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Neural mechanisms potentially contributing to the intersegmental phase lag in lamprey.I. Segmental oscillations dependent on reciprocal inhibition.

Factors contributing to the production of a phase lag along chains of oscillatory networks consisting of Hodgkin-Huxley type neurons are analyzed by means of simulations. Simplified network configurations are explored consisting of the basic building blocks of the spinal central pattern generator (CPG) generating swimming in the lamprey. It consists of reciprocally coupled crossed inhibitory C interneurons and ipsilateral excitatory E interneurons that activate C neurons and other E neurons. Oscillatory activity in the model network can, in the simplest case, be produced by a pair of reciprocally coupled C interneurons oscillating through an escape mechanism. Different levels of tonic excitation drive the network over a wide burst frequency range. In this type of network, powerful frequency-regulating factors are the effective inhibition produced by the active side, in combination with the tendency of the inactive side to escape from the inhibition. These two mechanisms can be affected by several factors, e.g. spike frequency adaptation (calcium-dependent K(+) channels), N-methyl-D-aspartate membrane properties as well as presence of low-voltage activated calcium channels. A rostrocaudal phase lag can be produced either by extending the contralateral inhibitory projections or the ipsilateral excitatory projections relatively more in the caudal than the rostral direction, since both an increased inhibition and a phasic excitation slow down the receiving network. The phase lag becomes decreased if the length of the intersegmental projections is increased or if the projections are extended symmetrically in both the rostral and the caudal directions. The simulations indicate that the conditions in the ends of an oscillator chain may significantly affect sign, magnitude and constancy of the phase lag. Also, with short and relatively weak intersegmental connections, the network remains robust against perturbations as well as intrinsic frequency differences along the chain. The phase lag (percentage of cycle duration) increases, however, with burst frequency also when the coupling strength is comparatively weak. The results are discussed and compared with previous "phase pulling" models as well as relaxation oscillators.

Animals↗

[Cerebral mechanisms of hypnosis].

The neural mechanisms underlying hypnosis and especially the modulation of pain perception by hypnosis remain obscure. Using PET we first described the distribution of regional cerebral blood flow during the hypnotic state. Hypnosis relied on revivification of pleasant autobiographical memories and was compared to imaging autobiographical material in < >. The hypnotic state was related to the activation of a widespread set of cortical areas involving occipital, parietal, precentral, premotor, and ventrolateral prefrontal and anterior cingulate cortices. This pattern of activation shares some similarities with mental imagery, from which it mainly differs by the relative deactivation of precuneus. Second, we looked at the anti-nociceptive effects of hypnosis. Compared to the resting state, hypnosis reduced pain perception by approximately 50 %. The hypnosis-induced reduction of affective and sensory responses to noxious thermal stimulation were modulated by the activity in the midcingulate cortex (area 24a'). Finally, we assessed changes in cerebral functional connectivity related to hypnosis. Compared normal alertness (i.e., rest and mental imagery), the hypnotic state, significantly enhanced the functional to modulation between midcingulate cortex and a large neural network involved in sensory, affective, cognitive and behavioral aspects of nociception. These findings show that not only pharmacological but also psychological strategies for pain control can modulate the cerebral network involved in noxious perception.

Brain↗

Structural change and development in real and artificial neural networks.

Two related but different fields are reviewed. Initially some basic facts about developing real brains are set out and then work on dynamic neural networks is described. A dynamic neural network is defined as any artificial neural network that automatically changes its structure through exposure to input stimuli. Various models are described and evaluated and the functional correlates of both regressive and progressive structural changes are discussed. The paper concludes that, if future modelling work is to be set within a more neurally-plausible framework, then it would be fruitful to examine networks in which the connectivity between extant units is progressively embellished.

Journal Article↗

A Jacksonian and biopsychosocial hypothesis concerning borderline and related phenomena.

OBJECTIVE: The aim of this paper is to develop an aetiological model for borderline personality disorder. METHOD: The postulates of Hughlings Jackson are used to provide a preliminary explanatory framework for borderline phenomena. As a necessary background to this discussion, the findings concerning abuse in the early history of borderline personality disorder (BPD) and other conditions, notably somatisation disorder and dissociative states, are briefly reviewed. Other data, including family studies, which might have significance in the aetiology of BPD are also reviewed. RESULTS: The hypothesis is put forward that the symptoms of BPD are due to the failure of 'experience-dependent' maturation of a cascade of neural networks, with prefrontal connections, which become active relatively late in development and which coordinate disparate elements of central nervous system function. These networks subserve higher psychological functions, including attentional focus and affect regulation. They also underpin the reflective function necessary to the emergence of self as the stream of consciousness, which appears at about the age of 4 years. CONCLUSION: Adverse developmental circumstances may produce an interrelated set of symptom clusters, with associated neural network disturbances that are amenable to investigation with psychometric and brain imaging techniques. Since these disturbances are seen as 'experience-dependent', they are considered reversible, at least in part.

