Structural and functional organization of a developing brain and formation of cognitive functions in child ontogeny

Results of multidisciplinary studies, including neuromorphological, neurophysiological, neuropsychological, and psychphysiological studies, are reviewed. They allow the brain mechanisms of cognition formation and development during maturation to be identified. The role of regulatory (modulatory) brain systems in forming the cognitive function in the child is demonstrated. Data on considerable changes in the brain systems responsible for the development of cognitive functions in children between the ages of five to six and seven to eight years are presented. At this age, the morphological and functional maturations of the frontal cortical areas and their descending connections with other cerebral structures increase the efficiencies of arbitrary selective attention, learning the activity program, inhibition of spontaneous responses, and regulation and organization of activity, i.e., the functions that are important for successful schooling.     

Aphasia and Alalia from the Perspective of Natal’ya N. Traugott’s Studies on Higher Cognitive Processes

The paper describes one of the central areas of research of Professor Natal’ya N. Traugott, a famous Russian neurophysiologist. In particular, Prof. Traugott identified the general neurophysiological mechanisms responsible for speech disorders in children with alalia and in adults with aphasia caused by focal brain lesions. Physiological experiments showed that both sensory alalia in children and sensory aphasia in adults are associated with the deficiency of auditory analyzer; such deficiency leads to disorders in the formation of conditional reactions to sounds and sound complexes. Moreover, a general development pattern was identified in the ontogeny of interaction of signal systems and in the degradation of such interaction caused by the lesions of particular analyzers. This finding of Prof. Traugott is very important in both theory of cerebral speech mechanisms and speech therapy practices aimed at speech system development and rehabilitation following cerebral dysfunctions.     

Development of the system of cognitive functions in right- and left-handed boys aged six to seven years: A study taking into consideration specific features of early ontogeny

Characteristics of early ontogeny and the formation of cognitive functions of left-and right-handed boys six to seven years of age have been studied with the genesis of handedness taken into account. A comparative analysis of cognition in right-and left-handed children has been performed using a unified approach to the history of early ontogeny with special emphasis on cognitive functions. The negative effect of pathological pregnancies and births, as well as disturbances in early ontogeny, on the development of cognitive functions in both left-and right-handed boys has been shown. The most “vulnerable” functions in right-handed boys with a history of various pathologies are the organization of activity and visuospatial perception; in left-handed boys, these are fine motor skills and speech development. In the absence of pathologies in the medical history, significantly higher indices of the organization of activity and visuomotor coordination have been found in right-handed boys and significantly higher indices of visuospatial perception, in left-handed boys.     

Formation of the functional organization of the cerebral cortex at rest in young schoolchildren varying in the maturity of cerebral regulatory systems: II. Analysis of EEG α-rhythm coherence

Coherence (COH) of rhythmic components of the EEG α rhythm at rest was analyzed to demonstrate that the maturation of deep regulatory systems (RSs) of the brain at different levels substantially affected the functional organization of the cerebral cortex and the time course of the formation of intercentral connections in young schoolchildren. The specific effect of fronto-thalamic regulatory system immaturity (FRSI) was a decrease in the α-rhythm COH predominantly in neighboring left-hemispheric derivations of foci in the anterior temporal area. A deficit of nonspecific activation had the strongest effect on the α-rhythm integration of right-hemispheric areas, although this effect was less distinct than that of FRSI and remained only as a tendency by the age of nine to ten years. Children with normal and functionally immature cerebral RSs differed from each other with respect to age-related changes in the corticocortical connections, especially in the left hemisphere. In the norm, intense growth of functional connections in the left hemisphere ceased in the period between seven to eight and nine to ten years of age; in contrast, children with RS immaturity exhibited a trend towards an increasingly greater amount of these connections in both hemispheres, which, apparently, corresponded to an earlier stage of ontogeny.     

