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PubMed2004

Stimulus-induced change in long-range temporal correlations and scaling behaviour of sensorimotor oscillations.

The human brain spontaneously generates large-scale network oscillations at around 10 and 20 Hz. The amplitude envelope of these oscillations fluctuates intermittently and was recently reported to exhibit power-law decay of the autocorrelation for hundreds of seconds. This indicates that the underlying networks are in a dynamic state resembling the self-organized critical state known to exist in many complex systems. Based on the mechanism of how correlations emerge in these systems, we hypothesized that the physiological basis of long-range power-law correlations is the buildup of a memory of past activity by a continuous modification of the network's functional connectivity by the ongoing oscillations. In this framework, exogenous perturbations of ongoing oscillations would degrade or abolish this dynamic network memory. We investigated the sensitivity of the temporal correlations in sensorimotor 10- and 20-Hz oscillations to median nerve stimulation that is known to have immediate effects on ongoing oscillations. Our results show that the amplitude fluctuations of these oscillations were effectively modulated by the somatosensory stimuli but still exhibited long-range temporal correlations and power-law scaling behaviour. The magnitude of the temporal correlations was, however, attenuated and the power-law exponents were decreased. This implies that the stimuli indeed degraded the network's memory of its past.

Adult↗

PubMed2001

The neural substrate of orientation working memory.

We have used positron emission tomography (PET) to identify the neural substrate of two major cognitive components of working memory (WM), maintenance and manipulation of a single elementary visual attribute, i.e., the orientation of a grating presented in central vision. This approach allowed us to equate difficulty across tasks and prevented subjects from using verbal strategies or vestibular cues. Maintenance of orientations involved a distributed fronto-parietal network, that is, left and right lateral superior frontal sulcus (SFSl), bilateral ventrolateral prefrontal cortex (VLPFC), bilateral precuneus, and right superior parietal lobe (SPL). A more medial superior frontal sulcus region (SFSm) was identified as being instrumental in the manipulative operation of updating orientations retained in the WM. Functional connectivity analysis revealed that orientation WM relies on a coordinated interaction between frontal and parietal regions. In general, the current findings confirm the distinction between maintenance and manipulative processes, highlight the functional heterogeneity in the prefrontal cortex (PFC), and suggest a more dynamic view of WM as a process requiring the coordinated interaction of anatomically distinct brain areas.

Adult↗

PubMed1981

The method of source derivation for the EEG.

The technical background to this work was described by Hjorth (1975). The derivation is a practical implementation of the Laplace operator and detects source activity as it appears on the surface level of the scalp. The advantages are improved topographical selectivity as compared to bipolar or referential derivation and simplicity of presentation as the activity at each electrode position is represented by only one channel, without the influence of a monopolar reference. Using the electrode positions in the 10-20 system, the derivations are implemented by means of resistive matrix networks connected between the EEG amplifiers, the source derivation is divided between two programmes, an anterior and a posterior. Personal experience with the method over the last 12 months has been assessed. 500 consecutive and otherwise unselected records were re-examined. Source derivation did not demonstrate an abnormality when the conventional derivations were normal. The principal finding was that localised abnormalities may be more obvious and their location more easily and accurately defined.

Adolescent↗

PubMed1995

Somatostatin and leu-enkephalin in the rat auditory brainstem during fetal and postnatal development.

A transient expression of the neuropeptide somatostatin has been described in several brain areas during early ontogeny and several opioid peptides, such as leu-enkephalin, have also been found in the brain at this stage in development. It is therefore believed that somatostatin and leu-enkephalin may play a role in neural maturation. The aim of the present study was to describe the spatiotemporal pattern of somatostatin and leu-enkephalin immunoreactivity in the auditory brainstem nuclei of the developing rat and to correlate it with other developmental events. In order to achieve this goal, we applied peroxidase-antiperoxidase immunocytochemistry to rat brains between embryonic day (E) 17 and adulthood. Somatostatin immunoreactivity (SIR) was found in all nuclei of the auditory brainstem, yet it was temporally restricted in most nuclei. SIR appeared prenatally and reached maximum levels around postnatal day (P) 7, when great numbers of immunoreactive neurons were present in the ventral cochlear nucleus (VCN) and in the lateral lemniscus. At that time relatively low numbers of cells were labeled in the dorsal cochlear nucleus, the lateral superior olive (LSO), and the inferior colliculus (IC). During the same period, when somata in the VCN were somatostatin-immunoreactive (SIR), a dense network of labeled fibers was also present in the LSO, the medial superior olive (MSO), and the medial nucleus of the trapezoid body (MNTB). As these nuclei receive direct input from VCN neurons, and as the distribution and morphology of the somatostatinergic fibers in the superior olivary complex (SOC) was like that of axons from VCN neurons, these findings suggest a transient somatostatinergic connection within the auditory system. Aside from the LSO, MSO, and MNTB, labeled fibers were found to a smaller extent in all other auditory brainstem nuclei. After P7, the SIR decreased and only a few immunoreactive elements were found in the adult auditory brainstem nuclei, indicating that somatostatin is transiently expressed in the rat auditory brainstem. Leu-enkephalin immunoreactivity showed a lower number and weaker intensity of labeled structures as compared to SIR, with E18 being the earliest day at which labeled fibers appeared in the SOC. At birth, immunoreactive fibers were also present in the cochlear nuclear complex and in the IC. Leu-enkephalin immunoreactive somata were found only after P12 in the CN and after P16 in the IC. Leu-enkephalin immunoreactivity was not transient, but increased progressively with age until about P21, when the adult levels were reached.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMedDate not supplied