Adolescent↗

The functional neuroanatomy of autism.

Autism is a neurodevelopmental syndrome characterized by impaired social and executive functions. Functional magnetic resonance imaging (fMRI) is a non-invasive technique that allows investigation of the neural networks underlying cognitive impairments in autism. In this article, brain imaging studies investigating the functional brain anatomy of autism are reviewed. Face recognition, theory of mind and executive functions have all been explored in functional neuroimaging studies involving autistic patients. The available literature suggests an involvement of abnormal functional mechanisms in face recognition, mentalization and executive functions in adults with high-functioning autism or Asperger's syndrome, possibly due to brain maturation abnormalities, and resulting in dysfunctional reciprocal cortico-subcortical connections. Future functional neuroimaging research should investigate subgroups of autistic children and adolescents longitudinally and attempt to integrate genetic, cognitive and empirical approaches. Such studies will be instrumental in furthering understanding of the pathophysiology of autism and in exploring the importance of dimensional measures of the broader phenotype currently defined as autism.

Adolescent↗

A grid computing infrastructure for MEG data analysis.

Magnetoencephalography (MEG) is widely used for studying brain functions, but clinical applications of MEG have been less prevalent. One reason is that only clinicians who have highly specialized knowledge can use MEG diagnostically, and such clinicians are found at only a few major hospitals. Another reason is that MEG data analysis is getting more and more complicated, and deals with a large amount of data, and thus requires high-performance computing. These problems can be solved by the collaboration of human and computing resources distributed in multiple facilities. A new computing infrastructure for brain scientists and clinicians in distant locations was therefore developed by the Grid technology, which provides virtual computing environments composed of geographically distributed computers and experimental devices. A prototype system connecting an MEG system at the AIST in Japan, a Grid environment composed of PC clusters at Osaka University in Japan and Nanyang Technological University in Singapore, and user terminals in Baltimore was developed. MEG data measured at the AIST were transferred in real-time through a 1-GB/s network to the PC clusters for processing by a wavelet cross-correlation method, and then monitored in Baltimore. The current system is the basic model for remote-access to MEG equipment and high-speed processing of MEG data.

Computing Methodologies↗

An EEG approach to the neurodevelopmental hypothesis of schizophrenia studying schizophrenics, normal controls and adolescents.

Based on an integrative brain model which focuses on memory-driven and EEG state-dependent information processing for the organisation of behaviour, we used the developmental changes of the awake EEG to further investigate the hypothesis that neurodevelopmental abnormalities (deviations in organisation and reorganisation of cortico-cortical connectivity during development) are involved in the pathogenesis of schizophrenia. First-episode, neuroleptic-naive schizophrenics and their matched controls and three age groups of normal adolescents were studied (total: 70 subjects). 19-channel EEG delta-theta, alpha and beta spectral band centroid frequencies during resting (baseline) and after verbal stimuli were used as measure of the level of attained complexity and momentary excitability of the neuronal network (working memory). Schizophrenics compared with all control groups showed lower delta-theta activity centroids and higher alpha and beta activity centroids. Reactivity centroids (centroid after stimulus minus centroid during resting) were used as measure of update of working memory. Schizophrenics showed partial similarities in delta-theta and beta reactivity centroids with the 11-year olds and in alpha reactivity centroids with the 13-year olds. Within the framework of our model, the results suggest multifactorially elicited imbalances in the level of excitability of neuronal networks in schizophrenia, resulting in network activation at dissociated complexity levels, partially regressed and partially prematurely developed. It is hypothesised that activation of age- and/or state-inadequate representations for coping with realities becomes manifest as productive schizophrenic symptoms. Thus, the results support some aspects of the neurodevelopmental hypothesis.

Adaptation, Psychological↗

Functional connectivity with the hippocampus during successful memory formation.

