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[The effect of blood-filled meshwork of arachnoid villi in connection with posttraumatic brain edema (author's transl)].

Based on the Kellie-Munro doctrine according to which the intracranial compartments--blood, brain, and CSF--are in a state of pressure and volume equilibrium, we examined if traumatic lesions of the liquor absorption passages could change the intracranial pressure (ICP). Therefore, we reviewed the arachnoid villi and granulations of patients which died as a result of head injuries. In cases of traumatic subarachnoidal hemorrhages the meshwork of arachnoid villi are filled throughout with blood. By microscopical examination we observed findings in the network of spaces of the villi like they are known in prestatic and static conditions of capillary system (clothing of erythrocytes). The pathophysiological significance of the findings, especially with regard to the dynamic of posttraumatic brain edema, is discussed.

Adult↗

From anatomic standardization analysis of perfusion SPECT data to perfusion pattern modeling: evidence of functional networks in healthy subjects and temporal lobe epilepsy patients.

RATIONALE AND OBJECTIVES: In the general context of perfusion pattern modeling from single-photon emission computed tomographic (SPECT) data, the purpose of this study is to characterize interindividual functional variability and functional connectivity between anatomic structures in a set of SPECT data acquired from a homogeneous population of subjects. MATERIALS AND METHODS: From volume of interest (VOI)-perfusion measurements performed on anatomically standardized SPECT data, we proposed to use correspondence analysis (CA) and hierarchical clustering (HC) to explore the structure of statistical dependencies among these measurements. The method was applied to study the perfusion pattern in two populations of subjects; namely, SPECT data from 27 healthy subjects and ictal SPECT data from 10 patients with mesio-temporal lobe epilepsy (MTLE). RESULTS: For healthy subjects, anatomic structures showing statistically dependent perfusion patterns were classified into four groups; namely, temporomesial structures, internal structures, posterior structures, and remaining cortex. For patients with MTLE, they were classified as temporomesial structures, surrounding temporal structures, internal structures, and remaining cortex. Anatomic structures of each group showed similar perfusion behavior so that they may be functionally connected and may belong to the same network. Our main result is that the temporal pole and lenticular nucleus seemed to be highly relevant to characterize ictal perfusion in patients with MTLE. This exploratory analysis suggests that a network involving temporal structures, lenticular nucleus, brainstem, and cerebellum seems to be involved during MTLE seizures. CONCLUSION: CA followed by HC is a promising approach to explore brain perfusion patterns from SPECT VOI measurements.

Adult↗

Brain-machine and brain-computer interfaces.

The idea of connecting the human brain to a computer or machine directly is not novel and its potential has been explored in science fiction. With the rapid advances in the areas of information technology, miniaturization and neurosciences there has been a surge of interest in turning fiction into reality. In this paper the authors review the current state-of-the-art of brain-computer and brain-machine interfaces including neuroprostheses. The general principles and requirements to produce a successful connection between human and artificial intelligence are outlined and the authors' preliminary experience with a prototype brain-computer interface is reported.

Animals↗

The role of intact frontostriatal circuits in error processing.

The basal ganglia have been suggested to play a key role in performance monitoring and resulting behavioral adjustments. It is assumed that the integration of prefrontal and motor cortico-striato-thalamo-cortical circuits provides contextual information to the motor anterior cingulate cortex regions to enable their function in performance monitoring. So far, direct evidence is missing, however. We addressed the involvement of frontostriatal circuits in performance monitoring by collecting event-related brain potentials (ERPs) and behavioral data in nine patients with focal basal ganglia lesions and seven patients with lateral prefrontal cortex lesions while they performed a flanker task. In both patient groups, the amplitude of the error-related negativity was reduced, diminishing the difference to the ERPs on correct responses. Despite these electrophysiological abnormalities, most of the patients were able to correct errors. Only in lateral prefrontal cortex patients whose lesions extended into the frontal white matter, disrupting the connections to the motor anterior cingulate cortex and the striatum, were error corrections severely impaired. In sum, the fronto-striato-thalamo-cortical circuits seem necessary for the generation of error-related negativity, even when brain plasticity has resulted in behavioral compensation of the damage. Thus, error-related ERPs in patients provide a sensitive measure of the integrity of the performance monitoring network.

Adult↗

[Attention: a complex cerebral function].

