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PubMed2004

A role for sleep in the processing of memory traces. Contribution of functional neuroimaging in humans.

Sleep is thought to participate in the consolidation of recent memory traces. We tested this hypothesis in humans, using functional neuroimaging (functional magnetic resonance imaging and positron emission tomography). First, following the training on a procedural visuo-motor learning task (pursuit task), total sleep deprivation on the first post-training night significantly deteriorates the gain in performance, which is usually observed after one complete night of sleep. In parallel, sleep deprivation hampers the changes in functional segregation and connectivity, which underpin the gain in performance usually observed in subjects allowed to sleep on the first post-training night. Second, following the training on an implicit memory task (probabilistic serial reaction time task), some brain areas are reactivated during REM sleep on the first post-training night. The reactivation was shown to be related to the processing of high-level material and to be modulated by the amount of learning achieved during the training session. These changes in activity do not involve isolated brain areas but entire macroscopic cortico-subcortical networks. Taken together, the results suggest an off-line processing of recent memory traces during sleep.

Brain↗

PubMed1985

A new statistical method for identifying interconnections between neuronal network elements.

A new method is proposed to analyse dependencies in point processes, which takes into account specific character of neuronal activity. Simulation modelling of neuronal network revealed that the estimated weight of connection depends monotonically on the value of the model synaptic strength. In contrast to the crosscorrelation, the method allows for nonlinear interconnections and does not require point processes to be stationary and samples to be large. Examples are presented of the method's application to neurophysiological data analysis.

Animals↗

PubMed1984

Thermoafferent signal processing in rats: an electrophysiological analysis of midbrain influences on thermoresponsive neurons in the ventrobasal thalamus.

The influence of electrical midbrain stimulation on thalamic cells which respond to scrotal skin warming with steep increases in firing rate was studied in anaesthetized rats. Square-wave stimuli of 200 microseconds duration and 30-250 microA intensity at 15 Hz were applied in trains lasting about 1 min. At low scrotal temperatures stimulation of the nucleus raphe dorsalis, the adjacent central grey or the median raphe nucleus was nearly always followed by a rise in thalamic activity. Inhibition occurred only in 4 of 75 experiments. Often midbrain stimulation caused neuronal responses similar to those following scrotal warming. Single stimulation experiments and the combination of electrical stimulation and electrolytic lesions indicated local interactions between excitatory and inhibitory neuronal networks in midbrain. Poststimulus latencies revealed polysynaptic midbrain/thalamic connections. Direct projections with no more than a few synaptic interruptions were seen in about 10% of the experiments. It is concluded that medial midbrain neurons influence the transmission of peripheral thermal information to the specific thalamus and contribute to the typical switching form of thalamic responses to scrotal warming.

Afferent Pathways↗

PubMed1995

Neuropsychological and olfactory dysfunction in schizophrenia: relationship of frontal syndromes to syndromes of schizophrenia.

Behavioural changes and cognitive impairments in schizophrenia have been linked to disturbances of complex neural networks involving both frontal and subcortical systems. Current literature has emphasised the role of the dorso-lateral prefrontal cortex (DLPFC) and its connections with hippocampus in the pathogenesis of schizophrenia. Based on a review of the literature, this paper examines other possible prefrontal areas that contribute to the manifestations of schizophrenia. We focus on the orbito-frontal cortex (OFC) and argue that it also plays an important role in the behavioural manifestations, symptoms and cognitive impairments observed in schizophrenia. The importance of fronto-striato-thalamic circuits connecting these prefrontal sites with subcortical structures is examined and the relevance of functions specific to these circuits or their components are briefly discussed. The subdivision of the functions of the prefrontal cortex into 'prefrontal' syndromes are examined and related to both the behavioural and symptom-based syndromes of schizophrenia. Possible dissociations of function of the various prefrontal syndromes and the relationship of these to schizophrenia syndromes may provide clues to the underlying neurobiology of schizophrenia. The use of tasks deemed specific to DLPFC and OFC networks may be useful as probes to examine the integrity of these circuits. We discuss such 'circuit-specific' tasks including delayed response, delayed alternation and object alternation tasks derived from the animal literature and other tasks such as olfactory identification ability. This approach raises the possibility that a number of prefrontal cortical areas and their subcortical connections are important in accounting for the heterogeneity of schizophrenia.

Brain Mapping↗

PubMed2005

Connectivity exploration with structural equation modeling: an fMRI study of bimanual motor coordination.