Dorsal and ventral streams: a framework for understanding aspects of the functional anatomy of language.

Despite intensive work on language-brain relations, and a fairly impressive accumulation of knowledge over the last several decades, there has been little progress in developing large-scale models of the functional anatomy of language that integrate neuropsychological, neuroimaging, and psycholinguistic data. Drawing on relatively recent developments in the cortical organization of vision, and on data from a variety of sources, we propose a new framework for understanding aspects of the functional anatomy of language which moves towards remedying this situation. The framework posits that early cortical stages of speech perception involve auditory fields in the superior temporal gyrus bilaterally (although asymmetrically). This cortical processing system then diverges into two broad processing streams, a ventral stream, which is involved in mapping sound onto meaning, and a dorsal stream, which is involved in mapping sound onto articulatory-based representations. The ventral stream projects ventro-laterally toward inferior posterior temporal cortex (posterior middle temporal gyrus) which serves as an interface between sound-based representations of speech in the superior temporal gyrus (again bilaterally) and widely distributed conceptual representations. The dorsal stream projects dorso-posteriorly involving a region in the posterior Sylvian fissure at the parietal-temporal boundary (area Spt), and ultimately projecting to frontal regions. This network provides a mechanism for the development and maintenance of "parity" between auditory and motor representations of speech. Although the proposed dorsal stream represents a very tight connection between processes involved in speech perception and speech production, it does not appear to be a critical component of the speech perception process under normal (ecologically natural) listening conditions, that is, when speech input is mapped onto a conceptual representation. We also propose some degree of bi-directionality in both the dorsal and ventral pathways. We discuss some recent empirical tests of this framework that utilize a range of methods. We also show how damage to different components of this framework can account for the major symptom clusters of the fluent aphasias, and discuss some recent evidence concerning how sentence-level processing might be integrated into the framework.

Aphasia↗

PubMed1989

Immunohistochemical demonstration of neurotensin and tyrosine hydroxylase in iris nerves of the rabbit eye.

In previous studies we have provided evidence that intracameral administration of neurotensin (NT), an endogenous tridecapeptide, produces strong miosis in the rabbit. The presence of NT immunoreactivity was investigated in rabbit iris whole mounts by light microscopic immunohistochemistry, and its distribution in the iris compared to that, of tyrosine hydroxylase (TH). A few scattered NT-positive cell bodies were localized in the dilator muscle. Both, the NT cell bodies and processes appeared parallel to the muscle cells. Extensive branching of NT-containing cell processes was observed in connection with the sphincter muscle. These NT-positive fibers formed a dense, randomly oriented network throughout the sphincter muscle cells. The distribution of TH immunoreactivity was similar to that of NT-positive cell processes, except that no TH-positive cell bodies were detected in any of the iris structures examined. Moderate branching of TH-positive fibers was observed in the dilator and sphincter iris muscles. These findings provide neuroanatomical support for an important role of NT in pupillary physiology. Its similar topographical distribution with TH suggests that NT and dopamine may be co-localized, as it has already been described in brain.

Animals↗

PubMed2004

A [17F]-fluoromethane PET/TMS study of effective connectivity.

We used transcranial magnetic stimulation (TMS) in combination with positron emission tomography (PET) to investigate the effective connectivity of four cortical regions within the same study. By employing [17F]-[CH3F] ([17F]-fluoromethane) as a radiotracer of blood-flow, we were able to obtain increased sensitivity compared to [15O]-H2O for both cortical and subcortical structures. The brain areas investigated were left primary motor cortex, right primary visual cortex, and left and right prefrontal areas. We found that each site of stimulation yielded a different pattern of activation/deactivation consistent with its anatomical connectivity. Moreover, we found that TMS of prefrontal and motor cortical areas gave rise to trans-synaptic activation of subcortical circuits.