INTRODUCTION: Attention is a brain neurocognitive state of preparing what precedes perception and action, and is a result of cortical and subcortical networks. Attention selectively focuses our consciousness while filtering the constant flow of sensory information, selects competent parallel processing among stimuli and activates brain zones for ordering appropriate responses. DEVELOPMENT: From a neurofunctional point of view this paper reviews and describes attention as a brain function regulated by three interrelated systems: Alertness or arousal providing tonic attention, dependent on the mesencephalic reticular activating system and its connections: posterior attention or attention of perceptive selectivity that depends on zones of the right posterior parietal cortex and its connections; and, anterior attention or supervisory attention that regulates deliberate attention, and supported by zones of the anterior cingulate and lateral prefrontal cortex and the connections of the zones.

Attention↗

Neuronal activity and the establishment of normal and epileptic circuits during brain development.

The question we attempted to address in this chapter is: Do brief but recurrent seizures in early life alter the ontogeny of hippocampal networks in ways that produce epileptic circuits? Results from the tetanus toxin model suggest that this is likely the case. Following seizures in Postnatal Weeks 2 and 3, most adult rats have a focal epilepsy that arises from hippocampus. Recordings from hippocampal slices support this conclusion since they demonstrated the occurrence of spontaneous network discharges in normal artificial cerebrospinal fluid. Moreover, when GABA-A receptor-mediated synaptic transmission was suppressed, slices from adult epileptic rats produced prolonged electrographic seizures which are never observed in control rats. This suggests that hyperexcitable recurrent excitatory networks contribute to hippocampal seizures in this model. In light of this, anatomical results from biocytin-filled neurons were surprising. Results suggest that recurrent axon arbors neither sprout additional branches as a result of seizure activity nor maintain their exuberant branching patterns of early life. Thus, excessive connectivity cannot explain seizure generation. Axon arbors either remodel in normal ways or prune additional collaterals as a result of ongoing epileptiform discharging. At the same time that axon arbors remodel, the dendrites of these cells have decreased dendritic spine density, suggesting a partial deafferentation. While a complete understanding of the origins of spine loss requires further investigation, we hypothesize that this loss is a product of a partial deafferentation that occurs due to excessive and abnormal selection of synaptic connections. Network-induced heterosynaptic LTD of noncoincidentally active afferants may be one mechanism that leads to a loss of synapses. Moreover, competition among and selection between individual recurrent excitatory synapses may contribute to spine loss as well. The "winners" of this competition, the most potent and effective early-formed recurrent excitatory synapses, are likely key contributors to seizure generation in this model and possibly in humans with early-onset temporal lobe epilepsy.

Aging↗

Schema design and implementation of the grasp-related mirror neuron system.

Mirror neurons within a monkey's premotor area F5 fire not only when the monkey performs a certain class of actions but also when the monkey observes another monkey (or the experimenter) perform a similar action. It has thus been argued that these neurons are crucial for understanding of actions by others. We offer the hand-state hypothesis as a new explanation of the evolution of this capability: the basic functionality of the F5 mirror system is to elaborate the appropriate feedback - what we call the hand state - for opposition-space based control of manual grasping of an object. Given this functionality, the social role of the F5 mirror system in understanding the actions of others may be seen as an exaptation gained by generalizing from one's own hand to an other's hand. In other words, mirror neurons first evolved to augment the "canonical" F5 neurons (active during self-movement based on observation of an object) by providing visual feedback on "hand state," relating the shape of the hand to the shape of the object. We then introduce the MNS1 (mirror neuron system 1) model of F5 and related brain regions. The existing Fagg-Arbib-Rizzolatti-Sakata model represents circuitry for visually guided grasping of objects, linking the anterior intraparietal area (AIP) with F5 canonical neurons. The MNS1 model extends the AIP visual pathway by also modeling pathways, directed toward F5 mirror neurons, which match arm-hand trajectories to the affordances and location of a potential target object. We present the basic schemas for the MNS1 model, then aggregate them into three "grand schemas" - visual analysis of hand state, reach and grasp, and the core mirror circuit - for each of which we present a useful implementation (a non-neural visual processing system, a multijoint 3-D kinematics simulator, and a learning neural network, respectively). With this implementation we show how the mirror system may learn to recognize actions already in the repertoire of the F5 canonical neurons. We show that the connectivity pattern of mirror neuron circuitry can be established through training, and that the resultant network can exhibit a range of novel, physiologically interesting behaviors during the process of action recognition. We train the system on the basis of final grasp but then observe the whole time course of mirror neuron activity, yielding predictions for neurophysiological experiments under conditions of spatial perturbation, altered kinematics, and ambiguous grasp execution which highlight the importance of the timing of mirror neuron activity.