The present fMRI study explores the connectivity among motor areas in a bimanual coordination task using the analysis framework of structural equation modeling (SEM). During bimanual finger tapping at different frequency ratios, temporal correlations of activations between left/right primary motor cortices (MI), left/right PMdc (caudal dorsal premotor area) and supplementary motor cortex (SMA) were detected and used as inputs to the SEM analysis. SEM was extended from its traditional role as a confirmatory analysis to be used as an exploratory technique to determine the most statistically significant connectivity model given a set of cortical areas based on anatomic constraints. The resultant network exhibits coupling from left MI to right MI, links from both PMs to the two MIs, a negative interaction from left PM to right PM, and functional influence from SMA to right MI and right PM, revealing contributions of these areas to bimanual coordination.

Adolescent↗

PubMed1993

Emerging principles of intrinsic hippocampal organization.

The hippocampal formation has a unique and highly distributed network of intrinsic connections. What are the principles of organization that govern information flow through this system? The notion that information processing in the hippocampal formation is segregated in autonomous chips or lamellae appears to be inconsistent with the extremely divergent nature of many of the intrinsic connections. Recent neuroanatomical data suggest, however, that information may be segregated in other ways as it negotiates the links from one hippocampal region to the next.

Animals↗

PubMed1998

Perivascular structures in corrosion casts of the human central nervous system: a confocal laser and scanning electron microscope study.

Scanning electron microscopy (SEM) of microvascular corrosion casts revealed perivascular structures that resembled smooth muscle and pericyte cells. Although these structures have been studied in widely different experimental contexts, their origin, function, and distribution pattern in different tissues are not understood. Microvascular corrosion casts from 15 fresh human brains and 20 lumbar spinal cords were studied by SEM. In five cerebral hemispheres a fluorescent resin was injected in order to study the vascular bed by confocal laser scanning microscopy (CLSM). Microvascular casts showed two perivascular structures on their surfaces: plastic strips, which formed a muff around arteriolar vessels, and pericyte-like structures that were present around the capillary network. Their morphological characteristics and distribution were similar to those of smooth muscle cells and pericytes, respectively. The SEM study showed that these structures were not tightly joined to the cast surface, but were connected to the vascular cast by narrow plastic connections. The CLSM showed that the resin invaded the subendothelial space, thus giving rise to these structures. Perivascular structures associated with arteriolar and capillary vessels appear to represent smooth muscle cells and pericytes. They are formed by the passage of the resin to the subendothelial space, probably through weak endothelial cell junctions. The effusion of resin into the subendothelial space may represent evidence for the structural basis of myocyte and pericyte cell control. Chemical communication by substances released locally or transported to these cells through these junctions may regulate their functions, allowing them to regulate blood flow.

Adult↗

PubMed1995

Three-dimensional structure of CA1 pyramidal cells in rat hippocampus--optical recording of LSM and computer simulation of fractal structure.

The optical recording of three-dimensional (3-D) reconstruction of CA1 pyramidal cells was derived from the studies on the CA1 region of the hippocampus in adult male Wistar rats. The recording was produced by the Confocal Laser Scan Microscope (LSM-10). The attemption was to outline the morphological neural network of CA1 pyramidal cells organization, following the trail of axo-dendritic connections in 3-D spatial distributions among neurons. The fractal structure of neurons with their dendritic and axonal trees using fractal algorithm was noticed, and 2-18 simulated cells were obtained using PC-486 computer. The simulational cells are similar in morphology to the natural CA1 hippocampal pyramidal cells. Therefore, the exploitation of an advanced neurohistological research technique combining optical recording of the LSM-10 and computer simulation of fractal structure can provide the quantitative fractal structural basis for chaosic dynamics of brain.

Animals↗

PubMed1988

Synaptic plasticity and functional stabilization in the hippocampal formation: possible role in Alzheimer's disease.

