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Cerebral mechanisms of prosodic integration: evidence from connected speech.

Using functional Magnetic Resonance Imaging (fMRI) and long connected speech stimuli, we addressed the question of neuronal networks involved in prosodic integration by comparing (1) differences in brain activity when hearing connected speech stimuli with high and low degrees of prosodic expression; (2) differences in brain activity in two different diotic listening conditions (normal speech delivery to both ears, i.e., NN; and low-pass-filtered speech delivery to both ears, i.e., FF); and (3) effects of high and low degrees of prosodic information in the NN and FF conditions. Twelve right-handed French men listened passively to the stimuli. Each stimulus induced a specific cerebral network, the flat one weakening activations, which were mainly reduced to the bilateral STG for both listening conditions. High degrees of prosodic information were found to trigger right specific activations in a wider neuronal network involved in speech integration (such as BA44, BA21-22 and BA39-40) than low degrees of prosodic information did. More precisely, the right BA44 was found to be specifically involved in the process of F(0) modulations, which are the main acoustic correlate of prosody. Not only do the results achieved in the present experiment using 30-s-long connected speech stimuli show the involvement of a bilateral neuronal network but they also strongly suggest that high degrees of prosodic information elicit activations in a wider neuronal network involved in speech perception than low degrees of prosodic information do.

Acoustic Stimulation↗

Electroencephalographic evidence of cortical network disruption preceding overt cardioinhibition during tilt-induced reflex syncope.

OBJECTIVE: Reflex syncope is a common cause of transient loss of consciousness. However, the early cerebral mechanisms underlying cardiovascular changes remain poorly understood. Our objective was to investigate early cerebral changes by quantitatively analyzing EEG activity preceding overt cardioinhibition during tilt-induced reflex syncope. METHODS: EEG recordings from patients undergoing tilt testing were retrospectively analyzed. Patients who experienced reflex syncope were compared to those who did not. Spectral and functional connectivity analyses were performed across baseline, pre-cardioinhibition, and syncopal phases. RESULTS: Prior to the onset of cardioinhibitory pathological reflex, a significant increase in theta-band spectral power was observed in the right temporal region, accompanied by a widespread increase in functional connectivity within the same frequency band. These findings suggest the involvement of brain networks before cardioinhibition. CONCLUSIONS: EEG changes in the theta band (power and functional connectivity) were observed before overt cardioinhibition during tilt-induced reflex syncope. SIGNIFICANCE: Our findings support the hypothesis of cortical processing preceding cardioinhibition in reflex syncope. EEG may represent a valuable complementary tool for improving the understanding and diagnosis of these events.

Humans↗

Tracing premotor brain stem networks of orienting movements.

Methods allowing a direct matching of movement-related firing patterns and connectivity of individual neurons have been used in the analysis of premotor networks controlling orienting movements. Advances have been made in the description of coding properties of orienting-related tectal output neurons, as well as in specifying their distributed connections in the brain stem and possible modes of coupling to saccadic pattern generators in the reticular formation. New data on the properties of signals and connectivity patterns have also been obtained for the tecto-recipient reticulo-spinal neurons. At least a small portion of the network performing the spatio-temporal transformations of orienting-related tectal efferent signals can now be described both in functional and in morphological terms.

Animals↗

White matter and behavioral neurology.

Although the study of higher brain function has traditionally focused on the cortical gray matter, recent years have witnessed the recognition that white matter also makes an important contribution to cognition and emotion. White matter comprises nearly half the brain volume and plays a key role in development, aging, and many neurologic and psychiatric disorders across the life span. More than 100 disorders exist in which white matter neuropathology is the primary or a prominent feature. A variety of neurobehavioral syndromes may result from these disorders; the concept of white matter dementia has been introduced as characteristic of many patients with white matter involvement, and a wide range of focal neurobehavioral syndromes and psychiatric disorders can also be related to dysfunction of myelinated tracts. Understanding the neurobehavioral aspects of white matter disorders is important for clinical diagnosis, treatment, prognosis, and research on brain-behavior relationships. Central to these investigations is the use of modern neuroimaging techniques, which have already provided substantial information on the characterization of white matter and its disorders, and which promise to advance our knowledge further with continued innovation. Diffusion tensor imaging is an exciting method that will assist with the identification of critical white matter tracts in the brain, and the localization of specific lesions that can be correlated with neurobehavioral syndromes. A behavioral neurology of white matter is thus emerging in which clinical observation combined with sophisticated neuroimaging will enable elucidation of the role of white matter connectivity in the distributed neural networks subserving higher brain function.