Animals↗

Characterizing spatial and temporal features of autobiographical memory retrieval networks: a partial least squares approach.

Conway (Conway, M.A., 1992. A structural model of autobiographical memory. In: Conway, M.A., Spinnler, H., Wagenaar, W.A. (Eds.), Theoretical Perspectives on Autobiological Memory. Kluwer Academic Publishers, Dordrecht, The Netherlands, pp. 167-194) proposed that two types of autobiographical memories (AMs) exist within a hierarchical AM system: unique, specific events and repeated, general memories. There is little research on whether retrieval of these AMs relies on different neural substrates. To investigate this issue, we used a multivariate image analysis technique, spatiotemporal partial least squares (PLS), to identify distributed patterns of activity most related to AM tasks that we have found to be associated with a medial and left-lateralized network. Using PLS, specific and general memories were more strongly associated with different parts of this retrieval network. Specific AM retrieval was associated more with activation of regions involved in imagery in episodic memory, including the left precuneus, left superior parietal lobule and right cuneus, whereas general AM retrieval was associated with activation of the right inferior temporal gyrus, right medial frontal cortex, and left thalamus. These two patterns emerged at different lags after stimulus onset, with the general AM pattern peaking between 2 and 6 s, and the specific AM pattern between 6 and 8 s. These lag differences are consistent with Conway's theory which posits that general AMs are the preferred level of entry to the AM system. A seed PLS analysis revealed that the regions functionally connected to the hippocampus during retrieval did not differentiate specific from general AM retrieval, which confirms our earlier univariate analysis indicating that some aspects of the memory retrieval network are shared by these memories.

Adult↗

Associative memory design using support vector machines.

The relation existing between support vector machines (SVMs) and recurrent associative memories is investigated. The design of associative memories based on the generalized brain-state-in-a-box (GBSB) neural model is formulated as a set of independent classification tasks which can be efficiently solved by standard software packages for SVM learning. Some properties of the networks designed in this way are evidenced, like the fact that surprisingly they follow a generalized Hebb's law. The performance of the SVM approach is compared to existing methods with nonsymmetric connections, by some design examples.

Algorithms↗

Free will versus survival: brain systems that underlie intrinsic constraints on behavior.

This article discusses the neuroanatomical systems involved in the related functions of fear and discernment of the consequences of one's actions, two internal constraints on free will and action. Both mechanisms are related to a system for control and modulation of visceral function stretching from the spinal cord to the ventromedial prefrontal cortex, including the ventral striatum, ventral pallidum, and mediodorsal thalamus, the amygdala, the hypothalamus, the periaqueductal gray (PAG), and the brainstem reticular formation and autonomic nuclei. Reflexes at the lower levels provide rapid visceral and somatic reactions to threatening stimuli, while the PAG and hypothalamus coordinate these to produce more concerted responses. The amygdala interacts with the cortical sensory systems in the assessment of fear-related stimuli and modulates the reflex responses through projections to the hypothalamus and brainstem. The ventromedial prefrontal cortex, especially the "medial prefrontal network," is connected to the amygdala, hypothalamus, and PAG, and allows cortical control over the system in relation to a wider set of emotions. This cortical region is involved both in the assessment of reward and in mood disorders and it plays a central role in the ability to discern the consequences of one's actions and make appropriate behavioral choices. It also forms an interconnected circuit with specific cortical areas in the rostral superior temporal cortex, posterior parahippocampal cortex, and retrosplenial/posterior cingulate cortex. The overall function of this circuit is unclear, but may be involved in introspective monitoring of the individual.

Amygdala↗

Disorders of cortical development and epilepsy.

