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PubMed1987

Detection and estimation of neural connectivity based on crosscorrelation analysis.

Crosscorrelation analysis of simultaneously recorded activity of pairs of neurons is a common tool to infer functional neural connectivity. The adequacy of crosscorrelation procedures to detect and estimate neural connectivity has been investigated by means of computer simulations of small networks composed of fairly realistic modelneurons. If the mean interval of neural firings is much larger than the duration of postsynaptic potentials, which will be the case in many central brain areas excitatory connections are easier to detect than inhibitory ones. On the other hand, inhibitory connections are revealed better if the mean firing interval is much smaller than post-synaptic potential duration. In general the effects of external stimuli and the effects of neural connectivity do not add linearly. Furthermore, neurons may exhibit a certain degree of timelock to the stimulus. For these reasons the commonly applied "shift predictor" procedure to separate stimulus and neural effects appears to be of limited value. In case of parallel direct and indirect neural pathways between two neurons crosscorrelation analysis does not estimate the direct connection but instead an effective connectivity, which reflects the combined influences of the parallel pathways.

Animals↗
PubMed2006

Single-chip microelectronic system to interface with living cells.

A high degree of connectivity and the coordinated electrical activity of neural cells or networks are believed to be the reason that the brain is capable of highly sophisticated information processing. Likewise, the effectiveness of an animal heart largely depends on such coordinated cell activity. To advance our understanding of these complex biological systems, high spatiotemporal-resolution techniques to monitor the cell electrical activity and an ideally seamless interaction between cells and recording devices are desired. Here we present a monolithic microsystem in complementary metal oxide semiconductor (CMOS) technology that provides bidirectional communication (stimulation and recording) between standard electronics technology and cultured electrogenic cells. The microchip can be directly used as a substrate for cell culturing, it features circuitry units per electrode for stimulation and immediate cell signal treatment, and it provides on-chip signal transformation as well as a digital interface so that a very fast, almost real-time interaction (2 ms loop time from event recognition to, e.g., a defined stimulation) is possible at remarkable signal quality. The corresponding spontaneous and stimulated electrical activity recordings with neuronal and cardiac cell cultures will be presented. The system can be used to, e.g., study the development of neural networks, reveal the effects of neuronal plasticity and study cellular or network activity in response to pharmacological treatments.

Action Potentials↗
PubMed2006

Morphological homeostasis in cortical dendrites.

Neurons have significant potential for the homeostatic regulation of a broad range of functional features, from gene expression to synaptic excitability. In this article, we show that dendritic morphology may also be under intrinsic homeostatic control. We present the results from a statistical analysis of a large collection of digitally reconstructed neurons, demonstrating that fluctuations in dendritic size in one given portion of a neuron are systematically counterbalanced by the remaining dendrites in the same cell. As a result, the total dendritic measure (e.g., number of branches, length, and surface area) of each neuron in a given morphological class is, on average, significantly less random than would be expected if trees (and their parts) were regulated independently during development. This observation is general across scales that range from gross basal/apical subdivisions to individual branches and bifurcations, and its statistical significance is robust among various brain regions, cell types, and experimental conditions. Given the pivotal dendritic role in signal integration, synaptic plasticity, and network connectivity, these findings add a dimension to the functional characterization of neuronal homeostasis.

Aging↗
PubMed2006

"Missing links" in borderline personality disorder: loss of neural synchrony relates to lack of emotion regulation and impulse control.

OBJECTIVE: Symptoms of borderline personality disorder (BPD) may reflect distinct breakdowns in the integration of posterior and frontal brain networks. We used a high temporal resolution measure (40-Hz gamma phase synchrony) of brain activity to examine the connectivity of brain function in BPD. METHODS: Unmedicated patients with BPD (n = 15) and age-and sex-matched healthy control subjects (n = 15) undertook a task requiring discrimination of salient from background tones. In response to salient stimuli, the magnitude and latency of peak gamma phase synchrony for early (0-150 ms post stimulus) and late (250-500 ms post stimulus) phases were calculated for frontal and posterior regions and for left and right hemispheres. We recorded skin conductance responses (SCRs) and reaction time (RT) simultaneously to examine the contribution of arousal and performance. RESULTS: Compared with controls, patients with BPD had a significant delay in early posterior gamma synchrony and a reduction in right hemisphere late gamma synchrony in response to salient stimuli. Both SCR onset and RT were also delayed in BPD, but independently from differences in synchrony. The delay in posterior synchrony was associated with cognitive symptoms, and reduced right hemisphere synchrony was associated with impulsivity. CONCLUSIONS: These findings suggest that distinct impairments in the functional connectivity of neural systems for orienting to salient input underlie core dimensions of cognitive disturbance and poor impulse control in BPD.

