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PubMed1975

[Nature of the distribution of synapses in the neurons of the reticular formation and some afferent nuclei].

Under study was the morphology of synaptic terminations of the brain reticular formation in cats and dogs as well as that of the afferent nuclei of the cat's posterior columns. The neurons of the Goll's and Burdach's nuclei have a richly ramified dendritic network. In this connection the main mass of synapses is disposed on the dendrites and their different branchings. The dendrites of the multipolar cells of the reticular formation have the main type of branching, but the cells are distributed from the nerve cell body at a considerable distance (up to 50 mu and more). The synapses are observed at the total length of the dendrite, so the axo-dendritic contacts quantitatively prevail over axo-somatic ones. The morphological data are compared with physiological axo-somatic and axo-dendritic concepts of the role of synapses in conducting the nerve impulse.

Animals↗
PubMed2004

Comparing dynamic causal models.

This article describes the use of Bayes factors for comparing dynamic causal models (DCMs). DCMs are used to make inferences about effective connectivity from functional magnetic resonance imaging (fMRI) data. These inferences, however, are contingent upon assumptions about model structure, that is, the connectivity pattern between the regions included in the model. Given the current lack of detailed knowledge on anatomical connectivity in the human brain, there are often considerable degrees of freedom when defining the connectional structure of DCMs. In addition, many plausible scientific hypotheses may exist about which connections are changed by experimental manipulation, and a formal procedure for directly comparing these competing hypotheses is highly desirable. In this article, we show how Bayes factors can be used to guide choices about model structure, both concerning the intrinsic connectivity pattern and the contextual modulation of individual connections. The combined use of Bayes factors and DCM thus allows one to evaluate competing scientific theories about the architecture of large-scale neural networks and the neuronal interactions that mediate perception and cognition.

Attention↗
PubMed2001

An examination of the effects of stimulus type, encoding task, and functional connectivity on the role of right prefrontal cortex in recognition memory.

Right anterior prefrontal cortex and other brain areas are active during memory retrieval but the role of prefrontal cortex and how it interacts with these other regions to mediate memory function remain unclear. To explore these issues we used positron emission tomography to examine the effects of stimulus material and encoding task on brain activity during visual recognition, assessing both task-related changes and functional connectivity. Words and pictures of objects were encoded using perceptual and semantic strategies, resulting in better memory for semantically encoded items. There was no significant effect of prior encoding strategy on brain activity during recognition. Right anterior prefrontal cortex was equally active during recognition of both types of stimuli irrespective of initial encoding strategy. Regions whose activity was positively correlated with activity in right anterior prefrontal cortex included widespread areas of prefrontal and inferior temporal cortices bilaterally. Activity in this entire network of regions was negatively correlated with recognition accuracy of semantically encoded items. These results suggest that initial encoding task has little impact on the set of brain regions that is active during subsequent recognition. Right anterior prefrontal cortex appears to be involved in retrieval mode, reflected in its equivalent activity across conditions differing in both stimulus type and encoding task, and also in retrieval effort, shown by the negative correlation between its functional connectivity and individual differences in recognition accuracy.

Adult↗
PubMed1995

Neuropoiesis: proposal for a connectionistic neurobiology.

Given current assumptions about the biology of neural organization, some connectionists believe that it may not be possible to accurately model the brain's neural architecture. We have identified five restrictive neurobiological dogmas that we believe have limited the exploration of more fundamental correlations between computational and biological neural networks. We postulate that: 1) the dendritic tree serves as a synapse storage device rather than a simple summation device; 2) connection strength between neurons depends on the number and location of synapses of similar weight, not on synapses of variable weights; 3) axonal sprouting occurs regularly in adult organisms; 4) the postsynaptic genome directly controls the presynaptic cell via mRNA, rather than indirectly by the expression of NCAMs, reverse neurotransmitters, etc.; 5) dendritic spines serve a trophic function by controlling development of new sprouts via a process we term retroduction. We entertain an alternative formulation of a computational neural element that is fully consistent with modern neuroscience research. We then show how our model neuron can learn under Hebbian conditions, and extend the model to explain non-Hebbian, one-trial learning. This work is significant because by stretching the theoretical boundaries of modern neuroscience, we show how connectionists can potentially create new, more biologically-based neural elements which, when, interconnected into networks, exhibit not only properties of existing backpropagation networks, but other physiological properties as well.

