The study of rodent behavior is an important tool in neuroscience and psychopharmacology; however, traditional behavioral tests aimed at assessing so-called anxiety-like behavior have a number of methodological limitations. This review examines key issues related to the interpretation of the obtained parameters, the reproducibility of research results, and the standardization of experimental conditions. Experimental data on the role of the controlled introduction of variability (multicenter studies, use of rodents from different stocks) in increasing the external validity and reproducibility of results are discussed. Particular attention is paid to modern approaches to behavioral analysis, such as long-term monitoring in home cages, behavioral pattern profiling, and the use of multivariate statistical analysis methods to identify cryptic patterns. It is emphasized that the integration of complex behavioral data obtained in this way with physiological and molecular indicators can increase the translational significance of the models and contribute to a more precise understanding of the mechanisms studied using them.
The aim of the study reported here was to identify the characteristics of myographic signals in stroke patients at rest and during motor imagery. In addition to the encephalogram, electromyograms were recorded in the projection of the elbow flexor muscles of the right and left arms. Electromyogram amplitude and the directed transfer function, which characterizes the strength of corticomuscular connections, were assessed. The experimental protocol included three conditions: rest, motor imagery of opening of the left hand, and motor imagery of opening of the right hand. Corticomuscular coherence in patients was greatest in the low-frequency ranges across all conditions. In the paretic arm, electromyogram amplitude and the directed transfer function were greater both at rest and during motor imagery. Afferent connections (from muscles to the cortex) in the paretic limb were predominant over efferent connections (from the cortex to muscles). During the transition from rest to motor imagery, the transfer function between the cortex and muscles of the paretic arm increased. During therapy, the strength of efferent and afferent connections increased significantly; EMG amplitude tended to decrease.
An open, non-comparative pilot study assessed the efficacy of a combined formulation containing melatonin and memantine (Miladean) as adjuvant therapy in 20 children and adolescents (8–15 years) with cognitive and behavioral disorders associated with hyperkinetic behavior disorder (F90.1, n = 7), schizotypal personality disorder (F21, n = 10), and schizophrenia (F20, n = 3). All patients received stable background therapy, to which Miladean was added for eight weeks (two tablets sublingually before bedtime). Cognitive tests (Raven’s Matrixes, Stroop test, computerized Go/No-Go test), sleep quality questionnaires (modified Spiegel scale), and the symptoms of attention deficit hyperactivity disorder scale (SNAP-IV) were used to evaluate progress. The medication demonstrated a good safety and tolerability profile. There were significant reductions in symptoms of inattention and hyperactivity–impulsivity on the SNAP-IV scale (p < 0.001), along with improvement in sleep quality (p = 0.002) and an increase in reaction speed in the Go/No-Go test (p = 0.001–0.033). A tendency towards improvement in performance on the Raven’s matrixes intelligence test (p = 0.067–0.077) was noted. The preliminary data obtained here indicate the potential effectiveness of Miladean in correcting cognitive and behavioral disorders in children in the contexts of a variety of disorders and provide grounds for further double-blind placebo-controlled studies.
Objective. To study the efficacy and safety of Cortexin as an additional therapy in patients with depressive disorder. Materials and methods. The study involved 98 patients (56 women and 42 men, mean age 44.0 (36.0; 52.0) years), who were divided into two groups: Group 1 (n = 48) received basic antidepressant treatment along with i.m. Cortexin at a dose of 10 mg once a day (in the morning) for 10 days; Group 2 (n = 50) received basic antidepressant treatment alone. Over the course of three visits (baseline and days 14 and 28), the severity of depression and changes in severity during therapy were analyzed on the Montgomery–Åsberg Depression Rating Scale (MADRS), social functioning was assessed on the Social Adjustment Scale (SASS), treatment efficacy was followed on the CGI scale with assessment of changes in condition at treatment weeks 2 and 4, and adverse events were recorded using the Udvalg for Kliniske Undersøgelser (UKU) scale. Results. At visit 2, there was a significant decrease in the severity of depression (MADRS scale), along with an improvement in the quality of life of patients with depressive disorder (SASS scale) and a decrease in adverse events (UKU scale), with significant between-group differences (p = 0.001). At the end of the study, a significantly higher proportion of patients in the study group rated the improvement from therapy as “significant” or “substantial” (p = 0.001). Conclusions. The use of Cortexin as an adjunctive therapy in patients with depressive disorder was effective and safe. Combination therapy with antidepressants and Cortexin was superior to antidepressant monotherapy in terms of therapeutic response and health-related quality of life. A more favorable safety profile was also demonstrated with the combined use of antidepressants and Cortexin.