Adult↗
PubMed1997

[The structure of pseudocystic formations in the temporal lobe in focal epilepsy].

The material obtained in open operative interventions from 117 patients with focal (temporal) epilepsy was studied. In 58% of the observations rounded and oval-shaped cavities with distinct borders without any lining, i.e. pseudocystic structures were found. By morphological traits they could be related to cribllurs as there is a vessel in each cavity. All-level disturbance of intracerebral vessels and damage of blood-brain barrier together with hypoxia associated with it are probably the reason for criblir development. Pseudocystic structures that are not connected with the vessel lesion could be of another, sometimes inflammatory genesis. Thus, pseudocystic structures that unite in a network of channels connected with subarachnoidal space occur in temporal lobe in focal epilepsy in over half of cases.

Adolescent↗
PubMed1988

Spatial organization and genetic information in brain development.

In the course of brain development neurons acquire qualitative and quantitative biochemical and morphological properties which depend on the position of the cells within the nervous system. In the dimensions tangential to multilayered cell sheets mechanisms contributing to spatial order include induction by adjacent tissue as well as internal generation of morphogenetic fields (presumably by reactions involving autocatalysis and lateral inhibition). In the dimensions across the sheet cells of different types are produced in one layer and sort into another layer, guided presumably by contact mediated cell interaction. Positional and directional cues encoded in the developing brain are essentially involved in axonal guidance and the formation of neuronal connections. In mammals and man, the number of neurons and their connections in the brain is much higher than the number of genes. This is possible because there are repetitive neuronal circuits in the brain, and there is topographic order of connections between different brain areas. For instance, few quantitatively graded markers would suffice for specifying the projection of one area of the nervous system onto another, generating spatial order for a large number of fibers while requiring only a limited amount of genetic information. Higher brain functions, such as learning and memory, may logically require only a neural network consisting of repetitive subunits. On the other hand, it is an evolutionary advantage for an organism to be endowed, from the outset, with a pattern of neural connections which is subtly and quantitatively tuned for efficiency in dealing with the environment, while remaining flexible for change and adaptation in the course of learning.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed2000

Differential learning-stage dependent patterns of c-Fos protein expression in brain regions during the acquisition and memory consolidation of an operant task in mice.

The present study analysed the effects of the stage of learning of an appetitive operant conditioning task on the spatial and temporal patterns of c-Fos protein levels in the brain of BALB/c mice. c-Fos levels were assessed by immunohistochemistry at either 60, 120 or 180 min after either the first, the second or the fifth daily training session and compared to sham animals. The results show an increase of c-Fos-positive nuclei in several subcortical and cortical brain regions, 60-min post-acquisition. Because these activations were a function of task mastery, the data indicate that they were specifically related to learning. Following the first acquisition session, significant increases in c-Fos-positive neurons were observed in the dorsal hippocampus (CA3), anterior cingulate, occipital and parietal cortices. Following the second daily training session, c-Fos was highly expressed in some subcortical regions, the hippocampus, the subiculum, the entorhinal, and posterior cingulate areas. Moreover, a significant correlation was found between the progression of performance from day 1 to day 2 and c-Fos expression on the hippocampal CA1 subfield. Following complete acquisition, no further task-dependent increases in c-Fos-labelled nuclei was observed in any brain region sampled, suggesting that the intervention of c-Fos-induced mechanisms in the consolidation process were terminated. The training stage-dependent changes in regional post-training c-Fos expression in the hippocampus and the connected limbic regions suggest that this neuronal network is actively engaged in memory consolidation processes.

Animals↗
PubMed2004

Impaired movement-related potentials in acute frontal traumatic brain injury.