In this chapter we have explored the hypothesis that reactive synaptogenesis is an adaptive mechanism that can compensate for loss of a fraction of a defined neuronal population. Partial cell loss occurs during the course of aging, neurodegenerative diseases, and minor traumatic brain injuries. As cells are lost or as their function severely declines, new connections made by healthy neurons from within the population can assume parallel functions (homotypic sprouting), or fibers from converging pathways (heterotypic sprouting) can act to boost weakened signals and maintain functional stability. When cell death (or disease) progresses to the point where the pathway is broken, sprouting can no longer maintain information flow along the circuit and thus is unable to preserve function, unless new circuits can also be compensatory as, for example, after unilateral injury. We have analyzed the consequences of cell loss on the nature of circuit regrowth within the primary hippocampal circuits--i.e., the entorhinal-dentate gyrus-CA3-CA1 pathways. Reactive synaptogenesis can occur throughout the system after loss of each major cell population. Homotypic sprouting predominates in several pathways (e.g., dentate gyrus after CA4 loss, CA1 field after CA3 loss), and heterotypic sprouting appears prominent in the dentate gyrus after entorhinal cell loss. Each reactive network as a result of the regrowth can, in principle, still function, if cell loss is partial. The observation that sprouting also occurs in Alzheimer's disease illustrates that a slow and fractional loss of a neuronal assembly can trigger reactive growth in humans even along with a severe neurodegenerative disease. Axon sprouting was predicted in the dentate gyrus after entorhinal cell loss from rodent studies and has now been demonstrated in the brain of Alzheimer's victims. Cholinergic septal inputs, if present, can sprout, thereby enhancing cholinergic function and transmission by entorhinal perforant path fibers. CA4 fibers also sprout, thereby increasing positive feedback on granule neurons. At present, however, the functional significance of these mechanisms has yet to be established in clinical studies. Alzheimer's disease has a prolonged course with progressive symptoms. We would propose that axon sprouting or reactive synapse formation provides additional stability beyond the decline predicted from cell loss alone (Fig. 8). Thus, the clinical threshold where functions disappear is postponed for longer periods of time. Some reports in the literature are consistent with rapid behavioral decline followed by intervening periods of stability.(ABSTRACT TRUNCATED AT 400 WORDS)

Alzheimer Disease↗

PubMed2003

Frontal lobe networks for effective processing of ambiguously expressed emotions in humans.

This study examines the neural substrates involved in the recognition of ambiguous facial expressions using functional magnetic resonance imaging. Subjects performed two tasks, one in which they judged facial expressions and another in which they identified gender. Subtraction between ambiguous expression and clear expression conditions revealed the activation of anterior cingulate (ACC), medial frontal (MeFG) and bilateral inferior frontal gyrus (IFG). Structural equation modeling showed that the functional connectivity between these areas was greater with the ambiguous expressions than with the clear ones. The activation of the ACC, MeFG, and right IFG was greater with ambiguous expressions than with ambiguous gender. These results suggest that the neural network involving these frontal regions plays a crucial role in the processing of the ambiguously expressed facial emotions.

Adult↗

PubMed2004

Fos-tau-LacZ mice expose light-activated pathways in the visual system.

We have employed fos-tau-LacZ (FTL) transgenic mice to examine functional activation in the visual areas of the nervous system. The FTL mice express the marker gene lacZ in neurons and their processes following many different stimuli, and allow the imaging of activation from the level of the entire brain surface through individual neurons and their projections. Analysis of FTL expression in the retinas of mice following diurnal exposure to light shows that bipolar cells, specific classes of amacrine cells, ganglion cells, and a dense network of processes in the inner plexiform layer are functionally activated. In animals deprived of light, there is almost no activity in the retina. In the lateral geniculate nucleus (LGN), light exposure appears responsible for FTL expression in dorsal nuclei, but not for expression in the ventral nuclei or the intergeniculate leaflet. In the superficial layers of the superior colliculus, FTL expression is highly dependent on light exposure. Similarly, light exposure is required for FTL expression in primary visual cortex (area 17), but some expression remains in area 18 of dark-adapted animals. Finally, using mice with one or both eyes missing, we have determined which parts of the visual system are dependent on the presence of a functional connectivity from the eye. These data demonstrate the usefulness of the FTL mice to map functional activation within the entire visual system. Furthermore, we can capture visual activation in a conscious animal. Our findings give an insight into the architecture of activity within the retina and throughout the visual system.

Animals↗

PubMed2004

Modulation of effective connectivity inside the working memory network in patients at the earliest stage of multiple sclerosis.

fMRI and structural equation modeling (SEM) were used to study effective connectivity inside the working memory network in patients at the earliest stage of multiple sclerosis (MS), while performing paced auditory serial addition test (PASAT), a sensitive task to reveal subtle cognitive impairments related to working memory and information speed processing. The path model used for SEM included bilateral connections between left and right BA 46, left and right BA 40, left and right anterior cingulate cortex (ACC), left BA 44 and left BA 40, right BA 44 and right BA 40, and unidirectional ipsilateral connections from BA 46 to BA 44, from ACC to BA 46, and from ACC to BA 44. Experimental data from the two groups fit accurately the working memory model, in patients [chi20(2) = 13, P = 0.877] as well as in controls [chi20(2) = 13.54, P = 0.853]. The omnibus test indicated a significant difference of model fits in patients and in controls [chi40(2) = 160.07, P < 0.0001]. Connectivity strengths from right BA 46 to left BA 46, from left ACC to left BA 46 were lower in patients than in controls, and higher from right ACC to right BA 46, from left to right and from right to left ACC (stacked model). Effective connectivity inside the working memory network appears altered in patients at the earliest stage of MS. Modulation of effective connectivity is present in patients inside the executive subsystems of working memory, and could be related to adaptive cognitive control processes that may limit the clinical manifestation of MS.