The Stroop test is one of the most frequently used test paradigms for investigating cognitive control functions in humans. Previous studies have indicated that the Stroop effect is caused by interference at both the sensory level and the response selection level, though how each type of conflict influences the components of event-related potentials recorded during test performance remains unclear. The study reported here examined the association of the P300, N450, and late positive complex components with different types of conflict. Data recorded from 31 channels from 41 healthy subjects aged 18–55 years were analyzed in the classic and reverse Stroop tests, with discrimination of interference types. The results indicate that the P300 component reflects conflict at the motor response level in both test types, while the N450 component reflects conflict at the sensory level and general conflict in the classic test, as well as general conflict in the reverse test, and the late positive complex is associated with general conflict in the classic test and all types of conflict in the reverse test.
Alzheimer’s disease (AD) is a neurodegenerative disorder with a progressive pattern of cognitive and behavioral impairments. Many vital cerebral processes, such as synaptic plasticity, calcium homeostasis, neurogenesis, glial and mitochondrial function, autophagy, and the balance of excitation and inhibition, are significantly impaired in AD. Spatial memory deficit is an early clinical sign of AD. Despite the abundance of studies on spatial memory, the mechanisms of impairment of fear memory at different stages of the development of AD remain poorly understood. The formation of associative fear memory, in which an animal develops protective reactions, is a necessity for survival in a constantly changing environment. This review presents experimental evidence of the main mechanisms of impairment of fear memory obtained in mice and rats in models of AD.
The effects of masking on the localization of a moving signal in the vertical plane were studied. A stationary masker was located above the subject’s head, and the stimulus moved from 8° to 42° upward toward the masker or downward away from it. Masking effects were assessed by varying the delay between the masker and the stimulus within the range 0–200 msec, with an additional delay of 1200 msec. At delays of up to 80 msec, sound image (SI) localization was alternative: either near the masker or at the moving stimulus. As the delay increased, the probability that the SI would be localized near the masker decreased, while the probability of localization near the stimulus increased. As the delay increased, the trajectory of the SI expanded, though it did not reach the control value in the quiet. The main factor narrowing the trajectory of the SI was displacement of its starting point in the direction of motion. The perceived position of the masker was displaced toward the presentation of the moving stimulus. The signal was detected most effectively when the stimulus moved away from the masker. Comparative analysis showed worse discrimination of a moving sound source during masking in the vertical plane as compared with masking in the horizontal plane.
This theoretical review consists of three parts. The first part provides an overview of the literature on the role of context in the organization of goal-directed behavior. It defines context and examines cognitive maps and the brain’s navigational abilities, the characteristics of contextual memory, engram retrieval pathways, and the mechanisms of consolidation and reconsolidation of contextual memory. The second part provides a brief overview of the literature on the role of motivation in the organization of goal-directed activity. This part examines the main neurophysiological theories of motivational behavior: the drive reduction and induction hypothesis, the role of operant movements in motivational behavior, the incentive motivation hypothesis, the hedonic hypothesis, and others. The third theoretical part examines possible mechanisms of interaction between context and motivation from the perspective of our concept of a functional system for the organization of goal-directed behavior. This concept explains the formation and significance of context and motivation, as well as their interaction in the consolidation and retrieval of memory engrams. It is suggested that motivational arousal selectively affects those neurons involved in the structure of the activated memory engram, leaving unactivated neurons unaffected. It is believed that the formation and plastic modification of a memory engram involve the formation of not only contextual maps of space, but also specialized “motivational keys” linked to them, or codes for decoding these maps. During memory consolidation, “motivational keys” activate contextual maps and facilitate the formation of associative links between the elements of the engram. Thus, the formation of a memory engram involves selective activation of specific neural networks in which contextual maps of space and the “motivational keys” to them overlap and function as a single complex. When retrieving an engram, motivational arousal “scans” memory and searches for the engram (or engrams) corresponding to the sought-after environment in which training was initially carried out leading to acquisition of the conditioned connection. Activation of this engram requires coincidence of the “motivational key” with the arrival of the corresponding contextual information in its neural network.
