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PubMed1999

[Not Available].

With the increasing application of imaging techniques, characteristic changes in the structure and functional activity of certain neuronal networks and transmitter Systems have been discovered in the brains of patients suffering from various psychiatric disorders. These findings have often been assumed to support biological concepts of the genetic background and causation of these disorders. However, several lines of research are converging to indicate that the initially established genetically programmed neuronal Connectivity is further elaborated, fine tuned and modified by usedependent neuronal and synaptic plasticity. In all socially organized species in general and in human subjects in particular, psychosocial experiences appear to represent the most important trigger of use-dependent adjustments of neuronal Connectivity through the facilitation, modification and reorganization of neuronal networks. In experimental animals, changes in psychosocial rearing conditions were shown to cause profound and persistent changes in the cytoarchitecture, dendritic arborization and synapse formation in individual brain regions as well as in the maturation of monoaminergic afferences. Based on these findings, the mechanisms of the biological affixation of psychosocial experiences are described and the implications of experience dependent neuronal and synaptic plasticity in the prevention and the therapy of mental disorders are outlined.

Attachment↗
PubMed2005

The neurobiology of aging.

Basic principles of the neurobiology of aging were reviewed within selected topic areas chosen for their potential relevance to epileptogenesis in the aging brain. The availability of National Institute on Aging-supported aged mouse and rat strains and other biological resources for studies of aging and age-associated diseases was presented, and general principles of animal use in gerontological research were discussed. Neurobiological changes during normal brain aging were compared and contrasted with neuropathological events of Alzheimer's disease (AD) and age-associated memory impairment (AAMI). Major themes addressed were the loss of synaptic connections as vulnerable neurons die and circuits deteriorate in AD, the absence of significant neuron loss but potential synaptic alteration in the same circuits in AAMI, and the effects of decreased estrogen on normal aging. The "calcium hypothesis of brain aging" was examined by a review of calcium dyshomeostasis and synaptic communication in aged hippocampus, with particular emphasis on the role of L-type voltage-gated calcium channels during normal aging. Established and potential mechanisms of hippocampal plasticity during aging were discussed, including long-term potentiation, changes in functional connectivity, and increased gap junctions, the latter possibly being related to enhanced network excitability. Lastly, application of microarray gene chip technology to aging brain studies was presented and use of the hippocampal "zipper slice" preparation to study aged neurons was described.

Aging↗
PubMed2005

New brain networks are active after right MCA stroke when moving the ipsilesional arm.

OBJECTIVE: To determine whether, like the paretic arm, movement of the ipsilesional arm after middle cerebral artery (MCA) stroke is associated with widespread neural activation changes in areas anatomically and functionally connected to the lesion. METHODS: In this fMRI experiment, seven patients with right MCA stroke and seven healthy control subjects performed a series of movements with their (nonparetic) right hand. Subjects either mimicked a visual display (visually guided) or generated the same motor task after a visual start signal (self-monitored). A multivariate linear discriminant analysis was used to determine the combinations of brain regions of interest (ROIs) that demonstrated maximum differences in activation between healthy and stroke subjects. The analysis was repeated within subject groups to differentiate self-monitored and visually guided movement. RESULTS: There was a significantly different network of neural regions recruited for movement with the nonparetic, ipsilesional arm in patients with stroke vs healthy control subjects. The anterior cingulate cortex was significantly more active when patients execute self-monitored movement than visually guided movement, suggesting changes in attentional processing required for the two tasks. The lesioned hemisphere was significantly more active in patients with stroke using the nonparetic arm than in control subjects during visually guided movement. CONCLUSIONS: These results support a model of widespread bihemispheric reorganization in the motor system after a focal right hemisphere lesion. Attentional demands of self-monitored movement may be much greater than visually guided movement in patients, possibly impacting rehabilitation protocols for these patients.

Aged↗
PubMed1999

[The neurobiology of slow-wave sleep].