Behavioral Sciences↗

Some radical implications of Bach-y-Rita's discoveries.

Bach-y-Rita's clinical results in restoring lost sensory function are based on several phenomena not widely appreciated in cognitive science. First, there is volume transmission. Extensive laboratory observation has shown that the brain is much more than a network of synaptically connected neurons. Bach-y-Rita has found that a key implication of volume transmission is that it is a functional component in adult brain plasticity, also widely observed experimentally. Plasticity has led him to conclude that the structure of brain dynamics is beyond the scope of algorithmic computation. If the brain is not a computer, this insight would have a significant impact on the development of new technologies based on brain function. Bach-y-Rita's work is being extended from restoration of lost senses to the creation of new senses. This in turn could lead to a new technology of "wiring a human-in-the-loop" that would be utterly unlike any computationally based technology. Instead of mere interaction with a machine, the human "becomes one" with it.

Brain↗

A hybrid neural network model for consciousness.

A new framework for consciousness is introduced based upon traditional artificial neural network models. This framework reflects explicit connections between two parts of the brain: one global working memory and distributed modular cerebral networks relating to specific brain functions. Accordingly this framework is composed of three layers, physical mnemonic layer and abstract thinking layer, which cooperate together through a recognition layer to accomplish information storage and cognition using algorithms of how these interactions contribute to consciousness: (1) the reception process whereby cerebral subsystems group distributed signals into coherent object patterns; (2) the partial recognition process whereby patterns from particular subsystems are compared or stored as knowledge; and (3) the resonant learning process whereby global workspace stably adjusts its structure to adapt to patterns' changes. Using this framework, various sorts of human actions can be explained, leading to a general approach for analyzing brain functions.

Algorithms↗

Controlling activity fluctuations in large, sparsely connected random networks.

Controlling activity in recurrent neural network models of brain regions is essential both to enable effective learning and to reproduce the low activities that exist in some cortical regions such as hippocampal region CA3. Previous studies of sparse, random, recurrent networks constructed with McCulloch-Pitts neurons used probabilistic arguments to set the parameters that control activity. Here, we extend this work by adding an additional, biologically appropriate, parameter to control the magnitude and stability of activity oscillations. The new constant can be considered to be the rest conductance in a shunting model or the threshold when subtractive inhibition is used. This new parameter is critical for large networks run at low activity levels. Importantly, extreme activity fluctuations that act to turn large networks totally on or totally off can now be avoided. We also show how the size of external input activity interacts with this parameter to affect network activity. Then the model based on fixed weights is extended to estimate activities in networks with distributed weights. Because the theory provides accurate control of activity fluctuations, the approach can be used to design a predictable amount of pseudorandomness into deterministic networks. Such nonminimal fluctuations improve learning in simulations trained on the transitive inference problem.

Computer Simulation↗

White matter tractography by anisotropic wavefront evolution and diffusion tensor imaging.

Determination of axonal pathways provides an invaluable means to study the connectivity of the human brain and its functional network. Diffusion tensor imaging (DTI) is unique in its ability to capture the restricted diffusion of water molecules which can be used to infer the directionality of tissue components. In this paper, we introduce a white matter tractography method based on anisotropic wavefront propagation in diffusion tensor images. A front propagates in the white matter with a speed profile governed by the isocontour of the diffusion tensor ellipsoid. By using the ellipsoid, we avoid possible misclassification of the principal eigenvector in oblate regions. The wavefront evolution is described by an anisotropic version of the static Hamilton-Jacobi equation, which is solved by a sweeping method in order to obtain correct arrival times. Pathways of connection are determined by tracing minimum-cost trajectories using the characteristic vector field of the resulting partial differential equation. A validity index is described to rate the goodness of the resulting pathways with respect to the directionality of the tensor field. Connectivity results using normal human DTI brain images are illustrated and discussed. We also compared our method with a similar level set-based tractography technique, and found that the anisotropic evolution increased the validity index of the obtained pathways by 18%.

Algorithms↗

Dynamic Fusion of Genomics and Functional Network Connectivity in UK Biobank Reveals Schizophrenia-Related SNP Manifolds.