Adult↗
PubMed2007

Entorhinal cortex of the monkey: VII. intrinsic connections.

The organization of intrinsic connections within the entorhinal cortex was investigated in Macaca fascicularis monkeys. Anterograde tracers ((3)H-amino acids, Phaseolus vulgaris-leucoagglutinin, biotinylated dextran amine, or Fluoro-Ruby) were injected into the deep or superficial layers of the entorhinal cortex in 24 animals. These injections labeled extensive intrinsic projections that terminated throughout all layers of the entorhinal cortex. Labeling was typically continuous i.e., there was no evidence of a patchy or columnar organization. Each injection produced a rostrocaudally oriented band of labeled fibers and terminals that extended for one-third to one-half of the length of the entorhinal cortex. The more extensive distributions of labeled fibers were more typical of caudally placed injection sites. Taken together, the projections identified at least two mediolaterally differentiated bands: a lateral band that encompasses fields Elr, Elc, and the most lateral aspect of fields Ec and Ecl and a wider, medially situated band that encompasses much of fields Er, Ei, Ec, and Ecl. We obtained some evidence that field Eo constitutes a third, very medially placed band. The rostrocaudal organization of labeled fibers and the extent of labeling within the deep and superficial layers were unrelated to the laminar position of the injection. These data suggest that intrinsic associatonal connections in the monkey entorhinal cortex are organized into separate associational networks. Our findings are discussed with reference to the role of interlaminar connections in mediating physiological interactions between the neocortex and the hippocampus.

Animals↗
PubMed1990

Holography in artificial neural networks.

The dense interconnections that characterize neural networks are most readily implemented using optical signal processing. Optoelectronic 'neurons' fabricated from semiconducting materials can be connected by holographic images recorded in photorefractive crystals. Processes such as learning can be demonstrated using holographic optical neural networks.

Algorithms↗
PubMed1998

Respiration-modulated membrane potential and chemosensitivity of locus coeruleus neurones in the in vitro brainstem-spinal cord of the neonatal rat.

1. The activity of locus coeruleus (LC) neurones (n = 126) was examined in whole-cell (conventional and amphotericin B-perforated patch) recordings, and the relationship of this activity to the respiratory discharge recorded on the C4 or C5 phrenic nerve roots was determined at different CO2 concentrations (2 and 8 %; bath pH 7. 8 and 7.2) in the in vitro brainstem-spinal cord preparation of the neonatal rat (1-5 days old). 2. In most neurones (n = 105) ongoing activity was modulated at respiratory frequency. Typically, this consisted of a phase of depolarization and increased discharge frequency synchronous with the phrenic burst, followed by a phase of hyperpolarization and inhibition of discharge (n = 94 of 105). The incidence of respiratory modulation decreased from 91 % on P1 to 57 % on P5. 3. Bath application of the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 5 microM) or the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV; 100 microM) abolished both phases of respiratory modulation. The hyperpolarizing phase alone was abolished by the adrenoceptor antagonists idazoxan (5 microM) or phentolamine (0.8 microM). These results indicate that excitatory amino acid pathways are involved in the transmission of both the excitatory and inhibitory components and that the latter involves in addition an alpha2-adrenoceptor-mediated pathway. 4. Increasing the CO2 concentration from 2 to 8 % resulted in a shortening of expiratory duration and weakening or loss of respiratory-phased inhibition; this was accompanied by depolarization, increased discharge frequency and, in those neurones where they were initially present (60 %), an increase in the frequency of subthreshold membrane potential oscillations. The depolarizing response was retained in the presence of tetrodotoxin (TTX, 0.2-1.0 microM). 5. These results indicate that in this neonatal preparation LC neurones form part of the synaptically connected brainstem respiratory network, and that the LC constitutes a site of CO2- or pH-dependent chemoreception.

