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Functional GABAergic synaptic connection in neonatal mouse barrel cortex.

Intracortical inhibition is crucial to proper functioning of the mature neocortex, yet, paradoxically, is reported to be rare or absent in the neonatal animal. We reexamined this issue by recording whole-cell postsynaptic currents (PSCs) of barrel cortex neurons in thalamocortical brain slices from neonatal mice. Monosynaptic, excitatory thalamocortical responses were elicited in layers V/VI neurons as early as postnatal day 0 (P0, the first 24 hr after birth) and in presumptive layer IV as early as P2. At very low stimulation frequencies, the monosynaptic response was invariably followed by a prolonged (up to 1 sec) synaptic barrage, which fatigued at stimulus repetition rates of 2/min or higher. This barrage consisted of postsynaptic responses to spiking activity in neighboring cortical cells, because (1) it could also be evoked by intracortical stimulation in coronal slices and (2) it was abolished by antagonists to NMDA receptors (NMDARs), even when NMDARs on the recorded cell were under a voltage-dependent block. Some of the larger polysynaptic events changed polarity at a negative reversal potential and were blocked by GABAA receptor (GABAAR) antagonists, with a concurrent enhancement of the extracellular field potential, indicating that they were GABAAR- mediated, CI-dependent inhibitory PSCs (IPSCs). We conclude that a network of functional intracortical GABAAR-mediated synaptic connections exists from the earliest postnatal ages, although it gives rise to responses that differ from mature IPSCs in reversal potential and latency.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Analysis of synchronization between two modules of pulse neural networks with excitatory and inhibitory connections.

To study the synchronized oscillations among distant neurons in the visual cortex, we analyzed the synchronization between two modules of pulse neural networks using the phase response function. It was found that the intermodule connections from excitatory to excitatory ensembles tend to stabilize the antiphase synchronization and that the intermodule connections from excitatory to inhibitory ensembles tend to stabilize the in-phase synchronization. It was also found that the intermodule synchronization was more noticeable when the inner-module synchronization was weak.

Action Potentials↗

Impaired thalamocortical connectivity in humans during general-anesthetic-induced unconsciousness.

Whereas converging lines of evidence suggest that anesthetic-induced unconsciousness may result from disruption of functional interactions within neural networks involving the thalamus and cerebral cortex, the effects anesthetics have on human thalamocortical connectivity remain unexamined with current neuroimaging techniques. To address this issue we retrospectively analyzed positron emission tomography data from 11 volunteers scanned for regional cerebral glucose utilization (rCMRglu) when awake and again during isoflurane- (n = 6) or halothane- (n = 5) induced unconsciousness using statistical parametric mapping (SPM99) and structural equation modeling. A main effect analysis, contrasting awake and unconscious metabolic activity, localized a discrete region of the left va/vl thalamus whose relative rCMRglu activity was significantly suppressed (P < 0.05, corrected) during the unconscious state. To identify brain regions whose functional connectivity with this region of the thalamus was impaired during the unconscious state, a psychophysiological interaction analysis was performed. This analysis revealed effects predominantly in topographically related areas of the primary motor and supplementary motor association cortices. Structural equation modeling of a neuroanatomical network encompassing these empirically identified regions revealed significant state-related changes in effective connectivity (chi(2)diff (6)-15.88; P < 0.05) which primarily involved impairment of thalamocortical and corticocortical projections during the unconscious state. These findings support the hypothesis that a mechanistic component underlying general-anesthetic-induced unconsciousness involves disruption of functional interactions within thalamocortical neural networks.

Anesthesia, General↗

Multi-chemical networking profile of the living human brain: potential relevance to molecular studies of cognition and behavior in normal and diseased brain.