Adult↗

PubMedDate not supplied

Physiologically realistic formation of autoassociative memory in networks with theta/gamma oscillations: role of fast NMDA channels.

Recordings from brain regions involved in memory function show dual oscillations in which each cycle of a low-frequency theta oscillation (5-8 Hz) is subdivided into about seven subcycles by high frequency gamma oscillations (20-60 Hz). It has been proposed (Lisman and Idiart 1995) that such networks are a multiplexed short-term memory (STM) buffer that can actively maintain about seven memories, a capability of human STM. A memory is encoded by a subset of principal neurons that fire synchronously in a particular gamma subcycle. Firing is maintained by a membrane process intrinsic to each cell. We now extend this model by incorporating recurrent connections with modifiable synapses to store long-term memory (LTM). The repetition provided by STM gradually modifies synapses in a physiologically realistic way. Because different memories are active in different gamma subcycles, the formation of autoassociative LTM requires that synaptic modification depend on N-methyl-D-aspartate (NMDA) channels having a time constant of deactivation that is of the same order as the duration of a gamma subcycle (15-50 msec). Many types of NMDA channels have longer time constants (150 msec), as for instance those found in the hippocampus, but both fast and slow NMDA channels are present in cortex. This is the first proposal for the special role of these fast NMDA channels. The STM for novel items must depend on activity-dependent changes intrinsic to neurons rather than recurrent connections, which have not developed the required selectivity. Because these intrinsic mechanisms are not error-correcting, STM will become slowly corrupted by noise. This limits the accuracy with which LTM can become encoded after a single presentation. Accurate encoding of items in LTM can be achieved by multiple presentations, provided different memory items are presented in a varied interleaved order. Our results indicate that a limited memory-capacity STM model can be integrated in the same network with a high-capacity LTM model.

Association↗

PubMed1991

["Expected motivation" in managing illness. A difficult social medicine-forensic problem].

The question if a patient can "reasonably be expected to make an effort of will" is of considerable importance when it comes to the psychological assessment of patients under social legislation as well as for private insurances. The problem in this connection is to what extent a human being can reasonably be expected to develop willpower in order to partially or completely overcome his mental/psychosomatic/painful illness with own effort. Even for a neurologist and psychiatrist it is difficult to answer this question, because "willpower or weakness of will" can neither be measured objectively nor can they be determined with the help of psychological tests. We must rather take a decision on the basis of the many years of experience we gained in dealing with patients and our knowledge of various types of personalities, of acquired organic processes of the brain, as well as of an existing social network. Taking all this into account, we must state whether a patient is able to take decisions of will or not. Being the result of an assessment, such a statement is of enormous significance for the patient as far as social and financial aspects are concerned.

Adaptation, Psychological↗

PubMed1999

Feedback interactions between neuronal pointers and maps for attentional processing.

Neural networks combining local excitatory feedback with recurrent inhibition are valuable models of neocortical processing. However, incorporating the attentional modulation observed in cortical neurons is problematic. We propose a simple architecture for attentional processing. Our network consists of two reciprocally connected populations of excitatory neurons; a large population (the map) processes a feedforward sensory input, and a small population (the pointer) modulates location and intensity of this processing in an attentional manner dependent on a control input to the pointer. This pointer-map network has rich dynamics despite its simple architecture and explains general computational features related to attention/intention observed in neocortex, making it interesting both theoretically and experimentally.

Attention↗

PubMed2000

Subcortical projections of area 25 (subgenual cortex) of the macaque monkey.

In several species, including primates, stimulation studies indicate that the infralimbic cortex, the most caudal part of the ventromedial prefrontal cortex, functions as a visceral motor region. In addition, recent positron emission tomography studies implicate the subgenual region in depression and mania. To determine the subcortical projections of this region in primates, injections of Phaseolus vulgaris leukoagglutinin, biotinylated dextran amine, or rhodamine-labeled dextran amine were placed in area 25 in three monkeys. In contrast to the efferents from area 25 previously described in the rat, there were no projections to autonomic effector regions, such as the nucleus of the solitary tract, magnocellular neurosecretory cell groups in the hypothalamus, ventrolateral medulla, or intermediolateral column of the spinal cord. However, projections were shown to a number of structures with probable roles in autonomic function and direct connections to some of the abovementioned autonomic effector regions, including bed nucleus of the stria terminalis, perifornical and anterior hypothalamus, periaqueductal gray, and lateral parabrachial nucleus. In addition, there were projections to several forebrain structures that receive projections from other components of the medial prefrontal network including the medial part of the caudate nucleus, lateral septum, midline and mediodorsal thalamic nuclei, the lateral parvocellular part of the basal accessory amygdaloid nucleus, and the magnocellular part of the basal amygdaloid. None of the injections resulted in labeling in the medulla. These connections support the idea of a role for cortical area 25 in emotional and autonomic responses, albeit less direct than that described in rodents.