Acidosis↗
PubMed2006

Neural network model of the primary visual cortex: from functional architecture to lateral connectivity and back.

The role of intrinsic cortical dynamics is a debatable issue. A recent optical imaging study (Kenet et al., 2003) found that activity patterns similar to orientation maps (OMs), emerge in the primary visual cortex (V1) even in the absence of sensory input, suggesting an intrinsic mechanism of OM activation. To better understand these results and shed light on the intrinsic V1 processing, we suggest a neural network model in which OMs are encoded by the intrinsic lateral connections. The proposed connectivity pattern depends on the preferred orientation and, unlike previous models, on the degree of orientation selectivity of the interconnected neurons. We prove that the network has a ring attractor composed of an approximated version of the OMs. Consequently, OMs emerge spontaneously when the network is presented with an unstructured noisy input. Simulations show that the model can be applied to experimental data and generate realistic OMs. We study a variation of the model with spatially restricted connections, and show that it gives rise to states composed of several OMs. We hypothesize that these states can represent local properties of the visual scene.

Action Potentials↗
PubMed2004

Mapping the brain in autism. A voxel-based MRI study of volumetric differences and intercorrelations in autism.

Autism is a disorder of neurodevelopment resulting in pervasive abnormalities in social interaction and communication, repetitive behaviours and restricted interests. There is evidence for functional abnormalities and metabolic dysconnectivity in 'social brain' circuitry in this condition, but its structural basis has proved difficult to establish reliably. Explanations for this include replication difficulties inherent in 'region of interest' approaches usually adopted, and variable inclusion criteria for subjects across the autism spectrum. Moreover, despite a consensus that autism probably affects widely distributed brain regions, the issue of anatomical connectivity has received little attention. Therefore, we planned a fully automated voxel-based whole brain volumetric analysis in children with autism and normal IQ. We predicted that brain structural changes would be similar to those previously shown in adults with autism spectrum disorder and that a correlation analysis would suggest structural dysconnectivity. We included 17 stringently diagnosed children with autism and 17 age-matched controls. All children had IQ >80. Using Brain Activation and Morphological Mapping (BAMM) software, we measured global brain and tissue class volumes and mapped regional grey and white matter differences across the whole brain. With the expectation that volumes of interconnected regions correlate positively, we carried out a preliminary exploration of 'connectivity' in autism by comparing the nature of inter-regional grey matter volume correlations with control. Children with autism had a significant reduction in total grey matter volume and significant increase in CSF volume. They had significant localized grey matter reductions within fronto-striatal and parietal networks similar to findings in our previous study, and additional decreases in ventral and superior temporal grey matter. White matter was reduced in the cerebellum, left internal capsule and fornices. Correlation analysis revealed significantly more numerous and more positive grey matter volumetric correlations in controls compared with children with autism. Thus, using similar diagnostic criteria and image analysis methods in otherwise healthy populations with an autistic spectrum disorder from different countries, cultures and age groups, we report a number of consistent findings. Taken together, our data suggest abnormalities in the anatomy and connectivity of limbic-striatal 'social' brain systems which may contribute to the brain metabolic differences and behavioural phenotype in autism.

Adolescent↗
PubMed2006

Functional and effective connectivity in an fMRI study of an auditory-related task.