OBJECTIVE: Focal brain lesions due to traumatic brain injury (TBI) do not only lead to functional deficits in the lesion area, but also disturb the structurally intact neuronal network connected to the lesion site. Therefore we hypothesized dysfunctions of the cortical motor network after frontal TBI. The movement related potential (MRP) is an EEG component related to voluntary movement consisting of the Bereitschaftspotential (BP), the negative slope (NS), and the motor potential (MP). The aim of our study was to demonstrate alterations in the movement related cortical network in the acute stage after TBI by comparing our patients' MRPs to those of a healthy control group. METHODS: EEGs of 22 patients with magnetic resonance imaging defined contusions of the prefrontal cortex were recorded within 8 weeks after TBI. We further recruited a healthy control group. The paradigm consisted of self-paced abductions of the right index finger. RESULTS: Compared to healthy controls, the BP in the patient group was significantly reduced and its onset delayed. Moreover, an enhanced contribution of the postrolandic hemisphere ipsilateral to the movement and a reduced contribution of the left frontal cortex, ipsilateral to the lesion in the majority of the patients, were observed during motor execution (MP). CONCLUSIONS: Anatomical connections between the prefrontal cortex and the supplementary motor area (SMA) are known to exist. We suggest that prefrontal lesions lead to reduced neuronal input into the SMA. This deficit in the preparatory motor network may cause the reduced BPs in our patients. Moreover, an increased need for attentional resources might explain the enhanced motor potentials during movement execution. In conclusion, we demonstrated altered MRPs in the acute stage after frontal TBI, which are a consequence of disturbed neuronal networks involved in the preparation and execution of voluntary movements.

Adolescent↗
PubMedDate not supplied

[Three-dimentional organization of synapses and astroglia in the hippocampus of rats and ground squirrels: new structural and functional paradigms of the synapse function].

The literature data and our own data on the synaptic plasticity and remodeling of synaptic organelles in the central nervous system are reviewed. Modern techniques of laser scanning confocal microscopy and serial thin sectioning for in vivo and in vitro studies of dendritic spines, including the relationship between morphological changes and the efficacy of synaptic transmission, are discussed using, in particular, a model of long-term potentiation. The organization of dendritic spines and postsynaptic densities of different categories as well as the role of filopodia in spine genesis were analyzed. It was shown that the method of serial ultrathin sections is the most effective for unbiased quantitative stereological analysis and 3D reconstructions. By using the refined method of serial ultrathin sections with subsequent three-dimensional reconstructions, the presence of giant mitochondria in hippocampal neuronal dendrites was demonstrated. It was shown that smooth endoplasmic reticulum forms a unified continuum with the outer membrane of the mitochondrial envelope within dendrites. It was suggested that this continuum provides calcium tunneling, which makes possible intracellular signal transduction during synaptic transmission. Evidence is presented indicating the presence of gap junctions ("electrical synapses") in the synapses of mammalian brain, as well as between glial processes, and between glial cells and neurons. Our data and the data of other authors show that glial cell processes form a structural and functional glial network, which modulates the functioning of the neuronal network. The connection of dendritic spines with the glial network is shown on 3D reconstructions by analyzing the neuropil volume in CA1 hippocampal area of ground squirrels in three functional states: normothermia, provoked arousal, and hibernation when brain temperature falls below 6 degrees C. The own data of the authors are discussed indicating the formation of more than five presynaptic boutons (multiple synapses) on both CA1 mushroom-like dendritic spines and CA3 thorny excrescences. On the basis of the analysis, new ideas of the organization and functioning of synapses were suggested.

Animals↗
PubMed1997

The connectionist simulation of aphasic naming.

The simulation of language disorders using interactive activation (IA) networks and connectionist systems is discussed. An existing IA account of aphasic naming is described, in which two network parameters (decay rate and connection strength) are varied to fit the error production of an aphasic patient. Fairly similar results can be obtained through modification of additional parameters, including the so-called "shared weight increase factor" linking lexical and semantic units. This leads us to consider simulation of aphasic naming using connectionist networks which do not require explicit variation of network parameters. A modular connectionist architecture is presented, in which semantic-lexical and phonological knowledge are instantiated using self-organizing Kohonen maps, while connections between them are implemented using Hebbian networks; a linear connectionist network (Madaline) is used to simulate nonword repetition. The Hebbian connections are lesioned in order to reproduce the patient's naming errors.

Aphasia↗
PubMed1996

Lectin histochemistry in the rats brain in experimental postresuscitation syndrome. (Early and late changes).

