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Results for “functional network connectivity”

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At least 91 records · Page 5Linked to original sources

PubMed2003

Altered effective connectivity during working memory performance in schizophrenia: a study with fMRI and structural equation modeling.

The present study aimed to explore altered effective connectivity in schizophrenic patients while performing a 2-back working memory task. Twelve right-handed, schizophrenic patients treated with typical or atypical antipsychotics and 6 healthy control subjects were studied with fMRI while performing a "2-back" working memory task. Effective connectivity within a cortical-subcortical-cerebellar network for mnemonic information processing was assessed and compared between both groups. The path model included cortico-cortical connections comprising the parietal association cortex, ventrolateral prefrontal cortex (VLPFC), and the dorsolateral prefrontal cortex (DLPFC) as well as a cortico-cerebellar feedback loop comprising prefrontal cortex, contralateral cerebellum, and thalamus. Group differences were analyzed with a stacked models approach. Relative to normal controls, both patient groups revealed a pattern of reduced connectivity within the prefrontal-cerebellar and the cerebellar-thalamic limbs but enhanced connectivity in the thalamo-cortical limb of the cortical-cerebellar circuit. Moreover, a direct comparison of both treatment groups revealed enhanced connectivity in the interhemispheric connections between the cortical association areas in patients treated with atypical antipsychotics. However, right prefrontal and left parieto-frontal path coefficients were lower in the patient group receiving atypical antispychotic drugs. The findings suggest that the relationship between pathology in cortical-subcortical cerebellar networks and associated functional connectivity is complex and may include aspects of increased and decreased levels of connectivity consistent with the notion of "cognitive dysmetria" in schizophrenia. The observed pronounced connectivity within thalamo-cortical projections could be attributed to a compensatory increase of thalamic input in the presence of disrupted effective connectivity within the preceding limb of the cortical-cerebellar circuitry. The study demonstrated the feasibility of structural equation modeling for the investigation of group and treatment-related differences in effective connectivity and provides a promising approach to further disentangle the relationship between altered functional capacity and associated fMRI signal changes.

Adult↗

PubMed1993

Effects of collateral inhibition in a model of the immature rat cerebellar cortex: multineuron correlations.

A model of the immature rat cerebellar cortex is used to simulate the effect of the inhibitory recurrent collateral axons of the Purkinje cells on the spike trains in the network. Inhibition induces an important overall change in the statistical characteristics of individual spike trains. It is also instrumental in producing a strong cooperativity between the different neurons. Moreover, a functional spatial anisotropy appears. A specific entropy index is used to analyze levels of information transfer between clustered and faraway neurons in the network. The formatting effect of recurrent collateral inhibition on spike trains and on network functional dynamics is studied by means of a model of the newborn rat cerebellar cortex. This immature structure has simpler morphological characteristics and fewer physiological parameters than the adult one. It is thus a good candidate for the comparison between experimental and theoretical data. The model network is made of 256 formal neurons (FN), arranged in a square lattice. Each neuron is coupled to its eight nearest neighbors by inhibitory links. All the parameters of the different elements of the model--in particular integration of inhibitory and excitatory inputs--are given anatomical and physiological values derived from biological data. Activities of single FNs and correlations between spatially distant ones are analyzed with classical statistical techniques as well as with a specific informational entropy method we introduce. Simulation results indicate that inhibition is instrumental in: (1) the transformation of the spike train characteristics. This includes a lengthening of the mean interspike interval as well as an overall change in the statistical distribution of intervals, with an emergence of long-lasting ones; (2) the functional structuration of the network. Inhibitory connections between nearest neighbors induce a strong cooperativity between FNs. Furthermore a clear spatial anisotropy occurs in the functioning of the network, with inhibitory effects extending beyond local connectivity in preferential directions. We propose an interpretation of this functional structuration in terms of the various routes followed by the inhibition, including relay effects. The parameters of the model (levels of activities, inhibition rules and connectivities) were varied in order to test the robustness of the above results. Finally, the results are compared with those obtained in an experimental situation.

Animals↗

PubMedDate not supplied

Genetic network identification by high density, multiplexed reversed transcriptional (HD-MRT) analysis in steroidogenic axis model cell lines.