This study investigates the sets of brain areas that are functionally connected during an auditory goal-directed task. We used a paradigm including a resting state condition and an active condition, which consisted in active listening to the footsteps of walking humans. The regional brain activity was measured using fMRI and the adjusted values of activity in brain regions involved in the task were analysed using both principal component analysis and structural equation modelling. A first set of connected areas includes regions located in Heschl's gyrus, planum temporale, posterior superior temporal sulcus (in the so-called 'social cognition' area), and parietal lobe. This network could be responsible for the perceptual integration of the auditory signal. A second set encompassing frontal regions is related to attentional control. Dorsolateral- and medial-prefrontal cortex have mutual negative influences which are similar to those described during a visual goal-directed task [T. Chaminade & P. Fonlupt (2003) Eur. J. Neurosci., 18, 675-679.]. Moreover, the dorsolateral prefrontal cortex (DLPFC) exerts a positive influence on the auditory areas during the task, as well as a strong negative influence on the visual areas. These results show that: (i) the negative influence between the medial and lateral parts of the frontal cortex during a goal-directed task is not dependent on the input modality (visual or auditory), and (ii) the DLPFC activates the pathway of the relevant sensory modality and inhibits the nonrelevant sensory modality pathway.

Acoustic Stimulation↗
PubMed2004

Self-organizing dual coding based on spike-time-dependent plasticity.

It has been a matter of debate how firing rates or spatiotemporal spike patterns carry information in the brain. Recent experimental and theoretical work in part showed that these codes, especially a population rate code and a synchronous code, can be dually used in a single architecture. However, we are not yet able to relate the role of firing rates and synchrony to the spatiotemporal structure of inputs and the architecture of neural networks. In this article, we examine how feedforward neural networks encode multiple input sources in the firing patterns. We apply spike-time-dependent plasticity as a fundamental mechanism to yield synaptic competition and the associated input filtering. We use the Fokker-Planck formalism to analyze the mechanism for synaptic competition in the case of multiple inputs, which underlies the formation of functional clusters in downstream layers in a self-organizing manner. Depending on the types of feedback coupling and shared connectivity, clusters are independently engaged in population rate coding or synchronous coding, or they interact to serve as input filters. Classes of dual codings and functional roles of spike-time-dependent plasticity are also discussed.

Action Potentials↗
PubMed2004

[Neuroprotection in brain ischemia--doubts and hopes].

In ischaemic stroke the two major potential therapeutic strategies are aimed at either improving cerebral blood flow or directly interacting with the cytotoxic cascade--a large body of evidence gained from animal studies is in support of them. In clinical trials direct neuroprotection by blocking the neurotoxic cascade remained ineffective, although there are several clinical trials still in progress. We summarize the experimental data and present the results of clinical trials and also discuss why so many drugs, which were effective in animal studies, failed in human trials. It is emphasized, that 1. in most animal studies the reduction of infarct size, i.e. the amount of saved penumbral tissue, was the outcome measure, whereas neurological function remained unassessed; 2. the recovery of intellectual performance and higher cortical functions are of major importance in the future quality of life in stroke victims; however, it is impossible to examine these parameters appropriately in animal studies; 3. in many clinical trials the patient population was rather heterogenous and low in number, the study protocol was not optimal and the critical analysis of the subacute and chronic phase was lacking or insufficient. We present the major experimental stroke models, discuss their similarities, differences and limitations as compared to the human pathophysiological processes. The pitfalls of extrapolating data from animal studies to clinical practice are also summarized. The complex network of functional and morphological intercellular connections, the long timescale of neurotoxic and reparative events and the lessons learned from clinical trials suggest, that the use of drug combinations (therapeutic cocktails) targeting multiple steps of the neurotoxic cascade would hopefully result in more effective treatment of ischaemic stroke. Strategies to facilitate brain plasticity and regeneration is an additional promising tool to enhance recovery in brain ischaemia.

Animals↗
PubMed2005

Hysterical conversion and brain function.