The mechanisms of the emergence, existence, and functioning of receptor clusters formed on the surfaces of nerve cells are considered. Both experimental data and model concepts describing and explaining these processes are presented. The roles of cholesterol, extracellular proteins, and the perimembrane cytoskeleton in the formation and maintenance of the structure of receptor clusters is discussed. In the cases of ionotropic glutamate and acetylcholine receptors, the possibility of increasing the sensitivity of neurons to mediators due to cooperative activation, when closely located receptors and channels of the same cluster influence each other’s activity, is considered.
The lateral cerebellar nucleus plays a critical role in the regulation of distal motor coordination and integration of learned motor responses. The present study investigated the functional consequences of unilateral lesion of the lateral cerebellar nucleus in rats and evaluated the effects of bacterial melanin on recovery processes. Adult rats were trained to perform a balance-dependent motor task on a rotating rod, followed by stereotaxic lesion of the nucleus. Animals were randomly assigned to receive either bacterial melanin or saline and were assessed daily over a 45-day period. Lesion of the lateral cerebellar nucleus resulted in marked impairment of distal motor coordination, with latency to fall reduced from 236 ± 8 s to markedly reduced values on the first postoperative day. In control animals, restoration of coordinated hindlimb movement required 40 ± 1.2 days, whereas melanin-treated animals recovered within 5 ± 1.2 days, corresponding to a mean difference of − 35 days (95
The studies reported here tracked the development of pathological aggression in male CD1 mice during the acquisition of experience of aggression and its possible enhancement after deprivation of aggression. The expression levels of genes in the hypothalamus and nucleus accumbens, which may reflect the development of pathological aggression, were also assessed. Three-month-old outbred male CD1 mice acquired long-term experience of aggression using a “sensory contact” model, where they were exposed to daily confrontations with male C57Bl/6 mice for 30 days. The animals were housed together in the same cage but were separated by a perforated partition, which was removed for only 10 min per day to allow physical contact between the mice. After experience of confrontation, the CD1 mice were housed for another 30 days in the same cages with a permanent C57Bl/6 partner separated by a perforated partition, but this time without physical contact between the animals (the period of deprivation of aggression, olfactory contact only). Aggressive behavior by CD1 males toward C57Bl/6 partners was assessed throughout the experiment (on days 3, 30, and 60), along with manifestations of pathological aggression in a test using introduction of unfamiliar mice: a juvenile conspecific (age one month) or an immobilized adult CD1 male. After the deprivation period, anxiety levels were assessed, along with the plasma corticosterone concentration and gene expression in the hypothalamus (Crh, Crhr1, Crhbp, Nr3c1, Fkbp5, Drd1) and nucleus accumbens (Nr3c1, Fkbp5, Drd1, Drd2, Drd3). Long-term experience of aggression and subsequent deprivation were found to lead to the development of several patterns of aggressive behavior in mice and allowed the animals to be divided into groups: pathological aggressors, non-pathological aggressors, and low-aggression mice. Pathological aggressors demonstrated high levels of abnormal aggression toward immobilized males, along with elevated anxiety after a period of deprivation. Experience of confrontations did not alter corticosterone levels or the expression of genes associated with the glucocorticoid system in the hypothalamus in any of the defined groups of aggressor mice. Changes in the hypothalamic-pituitary-adrenal and dopaminergic systems correlated only in the pathological aggressor group: glucocorticoid receptor gene expression correlated positively with the expression of the dopamine D1 receptor gene in the hypothalamus and nucleus accumbens. These studies also demonstrated that only the dopamine D1 receptor is involved in the development of pathological aggressive behavior and that this occurs in a region-specific manner: its expression was reduced in the hypothalamus and increased in the nucleus accumbens after deprivation of aggression. Thus, long-term experience of aggression leads to the development of a pathological type of behavior and is associated mainly with changes in the dopaminergic system.
Central auditory processing disorders (CAPD), primarily caused by age-related changes in peripheral hearing, are often associated with age-related cerebrovascular accidents and cognitive impairment. The present study compared spatial and speech hearing in patients with chronic mild sensorineural hearing loss (SNHL) and CAPD, with and without a history of acute cerebrovascular accident (ACVA). Thirty elderly and senile patients were examined using a dichotic numbers test, a binaural alternating speech test, tests of intelligibility of heterosyllabic words in quiet and noise, and the spatial hearing questionnaire (SHQ). Mean speech test scores in the two groups of patients were similar, with no significant difference. Use of the SHQ revealed significant differences between the study groups. Correlations were found between SHQ and speech test scores, and a strong relationship between speech and spatial hearing was found in the group with a history of ACVA.