Transcriptional network analysis in steroidogenic axis cell lines requires an understanding of cellular network composition and complexity. Previous studies have shown that absence of transcriptional network components in a cell line compromises that cell line's functional capacity for transcriptional regulation. Our goal was to analyze qualitatively steroidogenic axis-derived cell lines' expression of a putative transcriptional network involved in human and mouse development. To pursue this analysis we used Northern blots and a high density-multiplexed reverse transcription-polymerase chain reaction (HD-MRT-PCR) approach. Our results revealed that, while some members of this putative network were universally expressed, only a minority of the non-constitutive targeted transcripts were present in any single line. Based on our data and previously published results for contextual expression of these transcription factors, a model was constructed possessing the topology suggestive of a scale-free network: certain network members were highly connected nodes and would represent critical sites of vulnerability. The importance of these highly connected nodes for network function is supported by the severe phenotypes exhibited by human patients and animal models when these genes are mutated. We conclude that knowledge of network composition in specific cell lines is essential for their use as models to investigate functional interactions within selected subnetworks.

Alternative Splicing↗

PubMed1988

Neuronal activity and information processing in motor control: from stages to continuous flow.

Some years ago, we proposed, along with others, that the isomorphism between models of information processing by stages and the organization of neural pathways connecting functionally specialized neuronal networks was a guideline for conducting experiments in which the integration of methods and concepts of cognitive psychology and of neurophysiology was a promising approach to increase our knowledge of the processes responsible for motor control. At a time when models of serially organized information processing stages are being increasingly challenged, the deciphering of the underlying brain processes increasingly suggests that current views about the linkage between neural structures and behavioural functions must be reconsidered. First, at the "molar" level, the notion of a functional specialization of neuronal networks as, for example, being "sensory", "sensorimotor" or "motor", has to be viewed as a quantitative and not as a qualitative concept. Second, at the "molecular" level, the notion of a clear-cut functional differentiation between neuronal units, or between small sets of neurons, must similarly be revised: a neuron may be more or less "sensory" or "motor" and, moreover, may share both these functional properties to varying degrees. When the brain processes responsible for movement control are reconsidered in the light of these two concepts--that is a functional heterogeneity of structurally defined neuronal networks, as well as a continuum in functional specification of isolated neuronal units--data collected by using single-cell recording of neuronal activity fit well into the model of a continuous flow of information processing: neural pathways from the cortical parietal association areas to the corticospinal apparatus appear as a privileged sensorimotor information stream along which the amount of neuronal activity responsible for movement planning progressively decreases, while the amount of neuronal activity involved in movement execution progressively increases.

Animals↗

PubMed2026

Functional mapping of the Trypanosoma cruzi serinome by fluorophosphonate activity-based protein profiling.

Serine hydrolases (SHs) constitute one of the largest enzyme superfamilies in eukaryotes, yet their roles in Trypanosoma cruzi, the causative agent of Chagas disease, remain largely uncharacterized. Here, we report an activity-based chemoproteomic map of the T. cruzi epimastigote serinome by combining genome-informed in silico curation with whole-cell activity-based protein profiling (ABPP) using a panel of cell-permeable fluorophosphonate (FP)-alkyne probes. Whole-cell labelling followed by label-free quantitative proteomics (LFQ-MS) identified 37 enriched SH-like proteins, including 35 with conserved or partially conserved catalytic triad/dyad features, spanning lipases, peptidases, esterases, and previously uncharacterized hydrolases. The 35 SHs represent approximately 63% of the 56 predicted SHs retained after catalytic-site curation. Domain architecture analysis revealed broad structural diversity, while orthologue-based localization data suggested association with multiple subcellular compartments, including glycosomal, mitochondrial, and endosomal localizations. Gene Ontology enrichment highlighted lipid metabolic and catabolic processes as dominant functional themes, and protein-protein interaction network analysis supported functional connectivity among the captured enzymes. Several identified SHs, including oligopeptidase B, prolyl oligopeptidase Tc80, serine carboxypeptidase CPB1, and phospholipase A1 (PLA1) have previously been characterized in trypanosomatids, with roles linked to parasite virulence or host-pathogen interactions. Together, these findings establish a fluorophosphonate-based chemoproteomic resource for the kinetoplastid community and prioritize probe-accessible active T. cruzi SHs for future functional validation and antiparasitic inhibitor discovery.

Activity-based protein profiling↗

PubMed2002

The Eps15 homology (EH) domain.