Although it is well established that the hippocampus is critical for episodic memory, little is known about how the hippocampus interacts with cortical regions during successful memory formation. Here, we used event-related functional magnetic resonance imaging (fMRI) to identify areas that exhibited differential functional connectivity with the hippocampus during processing of novel objects that were subsequently remembered or forgotten on a postscan test. Functional connectivity with the hippocampus was enhanced during successful, as compared with unsuccessful, memory formation, in a distributed network of limbic cortical areas-including perirhinal, orbitofrontal, and retrosplenial/posterior cingulate cortex-that are anatomically connected with the hippocampal formation. Increased connectivity was also observed in lateral temporal, medial parietal, and medial occipital cortex. These findings demonstrate that successful memory formation is associated with transient increases in cortico-hippocampal interaction.

Adult↗

Seizures in paediatric Chiari type I malformation: the role of single-photon emission computed tomography.

UNLABELLED: Chiari type I malformation is one of the posterior fossa maldevelopments with which different clinical manifestations have been associated. Seizures have only recently been associated with Chiari type I malformation. This study reports on 4 children with epilepsy (2M, 2F; age range 8-15 y) diagnosed with Chiari type I malformation by brain magnetic resonance imaging (MRI), in whom no cortical structural involvement was observed. In these patients an interictal ethylcysteinate-dimer-single-photon emission computed tomographic (ECD-SPECT) study was performed to define more precisely the relationship between Chiari type I malformation and seizures. In these patients the hypoperfusion area correlated with electroencephalographic (EEG) focal abnormalities. These hypoperfusions may represent the functional aspect of a cerebral microdysgenesis; seizures and EEG epileptic anomalies may also be linked to the complex network connection between cortices and cerebellar hemispheres. A cerebellar hypoperfusion was also detected in two of the four examined patients, indicating a functional or structural involvement. CONCLUSION: Interictal SPECT scans are helpful for the clarification of seizures in patients with Chiari type I malformation.

Adolescent↗

Mirror neurons, procedural learning, and the positive new experience: a developmental systems self psychology approach.

In summary, we are impressed with the existence of a mirror neuron system in the prefrontal cortex that serves as part of a complex neural network, including afferent and efferent connections to the limbic system, in particular the amygdala, in addition to the premotor and motor cortex. We think it is possible to arrive at an integration that postulates the mirror neuron system and its many types of associated multimodal neurons as contributing significantly to implicit procedural learning, a process that underlies a range of complex nonconscious, unconscious, preconscious and conscious cognitive activities, from playing musical instruments to character formation and traumatic configurations. This type of brain circuitry may establish an external coherence with developmental systems self psychology which implies that positive new experience is meliorative and that the intentional revival of old-old traumatic relational configurations might enhance maladaptive procedural patterns that would lead to the opposite of the intended beneficial change. When analysts revive traumatic transference patterns for the purpose of clarification and interpretation, they may fail to appreciate that such traumatic transference patterns make interpretation ineffective because, as we have stated above, the patient lacks self-reflection under such traumatic conditions. The continued plasticity and immediacy of the mirror neuron system can contribute to positive new experiences that promote the formation of new, adaptive, implicit-procedural patterns. Perhaps this broadened repertoire in the patient of ways of understanding interrelational events through the psychoanalytic process allows the less adaptive patterns ultimately to become vestigial and the newer, more adaptive patterns to emerge as dominant. Finally, as we have stated, we believe that the intentional transferential revival of trauma (i.e., the old-old relational configuration) may not contribute to therapeutic benefit. In contrast, the revival of trauma in the old-new configuration (i.e., in the presence of a helpful other who can reduce anxiety and foster eventual positive new experience) can be beneficial, as trauma research has demonstrated. This is the process that promotes new implicit-procedural learning, new-new relational configurations, and a richer understanding of the self narrative.

Brain↗

[Intravital microscopic studies of the pial vessels in the animal experiment].

In cats, a direct observation of the brain surface was made possible by fenestration. The pial vessels were observed by means of intravital incident-light microscopy. Particular attention was paid to blood pressure, blood pH, pCO2 and pO2. Mainly with diffuse vasodilation (hypotension) the capillaries stood out as a close network. Normally, interarterial anastomoses were rarer than intravenous ones. Arteriovenous anastomoses were not found. The interarterial blood column rarely came to a standstill, the intervenously this was observed frequently. Two kinds of intervenous anastomoses were found: short connections between veins running close to each other and long venules between vessels of different outflow systems.

Animals↗

Voxel-based analysis of confounding effects of age and dementia severity on cerebral metabolism in Alzheimer's disease.