Role of the Right- and Left-Hemispheric Structures in Speech and Memory Formation in Children

The role of structures of the left and right cerebral hemispheres in formation of speech function and memory was studied on the basis of complex examination of children with developmental speech disorders. On the basis of EEG estimation of the functional state of the brain, children were classified in two groups depending on the side of localization of changes in electrical activity: those with local changes in electrical activity in the left hemisphere (group I) and those with changes in the right hemisphere (group II). The medical history suggested that the observed features of topography of local changes in electrical activity were linked with the character of prenatal and labor complications and their consequences leading to embryo- and ontogenetic disorders in development of different brain regions. Comparison of the results of neuropsychological examination of the two groups showed that different regions of the brain cortex of both the left and right hemispheres are involved in speech formation. However, a specific role of the right hemisphere in formation and actualization of automatic speech series was revealed. It was suggested that the integrity of gnostic functions of the right hemisphere and, primarily, the spatial organization of perception and movements is a necessary factor of development of auditory–speech and nominative memory.     

Peculiarities of interrelations of activation levels of frontal,temporal, and parietal cortex by parameters of ultraslow biopotentials in the 4–5-year-old children with the age norm and delayed speech development

Possibilities were considered of the integrative approach with use of parameters of the ultraslow informational-control brain and organism system in studying physiological grounds of the rest state, which determine structure and quality of the adaptive behavior. By using the proposal approach there were analyzed results of comparative studies of peculiarities of the wakefulness level, of its autonomous, hemodynamic, and oxygen-depended energy maintenance, and of activation levels and their interrelations in neocortical outputs of the brain systems of the frontal, temporal-parietal, and parietal cortex participating in organization of the higher integrative functions and speech in the 4–7-year-old children with the age norm of the general psychic and verbal development and with delay of the neuropsychic development, including development of speech.Translated from Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, Vol. 40, No. 5, 2004, pp. 455–468.Original Russian Text Copyright © 2004 by Ilyukhina, Krivoshchapova, Matveev, Ponomareva, Shaptilei.To the 100-Anniversary of N. N. Traugott     

Cortical-subcortical Interactions in the Development of the Emotions

In contrast to the cerebral systems regulating the level of activation, the dynamics of sleep, the organization of sensory functions, and the construction of movements, the structures responsible for emotional responses in humans and higher mammals remain a subject of bitter debate. Although modern physiology of the brain has accumulated much data indicating the functional specialization of cerebral structures classified as emotion-producing, these results have as yet defied attempts to fit them into a relatively coherent system that would clarify the specific contribution made by each particular formation to the development of a particular emotional state.     

Continuity and prospects of research in systemic integrative psychophysiology of functional states and cognitive activity

An important problem of psychophysiology related to the study of the integration of the mechanisms controlling the state of the brain and characteristics of the cerebral organization of cognitive activity is discussed. The fundamental role of the results of long-term research in the neurophysiology of functional states as the basis of the organization of mental activity under conditions of direct, long-term, sparing contact with the cortex and subcortical structures by means of long-term intracerebral electrodes carried out by Academician Bechtereva and her scientific school is demonstrated. The commensurability and complementarity of slow and ultraslow gradual neurophysiological processes with similar amplitude-time parameters recorded in intravitally identified zones of deep cerebral structures and from scalp sites corresponding to the cortical projections of the main integrative centers are substantiated. The notion of the brain as a complexly organized, “floating,” multicircuit neurodynamic suprasystem with hierarchically, probabilistically organized vital processes varying in rate and intensity that are involved in maintaining the state of rest, mental states, and cognitive activity are formulated and substantiated. While the set of universal neurodynamic languages is limited, the brain employs a multiregister mechanism controlling the state and selective mechanisms of integration, ensuring the contribution of gradual neurophysiological processes at different levels of the structural and functional organization that vary in terms of information content in the formation of the cerebral systems underlying specific cognitive activities.     

Dextrals and sinistrals (right-handers and left-handers): specificity of interhemispheric brain asymmetry and EEG coherence parameters

Data of literature about morphological, functional and biochemical specificity of the brain interhemispheric asymmetry of healthy right-handers and left-handers and about peculiarity of dynamics of cerebral pathology in patients with different individual asymmetry profiles are presented at the present article. Results of our investigation by using coherence parameters of electroencephalogram (EEG) in healthy right-handers and left-handers in state of rest, during functional tests and sleeping and in patients with different forms of the brain organic damage were analyzed too. EEG coherence analysis revealed the reciprocal changing of alpha-beta and theta-delta spectral bands in right-handers whilein left-handers synchronous changing of all EEG spectral bands were observed. Data about regional-frequent specificity of EEG coherence, peculiarity of EEG asymmetry in right-handers and left-handers, aslo about specificity of EEG spectral band genesis and point of view about a role of the brain regulator systems in forming of interhemispheric asymmetry in different functional states allowed to propose the conception about principle of interhermispheric brain asymmetry formation in left-handers and left-handers. Following this conception in dextrals elements of concurrent (summary-reciprocal) cooperation are predominant at the character of interhemispheric and cortical-subcortical interaction while in sinistrals a principle of concordance (supplementary) is preferable. These peculiarities the brain organization determine, from the first side, the quicker revovery of functions damaged after cranio-cerebral trauma in left-handers in comparison right-handers and from the other side - they determine the forming of the more expressed pathology in the remote terms after exposure the low dose of radiation.     