In the two last years my lectures were addressed to the biological bases of wakefulness and REM sleep. The present lecture is focused on slow wave sleep, which corresponds to stages 3 and 4 in humans. These two sleep stages both present high voltage slow waves in the EEG that belong to the delta band (less than 3 Hz). Slow wave sleep usually lasts between 70 and 90 minutes in normal individuals, and takes place during the first hours of the night, as though our organism was making sure we got this essential sleep. Slow wave sleep is: a) the first sleep stage to recuperate after sleep deprivation, b) the stage with the most constant length even in individuals who have very different sleep habits, and c) the sleep stage that remains constant during experiments of gradual sleep reduction for eight-hour sleepers. This sleep stage is the one in which growth hormone is released and it essential for physical and intellectual efficiency and normal behavior in young adult individuals. Slow wave sleep is remarkably reduced in old people. What brain structures are responsible for the bioelectric and behavioral events of the slow waves sleep? Both the cerebral cortex and thalamus are indispensable for the existence of the slow waves EEG characteristic to this stage. Other brain structures participate in slow wave sleep organization; these include the basal forebrain, the oral pontine reticular nucleus, the deep cerebellar nuclei and the solitary tract nucleus. In this presentation I consider the most relevant functions of these structures as well as their anatomical connections, mainly with the neuronal networks responsible for other stages of the sleep-wakefulness cycle.

Adult↗
PubMed2002

Retrograde trans-synaptic transfer of green fluorescent protein allows the genetic mapping of neuronal circuits in transgenic mice.

The function of the nervous system is a consequence of the intricate synaptic connectivity of its neurons. Our understanding of these highly complex networks has profited enormously from methods used over the past two decades that are based on the mechanical injection of tracer molecules into brain regions. We have developed a genetic system for the mapping of synaptic connections during development of the mammalian central nervous system and in the mature brain. It is based on the transsynaptic transfer of green fluorescent protein (GFP) in the brains of mice using a fusion protein with a nontoxic fragment of tetanus toxin (TTC) expressed in defined neurons. These transgenic mice allowed us to visualize neurons, at single-cell resolution, that are in synaptic contact by the detection of GFP in interconnected circuits. Targeted genetic expression with a specific promoter permitted us to transfer GFP to defined subsets of neurons and brain regions. GFP-TTC is coexpressed with a lacZ reporter gene to discriminate neurons that produce the tracer from cells that have acquired it transneuronally. The marker shows selective transfer in the retrograde direction. We have used electron microscopic detection of GFP to define the ultrastructural features of the system. Our work opens up a range of possibilities for brain slice and in vivo studies taking advantage of the fluorescence of GFP. We point the way toward the use of powerful multiphoton technology and set the stage for the transsynaptic transfer of other proteins in the brains of mice.

Animals↗
PubMed1992

Objective analysis of the topological organization of the primate cortical visual system.

The primate cortical visual system is composed of many structurally and functionally distinct areas, each receiving and sending about 10 projections from and to other cortical areas. The visual cortex is thus served by many cortico-cortical connections to form a network of considerable complexity. Thus the gross organization of this cortical processing system presents a formidable topological problem: although the spatial position of the areas in the brain is reasonably well established, the gross 'processing architecture' defined by the connections, is less well understood. Here I report an optimization approach that gives both qualitative and quantitative insight into the connectional topology of the primate cortical visual system. This approach supports suggestions that the system is divided into a dorsal 'stream' and a ventral 'stream' with limited cross-talk, that these two streams reconverge in the region of the principal sulcus (area 46) and in the superior temporal polysensory areas, that the system is hierarchically organized, and that the majority of the connections are from 'nearest-neighbour' and 'next-door-but-one' areas.

Animals↗
PubMed2006

Implementing Gaussian process inference with neural networks.

Gaussian processes compare favourably with backpropagation neural networks as a tool for regression, and Bayesian neural networks have Gaussian process behaviour when the number of hidden neurons tends to infinity. We describe a simple recurrent neural network with connection weights trained by one-shot Hebbian learning. This network amounts to a dynamical system which relaxes to a stable state in which it generates predictions identical to those of Gaussian process regression. In effect an infinite number of hidden units in a feed-forward architecture can be replaced by a merely finite number, together with recurrent connections.

Algorithms↗
PubMed2006

Propagation of spike and wave activity to the medial prefrontal cortex and dorsal raphe nucleus of WAG/Rij rats.