Alzheimer's disease is characterized by early hippocampal lesions, but neuropathological and functional imaging studies have also demonstrated involvement of associative cortices in patients suffering from this illness. New image-processing technologies have led to demonstration of predominant posteromedial cortical metabolic impairment in the disease. Confounding effects of both age and dementia severity on brain metabolism were assessed using categorical and correlational analyses performed with Statistical Parametric Mapping. Posterior cingulate and precuneus metabolism, assessed by positron emission tomography, was significantly correlated with age in a population of 46 patients with probable Alzheimer's disease. Metabolism in posterior cingulate and precuneus was higher in elderly than in younger patients with a diagnosis of Alzheimer's disease, even when dementia severity was taken as a confounding covariate. The data suggest that the sensitivity of positron emission tomography for the diagnosis of Alzheimer's disease is reduced in elderly cases, where less severe pathology is sufficient to induce clinical symptoms of dementia. Conversely, higher posteromedial metabolic impairment in early onset cases may reflect greater density of regional cerebral lesions or major decrease of functional afferences in a richly connected multimodal associative area. Posterior cingulate metabolism was also correlated to dementia severity, even when age was taken as a confounding covariate, whereas metabolism in the hippocampal formation was not shown to correlate with global cognitive deficit. Functional correlation was maintained between posterior cingulate and middle frontal cortex in demented patients as in elderly controls. The key role of posteromedial cortex in cognitive dysfunction assessed in Alzheimer's disease is probably related to its highly integrated position within attentional, visuospatial and memory neuronal networks.

Age Factors↗

Alzheimer's disease as a disorder of dynamic brain self-organization.

Mental function is based on the dynamic organization of neuronal networks. In particular, phylogenetically young brain areas (e.g., cortical associative circuits), involved in the realization of "higher brain functions" such as learning, memory, perception, self-awareness, and consciousness, are continuously re-adjusted even after development is completed. By this life-long self-optimization process, epigenetic information remodels the cognitive, behavioral and emotional reactivity of an individual to meet the environmental demands. To organize brain structures of increasing complexity during evolution, the process of selective dynamic stabilization and destabilization of synaptic connections becomes more and more important. The mechanisms of structural stabilization and labilization underlying a lifelong synaptic remodeling according to experience, are accompanied, however, by an increasing inherent potential of failure and may, thus, not only allow for the evolutionary acquisition of "higher brain function" but at the same time may provide the basis for selective neuronal vulnerability. The mechanisms of synaptic plasticity, i.e., of modifiable interneuronal connectivity, are largely based on external morphoregulatory cues and internal signaling pathways that nonneuronal cells have phylogenetically acquired to sense their relationship to the local neighborhood and to control proliferation and differentiation in the process of tissue repair and regeneration after development is completed. Differentiated neurons that have withdrawn from the cell cycle use these molecular machinery alternatively to control synaptic plasticity. The existence of these alternative effector pathways within a neuron puts it on the risk to erroneously convert signals derived from plastic synaptic changes into positional cues that will activate the cell cycle. This cell cycle activation potentially links synaptic plasticity to cell death. Preventing cell cycle activation by locking neurons in a differentiated but still highly plastic phenotype will, thus, be crucial to prevent neurodegeneration.

Alzheimer Disease↗

[The interrelations between neurons of the amygdala and hypothalamus during conditioning with selection of food reinforcement quality in cats].

Three cats were subjected to appetitive instrumental conditioning to light by the method of the "active choice" of the reinforcement quality. The short-delayed conditioned bar-pressings were reinforced by bread-meat mixture and the delayed response by meat. The animals differed in behavior strategy: two animals preferred bar-pressing with long delay (the so-called "self-control" group) and one animal preferred bar-pressing with short delay (the so-called "impulsive" group). The multiunit activity of the basolateral amygdala and nucleus lateralis of the hypothalamus was recorded through chronically implanted nichrome wire semimicroelecrodes. The interactions between the neighboring neurons in the lateral hypothalamus and basolateral amygdala (within the local neuronal network) and between the neurons of the basolateral amygdala and lateral hypothalamus (distributed neuronal networks in the direction amygdala--hypothalamus and vice versa) were evaluated by means of statistical crosscorrelation analysis of spike trains. The crosscorrelational interneuronal connections in the delay range of 0-100 ms were examined. It was shown that the number of crosscorrelations between the discharges on neurons both in the local networks of basolateral amygdala and distributed networks was significantly higher in "impulsive" cats. In both groups of animals, the percentage of crosscorrelations between neighbouring neurons in the local networks of the lateral hypothalamus was similar. We suggest that the local networks of the basolateral amygdala and amygdalar-hypothalamic distributed neuronal networks are involved in the system of brain structures which determine the individual features of animal behavior.