DEVELOPMENTAL AND REGIONAL VARIATIONS IN NEUROTRANSMITTER-SENSITIVE ADENYLATE CYCLASE SYSTEMS IN CELL-FREE PREPARATIONS FROM RAT BRAIN

Investigations have been carried out on regional and developmental variations in the properties of adenylate cyclase systems in participate preparations from rat brain. EGTA was routinely included in the assay medium to minimize differences in the state of activation of these systems resulting from variations in their exposure to endogenous Ca²⁺. At birth, adenylate cyclase activity was much higher in the hindbrain-medullary preparations than in comparable fractions from cerebellum, cerebral cortex or subcortex (including midbrain, corpus striatum, hypothalamus and hippocampus). Adenylate cyclase activity increased during early development in preparations from all areas of the brain. Maximal levels were reached at 14 days of age or later. These levels were not greatly altered in the young adult animal, except in the hindbrain-medullary area, where a decrease in activity was observed. Adenylate cyclase systems in cerebral cortical and subcortical preparations were activated by norepinephrine and dopamine throughout development. Serotonin also stimulated adenylate cyclase activity in these preparations from young animals but was much less effective in comparable fractions from adult rats. The response to dopamine was diminished with age in cerebral cortical preparations, but not in subcortical fractions. The responses to norepinephrine increased in both brain regions during early development. Adenylate cyclase systems in particulate preparations from the cerebellum and hindbrain-medullary areas exhibited relatively poor responses to the biogenic amines. Detailed studies of the properties of the cerebral cortical adenylate cyclase systems revealed enhancement of activity by Ca²⁺ and F^? at all stages of development with the maximal activation at 2–3 weeks of age. The results suggest that developmental differences in hormonal sensitivity of adenylate cyclase systems from diverse areas of the brain are related to changes in the proportions of the receptor-enzyme complexes responsive to the different biogenic amines.     

The reorganization of the electrical activity of the human brain during the depression of consciousness (comatose states)

To study the problem of consciousness an original structural-functional approach has been applied with the use of possibilities of spectral-coherent EEG analysis in evaluation of human brain functional state together with the specificity of the cerebral coma having local focal belonging. It is revealed that the most informative signs for characteristics of consciousness state are peculiarities of reconstruction of intercentral relations of the electrical brain processes: decrease of mean levels of the EEG coherence at progressive development of coma; staged approach to relative norm at regressive course of comatose state and recovery of consciousness; their stability on the low level at prolonged coma; increase in low or high (above optimum) frequencies band at neighbouring with coma states of consciousness. It may be considered that one of the necessary conditions of normal state of consciousness is preservation of the optimum level of correlation of electrical brain activity alongside with frequency-regional specificity of the EEG coherence spectrum. Any deviation from the optimum is unfavourable condition for normal course of cerebral reactions because of the disturbance of intercentral connections mosaic necessary for their realization.     

Disorders of System Brain Activity in Children with Motor (Expressive) Alalia

Motor alalia refers to a number of disorders of expressive speech that are caused by the dysfunction of cerebral structures in the period when the formation of the speech system is not complete. This form of speech disorder is considered as a language disorder characterized by a persistent disturbance of the assimilation of a system of linguistic units. The possible cause of deviations in the development of speech function in children is a disproportion in the levels of development of speech structures in the left and right hemispheres, and this temporary dominance is often associated with an increased activity in the right hemisphere. According to the results of electroencephalographic studies, in children aged five to six years, there are two types of changes of the bioelectric potential system interaction of the brain cortex. The disorders of the spatial organization of interregional EEG correlations are more pronounced in either the left or right hemispheres of the brain. Thus, motor alalia can be accompanied either by disturbances in the interaction between Broca’s and Wernicke’s areas of the left hemisphere, or between symmetrical areas of the right hemisphere.     