Although there is pharmacological evidence for the involvement of the serotonergic system in the expression of spike and wave discharges (SWDs) in experimental absence epilepsy, no direct investigation of this paroxysm in the dorsal raphe nucleus (DRN), one of the main serotonergic nuclei, has been carried out. We have now recorded the EEG simultaneously with local field potentials and unit activity in DRN from WAG/Rij rats, one of the best established models of absence epilepsy during spontaneous SWDs. We have also compared this activity to that in the thalamocortical networks, where SWDs are generated, and in the medial prefrontal cortex (mPFC), as this brain area is reciprocally connected to the DRN. We have found that SWDs propagate to the DRN with a short delay, and that the firing rate of its neurons changes during this type of paroxysm. These results provide the first direct evidence for clear alterations in the firing properties of mPFC and DRN neurons during spontaneous SWDs.

Action Potentials↗
PubMed2025

Exploring the transmission of cognitive task information through optimal brain pathways.

Understanding the large-scale information processing that underlies complex human cognition is the central goal of cognitive neuroscience. While emerging activity flow models demonstrate that cognitive task information is transferred by interregional functional or structural connectivity, graph-theory-based models typically assume that neural communication occurs via the shortest path of brain networks. However, whether the shortest path is the optimal route for empirical cognitive information transmission remains unclear. Based on a large-scale activity flow mapping framework, we found that the performance of activity flow prediction with the shortest path was significantly lower than that with the direct path. The shortest path routing was superior to other network communication strategies, including search information, path ensembles, and navigation. Intriguingly, the shortest path outperformed the direct path in activity flow prediction when the physical distance constraint and asymmetric routing contribution were simultaneously considered. This study not only challenges the shortest path assumption through empirical network models but also suggests that cognitive task information routing is constrained by the spatial and functional embedding of the brain network.

Humans↗
PubMed2004

Functional connectivity during working memory maintenance.

Neurophysiological experiments with monkeys have demonstrated that working memory (WM) is associated with persistent neural activity in multiple brain regions, such as the prefrontal cortex (PFC), the parietal cortex, and posterior unimodal association areas. WM maintenance is believed to require the coordination of these brain regions, which do not function in isolation but, rather, interact to maintain visual percepts that are no longer present in the environment. However, single-unit physiology studies and traditional univariate analyses of functional brain imaging data cannot evaluate interactions between distant brain regions, and so evidence of regional integration during WM maintenance is largely indirect. In this study, we utilized a recently developed multivariate analysis method that allows us to explore functional connectivity between brain regions during the distinct stages of a delayed face recognition task. To characterize the neural network mediating the on-line maintenance of faces, the fusiform face area (FFA) was defined as a seed and was then used to generate whole-brain correlation maps. A random effects analysis of the correlation data revealed a network of brain regions exhibiting significant correlations with the FFA seed during the WM delay period. This maintenance network included the dorsolateral and ventrolateral PFC, the premotor cortex, the intraparietal sulcus, the caudate nucleus, the thalamus, the hippocampus, and occipitotemporal regions. These findings support the notion that the coordinated functional interaction between nodes of a widely distributed network underlies the active maintenance of a perceptual representation.

Brain↗
PubMed2006

Increased local and decreased remote functional connectivity at EEG alpha and beta frequency bands in opioid-dependent patients.

RATIONALE: Although researchers now have a working knowledge of key brain structures involved in realization of actions of substance abuse and addiction, deeper understanding will require examination of network interactions between cortical neuronal assemblies and their subcortical tails in the effects of opioid dependence. OBJECTIVES: Given that repeated exposure to opiates initiates a widespread reorganization of cortical regions, we predict that opioid dependence would result in a considerable reorganization of local and remote functional connectivity in the neocortex. METHODS: We applied the novel operational architectonics approach that enables us to estimate two local and remote functional cortex connectivities by means of electroencephalogram structural synchrony measure. RESULTS: In 22 opioid-dependent patients, we found the evidence that brain functional connectivity was indeed disrupted by chronic opioid abuse (i.e., the local functional connectivity increased and remote functional connectivity decreased in opioid abusers). This significant difference between "opioid" and "control" populations was the same for alpha and beta frequency bands. Additionally, significant negative relations between duration (years) of daily opioid abuse and the number/strength of functional connections in the posterior section of the cortex were found.