The Eps15 homology (EH) domain was originally identified as a motif present in three copies at the NH2-termini of Eps15 and of the related molecule Eps15R. Both of these molecules are substrates for the tyrosine kinase activity of the epidermal growth factor receptor and hence the name 'Eps15 homology' or EH domain [Wong et al. (1994) Oncogene 9, 1591-1597; Wong et al. (1995) Proc. Natl. Acad. Sci. USA 92, 9530-9534; Fazioli et al. (1993) Mol. Cell. Biol. 13, 5814-5828] was derived. The motif was subsequently found in several proteins from yeast to nematode, thus establishing its evolutionary conservation. Initial studies with filter-binding assays and phage-displayed libraries demonstrated its protein:protein interaction abilities and identified specific ligands. Subsequently, structural analyses established the molecular bases of recognition between EH domains and cognate peptides. To date, several EH-containing and EH-binding proteins have been identified, which establish in the cell a network of protein:protein interactions, defined as the EH network. This network coordinates cellular functions connected with endocytosis, actin remodeling and intracellular transduction of signals.

Amino Acid Sequence↗

PubMed2004

The focality of the global Alzheimer brain process: is the selective vulnerability of neurons a specific phenomenon of primary neuronal pathobiology?

A focality in the development of a global series of predisposing factors that conditions a progressiveness in the neurodegenerative process of Alzheimer type would appear to arise as a specific lesion of the neuron. Such a neuronal lesion would perhaps disrupt functional connectivity of neuronal networks in a process involving loss of neuronal viability. Indeed, a strict concept of selective vulnerability of neurons in the Alzheimer brain might be simply a preconditioning by microenvironmental factors that interacts with the individual neuron in terms of cellular component depletion or in terms of plasmalemmal disruption. In a final analysis, perhaps, the individual neuron would appear as the essential focus of a process that would account for a conditioning globality of the Alzheimer process that promotes both progressiveness and irreversibility of the brain pathology.

Alzheimer Disease↗

PubMed2004

Error-driven global transition in a competitive population on a network.

We show, both analytically and numerically, that erroneous data transmission generates a global transition within a competitive population playing the "Minority Game" on a network. This transition, which resembles a phase transition, is driven by a "temporal symmetry breaking" in the global outcome series. The phase boundary, which is a function of the network connectivity p and the error probability q, is described quantitatively by the crowd-anticrowd theory.

Adaptation, Physiological↗

PubMed1989

Logistic patterning of brain activity.

Brain activity is a set of electrochemical events in the neural tissue during a specified period of time. Neural networks are the functionally connected and dynamically organized population of neurons and neuroglial cells, serving as a unified interface between environmental input and behavioral output at a specified time. They are patterned dynamically in neural space, time and intensity. It is proposed that 1. the electrophysiological patterning of brain activity follows the laws of logistic growth, decay and impulse response function and 2. that this process of logistic transform (LOGIT) of electrochemical processes is itself the general code of information transfer in the brain. A mathematical model of logistic transformation and new electrophysiological data based on the topographic mapping of event-related potentials (ERP) during selective auditory attentional tasks from nine healthy adults is presented. The N100-P200 and the N200-P300 segments of ERP's were analyzed at 20 ms intervals. Logarithmic latencies and voltages were highly correlated. Significant correlation was found between the mathematically estimated and actual values. The interpeak latencies also followed the logistic growth pattern and could be predicted by the model. A general equation of logistic transformation of brain activity, including variables of cortical voltage and frequency is proposed.

Adult↗

PubMed2005

A genomic map of p53 binding sites identifies novel p53 targets involved in an apoptotic network.

The transcriptional activity of the p53 protein is central to its role in tumor suppression. Identification of the complete repertoire of p53-regulated genes is critical for dissecting the complexity of the p53 network. Although several different approaches have been used to characterize the p53 genetic program, we still lack a comprehensive molecular understanding of how p53 prevents cancer. Using a computational approach, we generated a genome-wide map of p53 binding sites (p53BS) to identify novel p53 target genes. We show that the presence of nearby p53BS can identify new proapoptotic members of the Bcl2 family. We show that p53 binds to p53BS identified in the BCL-G/BCL2L14 gene and that induction of this gene contributes to p53-mediated apoptosis. We found that p53 activates the COL18A1 gene encoding the precursor for the antiangiogenic factor endostatin. We also show that p53 up-regulates the MAP4K4 gene and activates the c-Jun NH2-terminal kinase (JNK) pathway to drive apoptosis. Thus, unbiased mapping of the genomic landscape of p53BS provides a systematic and complementary approach to identify novel factors and connections in the p53 genetic network. Our study illustrates how systematic genomic approaches can identify binding sites that are functionally relevant for a p53 transcriptional program. The genetic link among p53, antiangiogenic factors, and the JNK signaling pathway adds new dimensions to understanding p53 function in highly connected genetic networks.