Anatomical, electrophysiological and functional neuroimaging studies show that the human brain is a complex network, where cortico-cortical and thalamo-cortical connections are organized in a specific pattern giving rise to brain function. In our recent studies we found that chemical connectivity between brain regions might be changed in different conditions (e.g. aging, chronic pain, cognitive interference). The elucidation of properties of the human brain multi-chemical networking profile is the subject of this study. In vivo proton magnetic resonance spectroscopy was used to determine relative concentrations of multiple chemicals (N-Acetyl aspartate, choline, glutamate, glutamine, GABA, inositol, glucose, and lactate in relation to creatine/phosphocreatine complex) in 6 brain regions: thalamus, and cingulate, insula, sensorimotor, orbital frontal, and dorsolateral prefrontal cortices. The properties of the brain multi-chemical networking profile within and across the studied regions were examined using correlation analysis. Strong positive correlations were seen between chemicals within brain regions. Negative correlations were primarily seen across brain regions. The cortical connectivity for both neurotransmitters (GABA and glutamate) was stronger than for the other chemicals, and was stronger than for the same neurotransmitters in the thalamus. Factor analysis indicated that the natural clustering of regional chemical concentrations is by brain region and not by chemicals. These findings support the idea for the existence of a specific pattern of multi-chemical networking profile in the brain where the major excitatory and inhibitory neurotransmitters in neocortex perform a regulatory function.

Adult↗

Anatomy of attentional networks.

Attention is a central theme in psychological science. As with other biological systems, attention has a distinct anatomy that carries out basic psychological functions. Disparate attentional networks correlate with discrete neural circuitry and can be influenced by specific brain injuries, states, and drugs. Accordingly, thinking about attention as an organ system is advantageous for understanding the details of this complex cognitive process. In the context of an influential model of attention, this article introduces the broad notion of attention, then addresses its prominent characteristics, mechanisms, and theories. The presentation emphasizes the role of recent neuroimaging data in outlining the functional neuroanatomy subserving distinct attentional networks. A discussion of pertinent results connects attentional networks with self-regulation, development, and rehabilitation training.

Attention↗

Effect of delay on the boundary of the basin of attraction in a system of two neurons.

The behavior of neural networks may be influenced by transmission delays and many studies have derived constraints on parameters such as connection weights and output functions which ensure that the asymptotic dynamics of a network with delay remains similar to that of the corresponding system without delay. However, even when the delay does not affect the asymptotic behavior of the system, it may influence other important features in the system's dynamics such as the boundary of the basin of attraction of the stable equilibria. In order to better understand such effects, we study the dynamics of a system constituted by two neurons interconnected through delayed excitatory connections. We show that the system with delay has exactly the same stable equilibrium points as the associated system without delay, and that, in both the network with delay and the corresponding one without delay, most trajectories converge to these stable equilibria. Thus, the asymptotic behavior of the network with delay and that of the corresponding system without delay are similar. We obtain a theoretical characterization of the boundary separating the basins of attraction of two stable equilibria, which enables us to estimate the boundary. Our numerical investigations show that, even in this simple system, the boundary separting the basins of attraction of two stable equilibrium points depends on the value of the delays. The extension of these results to networks with an arbritrary number of units is discussed.

Journal Article↗

Calcium: outside/inside homeostasis and signalling.

More and more data accumulate concerning calcium dependent effects in all compartments of cells. The higher the organism in evolution the more calcium becomes involved. Inspection of the data while looking for an explanation of the involvement of calcium in metabolism, nuclear functions, control over pumps, external activities, mineralisation and so on leads one to suppose that calcium has an integrating function. The implication is that calcium flow is a large network connecting the environment, the cytoplasm, vesicles, organelles, the nucleus and in higher species, organs. There is the possibility then that calcium ion functions are being analysed, often in vitro, in a bit by bit reductionist manner while in vivo calcium is the equivalent of an electron in complicated electrical circuits. We then should look for its connections to energy, to effects where conformational switching by calcium pulses is equivalent to magnetic triggering by electron flow and where storage in vesicles is equivalent to condenser-like devices and so on. The appearance of pulsing, of time delays in parts of circuits, and other properties of electronic circuits seen in calcium triggering are then explicable as part of calcium circuit design. No other ion can operate in the same way due to the peculiarities of the calcium ion, its size, charge, ionisation potential and its availability which allow it both to flow rapidly yet to bind considerably.

Adenosine Triphosphate↗

Social and emotional self-regulation.