Adult↗
PubMedDate not supplied

[A statistical analysis of the functional connections between the neurons of the visual and motor cortex in different forms of conditioned-reflex behavior].

In experiments on cats with elaboration of delayed alimentary operant reflexes to light organization was studied of interneuronal cortical connections. By means of cross-correlation analysis the dynamics of intra- and interstructural neuronal network was revealed at the level of cortical projections (visual and motor) of cats brain zones at three forms of behaviour: CR realization, in intersignal period with the presence and absence of operant movements. Depending on the forms of behaviour, predominance of "informational" or "motivational" interneuronal connections was observed.

Animals↗
PubMed1990

Co-localization of FLRF- and vasopressin-like immunoreactivity in a single pair of sexually dimorphic neurones in the nervous system of the locust.

The distribution of Phe-Leu-Arg-Phe (FLRF)-like immunoreactivity is described in the brain and in the ganglia of the ventral nerve cord of the locust Schistocerca gregaria. A single homologous pair of immunoreactive cell bodies occurs ventrally and medially in the suboesophageal ganglion. Each cell sends a process dorsally which bifurcates into anteriorly and posteriorly running neurites. The single anterior neurite passes along the circumoesophageal connectives to the brain where it ascends in a posterior running tract, giving off branches to innervate the tritocerebral neuropile and ending in an extensive network of highly varicose immunoreactive processes in the protocerebral neuropile. No processes are seen in the optic lobes or associated with the structured neuropiles of the muschroom bodies. The single posterior neurite from each cell passes into the suboesophageal-prothoracic connectives. It runs in the lateral dorsal tract of each ganglion in the ventral nerve cord as a highly varicose process and in each ganglion gives rise to an ipsilateral network of varicose processes in the dorsal and lateral neuropiles. In the seventh and terminal abdominal ganglia the innervation pattern exhibits sexual dimorphism. Vasopressin-like immunoreactivity is co-localized in the same pair of suboesophageal neurones and their processes. A similar pair of ventral median neurones stains with both antibodies in the suboesophageal ganglion of another species of locust, Locusta migratoria. Although the basic distribution pattern of immunoreactive processes is similar in both species there are also marked species differences in the pattern.

Amino Acid Sequence↗
PubMed2001

Evidence for distinct beta resonance frequencies in human EEG related to specific sensorimotor cortical areas.

OBJECTIVE: We studied event-related synchronization (ERS) of beta rhythms related to voluntary movement vs. stimulation of upper and lower limbs. The aim of this study was to investigate whether the frequency of the beta response is related to specific regions within the sensorimotor strip. METHODS: Self-paced movement and electrical stimulation of the dominant hand and foot/leg was investigated in 10 right-handed volunteers. The electroencephalogram was recorded from closely spaced electrodes over central areas and processed time-locked to movement-offset or stimulation. In order to identify the dominant frequency of the induced beta oscillations, time-frequency maps were calculated using the continuous wavelet transformation. For the specific beta frequency bands, the band power time courses were analyzed by quantifying the event-related (de-)synchronization (ERD/ERS). RESULTS: Both limb movement and somatosensory stimulation induced bursts of beta oscillations appearing within 1 s after movement/stimulation with a clear focus close to the corresponding sensorimotor representation area. The peak frequency was significantly lower over the hand area (below approximately 20 Hz) than at mid-central sites overlying the foot representation area (above approximately 20 Hz). But no difference was found between movement and stimulation of the respective limb. CONCLUSIONS: Analyzing the frequency of induced beta activity revealed concomitant oscillations at slightly different frequencies over neighboring cortical areas. These oscillations might be indicative for a resonance-like behavior of connected sub-networks in sensorimotor areas.

Adult↗
PubMed1987

Detection and estimation of neural connectivity based on crosscorrelation analysis.