The morphological and histochemical changes in the rat brain, resulting from global cerebral ischemia due to cardiac arrest and cessation of respiratory function, connected with the disturbances of blood-brain barrier mechanisms inclined us to perform a series of studies on the localization of specific sugar residues in the membrane glycoprotein chains, using lectin techniques. Chosen lectins, represented by synthetic plant glycoproteins which are specifically bound to particular sugar residues located on the cell surfaces, made it possible to localize the following sugar residues: beta-D-galactose (using Ricinus communis agg.-RCA-1); beta-D-galactosyl (Ricinus communis agglutinin ), N-acetyl-glucosaminyl and N-acetyl-neuraminic acid (Wheat germ agglutinin WGA), N-acetyl-glucosaminyl (Helix pomatia agglutinin and Dolichos biflorus agglutinin ), N-acetyl and N-glycol-neuraminic acid (Limax flavus agglutinin ), alpha-D-galactosyl and D-galactosyl neuraminic acid (Peanut agglutinin ), alpha-D-galactosyl and alpha-D-mannosyl (Concanavalin A ), alpha-D-galactosyl and alpha-D-galactopyranoside (Bandeirea simplicifolia agglutinin A ). In the presented paper changes in the localization of examined glycoconjugates found both in the vascular network as well as in other morphological elements of the brain (neurons, glial cells and neuropil), resulting from 10 min cardiac arrest, connected with global cerebral ischemia are characterized. In the group of control animals the strongest reaction of the vessels was obtained with RCA-1 and BSA, weaker with WGA and the weakest with DBA and LFA. Experimental rats, examined at different time following resuscitation showed significant changes in the histochemical reaction with use of different lectins. Sugar residues revealed by BSA disappeared from the brain vessels already 3 h following clinical death reappearing at 3 and 14 days after ischemia and regaining the picture described in control animals one year later. Additionally the experimental animals were characterized by a remarkably weaker reaction with WGA while location and intensity of RCA-1 receptors in the brain blood vessels remained unchanged or even increased. Additionally in the group of rats which survived 3 days after ischemia, the number of vascular receptors revealed by DBA also increased. The neuropil was characterized by a strong affinity to the sugar residues recognized by DBA, HPA, BSA, PNA, and LFA. As a rule it was stronger in the white structures of the brain than in the gray ones. Starting from the 24 h of postresuscitation till the end of the observation (1 year) staining reaction of neuropil with the above mentioned lectins was reduced. From the group of glycoconjugates used the strongest reaction in parenchymal brain cellular elements concerned those sugar residues which are identified Con A and HPA. In a group of experimental animals staining reaction with Con A was decreased whereas that with HPA was remarkably increased in all animals which survived ischemia. Additionally, BSA-recognized residues not detectable in normal conditions appeared in the neurons and glial cells of hippocampus and subiculum. The presented results indicate deep histochemical and probably functional changes taking place in endothelial cells as well as in other cellular elements of the brain and in neuropil of animals which survived clinical death. The abnormalities appearing in the early postischemic stage persisted for the long observation time indicating an active and progressing process leading to postischemic encephalopathy.

Animals↗
PubMed2003

Self-organizing neural network model of motion processing in the visual cortex during smooth pursuit.

A physiologically based neural network model was constructed to study cortical motion processing during pursuit eye movements. The model consists of three layers of computational units, simulating information processing by direction selective neurons in the primary visual cortex (V1), motion selective neurons in the middle-temporal area, and pursuit selective neurons in the middle-superior-temporal (MST) area. MST units integrate visual and eye-movement related information, and their connections develop during an unsupervised training process. The resulting MST units represent a transition from retinal to real-world reference frame. By analyzing the model connectivity, mechanisms underlying the functions performed by the network are studied.

Brain Mapping↗
PubMed2006

Measurements and models of cerebral function in the severely injured brain.

We review the emerging applications of functional and structural neuroimaging techniques for the assessment of patients with disorders of consciousness. Measurements of brain function from patients in the vegetative state (VS) and minimally conscious state (MCS) are compared, and a conceptual organization is developed that suggests models of brain mechanisms associated with different functional levels of recovery. We emphasize developing strategies to place complex brain injuries on a more equal footing using global and regional quantification of resting or activated brain activity using functional imaging techniques alongside more detailed structural assessments of neuronal integrity and axonal connectivity now available. Preliminary studies from several investigative groups suggest that some MCS patients may harbor a functional reserve in the form of recruitable cerebral networks. These findings support developing systematic characterizations of the severely injured brain and suggest that some patients may benefit from improved diagnostic assessments.

Brain Injuries↗
PubMed2000

Neurological bases of behavioral development in infancy.