There has been an impressive increase in our ability to identify and categorize patients with cortical development lesions over the past decade. The clinical features associated with disorders of cortical development (DCD) have been described, and epilepsy has been shown to be a frequent symptom. In this review, we categorize DCD based on their structure and discuss their underlying causes and clinical features. Just as the cause of each type of disorder is thought to be unique, each disorder also has distinct types of seizures, treatment strategies, and electroencephalographic features. Studies in human tissue and animal models of DCD have begun to shed light on why DCD are associated with epilepsy. Aberrant synaptic connections within the dysplastic tissue and between the dysplastic tissue and more normal-appearing adjacent tissue form an abnormal, hyperexcitable network that increases seizure susceptibility. In the future, strategies for blocking formation of the aberrant networks may prevent the development of epilepsy.

Animals↗

A study on the microvasculature of the cerebellar cortex. The fundamental architecture and its senile change in the cerebellar hemisphere.

The arterial structure of the cerebellar cortex was studied by vascular stain and in diaphanized specimens after intra-arterial barium injections. A scanning electron microscope study on the corrosion cast of the arteries was also performed. Arteries distributed in the cerebellar hemisphere are classified into cortical, subcortical, and medullary arteries. The patterns of arterial distribution are similar to those in the cerebral cortex. The cortical arteries are subclassified into superficial, middle, and deep cortical branches. The superficial branches are very fine, forming capillary networks in the molecular layer. The middle cortical branches terminate in the Purkinje cell layer, by dividing into several branches extending parallel to the plane of this layer. These branches connect with capillaries in both the molecular and the granular layers. The deep cortical branches give off some collaterals along the Purkinje cell layer and terminate in the granular layer, by breaking up into capillary networks. The Purkinje cell layer is marked by arterial branches ramified from the middle and deep cortical branches and no particular dense capillary networks are formed in the Purkinje cell layer. The brains of older patients show intertwining of the middle and deep cortical branches, some forming "rope-like" appearance. These patterns are similar to those seen in the cerebral cortex, but they were found, in older people, in the cerebrum.

Aged↗

Morphological differentiation of bone marrow stromal cells into neuron-like cells after co-culture with hippocampal slice.

Adult green mice marrow stromal cells were co-cultured with hippocampal slices. Differentiation to neuron-like or non-neuron-like cells occurred exclusively inside slice boundaries starting at day 3, and then decreased gradually over 35 days. Neuron-like cells tended to form network-like connections around day 14. The use of retinoic acid greatly increased the number of differentiated cells, and the most effective concentration was 10(-6) M. NeuN immunohistochemistry was positive in 9.6+/-1.7% of morphologically differentiated neuron-like cells. Both GFAP and Iba1 immunostaining were negative. We concluded that bone marrow stromal cells can be differentiated into neurons, and direct contact with the host brain tissue is essential for this to occur. Retinoic acid significantly increases the number of differentiated cells, as has been reported with other stem cells.

Animals↗

Some proposals regarding the organization of the central nervous system control of penile erection.

Recent research on the central nervous control of penile erection is discussed. A framework for this control is based upon principles put forward by Frank Beach regarding the neuroendocrine regulation of male copulatory behavior. The current discussion is focused primarily on a subset, penile erection. The spinal cord contains all the necessary components for the production of penile erection. This requires a multisegmental coordination among penile vasodilator and vasoconstrictor autonomic neurons, pudendal motoneurons responsible for penile rigidity and autonomic neurons which control extra-penile blood flow. Genital sensory stimulation can activate this spinal network. The spinal cord is also under excitatory and inhibitory control from supraspinal sites. Penile erection can be driven by supraspinal input alone and supraspinal control can inhibit the erectile effects of genital stimulation.An important aspect of the CNS control of penile erection is that there are extensive interconnections between most of the brain sites identified to date. Most of the pathways are characterized by reciprocal connections. A large number of the CNS sites also receive genital sensory information. Thus, descending control may itself be modulated by ascending sensory pathways which relay information from the genitalia. This raises the possibility that penile erection may involve a positive feedback system. Receptors for gonadal hormones have been identified throughout the neuraxis. However, strong evidence for the control of male sexual function by gonadal hormones has been identified only for forebrain sites. The functional role of brainstem and spinal gonadal hormone receptors has not yet been clarified.

Animals↗

Is imitation learning the route to humanoid robots?