Hysterical conversion disorders represent "functional" or unexplained neurological deficits such as paralysis or somatosensory losses that are not explained by organic lesions in the nervous system, but arise in the context of "psychogenic" stress or emotional conflicts. After more than a century of both clinical and theoretical interest, the exact nature of such emotional disorders responsible for hysterical symptoms, and their functional consequences on neural systems in the brain, still remain largely unknown. However, several recent studies have used functional brain imaging techniques (such as EEG, fMRI, PET, or SPECT) in the attempt to identify specific neural correlates associated with hysterical conversion symptoms. This article presents a general overview of these findings and of previous neuropsychologically based accounts of hysteria. Functional neuroimaging has revealed selective decreases in the activity of frontal and subcortical circuits involved in motor control during hysterical paralysis, decreases in somatosensory cortices during hysterical anesthesia, or decreases in visual cortex during hysterical blindness. Such changes are usually not accompanied by any significant changes in elementary stages of sensory or motor processing as measured by evoked potentials, although some changes in later stages of integration (such as P300 responses) have been reported. On the other hand, several neuroimaging results have shown increased activation in limbic regions, such as cingulate or orbitofrontal cortex during conversion symptoms affecting different sensory or motor modalities. Taken together, these data generally do not support previous proposals that hysteria might involve an exclusion of sensorimotor representations from awareness through attentional processes. They rather seem to point to a modulation of such representations by primary affective or stress-related factors, perhaps involving primitive reflexive mechanisms of protection and alertness that are partly independent of conscious control, and mediated by dynamic modulatory interactions between limbic and sensorimotor networks. A better understanding of the neuropsychobiological bases of hysterical conversion disorder might therefore be obtained by future imaging studies that compare different conversion symptoms and employ functional connectivity analyses. This should not only lead to improve clinical management of these patients, but also provide new insights on the brain mechanisms of self-awareness.

Brain↗
PubMed2001

Principles underlying mammalian neocortical scaling.

The neocortex undergoes a complex transformation from mouse to whale. Whereas synapse density remains the same, neuron density decreases as a function of gray matter volume to the power of around -1/3, total convoluted surface area increases as a function of gray matter volume to the power of around 8/9, and white matter volume disproportionately increases as a function of gray matter volume to the power of around 4/3. These phylogenetic scaling relationships (including others such as neuron number, neocortex thickness, soma radius, and number of cortical areas) are clues to understanding the principles driving neocortex organization, but there is currently no theory that can explain why these neocortical quantities scale as they do. Here I present a two-part model that explains these neocortical allometric scaling laws. The first part of the model is a special case of the physico-mathematical model recently put forward to explain the quarter power scaling laws in biology. It states that the neocortex is a space-filling neural network through which materials are efficiently transported, and that synapse sizes do not vary as a function of gray matter volume. The second part of the model states that the neocortex is economically organized into functionally specialized areas whose extent of area-interconnectedness does not vary as a function of gray matter volume. The model predicts, among other things, that the number of areas and the soma radius increase as a function of gray matter volume to the power of 1/3 and 1/9, respectively, and empirical support is demonstrated for each. Also, the scaling relationships imply that, although the percentage of the total number of neurons to which a neuron connects falls as a function of gray matter volume with exponent -1/3, the network diameter of the neocortex is invariant at around two. Finally, I discuss how a similar approach may have promise in explaining the scaling relationships for the brain and other organs as a function of body mass.

Animals↗
PubMed2006

Using graph theoretical analysis of multi channel EEG to evaluate the neural efficiency hypothesis.