Amygdala↗

Memory in the cortex of the primate.

Memory is viewed as hierarchical and distributed in primary and association areas of cerebral cortex. Different memory neural networks are interconnected at various levels in this hierarchy, sharing neurons and connections. All memory is essentially associative in its generation, structure and retrieval. External and internal stimuli, to which we attend by virtue of their biological relevance or for other reason, can at any time activate ("turn on") the neuronal network to which they belong by previous association. This is the basis of knowledge and remembering. The reverberation in recurrent circuits may keep the network in an active state, that is, serving behavior, attention and consciousness. Monkey neuropsychological and electrophysiological data, and human tomographic (brain metabolism) evidence are presented supporting these concepts.

Animals↗

Intrinsic connections of the rat amygdaloid complex: projections originating in the central nucleus.

Inputs from the amygdaloid and extraamygdaloid areas terminate in various divisions of the central nucleus. To elucidate the interconnections between the different regions of the central nucleus and its connectivity with the other amygdaloid areas, we injected the anterograde tracer, Phaseolus vulgaris-leucoagglutinin (PHA-L) into the capsular, lateral, intermediate, and medial divisions of the central nucleus in rat. There were a number of labeled terminals near the injection site within each division. The intrinsic connections between the various divisions of the central nucleus were organized topographically and originated primarily in the lateral division, which projected to the capsular and medial divisions. Most of the connections were unidirectional, except in the capsular division, which received a light reciprocal projection from its efferent target, the medial division. The intermediate division did not project to any of the other divisions of the central nucleus. Extrinsic projections from the central nucleus to the other amygdaloid nuclei were meager. Light projections were observed in the parvicellular division of the basal nucleus, the anterior cortical nucleus, the amygdalohippocampal area, and the anterior amygdaloid area. No projections to the contralateral amygdala were found. These data show that the central nucleus has a dense network of topographically organized intradivisional and interdivisional connections that may integrate the intraamygdaloid and extraamygdaloid information entering the different regions of the central nucleus. The sparse reciprocal connections to the other amygdaloid nuclei suggest that the central nucleus does not regulate the other amygdaloid regions but, rather, executes the responses evoked by the other amygdaloid nuclei that innervate the central nucleus.

Amygdala↗

Autism, Asperger syndrome and brain mechanisms for the attribution of mental states to animated shapes.

Ten able adults with autism or Asperger syndrome and 10 normal volunteers were PET scanned while watching animated sequences. The animations depicted two triangles moving about on a screen in three different conditions: moving randomly, moving in a goal-directed fashion (chasing, fighting), and moving interactively with implied intentions (coaxing, tricking). The last condition frequently elicited descriptions in terms of mental states that viewers attributed to the triangles (mentalizing). The autism group gave fewer and less accurate descriptions of these latter animations, but equally accurate descriptions of the other animations compared with controls. While viewing animations that elicited mentalizing, in contrast to randomly moving shapes, the normal group showed increased activation in a previously identified mentalizing network (medial prefrontal cortex, superior temporal sulcus at the temporo-parietal junction and temporal poles). The autism group showed less activation than the normal group in all these regions. However, one additional region, extrastriate cortex, which was highly active when watching animations that elicited mentalizing, showed the same amount of increased activation in both groups. In the autism group this extrastriate region showed reduced functional connectivity with the superior temporal sulcus at the temporo-parietal junction, an area associated with the processing of biological motion as well as with mentalizing. This finding suggests a physiological cause for the mentalizing dysfunction in autism: a bottleneck in the interaction between higher order and lower order perceptual processes.

Adult↗

Components and connections of the circadian timing system in mammals.

The circadian timing system is a neural network consisting of the hypothalamic suprachiasmatic nucleus, aided by the retina, other hypothalamic nuclei, autonomic regions of the spinal cord, sympathetic ganglia and the pineal gland. Extensive studies conducted over the last two decades have unravelled the principal items of its functional neuroanatomy. The system is responsible for the generation of the circadian rhythm, its synchronization by environmental factors such as light, and its mediation with respect to morphological, physiological and biochemical parameters of mammals that exhibit distinct alterations throughout the 24-h cycle. This review characterizes the brain sites involved and the pathways responsible for the generation and maintenance of circadian rhythmicity.

Animals↗