Animals↗

PubMed2006

Bursting without slow kinetics: a role for a small world?

Bursting, a dynamical phenomenon whereby episodes of neural action potentials are punctuated by periodic episodes of inactivity, is ubiquitous in neural systems. Examples include components of the respiratory rhythm generating circuitry in the brain stem, spontaneous activity in the neonatal rat spinal cord, and developing neural networks in the retina of the immature ferret. Bursting can also manifest itself in single neurons. Bursting dynamics require one or more kinetic processes slower than the timescale of the action potentials. Such processes usually manifest themselves in intrinsic ion channel properties, such as slow voltage-dependent gating or calcium-dependent processes, or synaptic mechanisms, such as synaptic depression. In this note, we show rhythmic bursting in a simulated neural network where no such slow processes exist at the cellular or synaptic level. Rather, the existence of rhythmic bursting is critically dependent on the connectivity of the network and manifests itself only when connectivity is characterized as small world. The slow process underlying the timescale of bursting manifests itself as a progressive synchronization of the network within each burst.

Action Potentials↗

PubMed2006

Electrical synapses--gap junctions in the brain.

In the nervous system, interneuronal communication can occur via indirect or direct transmission. The mode of indirect communication involves chemical synapses, in which transmitters are released into the extracellular space to subsequently bind to the postsynaptic cell membrane. Direct communication is mediated by electrical synapses, and will be the focus of this review. The most prevalent group of electrical synapses are neuronal gap junctions (both terms are used interchangeably in this article), which directly connect the intracellular space of two cells by gap junction channels. The structural components of gap junction channels in the nervous system are connexin proteins, and, as recently identified, pannexin proteins. Connexin gap junction channels enable the intercellular, bidirectional transport of ions, metabolites, second messengers and other molecules smaller than 1 kD. More than 20 connexin genes have been found in the mouse and human genome. With the cloning of connexin36 (Cx36), a connexin protein with predominantly neuronal expression, the biochemical correlate of electrotonic transmission between neurons was identified. We outline the distribution of Cx36 as well as two other neuronal connexins (Cx57 and Cx45) in the nervous system, describing their spatial and temporal expression patterns. One focus in this review was the retina, as it shows many and diverse electrical synapses whose connexin components have been identified in fish and mammals. In view of the function of neuronal gap junctions, the network of inhibitory interneurons will be reviewed in detail, focussing on the hippocampus. Although in vivo data on pannexin proteins are still restricted to information on mRNA expression, electrophysiological data and the expression pattern in the nervous system have been included.

Animals↗

PubMed1999

Emergence of symmetric, modular, and reciprocal connections in recurrent networks with Hebbian learning.

While learning and development are well characterized in feedforward networks, these features are more difficult to analyze in recurrent networks due to the increased complexity of dual dynamics - the rapid dynamics arising from activation states and the slow dynamics arising from learning or developmental plasticity. We present analytical and numerical results that consider dual dynamics in a recurrent network undergoing Hebbian learning with either constant weight decay or weight normalization. Starting from initially random connections, the recurrent network develops symmetric or near-symmetric connections through Hebbian learning. Reciprocity and modularity arise naturally through correlations in the activation states. Additionally, weight normalization may be better than constant weight decay for the development of multiple attractor states that allow a diverse representation of the inputs. These results suggest a natural mechanism by which synaptic plasticity in recurrent networks such as cortical and brainstem premotor circuits could enhance neural computation and the generation of motor programs.

Animals↗

PubMed2006

Constantin von Monakow (1853-1930): a pioneer in interdisciplinary brain research and a humanist.