In humans, frontal lesions result in deficits of social and emotional behavior that are often surprising in the presence of intact language and other cognitive skills. The connections between the motivation and memory functions of limbic cortex and the motor planning functions of frontal neocortex must be fundamental to meeting the daily challenges of self-regulation. The connectional architecture of limbic and neocortical networks suggests a model of function. The densely interconnected paralimbic cortices may serve to maintain a global motivational context within which specific actions are articulated and sequenced within frontal neocortical networks. The paralimbic networks represent the visceral and kinesthetic information that is integral to the representation of the bodily self. In a general sense, the implicit self-representation within paralimbic networks may shape the significance of perceptions and the motivational context for developing actions. The network architecture of the frontal lobe reflects the dual limbic origins of frontal cortex, in the dorsal archicortical and ventral paleocortical structures. In this paper, we speculated that these two limbic-cortical pathways apply different motivational biases to direct the frontal lobe representation of working memory. The dorsal limbic mechanisms projecting through the cingulate gyrus may be influenced by hedonic evaluations, social attachments, and they may initiate a mode of motor control that is holistic and impulsive. In contrast, the ventral limbic pathway from the amygdala to orbital frontal cortex may implement a tight, restricted mode of motor control that reflects adaptive constraints of self-preservation. In the human brain, hemispheric specialization appears to have led to asymmetric elaborations of the dorsal and ventral pathways. Understanding the inherent asymmetries of corticolimbic architecture may be important in interpreting the increasing evidence that the left and right frontal lobes contribute differently to normal and pathological forms of self-regulation.

Brain Diseases↗

The role of axonal delay in the synchronization of networks of coupled cortical oscillators.

Coupled oscillator models use a single phase variable to approximate the voltage oscillation of each neuron during repetitive firing where the behavior of the model depends on the connectivity and the interaction function chosen to describe the coupling. We introduce a network model consisting of a continuum of these oscillators that includes the effects of spatially decaying coupling and axonal delay. We derive equations for determining the stability of solutions and analyze the network behavior for two different interaction functions. The first is a sine function, and the second is derived from a compartmental model of a pyramidal cell. In both cases, the system of coupled neural oscillators can undergo a bifurcation from synchronous oscillations to waves. The change in qualitative behavior is due to the axonal delay, which causes distant connections to encourage a phase shift between cells. We suggest that this mechanism could contribute to the behavior observed in several neurobiological systems.

Axons↗

Noradrenergically mediated plasticity in a human attentional neuronal network.

Noradrenaline is implicated in the modulation of attention and arousal, but the neuroanatomical basis of this effect in humans is unknown. A previous functional neuroimaging study failed to find clear effects of clonidine (alpha2 adrenoceptor agonist) on activity of brain regions implicated in attention. Therefore, we now investigate whether clonidine affects the functional integration of a neuroanatomical attentional network, by modulating connectivity between brain regions rather than activity within discrete regions. Following infusion of either clonidine or placebo, positron emission tomography measurements of brain activity were collected in 13 normal subjects while they were either resting or performing an attentional task. Effective connectivity analysis showed that during rest, clonidine decreased the functional strength of connections both from frontal cortex to thalamus and in pathways to and from visual cortex. Conversely, during the attentional task, functional integration generally increased, with changes being centered on parietal cortex (increased connectivity from locus coeruleus to parietal cortex and from parietal cortex to thalamus and frontal cortex). A drug-induced increase in the modulatory effects of frontal cortex on projections from locus coeruleus to parietal cortex was also observed. Collectively, these results highlight cognitively dissociable effects of clonidine on interactions among functionally integrated brain regions and implicate the noradrenergic system in mediating the functional integration of attentional brain systems. The context-sensitive nature of the changes are consistent with observations that noradrenergic drugs have differential effects on brain processes depending on subjects' underlying arousal levels. More generally, the results illustrate the dynamic plasticity of cognitive brain systems following neurochemical challenge.

Adolescent↗

The effects of anesthetics on brain activity and cognitive function.