Crosscorrelation analysis of simultaneously recorded activity of pairs of neurons is a common tool to infer functional neural connectivity. The adequacy of crosscorrelation procedures to detect and estimate neural connectivity has been investigated by means of computer simulations of small networks composed of fairly realistic modelneurons. If the mean interval of neural firings is much larger than the duration of postsynaptic potentials, which will be the case in many central brain areas excitatory connections are easier to detect than inhibitory ones. On the other hand, inhibitory connections are revealed better if the mean firing interval is much smaller than post-synaptic potential duration. In general the effects of external stimuli and the effects of neural connectivity do not add linearly. Furthermore, neurons may exhibit a certain degree of timelock to the stimulus. For these reasons the commonly applied "shift predictor" procedure to separate stimulus and neural effects appears to be of limited value. In case of parallel direct and indirect neural pathways between two neurons crosscorrelation analysis does not estimate the direct connection but instead an effective connectivity, which reflects the combined influences of the parallel pathways.

Animals↗
PubMed2006

Single-chip microelectronic system to interface with living cells.

A high degree of connectivity and the coordinated electrical activity of neural cells or networks are believed to be the reason that the brain is capable of highly sophisticated information processing. Likewise, the effectiveness of an animal heart largely depends on such coordinated cell activity. To advance our understanding of these complex biological systems, high spatiotemporal-resolution techniques to monitor the cell electrical activity and an ideally seamless interaction between cells and recording devices are desired. Here we present a monolithic microsystem in complementary metal oxide semiconductor (CMOS) technology that provides bidirectional communication (stimulation and recording) between standard electronics technology and cultured electrogenic cells. The microchip can be directly used as a substrate for cell culturing, it features circuitry units per electrode for stimulation and immediate cell signal treatment, and it provides on-chip signal transformation as well as a digital interface so that a very fast, almost real-time interaction (2 ms loop time from event recognition to, e.g., a defined stimulation) is possible at remarkable signal quality. The corresponding spontaneous and stimulated electrical activity recordings with neuronal and cardiac cell cultures will be presented. The system can be used to, e.g., study the development of neural networks, reveal the effects of neuronal plasticity and study cellular or network activity in response to pharmacological treatments.

Action Potentials↗
PubMed2006

Morphological homeostasis in cortical dendrites.

Neurons have significant potential for the homeostatic regulation of a broad range of functional features, from gene expression to synaptic excitability. In this article, we show that dendritic morphology may also be under intrinsic homeostatic control. We present the results from a statistical analysis of a large collection of digitally reconstructed neurons, demonstrating that fluctuations in dendritic size in one given portion of a neuron are systematically counterbalanced by the remaining dendrites in the same cell. As a result, the total dendritic measure (e.g., number of branches, length, and surface area) of each neuron in a given morphological class is, on average, significantly less random than would be expected if trees (and their parts) were regulated independently during development. This observation is general across scales that range from gross basal/apical subdivisions to individual branches and bifurcations, and its statistical significance is robust among various brain regions, cell types, and experimental conditions. Given the pivotal dendritic role in signal integration, synaptic plasticity, and network connectivity, these findings add a dimension to the functional characterization of neuronal homeostasis.

Aging↗
PubMed2006

"Missing links" in borderline personality disorder: loss of neural synchrony relates to lack of emotion regulation and impulse control.

OBJECTIVE: Symptoms of borderline personality disorder (BPD) may reflect distinct breakdowns in the integration of posterior and frontal brain networks. We used a high temporal resolution measure (40-Hz gamma phase synchrony) of brain activity to examine the connectivity of brain function in BPD. METHODS: Unmedicated patients with BPD (n = 15) and age-and sex-matched healthy control subjects (n = 15) undertook a task requiring discrimination of salient from background tones. In response to salient stimuli, the magnitude and latency of peak gamma phase synchrony for early (0-150 ms post stimulus) and late (250-500 ms post stimulus) phases were calculated for frontal and posterior regions and for left and right hemispheres. We recorded skin conductance responses (SCRs) and reaction time (RT) simultaneously to examine the contribution of arousal and performance. RESULTS: Compared with controls, patients with BPD had a significant delay in early posterior gamma synchrony and a reduction in right hemisphere late gamma synchrony in response to salient stimuli. Both SCR onset and RT were also delayed in BPD, but independently from differences in synchrony. The delay in posterior synchrony was associated with cognitive symptoms, and reduced right hemisphere synchrony was associated with impulsivity. CONCLUSIONS: These findings suggest that distinct impairments in the functional connectivity of neural systems for orienting to salient input underlie core dimensions of cognitive disturbance and poor impulse control in BPD.

Adult↗