Studies in a model of combined brain and spinal cord injury in Wistar rats showed that the NO content in the injured area of the left frontal lobe of the brain decreased significantly and consistently 24 h after injury. In the contralateral area of the brain (the right frontal lobe), a significant decrease in NO content relative to the level in the control group was also observed, though this was smaller in magnitude and not consistent. The observed decrease in NO content in the frontal lobe tissues of rats 24 h after combined brain and spinal cord injury replicated the reduced NO content in these tissues demonstrated in our previous study one week after the same injury. These results provide new information on the content of free NO in brain tissue damaged during combined brain injury for a period of one day to one week and open up opportunities for seeking new therapeutic methods.
This paper presents the results of a psychophysical study of the characteristics of the auditory perception of rhythmic sound sequences in an at-risk group for developing age-related hearing loss, i.e., elderly people aged 60–78 years (group 1: n = 39; M = 15, F = 24, normal hearing according to pure tone threshold audiometry). Comparison groups were: young subjects aged 18–30 years with normal hearing (group 2: n = 47; 24 men and 23 women) and elderly people aged 62–76 years with grade 2 bilateral sensorineural hearing loss who were not using hearing aids (group 3: n = 30; 14 men and 16 women). Age- and sex-related differences in rhythm recognition were analyzed. Experimental stimuli corresponded to sequences of three tone bursts (F = 1000 Hz) of different durations (300 or 600 msec; 150-msec pause), forming six rhythmic pattern variants (long-short-long, short-short-long, etc.). Additionally, 20 elderly subjects from Group 1 and 22 young subjects from Group 2 took part in short-term auditory memory testing using the auditory digit series reproduction method (Jacobs test). Correlations between indicators of rhythmic pattern recognition and auditory memory were assessed. The data obtained here confirmed that age and hearing condition influence rhythm perception, with significant decreases in measures (p < 0.01) seen in elderly subjects with normal hearing thresholds. This group also showed sex-related differences in the “success” of auditory rhythm perception in relation to the characteristics of short-term auditory memory. The results are discussed in the context of using rhythmic sound sequences in testing programs and sensory-cognitive training for the early detection and prevention of age-related hearing problems, including the processes of central auditory analysis and auditory memory.
Hyperacusis – increased sensitivity to environmental sounds – is a debilitating disorder that signifi cantly impairs quality of life and can lead to social isolation and depression. Hyperacusis has received less study than hypoacusis. Its prevalence and the risk factors for its development are unknown. Hyperacusis lacks objective markers, classification, diagnostic and treatment algorithms, and protocols. Even the definition of the term “hyperacusis” is controversial. It is therefore difficult to identify the causes of this condition, to carry out the clinical management of patients, and to evaluate the effectiveness of treatment methods. Analysis of published data allowed us to compile a classification of hyperacusis, which should expedite and simplify history-taking and the search for causes. Given the ambiguity of the pathogenetic mechanisms, it seems appropriate to define the type of hyperacusis, its cause, and its combination with other hearing disorders.
The development of preventive and therapeutic methods based on the principles of hypoxic conditioning is a pressing issue for experimental research, given the high efficacy of such interventions in the prevention and correction of a wide range of pathological conditions. We have previously developed hypoxic conditioning regimens using moderate periodic normobaric hypoxia (PNH) created by inhaling gas mixtures with reduced oxygen content. The aim of the present study was to investigate the behavioral effects of the PNH regimens developed in our work and applied independently rather than as conditioning for pathological states in rats. No significant differences in behavioral measures of rats subjected to PNH as compared with control animals were found in the open field, elevated plus maze, or novel object recognition tests. Thus, the PNH regimens used here do not have intrinsic effects on behavior and can be used for conditioning without the risk of side effects.