Apoptosis↗

PubMed1980

[Structuro-functional organization of the vegetative (autonomic) nervous system].

On the basis of a number of structural and functional indices, application of pharmacological analysis as well as recording of neuronal activity, the autonomic nervous system is subdivided into the sympathetic, parasympathetic and metasympathetic parts. The metasympathetic system includes the complex of microganglia situated in the walls of vosceral organs and having marked motility activity (the heart, ureters, intestine, stomach). According to the localization, separate areas of this system can be defined by its site (for example, the cardiometasympathetic area in the heart). The metasympathetic system attains the features of true autonomy. Its cells have no direct connection with the high centers: this connection is established through mono- and polysynaptic sensory and afferent units of sympathetic and parasympathetic nature. The system has a definite set of functional elements including sensory ones (mechano-, chemo- and thermosensitive those), oscillators, interneurons, tonic neurons. Neurons of the metasympathetic system are incorporated through interganglionic connections into the common functional network of the organ. A typical excitatory pattern suggests the presence of a temorary connection in the work of at least two neurons according to the "driver--follower" type. In addition to excitatory patterns there are also patterns showing inhibitory interactions. Besides well known systems of mediation including cholinergic and adrenergic ones, the metasympathetic system has its peculiar purinergic transmission.

Adenosine Triphosphate↗

PubMed1992

An associationist model of the paranoid process: application of phase transitions in spreading activation networks.

We propose an associationist model of the paranoid process in which the initial paranoid state is characterized by the formation of cognitive associations among temporally contiguous perceptions, an internally generated explanatory schema is produced to give meaning to the associations, and the schema then becomes learned and perpetuated as a crystallized delusion. We suggest that the genesis of the initial paranoid state can be modeled by a spreading activation network of learning and memory whose parameters of activation spread, including connectivity and relaxation rate, are varying over time. Moreover, recently demonstrated abrupt phase transitions that occur in such networks as a function of connectivity provide a particularly useful means for understanding the process by which an initial paranoid state becomes crystallized into a fixed delusion.

Association Learning↗

PubMed2006

Prediction of the main cortical areas and connections involved in the tactile function of the visual cortex by network analysis.

We explored the cortical pathways from the primary somatosensory cortex to the primary visual cortex (V1) by analysing connectional data in the macaque monkey using graph-theoretical tools. Cluster analysis revealed the close relationship of the dorsal visual stream and the sensorimotor cortex. It was shown that prefrontal area 46 and parietal areas VIP and 7a occupy a central position between the different clusters in the visuo-tactile network. Among these structures all the shortest paths from primary somatosensory cortex (3a, 1 and 2) to V1 pass through VIP and then reach V1 via MT, V3 and PO. Comparison of the input and output fields suggested a larger specificity for the 3a/1-VIP-MT/V3-V1 pathways among the alternative routes. A reinforcement learning algorithm was used to evaluate the importance of the aforementioned pathways. The results suggest a higher role for V3 in relaying more direct sensorimotor information to V1. Analysing cliques, which identify areas with the strongest coupling in the network, supported the role of VIP, MT and V3 in visuo-tactile integration. These findings indicate that areas 3a, 1, VIP, MT and V3 play a major role in shaping the tactile information reaching V1 in both sighted and blind subjects. Our observations greatly support the findings of the experimental studies and provide a deeper insight into the network architecture underlying visuo-tactile integration in the primate cerebral cortex.

Algorithms↗

PubMed2005

Dynamical patterns of epidemic outbreaks in complex heterogeneous networks.

We present a thorough inspection of the dynamical behavior of epidemic phenomena in populations with complex and heterogeneous connectivity patterns. We show that the growth of the epidemic prevalence is virtually instantaneous in all networks characterized by diverging degree fluctuations, independently of the structure of the connectivity correlation functions characterizing the population network. By means of analytical and numerical results, we show that the outbreak time evolution follows a precise hierarchical dynamics. Once reached the most highly connected hubs, the infection pervades the network in a progressive cascade across smaller degree classes. Finally, we show the influence of the initial conditions and the relevance of statistical results in single case studies concerning heterogeneous networks. The emerging theoretical framework appears of general interest in view of the recently observed abundance of natural networks with complex topological features and might provide useful insights for the development of adaptive strategies aimed at epidemic containment.