Acoustic Stimulation↗

PubMedDate not supplied

Intrinsic circuitry in the deep layers of the cat superior colliculus.

The mammalian superior colliculus is involved in the transformation of sensory signals into orienting behaviors. Sensory and motor signals are integrated in the colliculus to produce movements of the eyes, head, and neck. While there is a considerable amount of information available on the afferent and efferent connections of the colliculus, almost nothing is known about its intrinsic circuitry, particularly that of its deepest layers. It is likely that intrinsic connections in these deeper layers of the colliculus participate in the sensory-motor transformations leading to orienting movements. In this study, we used the neuroanatomical tracer biocytin to label small groups of neurons in the deeper layers of the cat superior colliculus and examine the distribution of their axons and terminals. We found a broadly distributed network of intrinsic projections throughout the deep layers of the superior colliculus. While the majority of terminals were found in a 1-2 mm radius around the injection site, labeled terminals were found throughout the deep layers of the colliculus up to 5 mm from the injection site. In addition, these injections sometimes labeled terminals in the superficial tectum. Extensive projections were demonstrated by the more superficial injections, but few terminals were found when injections were confined to the deepest layers of the colliculus. There was no evidence of anisotropy in the distribution of terminals from injections made at different rostrocaudal or mediolateral locations; neurons located in any one region in the colliculus could potentially influence any other region. This network of intrinsic connections in the cat superior colliculus could provide a means for deeper-layer efferent neurons to associate, and to modulate or coordinate their output. Interneurons could also provide a substrate for mutual inhibition between neurons at the rostral pole of the colliculus that are active during fixation, and more caudally located neurons whose activity is associated with saccadic eye movements.

Animals↗

PubMed1999

GABAergic excitatory synapses and electrical coupling sustain prolonged discharges in the prey capture neural network of Clione limacina.

Afterdischarges represent a prominent characteristic of the neural network that controls prey capture reactions in the carnivorous mollusc Clione limacina. Their main functional implication is transformation of a brief sensory input from a prey into a lasting prey capture response. The present study, which focuses on the neuronal mechanisms of afterdischarges, demonstrates that a single pair of interneurons [cerebral A interneuron (Cr-Aint)] is responsible for afterdischarge generation in the network. Cr-Aint neurons are electrically coupled to all other neurons in the network and produce slow excitatory synaptic inputs to them. This excitatory transmission is found to be GABAergic, which is demonstrated by the use of GABA antagonists, uptake inhibitors, and double-labeling experiments showing that Cr-Aint neurons are GABA-immunoreactive. The Cr-Aint neurons organize three different pathways in the prey capture network, which provide positive feedback necessary for sustaining prolonged spike activity. The first pathway includes electrical coupling and slow chemical transmission from the Cr-Aint neurons to all other neurons in the network. The second feedback is based on excitatory reciprocal connections between contralateral interneurons. Recurrent excitation via the contralateral cell can sustain prolonged interneuron firing, which then drives the activity of all other cells in the network. The third positive feedback is represented by prominent afterdepolarizing potentials after individual spikes in the Cr-Aint neurons. Afterdepolarizations apparently represent recurrent GABAergic excitatory inputs. It is suggested here that these afterdepolarizing potentials are produced by GABAergic excitatory autapses.

Action Potentials↗

PubMed1992

[Surveying the brain-psyche connection. The frontal lobes control cerebral and mental "timing"].

Regional variations in the brain related to various forms of mental activity can be mapped with rapid isotope methods. Normal resting consciousness entails a high level of activity in large parts of the central nervous system (CNS)--particularly in the frontal lobes. Here the level of activity is reduced during loss of consciousness, intoxication, coma, and also during sleep. Specific functional landscapes can be recorded during perception of sensory stimuli, production of voluntary movements and speech, and in connexion with problem solving, mental imagery, thinking, etc. Effects of emotional stimuli can also be traced. These findings support the idea that a prerequisite for mental activity is a serial activity in multiple distributed networks. In this review, emphasis is laid upon the serial nature (the temporal organisation) of both neurophysiological and mental events. Much new evidence suggests that the serial nature of brain activity and of the cognition is governed by the frontal lobes.

Brain Mapping↗

PubMed1994

Multiplicative contexts in associative memories.