This review investigates two recent developments in artificial intelligence and neural computation: learning from imitation and the development of humanoid robots. It is postulated that the study of imitation learning offers a promising route to gain new insights into mechanisms of perceptual motor control that could ultimately lead to the creation of autonomous humanoid robots. Imitation learning focuses on three important issues: efficient motor learning, the connection between action and perception, and modular motor control in the form of movement primitives. It is reviewed here how research on representations of, and functional connections between, action and perception have contributed to our understanding of motor acts of other beings. The recent discovery that some areas in the primate brain are active during both movement perception and execution has provided a hypothetical neural basis of imitation. Computational approaches to imitation learning are also described, initially from the perspective of traditional AI and robotics, but also from the perspective of neural network models and statistical-learning research. Parallels and differences between biological and computational approaches to imitation are highlighted and an overview of current projects that actually employ imitation learning for humanoid robots is given.

Journal Article↗

MAPK, CREB and zif268 are all required for the consolidation of recognition memory.

There has been nearly a century of interest in the idea that encoding and storage of information in the brain requires changes in the efficacy of synaptic connections between neurons that are activated during learning. Recent research into the molecular mechanisms of long-term potentiation (LTP) has brought about new knowledge that has provided valuable insights into the neural mechanisms of memory storage. The evidence indicates that rapid activation of the genetic machinery can be a key mechanism underlying the enduring modification of neural networks required for the stability of memories. In recent years, a wealth of experimental data has highlighted the importance of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signalling in the regulation of gene transcription in neurons. Here, we briefly review experiments that have shown MAPK/ERK, cAMP response element-binding protein (CREB) and the immediate early gene (IEG) zif268 are essential components of a signalling cascade required for the expression of late phase LTP and of certain forms of long-term memory. We also present experiments in which we have assessed the role of these three molecules in recognition memory. We show that pharmacological blockade of MAPK/ERK phosphorylation, functional inactivation of CREB in an inducible transgenic mouse and inactivation of zif268 in a mutant mouse result in a similar deficit in long-term recognition memory. In the continuing debate about the role of LTP mechanisms in memory, these findings provide an important complement to the suggestion that synaptic changes brought about by LTP and memory consolidation and storage share, at least in part, common underlying molecular mechanisms.

Animals↗

The role of repulsive guidance molecules in the embryonic and adult vertebrate central nervous system.

During the development of the nervous system, outgrowing axons often have to travel long distances to reach their target neurons. In this process, outgrowing neurites tipped with motile growth cones rely on guidance cues present in their local environment. These cues are detected by specific receptors expressed on growth cones and neurites and influence the trajectory of the growing fibres. Neurite growth, guidance, target innervation and synapse formation and maturation are the processes that occur predominantly but not exclusively during embryonic or early post-natal development in vertebrates. As a result, a functional neural network is established, which is usually remarkably stable. However, the stability of the neural network in higher vertebrates comes at an expensive price, i.e. the loss of any significant ability to regenerate injured or damaged neuronal connections in their central nervous system (CNS). Most importantly, neurite growth inhibitors prevent any regenerative growth of injured nerve fibres. Some of these inhibitors are associated with CNS myelin, others are found at the lesion site and in the scar tissue. Traumatic injuries in brain and spinal cord of mammals induce upregulation of embryonic inhibitory or repulsive guidance cues and their receptors on the neurites. An example for embryonic repulsive directional cues re-expressed at lesion sites in both the rat and human CNS is provided with repulsive guidance molecules, a new family of directional guidance cues.

Animals↗

Associative recognition and storage in a model network of physiological neurons.

We consider a neural network model in which the single neurons are chosen to closely resemble known physiological properties. The neurons are assumed to be linked by synapses which change their strength according to Hebbian rules on a short time scale (100 ms). The dynamics of the network--the time evolution of the cell potentials and the synapses--is investigated by computer simulation. As in more abstract network models (Cooper 1973; Hopfield 1982; Kohonen 1984) it is found that the local dynamics of the cell potentials and the synaptic strengths result in global cooperative properties of the network and enable the network to process an incoming flux of information and to learn and store patterns associatively. A trained net can associate missing details of a pattern, can correct wrong details and can suppress noise in a pattern. The network can further abstract the prototype from a series of patterns with variations. A suitable coupling constant connecting the dynamics of the cell potentials with the synaptic strengths is derived by a mean field approximation. This coupling constant controls the neural sensitivity and thereby avoids both extremes of the network state, the state of permanent inactivity and the state of epileptic hyperactivity.

Animals↗