Levodopa Effects on Hand and Speech Movements in Patients with Parkinson’s Disease: A fMRI Study

Levodopa (L-dopa) effects on the cardinal and axial symptoms of Parkinson’s disease (PD) differ greatly, leading to therapeutic challenges for managing the disabilities in this patient’s population. In this context, we studied the cerebral networks associated with the production of a unilateral hand movement, speech production, and a task combining both tasks in 12 individuals with PD, both off and on levodopa (L-dopa). Unilateral hand movements in the off medication state elicited brain activations in motor regions (primary motor cortex, supplementary motor area, premotor cortex, cerebellum), as well as additional areas (anterior cingulate, putamen, associative parietal areas); following L-dopa administration, the brain activation profile was globally reduced, highlighting activations in the parietal and posterior cingulate cortices. For the speech production task, brain activation patterns were similar with and without medication, including the orofacial primary motor cortex (M1), the primary somatosensory cortex and the cerebellar hemispheres bilaterally, as well as the left- premotor, anterior cingulate and supramarginal cortices. For the combined task off L-dopa, the cerebral activation profile was restricted to the right cerebellum (hand movement), reflecting the difficulty in performing two movements simultaneously in PD. Under L-dopa, the brain activation profile of the combined task involved a larger pattern, including additional fronto-parietal activations, without reaching the sum of the areas activated during the simple hand and speech tasks separately. Our results question both the role of the basal ganglia system in speech production and the modulation of task-dependent cerebral networks by dopaminergic treatment.     

Administration of Histidine to Female Rats Induces Changes in Oxidative Status in Cortex and Hippocampus of the Offspring

Histidinemia is an inherited metabolic disorder biochemically characterized by high concentrations of histidine in biological fluids. Usually affected patients are asymptomatic although some individuals have mental retardation and speech disorders. Considering the high prevalence of histidinemia and the scarce information on the effects of maternal histidinemia on their progeny, we investigated various parameters of oxidative stress in brain cortex and hippocampus of the offspring from female rats that received histidine (0.5 mg/g of body weight) in the course of pregnancy and lactation. At 21 days of age we found a significant increase of thiobarbituric acid reactive substances (TBARS), 2′,7′-dihydrodichlorofluorescein oxidation, superoxide dismutase (SOD) activity, catalase (CAT) activity, total sulfhydryls and glutathione (GSH) content in cerebral cortex and hippocampus. We also verified that at 60 days of age, GSH, SOD and total sulfhydryls returned to normal levels in brain cortex, while the other parameters decreased in the same structure. In the hippocampus, at 60 days of age GSH returned to normal levels, CAT persisted elevated and the other parameters decreased. These results indicate that histidine administration to female rats can induce oxidative stress in the brain from the offspring, which partially recovers 40 days after breastfeeding stopped.     

Functional maturation of the brain and formation of the neurophysiological mechanisms of selective voluntary attention in young schoolchildren

A particular role was demonstrated for functional maturation of the frontothalamic system (FTS) of the brain in forming the cerebral organization of selective voluntary attention in ontogeny. Analysis of the coherence of the rhythmic components of the EEG α range in adults and seven-to eight-and nine-to ten-year-old children showed that, if the functional state of the control structures corresponds to the age, the formation of the neurophysiological mechanisms selectively modulating cortical activity and supporting selective tuning of the cerebral structures to the cognitive task is completed by the age of seven or eight years. Unlike adults, children demonstrated no interhemispheric features of the intercenter integration of cortical zones in the prestimulus period of voluntary attention. Children with a functionally immature FTS lacked selective specific integration of cortical zones in the pretuning period. The deficit of selective modulation of cortical activity in children with a functionally immature FTS is considered as the neurophysiological factor that delays the formation of voluntary attention and voluntary control of activity and, finally, leads to learning difficulties.     

Association Process and Functional Brain Asymmetry

Analysis is presented of word associations produced by subjects with left hemispheric (group 1), right hemispheric (group 2), and bilateral (group 3) speech representation. The strategy for producing extralinguistic responses was found to prevail over the strategy for producing linguistic associations in all subjects, irrespective of their type of speech representation. This strategy was more pronounced in subjects with right hemispheric speech laterality, suggesting a correlation between the generation of extralinguistic associations and functional brain asymmetry. Producing linguistic associations also depended on the type of cerebral organization of speech. The most important linguistic associations are syntagmatic. Syntagmatic associations were more closely related to the lateralization of speech to the left hemisphere. The data are compared to the results of studies of the ontogeny of associative processes.     