This article presents selected psychological competences that emerge in children during the first 2 years, together with correlated structural, biochemical and physiological changes in the brain. Major behavioral events of the 1st year are the disappearance of the neonatal reflexes, the improvement of recognition and working memory and the appearance of the universal fears of strangers and of separation from the caretaker. These behaviors are correlated in time with changes in the brain that allow the increased ability of the cortex to inhibit brainstem reflexes, with processes in the prefrontal cortex and hippocampus that facilitate the formation, storage and retrieval of memories, and with strengthened connections between the cortex and limbic system. Behavioral events of the 2nd year include the explosion of language and the emergence of self-awareness, both of which depend on the capacity for inference. The emergence of these capabilities is correlated with the intensified connectivity of the two hemispheres, the maturation of the prefrontal cortex and cortical-subcortical network.

Behavior↗
PubMed2005

Knowledge-based classification of neuronal fibers in entire brain.

This work presents a framework driven by parcellation of brain gray matter in standard normalized space to classify the neuronal fibers obtained from diffusion tensor imaging (DTI) in entire human brain. Classification of fiber bundles into groups is an important step for the interpretation of DTI data in terms of functional correlates of white matter structures. Connections between anatomically delineated brain regions that are considered to form functional units, such as a short-term memory network, are identified by first clustering fibers based on their terminations in anatomically defined zones of gray matter according to Talairach Atlas, and then refining these groups based on geometric similarity criteria. Fiber groups identified this way can then be interpreted in terms of their functional properties using knowledge of functional neuroanatomy of individual brain regions specified in standard anatomical space, as provided by functional neuroimaging and brain lesion studies.

Algorithms↗
PubMed1982

Electrolytic entorhinal lesions cause seizures.

The entorhinal cortex is a key site of interneuronal communication between a variety of cortical and subcortical areas and hippocampal formation. Lesioning the entorhinal cortex is commonly used in studies of the hippocampal formation, animal behavior and neuronal plasticity. We have found that electrolytic destruction of the entorhinal cortex consistently produces limbic seizure activity in rats. The propensity of lesions in this area for producing seizure activity may facilitate insights into the normal function of this network of neural connections. This unexpected phenomenon represents a potential confounding variable for all researchers using this method for making brain lesions.

Animals↗
PubMed1992

In vitro study of newborn rat brain maturation: implication for sudden infant death syndrome.

We have used slice preparation from newborn rats to study the development of the nucleus tractus solitarius neuronal network and brain intracellular phosphorus metabolites. As shown previously on adults, the newborn preparation retains local excitatory and inhibitory synaptic connections and enables study of intrinsic electrical properties in the nucleus tractus solitarius. Electrophysiological investigation of inhibitory synaptic transmission demonstrated a maturational step at days 4-6 after birth. Nuclear magnetic resonance spectroscopy of brain slices revealed a metabolic maturation between postnatal days 11 and 17. Results emphasize the differential maturation steps during the postnatal development of rat central nervous system. Possibly, Sudden Infant Death Syndrome may result from the abnormal timing in the occurrence of these steps.

Adenosine Triphosphate↗
PubMed1999

Neurobiological bases of behavioral development in the second year.

We discuss selected psychological competences that develop and become noticeable between one and two years of age and are temporally correlated to structural, biochemical and physiological changes in the brain. The psychological competences are: Language development, a sense of "right" and "wrong", self-awareness, and the ability to make inferences. The accompanying changes in the brain involve the prefrontal cortex, language-related cortical areas, hippocampus, cerebellum, basal ganglia and an increase in the connectivity of the network. Of special interest are the maturational changes in layers III-IV of the prefrontal cortex. Layer III is the origin and target of callosal and commissural axons linking the two hemispheres and the target of associational axons linking ipsilateral areas within each hemisphere. Layer IV, the target for axons from the mediodorsal nucleus of the thalamus, conveys information from other associational cortices, cerebellum, basal ganglia, and the reticular and limbic systems. In the second year, intensive dendritic growth and synaptogenesis in these layers increase the linking of these two layers and form a neural basis for a more efficient convergence and integration of information from the two hemispheres, which are functionally asymmetric. It is our hypothesis that these changes, together with the maturational changes in the cortico-subcortical network, are a basis for the observed emergence of the psychological competences. We are aware that temporal correlations cannot prove firm causal relationships. However, knowledge of these correlations is useful in generating specific hypotheses that can be tested directly.

Axons↗