Previous studies demonstrated that intelligence is significantly related to an impressive array of psychological, social, biological and genetic factors and that working memory (WM) can be considered as a general cognitive resource strongly related with a wide variety of higher order cognitive competencies and intelligence. Also, evaluating the WM of subjects might allow one to test the neural efficiency hypothesis (NEH). WM typically involves functional interactions between frontal and parietal cortices. We recorded EEG signals to study neuronal interactions during one WM test in individuals who had few years of formal education (LE) as compared to individuals with university degrees (UE). The two groups of individuals differed in the scores they obtained in psychological tests. To quantify the synchronization between EEG channels in several frequency bands, we evaluated the "synchronization likelihood" (SL), which takes into consideration nonlinear processes as well as linear ones. SL was then converted into graphs to estimate the distance from "small-world network" (SWN) organization, i.e., an optimally organized network that would give rise to the data. In comparison to LE subjects, those with university degrees exhibited less prominent SWN properties in most frequency bands during the WM task. This finding supports the NEH and suggests that the connections between brain areas of well-educated subjects engaged in WM tasks are not as well-organized in the sense of SWN.

Adult↗
PubMed2004

Connectivity and dynamics of neural information processing.

In this article, we systematically review the current literature on neural connectivity and dynamics, or equivalently, structure and function. In particular, we discuss how changes in the connectivity of a neural network affect the spatiotemporal network dynamics qualitatively. The three major criteria of comparison are, first, the local dynamics at the network nodes which includes fixed point dynamics, oscillatory and chaotic dynamics; second, the presence of time delays via propagation along connecting pathways; and third, the properties of the connectivity matrix such as its statistics, symmetry, and translational invariance. Since the connection topology changes when anatomical scales are traversed, so will the corresponding network dynamics change. As a consequence different types of networks are encountered on different levels of neural organization.

Animals↗
PubMed2004

The repulsive guidance molecule RGMa is involved in the formation of afferent connections in the dentate gyrus.

In the developing dentate gyrus, afferent fiber projections terminate in distinct laminas. This relies on an accurately regulated spatiotemporal network of guidance molecules. Here, we have analyzed the functional role of the glycosylphosphatidylinositol (GPI)-anchored repulsive guidance molecule RGMa. In situ hybridization in embryonic and postnatal brain showed expression of RGMa in the cornu ammonis and hilus of the hippocampus. In the dentate gyrus, RGM immunostaining was confined to the inner molecular layer, whereas the outer molecular layers targeted by entorhinal fibers remained free. To test the repulsive capacity of RGMa, different setups were used: the stripe and explant outgrowth assays with recombinant RGMa, and entorhino-hippocampal cocultures incubated either with a neutralizing RGMa antibody (Ab) or with the GPI anchor-digesting drug phosphatidylinositol-specific phospholipase C. Entorhinal axons were clearly repelled by RGMa in the stripe and outgrowth assays. After disrupting the RGMa function, the specific laminar termination pattern in entorhino-hippocampal cocultures was lost, and entorhinal axons entered inappropriate hippocampal areas. Our data indicate an important role of RGMa for the layer-specific termination of the perforant pathway as a repulsive signal that compels entorhinal fibers to stay in their correct target zone.

Afferent Pathways↗
PubMed2004

Functional roles of the cingulo-frontal network in performance on working memory.

We examined the relationship between brain activities and task performance on working memory. A large-scale study was initially administered to identify good and poor performers using the operation span and reading span tasks. On the basis of those span scores, we divided 20 consenting participants into high- and low-span groups. In an fMRI study, the participants performed verification of arithmetic problems and retention of target words either concurrently or separately. The behavioral results showed that performance was better in the high-span group than in the low-span group under a dual-task condition, but not under two single-task conditions. The anterior cingulate cortex (ACC), left prefrontal cortex (PFC), left inferior frontal cortex, and bilateral parietal cortex were primarily activated for both span groups. We found that signal changes in the ACC were greater in the high-span group than in the low-span group under the dual-task condition, but not under the single-task conditions. Structural equation modeling indicated that an estimate of effective connectivity from the ACC to the left PFC was positive for the high-span group and negative for the-low span group, suggesting that closer cooperation between the two brain regions was strongly related to working memory performance. We conclude that central executive functioning for attention shifting is modulated by the cingulo-frontal network.

Adult↗