A system of networks, consisting of a first net that constructs the Kronecker product between two vectors and then sends it to a second net that sustains a correlation memory, defines a context-dependent associative memory. In the real nervous system of higher mammals, the anatomy of the neural connections surely exhibits a considerable amount of local imprecision superimposed on a regular global layout. In order to evaluate the potentialities of the multiplicative devices to constitute plausible biological models, we analyse the performances of a context-dependent memory when the multiplicative net, responsible of the construction of the Kronecker product, presents an incomplete connectivity. Our study shows that a large dimensional system is able to support a considerable amount of incompleteness in the connectivity without a great deterioration of the memory. We establish a scaling relationship between the degree of incompleteness, the capacity of the memory, and the tolerance threshold to imperfections in the output. We then analyse some performances that show the versatility of this kind of network to represent a variety of functions. These functions include a context-modulated novelty filter, a network that computes logical modalities and an adaptive searching device.

Animals↗

PubMed1999

A comparative fMRI study of cortical representations for thermal painful, vibrotactile, and motor performance tasks.

Cortical activity due to a thermal painful stimulus applied to the right hand was studied in the middle third of the contralateral brain and compared to activations for vibrotactile and motor tasks using the same body part, in nine normal subjects. Cortical activity was demonstrated utilizing multislice echo-planar functional magnetic resonance imaging (fMRI) and a surface coil. The cortical activity was analyzed based upon individual subject activity maps and on group-averaged activity maps. The results show significant differences in activations across the three tasks and the cortical areas studied. The study indicates that fMRI enables examination of cortical networks subserving pain perception at an anatomical detail not available with other brain imaging techniques and shows that this cortical network underlying pain perception shares components with the networks underlying touch perception and motor execution. However, the thermal pain perception network also has components that are unique to this perception. The uniquely activated areas were in the secondary somatosensory region, insula, and posterior cingulate cortex. The posterior cingulate cortex activity was in a region that, in the monkey, receives nociceptive inputs from posterior thalamic medial and lateral nuclei that in turn are targets for spinothalamic terminations. Discrete subdivisions of the primary somatosensory and motor cortical areas were also activated in the thermal pain task, showing region-dependent differences in the extent of overlap with the other two tasks. Within the primary motor cortex, a hand region was preferentially active in the task in which the stimulus was painful heat. In the primary somatosensory cortex most activity in the painful heat task was localized to area 1, where the motor and vibratory task activities were also coincident. The study also indicates that the functional connectivity across multiple cortical regions reorganizes dynamically with each task.

Adult↗

PubMed2006

Dynamic causal modeling of evoked responses in EEG and MEG.

Neuronally plausible, generative or forward models are essential for understanding how event-related fields (ERFs) and potentials (ERPs) are generated. In this paper, we present a new approach to modeling event-related responses measured with EEG or MEG. This approach uses a biologically informed model to make inferences about the underlying neuronal networks generating responses. The approach can be regarded as a neurobiologically constrained source reconstruction scheme, in which the parameters of the reconstruction have an explicit neuronal interpretation. Specifically, these parameters encode, among other things, the coupling among sources and how that coupling depends upon stimulus attributes or experimental context. The basic idea is to supplement conventional electromagnetic forward models, of how sources are expressed in measurement space, with a model of how source activity is generated by neuronal dynamics. A single inversion of this extended forward model enables inference about both the spatial deployment of sources and the underlying neuronal architecture generating them. Critically, this inference covers long-range connections among well-defined neuronal subpopulations. In a previous paper, we simulated ERPs using a hierarchical neural-mass model that embodied bottom-up, top-down and lateral connections among remote regions. In this paper, we describe a Bayesian procedure to estimate the parameters of this model using empirical data. We demonstrate this procedure by characterizing the role of changes in cortico-cortical coupling, in the genesis of ERPs. In the first experiment, ERPs recorded during the perception of faces and houses were modeled as distinct cortical sources in the ventral visual pathway. Category-selectivity, as indexed by the face-selective N170, could be explained by category-specific differences in forward connections from sensory to higher areas in the ventral stream. We were able to quantify and make inferences about these effects using conditional estimates of connectivity. This allowed us to identify where, in the processing stream, category-selectivity emerged. In the second experiment, we used an auditory oddball paradigm to show that the mismatch negativity can be explained by changes in connectivity. Specifically, using Bayesian model selection, we assessed changes in backward connections, above and beyond changes in forward connections. In accord with theoretical predictions, there was strong evidence for learning-related changes in both forward and backward coupling. These examples show that category- or context-specific coupling among cortical regions can be assessed explicitly, within a mechanistic, biologically motivated inference framework.

Auditory Pathways↗