Many mental disorders show strong genetic influence. In parallel, dynamic functional network connectivity (dFNC) has shown high sensitivity to brain changes related to mental disorders. However, previous studies linking dFNC to genetics largely follow a paradigm to identify associations between one set of genetic factors and multiple sets of connectivity features from different dFNC states, ignoring the potential variability in genetic correlates across states. We propose a novel joint ICA (jICA)-based "dynamic fusion" framework to identify dynamically tuned genetic manifolds. A sliding window approach was utilized to estimate four dFNC states and compute subject-level state-average dFNC (sa-dFNC) features. The sa-dFNC features of each state were combined with schizophrenia risk single nucleotide polymorphisms (SNPs) within a jICA fusion framework, resulting in four parallel fusions in 32,861 individuals of the UK Biobank cohort. The extracted four sets of joint SNP-dFNC components were further validated for clinical relevance in a combined schizophrenia cohort of 820 individuals (348 patients). The similarity of SNP-dFNC components across four parallel fusions was evaluated as a measure of state variability. We observed a mixture of "state-invariant" and "state-variant" components for SNP and dFNC modalities. Particularly, the schizophrenia-related state-variant SNP components, or manifolds, complemented each other by capturing different SNPs involved in the same biological functions, revealing a partition of genomic risk particularly elicited by the dynamics of brain function. By augmenting the SNP factors to state-variant manifolds, this dynamic fusion framework promises additional insights into the underlying genetic risk of disease-related alterations in dynamic brain function.

Humans↗

Learning, plasticity, and recovery in the central nervous system.

Cerebral functions can be described by the interaction of different brain regions as parts of distributed networks. Learning is seen as a refinement of the connection between the various parts of these networks. Plastic changes, as illustrated in brain charting techniques, are the result of learning (or use) in normal brains or found as adaptation (active or passive) after peripheral or central lesions. The relation between brain reorganization and recovery of function is investigated by two recent studies relating the training-induced improvement of lost function to changes in the brain. Others search for the effects of passive stimulation and drug influences. Independently of the approach, however, the general idea is that recovery can be seen as a reconnection between the remaining parts of the disturbed network.

Adaptation, Physiological↗

Characterization of the perivascular reticulin network in a case of primary brain lymphoma. Immunohistochemical demonstration of collagen types I, III, IV, and V; laminin; and fibronectin.

The character of the silver positive reticulin network was analyzed with immunofluorescence and immunoperoxidase methods in an intra vitam diagnosed case of primary brain lymphoma. The network was shown to contain connective tissue proteins rich in hexose-sugars, such as type III collagen (classical "reticulin"), basal lamina constituents type IV collagen and laminin, pericellular type V collagen, as well as fibronectin (protein involved in cell adhesion). On the other hand, very little of the fibrous type I collagen was discernible. Similarly as the silver positive network, the immunohistochemically demonstrable reticulum seemed to hold the cells in the perivascular location, and once it was broken diffuse spread into the tissue occurred. Since malignant cells of B-lymphocyte origin are not known to synthesize so-called reticulin, it is suggested that the network in primary brain lymphomas is produced by cells in the brain parenchyma (possibly pericytes or astrocytes) as a protective attempt to restrict the spread of foreign cells into the brain.

Brain↗

In vivo measurements of neurotransmitters by microdialysis sampling.

The brain contains a vast network of neurons that connect with each other at specialized junctions called synapses.A synapse consists of a presynaptic terminal (the "sending"neuron) and a postsynaptic bouton (the "receiving" neuron)that are separated by a gap of 5-50 nm (Figure 1). Chemicals released into this synaptic gap interact with receptors on the postsynaptic neuron. This leads to intracellular changes in the postsynaptic neuron-for example, an altered membrane potential or gene expression. The chemical signal is terminated by transporter proteins that transfer transmitter molecules across the membrane to the intracellular space (a process known as "reuptake")or enzymes that degrade the transmitter in the vicinity of the synapse (Figure 1). This classical view of neurotransmission might be considered point-to-point or"wired" communication because neurons communicate only with neurons to which they are specifically connected. In addition,neurotransmitters can activate receptors at more distant sites either by escaping the synapse or by being directly released into extrasynaptic space. This longer-range communication has been called "volume" transmission (1, S1; S references can be found in Supporting Information). All brain functions, from controlling movement to emotions, involve these two forms of chemical communication. Analytical chemistry has an important role to play in developing our understanding of the brain by providing tools for identification and measurement of the many chemicals involved in neurotransmission.

