机制和评价睡眠剥夺对认知的影响提供了一条思路。     

A component analysis and principles derived for the understanding of evoked potentials of the brain: Studies in the hippocampus

The hippocampal averaged evoked potentials (AEPs) of the cat brain were analysed using a theoretical filtering method. Application of ideal low pass filters with different cutoff frequencies supports and enlarges previous findings and interpretations of Baar and Özesmi (1972) based on frequency characteristics of the hippocampus: This brain structure has significant beta frequency (18–35 Hz) selectivity near its typical theta (3–8 Hz) resonance. Moreover oscillatory hippocampal waveforms are predicted. The use of pass band and stop band filters allows one to derive conclusions and principles for the analysis and understanding of averaged evoked potentials in general.     

Infant Auditory Processing and Event-related Brain Oscillations

Rapid auditory processing and acoustic change detection abilities play a critical role in allowing human infants to efficiently process the fine spectral and temporal changes that are characteristic of human language. These abilities lay the foundation for effective language acquisition; allowing infants to hone in on the sounds of their native language. Invasive procedures in animals and scalp-recorded potentials from human adults suggest that simultaneous, rhythmic activity (oscillations) between and within brain regions are fundamental to sensory development; determining the resolution with which incoming stimuli are parsed. At this time, little is known about oscillatory dynamics in human infant development. However, animal neurophysiology and adult EEG data provide the basis for a strong hypothesis that rapid auditory processing in infants is mediated by oscillatory synchrony in discrete frequency bands. In order to investigate this, 128-channel, high-density EEG responses of 4-month old infants to frequency change in tone pairs, presented in two rate conditions (Rapid: 70 msec ISI and Control: 300 msec ISI) were examined. To determine the frequency band and magnitude of activity, auditory evoked response averages were first co-registered with age-appropriate brain templates. Next, the principal components of the response were identified and localized using a two-dipole model of brain activity. Single-trial analysis of oscillatory power showed a robust index of frequency change processing in bursts of Theta band (3 - 8 Hz) activity in both right and left auditory cortices, with left activation more prominent in the Rapid condition. These methods have produced data that are not only some of the first reported evoked oscillations analyses in infants, but are also, importantly, the product of a well-established method of recording and analyzing clean, meticulously collected, infant EEG and ERPs. In this article, we describe our method for infant EEG net application, recording, dynamic brain response analysis, and representative results.     

Evoked potentials to electrical stimulation of the facial nerve in the carp tectum mesencephali

Tectal evoked potentials to stimulation of the facial nerve, containing afferent fibers of nonolfactory chemoreception, in the carp are positive evoked potentials with a latent period of 5 to 25 msec which show no phase shift as the microelectrode is advanced to a depth of 600 µ. Depending on the amplitude and latency of evoked potentials seven active zones differing in one or both parameters were distinguished in the ipsilateral tectum mesencephali. The role of impulses from the medulla in the mechanism of tectal evoked potentials to facial nerve stimulation is proved by differences in latent periods and disappearance of the tectal response (although it is preserved in the primary center) after severance of connections between the two parts of the brain. Descending influences from the tectum on the primary center were found: its extirpation disturbs evoked potential generation in several parts of the medullla, so that they either disappear completely or their parameters are modified.A. A. Zhdanov State University, Leningrad. Translated from Neirofiziologiya, Vol. 8, No. 1, pp. 39–46, January–February, 1976.     

Change in the nociceptive reactions caused by dental pulp stimulation during excitation of the midbrain]

It was demonstrated in chronic experiments on cats that stimulation of certain midbrain regions decreased or fully depressed the pain reaction evoked by dental pulp stimulation. The antinociceptive effect depending on the parameters of the brain stimulation was shown in differential change of the separate motor and vegetative and emotional - behaviour components, forming a general pain reaction. A poststimulation analgesia was revealed and the dynamic of restoration of different pain manifestations after the cessation of brain stimulation was traced. Possible mechanism of the realization of the antinociceptive effect are discussed.     

时域相干刺激研究进展

脑深部电刺激已成为许多神经和精神疾病的有效治疗方法。然而,侵入性的电极植入会带来手术并发症的风险,并且刺激靶区在植入后很难改变。经颅磁刺激和经颅电刺激等非侵入性刺激方法为调节大脑功能提供了新的途径。但是,尚未证明这些非侵入性脑刺激方法可以直接调节脑深部神经元活动而不影响皮层神经元。因此,这些方法主要用于调节大脑表层脑区的神经活动。时域相干（temporal interference,TI）刺激是通过两个高频电场相互作用,产生低频包络调节神经活动的一种非侵入式脑深部电刺激的新方法,该方法有望解决无创脑深部刺激的需求。本文首先介绍TI刺激的概念以及安全性,然后阐述TI刺激现有研究中的电场分析方法,并讨论电场分析相关的生理模型建模方法和仿真平台以及TI刺激诱发场分布的研究进展与在动物和人体中的应用进展。最后,本文展望了TI刺激技术未来发展方向,以期为无创脑深部刺激研究提供新的研究思路。