Electroencephalogram and event-related potentials in the selective attention paradigm as related to the levels of some metabolites in the prefrontal cortex

The results of preliminary analysis at the first stage of the study have demonstrated significant relationships between electrophysiological parameters and the levels of a number of metabolites (measured by proton magnetic resonance spectroscopy) in the dorsolateral prefrontal cortex of the left cerebral hemisphere. The observed relationships are assumed to be mediated by individual-specific characteristics of activation of this cerebral region and its contribution to information processing. The neurophysiological markers of the weakened functional state of the brain are associated with decreased levels of N-acetyl aspartate and choline-containing compounds and an increased level of creatin/phosphocreatin in the tested area of the left prefrontal cortex.     

Dopamine,cocaine and the development of cerebral cortical cytoarchitecture: A review of current concepts

Exposure of the developing fetus to cocaine produces lasting adverse effects on brain structure and function. Animal models show that cocaine exerts its effects by interfering with monoamine neurotransmitter function and that dopamine is cocaine's principal monoamine target in the fetal brain. This review will examine the role of dopamine receptor signaling in the regulation of normal development of the cerebral cortex, the seat of higher cognitive functions, and discuss whether dopamine receptor signaling mechanisms are the principal mediators of cocaine's deleterious effects on the ontogeny of cerebral cortical cytoarchitecture.     

DEVELOPMENTAL CHANGES IN Na+, K+ AND ATP AND IN THE LEVELS AND TRANSPORT OF AMINO ACIDS IN INCUBATED SLICES OF RAT BRAIN

Abstract—

• 1 Upon incubation, slices of brain tissue took up fluid; the degree of swelling increased with increasing age. No sweiling occurred in slices from foetal brain. Since this swelling was associated with increases in the inulin space, the percentage of inulin space in slices at the end of incubation increased during brain development.
• 2 Most of the capacity for ion transport seemed to be absent from foetal brain. In vivo and in slices, Na⁺ was very high and K⁺ was very low in comparison to levels at other ages. There was a rapid change around birth, but no significant change at later ages. Upon incubation, Na⁺ levels increased in other slices, but not in slices of foetal brain.
• 3 Upon incubation of the slices, ATP levels were restored to levels close to those in the living brain; there were no significant alterations in available energy during development to explain changes in amino acid transport.
• 4 The composition of the free pool of cerebral amino acids in vivo changed with development, with some compounds (glutamic acid and related compounds) increasing, others (mostly‘essential’amino acids) decreasing, with age. These changes were not linear with time, and the level of a compound might exhibit several peaks during development.
• 5 The uptake (influx) of taurine, glutamate and glycine into brain slices increased rapidly during the foetal and early neonatal periods, reached a maximum between 2 and 3 weeks of postnatal age and then declined to adult levels. The levels of steady-state uptake with glycine also exhibited a maximal peak at 2-3 weeks of postnatal age. Steady-state uptake of taurine and glutamate reached adult levels by about 3 weeks of age.
• 6 The pattern of inhibition of amino acid transport by two specific amino acid analogues changed during development for some amino acids (GABA, glycine and glutamate), indicating an alteration in substrate specificity.
• 7 The results demonstrate complex changes in cerebral amino acid transport during development, with several maxima or minima and with changes in specificity for at least some compounds.

     

The organization of human EEG rhythms in special states of consciousness

In the paper the results are presented of studying of the electrical brain activity of a specific contingent of subjects which by subjective evaluations considered themselves a category of sensitives (extrasenses). The EEG of these subjects was studied in various functional states--a state of relative rest (background) during diagnostics, of directed influence on the percipient and during meditation. Specificity of spatial-temporal organization of the brain electrical processes of operators--sensitives was revealed, the structure of which correlated with the state of mind. The character of changes in the EEG of these subjects in the background and especially during autogenous activity allows to suggest the formation of a spontaneous focus of stimulation in regulatory brain systems with a leading role of the frontal cerebral regions in these processes as one of the ways of organization of cerebral functions for the regulation of the extrasensory activity.