Communicable Disease Control↗

PubMed2003

Evolutionarily conserved networks of residues mediate allosteric communication in proteins.

A fundamental goal in cellular signaling is to understand allosteric communication, the process by which signals originating at one site in a protein propagate reliably to affect distant functional sites. The general principles of protein structure that underlie this process remain unknown. Here, we describe a sequence-based statistical method for quantitatively mapping the global network of amino acid interactions in a protein. Application of this method for three structurally and functionally distinct protein families (G protein-coupled receptors, the chymotrypsin class of serine proteases and hemoglobins) reveals a surprisingly simple architecture for amino acid interactions in each protein family: a small subset of residues forms physically connected networks that link distant functional sites in the tertiary structure. Although small in number, residues comprising the network show excellent correlation with the large body of mechanistic data available for each family. The data suggest that evolutionarily conserved sparse networks of amino acid interactions represent structural motifs for allosteric communication in proteins.

Allosteric Regulation↗

PubMed2006

Connective tissue: a body-wide signaling network?

Unspecialized "loose" connective tissue forms an anatomical network throughout the body. This paper presents the hypothesis that, in addition, connective tissue functions as a body-wide mechanosensitive signaling network. Three categories of signals are discussed: electrical, cellular and tissue remodeling, each potentially responsive to mechanical forces over different time scales. It is proposed that these types of signals generate dynamic, evolving patterns that interact with one another. Such connective tissue signaling would be affected by changes in movement and posture, and may be altered in pathological conditions (e.g. local decreased mobility due to injury or pain). Connective tissue thus may function as a previously unrecognized whole body communication system. Since connective tissue is intimately associated with all other tissues (e.g. lung, intestine), connective tissue signaling may coherently influence (and be influenced by) the normal or pathological function of a wide variety of organ systems. Demonstrating the existence of a connective signaling network therefore may profoundly influence our understanding of health and disease.

Animals↗

PubMed2004

Global mapping of the yeast genetic interaction network.

A genetic interaction network containing approximately 1000 genes and approximately 4000 interactions was mapped by crossing mutations in 132 different query genes into a set of approximately 4700 viable gene yeast deletion mutants and scoring the double mutant progeny for fitness defects. Network connectivity was predictive of function because interactions often occurred among functionally related genes, and similar patterns of interactions tended to identify components of the same pathway. The genetic network exhibited dense local neighborhoods; therefore, the position of a gene on a partially mapped network is predictive of other genetic interactions. Because digenic interactions are common in yeast, similar networks may underlie the complex genetics associated with inherited phenotypes in other organisms.

Amino Acid Sequence↗

PubMed2005

Intrinsic connections of the cingulate cortex in the rat suggest the existence of multiple functionally segregated networks.

The cingulate cortex is a functionally and morphologically heterogeneous cortical area comprising a number of interconnected subregions. To date, the exact anatomy of intracingulate connections has not been studied in detail. In the present study we aimed to determine the topographical and laminar characteristics of intrinsic cingulate connections in the rat, using the anterograde tracers Phaseolus vulgaris-leucoagglutinin and biotinylated dextran amine. For assessment of these data we further refined and compared the existing cytoarchitectonic descriptions of the two major cingulate constituents, the anterior cingulate and retrosplenial cortices. The results of this study demonstrate that rostral areas, i.e. the infralimbic and prelimbic cortices and the rostral one third of the dorsal anterior cingulate cortex are primarily interconnected with each other and not with other cingulate areas. The caudal two thirds of the dorsal anterior cingulate cortex project to the caudal part of the ventral anterior cingulate cortex, whereas the entire ventral anterior cingulate cortex projects to only the mid-rostro-caudal part of the dorsal anterior cingulate cortex. Dense reciprocal connections exist between the remaining, i.e. the supracallosal parts of the anterior cingulate and retrosplenial cortices with a general rostro-caudal topography, in the sense that the rostral part of the anterior cingulate cortex and caudal part of the retrosplenial cortex are interconnected and the same holds true for the caudal part of the anterior cingulate cortex and rostral part of the retrosplenial cortex. This topographical pattern of intracingulate connections relates to the results of several functional studies, suggesting that specific cingulate functions depend on a number of interconnected cingulate subregions. Through their intricate associational connections, these subregions form functionally segregated networks.

Animals↗