PURPOSE OF THIS REVIEW: This review presents an overview of recent findings related to changes in brain activity with increasing anesthesia mainly obtained with brain imaging and electrophysiological techniques in humans. RECENT FINDINGS: Recent studies have revealed that the brain as a whole is not affected to the same degree by anesthetics, but that specific brain regions (and particular cognitive processes mediated by these regions) are more sensitive to anesthesia and sedation than others. Inhibition of activity in multimodal association cortices (such as parietal and prefrontal association cortices) by sedative concentrations of anesthetics produces amnesia and attention deficits, whereas activity in unimodal cortices and in the thalamus remains largely unaffected by low doses of anesthetics. Activity in the midbrain reticular formation, thalamus, and unimodal cortices appears to be suppressed only by anesthetic concentrations causing unconsciousness. Besides those regional suppressive effects, anesthetics impair functional connections between neurons in distributed cortical and thalamocortical networks, which also contributes to the state of anesthesia. SUMMARY: Anesthetics produce changes in the patient's behavioral state by interacting with brain activity via at least two mechanisms: the dose-dependent global and regionally specific suppression of neuronal activity and the disruption of functional interactivity within distributed neural networks.

Journal Article↗

Structural characterization of the neural circuit responsible for control of cardiovascular functions in higher vertebrates.

A comparison of structural properties of a biological neural system responsible for cardiovascular function control in higher vertebrates with randomly connected networks was pursued using matrix representations of those circuits. The biological circuit was characterized by the presence of some heavily connected nuclei in contrast to the random networks that had equally distributed connections between their elements. This property of the analysed biological circuit was shown to account for a high logarithmic correlation found between two indexes defined to represent pointwise features of the nuclei and their global contribution to the whole network. The first index is obtained by the product of the number of inputs and of outputs of a nucleus and was called power index (PI). The second one, called occurrence index (OI), defines how many times a specific nucleus is crossed when all possible pathways joining two nuclei of the circuit are obtained. This PI-OI correlation was clearly dependent on the pathway length distribution (expressed in number of synapses), and was maximal considering pathways with a low number of synapses. When randomly connected circuits were analysed lower correlation was found between the same two indexes and only for much longer pathways. Therefore, it is proposed that the analysis of the PI-OI correlation can be useful to quantify structural differences between biological neural circuits as distinguished from randomly connected networks and also between neural systems at different levels of phylogenetic and ontogenetic development.

Animals↗

A hybrid generative and predictive model of the motor cortex.

We describe a hybrid generative and predictive model of the motor cortex. The generative model is related to the hierarchically directed cortico-cortical (or thalamo-cortical) connections and unsupervised training leads to a topographic and sparse hidden representation of its sensory and motor input. The predictive model is related to lateral intra-area and inter-area cortical connections, functions as a hetero-associator attractor network and is trained to predict the future state of the network. Applying partial input, the generative model can map sensory input to motor actions and can thereby perform learnt action sequences of the agent within the environment. The predictive model can additionally predict a longer perception- and action sequence (mental simulation). The models' performance is demonstrated on a visually guided robot docking manoeuvre. We propose that the motor cortex might take over functions previously learnt by reinforcement in the basal ganglia and relate this to mirror neurons and imitation.

Brain Mapping↗

[Changes in the emotional processing in depressive patients: a study with functional magnetoresonance tomography under the employment of pictures with affective contents].

OBJECTIVE: The influence of emotional contents on brain activation was examined using functional magnetic resonance tomography (fMRT). METHOD: Aquiring 100 EPI-measurements of the whole brain, series of positive and negative pictures from the International Affective Picture System (IAPS) were shown to eight depressed males and to healthy controls. RESULTS: In depression, there was an overactivation in hippocampal area during positive stimulation, whereas an overactivation of amygdala, orbital and prefrontal regions was seen during negative stimulation. CONCLUSIONS: These results emphasize the importance of functional interaction between the neural network associated with emotion. We could show that depression is connected to dysregulation and disturbed functional connectivity during emotional processing.

Adult↗

Selective amplification of neocortical neuronal output by fast prepotentials in vivo.