Constantin von Monakow (1853-1930), director of the Brain Anatomy Institute in Zurich, was a pioneer in the early history of interdisciplinary brain sciences. The elucidation of connectivity in sensory and motor pathways was richly illustrated in two landmark monographs: Pathologie du cerveau (1897) and La localisation de l'encephale et la dégradation fonctionelle par des lésions circonscrites du cortex cérébral (1914). His special merit was to conceptualize his accumulating results. As to his term 'diaschisis': (1) neurological lesion are rarely restricted to a histologically defined neural structure; (2) any brain focus is interconnected with remote structures - thus, dependent structures are deafferented from the lesioned territory (= 'diaschisis') -; (3) dependent structures, however, gradually regain some autonomy, as reflected in partial behavioral recovery. His term 'chronogenic localization' was used for the brain's fundamental organization in time-dependent network constellations. Monakow attracted many researchers, particularly from Japan. He was an engaged member of the International Brain Commission until its dissolution during World War I.

Brain↗

PubMed2006

Network neighborhood analysis with the multi-node topological overlap measure.

MOTIVATION: The goal of neighborhood analysis is to find a set of genes (the neighborhood) that is similar to an initial 'seed' set of genes. Neighborhood analysis methods for network data are important in systems biology. If individual network connections are susceptible to noise, it can be advantageous to define neighborhoods on the basis of a robust interconnectedness measure, e.g. the topological overlap measure. Since the use of multiple nodes in the seed set may lead to more informative neighborhoods, it can be advantageous to define multi-node similarity measures. RESULTS: The pairwise topological overlap measure is generalized to multiple network nodes and subsequently used in a recursive neighborhood construction method. A local permutation scheme is used to determine the neighborhood size. Using four network applications and a simulated example, we provide empirical evidence that the resulting neighborhoods are biologically meaningful, e.g. we use neighborhood analysis to identify brain cancer related genes. AVAILABILITY: An executable Windows program and tutorial for multi-node topological overlap measure (MTOM) based analysis can be downloaded from the webpage (http://www.genetics.ucla.edu/labs/horvath/MTOM/).

Algorithms↗

PubMed2000

Large scale neurocognitive networks underlying episodic memory.

Large-scale networks of brain regions are believed to mediate cognitive processes, including episodic memory. Analyses of regional differences in brain activity, measured by functional neuroimaging, have begun to identify putative components of these networks. To more fully characterize neurocognitive networks, however, it is necessary to use analytical methods that quantify neural network interactions. Here, we used positron emission tomography (PET) to measure brain activity during initial encoding and subsequent recognition of sentences and pictures. For each type of material, three recognition conditions were included which varied with respect to target density (0%, 50%, 100%). Analysis of large-scale activity patterns identified a collection of foci whose activity distinguished the processing of sentences vs. pictures. A second pattern, which showed strong prefrontal cortex involvement, distinguished the type of cognitive process (encoding or retrieval). For both pictures and sentences, the manipulation of target density was associated with minor activation changes. Instead, it was found to relate to systematic changes of functional connections between material-specific regions and several other brain regions, including medial temporal, right prefrontal and parietal regions. These findings provide evidence for large-scale neural interactions between material-specific and process-specific neural substrates of episodic encoding and retrieval.

Adult↗

PubMed2004

Oculomotor areas of the primate frontal lobes: a transneuronal transfer of rabies virus and [14C]-2-deoxyglucose functional imaging study.

We used the [14C]-2-deoxyglucose method to study the location and extent of primate frontal lobe areas activated for saccades and fixation and the retrograde transneuronal transfer of rabies virus to determine whether these regions are oligosynaptically connected with extraocular motoneurons. Fixation-related increases of local cerebral glucose utilization (LCGU) values were found around the fundus of the inferior limb of the arcuate sulcus (AS) just ventral to its genu, in the dorsomedial frontal cortex (DMFC), cingulate cortex, and orbitofrontal cortex. Significant increases of LCGU values were found in and around both banks of the AS, DMFC, and caudal principal, cingulate, and orbitofrontal cortices of monkeys executing visually guided saccades. All of these areas are oligosynaptically connected to extraocular motoneurons, as shown by the presence of retrogradely transneuronally labeled cells after injection of rabies virus in the lateral rectus muscle. Our data demonstrate that the arcuate oculomotor cortex occupies a region considerably larger than the classic, electrical stimulation-defined, frontal eye field. Besides a large part of the anterior bank of the AS, it includes the caudal prearcuate convexity and part of the premotor cortex in the posterior bank of the AS. They also demonstrate that the oculomotor DMFC occupies a small area straddling the ridge of the brain medial to the superior ramus of the AS. Our results support the notion that a network of several interconnected frontal lobe regions is activated during rapid, visually guided eye movements and that their output is conveyed in parallel to subcortical structures projecting to extraocular motoneurons.

Animals↗