Brain Chemistry↗

[Neurocognition and PET. Strategies for data analysis in activation studies on working memory].

AIM: In cognitive neuroscience regional cerebral blood flow (rCBF) imaging with positron-emission-tomography (PET) is a powerful tool to characterize different aspects of cognitive processes by using different data analysis approaches. By use of an n-back verbal working memory task (varied from 0- to 3-back) we present cognitive subtraction analysis as basic strategy as well as parametric and covariance analyses and discuss the results. METHODS: Correlation analyses were performed using the individual performance rate as an external covariate, computing inter-regional correlations, and as network analysis applying structural equation modelling to evaluate the effective connectivity between the involved brain regions. RESULTS: Subtraction analyses revealed a fronto-parietal neuronal network also including the anterior cingulate cortex and the cerebellum. With higher memory load the parametric analysis evidenced linear rCBF increases in prefrontal, pre-motor and inferior parietal areas including the precuneus as well as in the anterior cingulate cortex. The rCBF correlation with the individual performance as external covariate depicted negative correlations in bilateral prefrontal and inferior parietal regions, in the precuneus and the anterior cingulate cortex. The network analysis demonstrated mainly occipito-frontally directed interactions which were predominantly left-hemispheric. Additionally, strong linkages were found between extrastriate and parietal regions as well as within the parietal cortex. CONCLUSION: The data analysis approaches presented here contribute to an extended and more elaborated understanding of cognitive processes and their different sub-aspects.

Brain↗

A novel method for visualizing functional connectivity using principal component analysis.

Functional connectivity is a useful measure of voxel-wise functional magnetic resonance imaging signals that allows for the identification of functionally related brain areas and distributed networks. However, the high dimensionality of functional connectivity makes it difficult to visualize. In most studies, a small percentage of the total functional connectivity is visualized through diagrams that are constructed using individual seed voxels. In the present study describes a new method for visualizing most of the functional connectivity through a single diagram. This method does not rely on seed voxels, but rather employs a reduction of the high-dimensionality of the functional connectivity via a projection onto a three-dimensional color space using principal components analysis. With this new method, most of the information contained in a functional connectivity matrix can be represented through a single color-coded functional connectivity map, thereby facilitating a greater visual appreciation of functional connectivity.

Brain↗

Mechanisms of axon guidance in the developing nervous system.

The human brain assembles an incredible network of over a billion neurons. Understanding how these connections form during development in order for the brain to function properly is a fundamental question in biology. Much of this wiring takes place during embryonic development. Neurons are generated in the ventricular zone, migrate out, and begin to differentiate. However, neurons are often born in locations some distance from the target cells with which they will ultimately form connections. To form connections, neurons project long axons tipped with a specialized sensing device called a growth cone. The growing axons interact directly with molecules within the environment through which they grow. In order to find their targets, axonal growth cones use guidance molecules that can either attract or repel them. Understanding what these guidance cues are, where they are expressed, and how the growth cone is able to transduce their signal in a directionally specific manner is essential to understanding how the functional brain is constructed. In this chapter, we review what is known about the mechanisms involved in axonal guidance. We discuss how the growth cone is able to sense and respond to its environment and how it is guided by pioneering cells and axons. As examples, we discuss current models for the development of the spinal cord, the cerebral cortex, and the visual and olfactory systems.

Animals↗

Chemical network of the living human brain. Evidence of reorganization with aging.