Neocortical cells integrate inputs from thousands of presynaptic neurons distributed along their dendritic arbors. Propagation of postsynaptic potentials to the soma is crucial in determining neuronal output. Using intracellular recordings in anesthetized and non-anesthetized, naturally awake and sleeping cats, we found evidence for generation of fast, all-or-none events recorded at the soma in about 20% of regular-spiking and intrinsically-bursting neurons. These events, termed fast prepotentials (FPPs), were suppressed by hyperpolarizing the neurons or by inhibiting synaptic transmission with perfusion of Ca2+-free artificial cerebrospinal fluid. FPPs could be evoked by activation of specific cortical inputs and allowed neurons to fire at more hyperpolarized levels of membrane potentials. Thus, FPPs represent a powerful mechanism to boost the output of neocortical neurons in response to given inputs. We further found evidence for modulation of FPPs generation across the waking-sleep cycle, indicating important changes in the integrative properties of neocortical neurons in different states of vigilance. We suggest that FPPs represent attenuated spikes generated in hot spots of the dendritic arbor and constitute a powerful mechanism to reinforce the functional connections between specific elements of the cortical networks.

Animals↗

Effects of healthy aging on hippocampal and rhinal memory functions: an event-related fMRI study.

Event-related functional magnetic resonance imaging was used to study the effects of healthy aging on hippocampal and rhinal memory functions. Memory for past events can be based on retrieval accompanied by specific contextual details (recollection) or on the feeling that an event is old or new without the recovery of contextual details (familiarity). There is evidence that recollection is more dependent on hippocampus, whereas familiarity is more dependent on the rhinal cortex, and that healthy aging has greater effects on recollection than on familiarity. However, little evidence is available about the neural correlates of these effects. Here, we isolated activity associated with recollection and familiarity by distinguishing between linear and quasi-exponential "perceived oldness" functions derived from recognition confidence levels. The main finding was a double dissociation within the medial temporal lobes between recollection-related activity in hippocampus, which was reduced by aging, and familiarity-related activity in rhinal cortex, which was increased by aging. In addition, age dissociations were found within parietal and posterior midline regions. Finally, aging reduced functional connectivity within a hippocampal-retrosplenial/parietotemporal network but increased connectivity within a rhinal-frontal network. These findings indicate that older adults compensate for hippocampal deficits by relying more on rhinal cortex, possibly through a top-down frontal modulation. This finding has important clinical implications because early Alzheimer's disease impairs both hippocampus and rhinal cortex.

Adult↗

A plaidoyer for 'systems immunology'.

A complete understanding of the immune system will ultimately require an integrated perspective on how genetic and epigenetic entities work together to produce the range of physiologic and pathologic behaviors characteristic of immune function. The immune network encompasses all of the connections and regulatory associations between individual cells and the sum of interactions between gene products within a cell. With 30,000+ protein-coding genes in a mammalian genome, further compounded by microRNAs and yet unrecognized layers of genetic controls, connecting the dots of this network is a monumental task. Over the past few years, high-throughput techniques have allowed a genome-scale view on cell states and cell- or system-level responses to perturbations. Here, we observe that after an early burst of enthusiasm, there has developed a distinct resistance to placing a high value on global genomic or proteomic analyses. Such reluctance has affected both the practice and the publication of immunological science, resulting in a substantial impediment to the advances in our understanding that such large-scale studies could potentially provide. We propose that distinct standards are needed for validation, evaluation, and visualization of global analyses, such that in-depth descriptions of cellular responses may complement the gene/factor-centric approaches currently in favor.

Allergy and Immunology↗

A neural network based artificial vision system for licence plate recognition.

This paper presents a neural network based artificial vision system able to analyze the image of a car given by a camera, locate the registration plate and recognize the registration number of the car. The paper describes in detail various practical problems encountered in implementing this particular application and the solutions used to solve them. The main features of the system presented are: controlled stability-plasticity behavior, controlled reliability threshold, both off-line and on-line learning, self assessment of the output reliability and high reliability based on high level multiple feedback. The system has been designed using a modular approach. Sub-modules can be upgraded and/or substituted independently, thus making the system potentially suitable in a large variety of vision applications. The OCR engine was designed as an interchangeable plug-in module. This allows the user to choose an OCR engine which is suited to the particular application and to upgrade it easily in the future. At present, there are several versions of this OCR engine. One of them is based on a fully connected feedforward artificial neural network with sigmoidal activation functions. This network can be trained with various training algorithms such as error backpropagation. An alternative OCR engine is based on the constraint based decomposition (CBD) training architecture. The system has showed the following performances (on average) on real-world data: successful plate location and segmentation about 99%, successful character recognition about 98% and successful recognition of complete registration plates about 80%.

Algorithms↗