We have previously demonstrated that gaze is focused on areas of faces characterized by the greatest increase in total contrast. Total contrast is defined as the sum of the contrasts of all luminance gradients in the image region being analyzed, and increases in this indicator are taken as the difference from the total contrast of the surrounding region. To demonstrate that these regions are determined preattentively as attentional targets, the present study used stimuli in which the regions of interest could not be predetermined endogenously on the basis of the semantic properties of the image. Subjects were presented with fragments of natural scenes. For each stimulus, averaged fixation density distribution maps were constructed. Images were processed using a program determining the distribution of total contrast across the image. For each spatial frequency, two 2D maps of the locations of regions characterized by the greatest (max) and smallest (min) increases in total contrast were calculated. Empirical maps were compared with the calculated min and max maps using two complementary metrics: CC and NSS. Similarity between the calculated and empirical maps was found to increase significantly with increases in the difference in the total contrast between software-selected areas and their surroundings. Max maps were then compared with random (ran) maps obtained by randomly placing “regions of interest” within the images. Again, similarity of the empirical maps to the max maps was significantly greater than similarity to the ran maps. These results lead to the conclusion that the targets of exogenous attention are the image areas with the greatest increase in total contrast. These areas of perceptual salience are automatically extracted from the input image in different spatial-frequency ranges by second-order visual filters which combine information about local luminence gradients.
The characteristics of spontaneous and evoked neuronal activity are known to undergo changes over time. These changes are typically studied dynamically in acute and subacute experiments (drug-induced anesthesia, the sleep–waking cycle, etc.). Longer-term (weeks, months) recording of the activity of identified neurons is methodologically quite complex. Questions as to whether changes occur, what their nature is, and whether they affect the functional properties of neurons and neuronal populations therefore require further study. In particular, we are not aware that such studies have been conducted at the level of olfactory bulb (OB) neurons, including those related to the perception of odorants at ultra-low concentrations. The aim of the present work was to carry out a longitudinal study of the characteristics of spontaneous activity and activity evoked in identified mitral and tufted neurons (M/T cells) of the olfactory bulb by presentation of odorant vapor (sulcatone) at ultra-low concentrations ( 1·10-15 g/cm3). The activity of OB M/T neurons was periodically (no more than once a week) recorded in five rats for at least one month (maximum 121 days) under xylazine–tiletamine–zolazepam anesthesia. Analysis showed that the characteristics of both spontaneous and odorant-evoked activity of M/T neurons remained stable for quite long periods of time, which is important in terms of conducting research seeking to develop technologies for biohybrid sensory systems for the identification of target substances at ultra-low concentrations.
A digital infrared oculograph was developed to record eye movements. Miniature cameras with a frame rate of 500 Hz and a high spatial resolution of 1440 × 1080 px, mounted on spectacle frames, were used. A technique for analysis of oculograms was developed and an algorithm for detecting the temporal characteristics of saccades and gaze fixations was developed. The oculogram analysis algorithm was coordinated with measurements of other physiological parameters. Discriminant analysis was used for statistical processing and evaluation of the effectiveness of the algorithm. The technology was tested in a study of eye movements in 500 subjects. The duration and speed of eye movements were measured in 16 experiments. Oculograms were analyzed and datasets corresponding to fixations and saccades were obtained. An algorithm for automatically searching for these parameters was developed. A description of the coordinates of the receiving matrixes of the video cameras and displays on which the stimuli were presented was coordinated for the spectacle-based oculograph. An algorithm for detecting the main temporal and spatial characteristics classifies saccades and gaze fixations (between saccades) during target searches by the operator in different conditions. The system corrects for coordinate systems when the monitor and video camera origins mismatch and takes account of the offset and rotation of the video camera coordinate system relative to the monitor coordinate system. The algorithm is shown to yield reliable results for subsequent analysis and interpretation of gaze movements with a recognition level of 0.97. The algorithm is included in the Neurobureau hardware and software system, which is in demand in management structures, industry, transport, marketing, and medicine. The device is coordinated with other devices for physiological monitoring of cognitive functions during research, monitoring, and correction of operator actions during target searches.
The pressing issue of sleep regulation in humans requires the development of non-pharmacological interventions aimed at improving sleep quality, eliminating insomnia, and solving problems with falling asleep. We reviewed the state of research in this area in 2011, noting the high efficiency of methods using computer technologies for recording and analyzing the electroencephalogram (EEG). Modern technologies of neurofeedback and adaptive sound neurostimulation, using feedback from the subject’s EEG, are now beginning to dominate among such methods. The aims of the present work were to analyze publications from the last five years and to consider the effects of the technologies used depending on the conditions and parameters of their organization. Based on our own research, we describe the features of both technologies, analyze examples of their successful application in eliminating various sleep disorders, and indicate the advantages and disadvantages of each technology.