We recently described the chemical network properties of the human brain using in vivo proton magnetic resonance spectroscopy ((1)H MRS). In a separate study of aging we found increased concentration of chemicals in the prefrontal and sensorimotor cortices up to the third decade of life, and subsequent decrease of chemical concentrations in the same brain regions after the third decade between young and middle age. We anticipated that these age-dependent differences in chemical concentrations might be a reflection of the chemical network reorganization of the brain during aging. The pattern of chemical connectivity within and across brain regions for all regional chemicals, and specific patterns of chemical connectivity for each chemical type were examined for young and middle age groups using (1)H MRS and correlation analysis. For all studied ages, the dominant positive correlations occurred within brain regions and negative correlations were seen across brain regions. However, the pattern of negative chemical connectivity across brain regions was weaker in middle-aged group (F = 40.4, P < 10(-7) comparing r-values between the two age groups, ANOVA). Within brain regions, the age effects on chemical correlations were seen in the cingulate cortex (46% decrease in the middle-aged group, F = 7.2, P < 0.007) and sensorimotor cortex (SMC) (27% decrease, F = 8.9, P<0.003). Between brain regions, the age effects on chemical correlations were seen in the chemical interactions between the thalamus (433.3% increase in the middle-aged group, F = 11.7, P < 0.003), SMC (280% increase, F=20.1, P < 10(-5)), cingulate cortex (100.7% increase, F = 21.3, P < 10(-7)), and other brain regions. We found also age-differential patterns of chemical connectivity across the studied brain regions for most chemical types. The results provide evidence that normal aging is associated with reorganization of chemical network of the human brain.

Adult↗

[Neural pathways--neural networks].

During the past two decades, the introduction of several modern neuroanatomical approaches resulted in a rapidly growing body of informations about neuronal pathways in the central nervous system. Several new neuronal connections between brain areas have been discovered, and the chemical nature (neurotransmitter content) of pathways has been determined by using highly specific neurochemical and immunohistochemical techniques. On the basis of these new informations, our knowledge and attitude to the general organization of neuronal connections have been changed substantially: 1. Neuronal pathways are multi-neuronal networks rather than simple chain of neurons, wherein informations are forwarded between two brain areas bidirectionally, meanwhile several additional brain regions are inter-connected by axon-collaterals. 2. A single neuronal cell may synthesize several neuropeptides which co-localized in and released from nerve terminals, and depending on the target sites they may act as neurotransmitters or neurohormones. In certain conditions, neuropeptides may also function as nerve growth factors by supporting the survival or the restitution of neuronal cells. 3. By the introduction of molecular imaging in neuroscience (visualization of oncogenes, specific mRNA's, etc), topographical studies on neuronal pathways are more and more completed by functional informations.

Brain↗

Immunoreactivity in Limulus: III. Morphological and biochemical studies of FMRFamide-like immunoreactivity and colocalized substance P-like immunoreactivity in the brain and lateral eye.

FMRFamide-like immunoreactivity (FLI) and the colocalization of FMRFamide and substance P-like (SPLI) immunoreactivities were examined in the brain and lateral eye of the horseshoe crab with FITC- and TRITC-labeled secondary antibody techniques. In the brain, fibers with FLI were localized in the neuropils of the lamina, medulla, central body, corpus pedunculatum, optic tract, circumesophageal connective, and central neuropil. An extensive network of reactive fibers innervatives the brain's vascular sheath. Somata with FLI were found in the dorsal medial group, dorsal lateral posterior groups #1 and #2, and ventral posterior lateral groups #1 and #2. Several distinct subgroups of reactive somata were noted in both the medullar and ventral medial groups. The distribution of fibers in the brain with colocalized FLI and SPLI includes those which innervate the vascular sheath and widespread populations of small-diameter beaded fibers in the central neuropil and circumesophageal connective. Somata with colocalized FLI and SPLI constitute minority populations in the medullar and dorsal medial groups but form the majority population of a subgroup in the ventral medial group. Overall localization of SPLI was reevaluated and is reported here according to the nomenclature of the new Chamberlain and Wyse brain atlas. In addition to those previously reported, somata with SPLI were found in the dorsal lateral posterior groups #1 and #2, the ventral lateral posterior groups #1 and #2, and several distinct subgroups of the medial and ventral medial groups. In the retina of the lateral eye, fibers with both FLI and SPLI ramify in the lateral plexus and ultimately innervate the corneal epidermis. Brain homogenates were examined for immunoreactive (ir) FMRFamide and ir-substance P with radioimmunoassay techniques. Ir-FMRFamide and ir-substance P eluted in different fractions from both gel filtration chromatography and HPLC. Furthermore, the binding curves for both substances were similar to those of the corresponding synthetic compounds. Brain homogenates were also bioassayed on the lateral eye. Three gel filtration fractions mimic natural circadian activity by increasing the sensitivity of the lateral eye, but they were not coincident with ir-FMRFamide or ir-substance P. Although it is not completely resolved what the active molecules in these fractions are, it is clear that neither ir-FMRFamide nor ir-substance P is a possible candidate.

Animals↗