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PubMed1999

Associative memory in a multi-modular network.

Recent imaging studies suggest that object knowledge is stored in the brain as a distributed network of many cortical areas. Motivated by these observations, we study a multimodular associative memory network, whose functional goal is to store patterns with different coding levels--patterns that vary in the number of modules in which they are encoded. We show that in order to accomplish this task, synaptic inputs should be segregated into intramodular projections and intermodular projections, with the latter undergoing additional nonlinear dendritic processing. This segregation makes sense anatomically if the intermodular projections represent distal synaptic connections on apical dendrites. It is then straightforward to show that memories encoded in more modules are more resilient to focal afferent damage. Further hierarchical segregation of intermodular connections on the dendritic tree improves this resilience, allowing memory retrieval from input to just one of the modules in which it is encoded.

Algorithms↗
PubMed2002

Gene control of synaptic plasticity and memory formation: implications for diseases and therapeutic strategies.

There has been nearly a century of interest in the idea that information is stored in the brain as changes in the efficacy of synaptic connections between neurons that are activated during learning. The discovery and detailed report of the phenomenon generally known as long-term potentiation opened a new chapter in the study of synaptic plasticity in the vertebrate brain, and this form of synaptic plasticity has now become the dominant model in the search for the cellular and molecular bases of learning and memory. Accumulating evidence suggests that the rapid activation of the genetic machinery is a key mechanism underlying the enduring modification of neural networks required for the laying down of memory. Here we briefly review these mechanisms and illustrate with a few examples of animal models of neurological disorders how new knowledge about these mechanisms can provide valuable insights into identifying the mechanisms that go awry when memory is deficient, and how, in turn, characterisation of the dysfunctional mechanisms offers prospects to design and evaluate molecular and biobehavioural strategies for therapeutic prevention and rescue.

Aging↗
PubMed2005

Brain networks associated with cognitive reserve in healthy young and old adults.

In order to understand the brain networks that mediate cognitive reserve, we explored the relationship between subjects' network expression during the performance of a memory test and an index of cognitive reserve. Using H2(15)O positron emission tomography, we imaged 17 healthy older subjects and 20 young adults while they performed a serial recognition memory task for nonsense shapes under two conditions: low demand, with a unique shape presented in each study trial; and titrated demand, with a study list size adjusted so that each subject recognized shapes at 75% accuracy. A factor score that summarized years of education, and scores on the NART and the WAIS-R Vocabulary subtest was used as an index of cognitive reserve. The scaled subprofile model was used to identify a set of functionally connected regions (or topography) that changed in expression across the two task conditions and was differentially expressed by the young and elderly subjects. The regions most active in this topography consisted of right hippocampus, posterior insula, thalamus, and right and left operculum; we found concomitant deactivation in right lingual gyrus, inferior parietal lobe and association cortex, left posterior cingulate, and right and left calcarine cortex. Young subjects with higher cognitive reserve showed increased expression of the topography across the two task conditions. Because this topography, which is responsive to increased task demands, was differentially expressed as a function of reserve level, it may represent a neural manifestation of innate or acquired reserve. In contrast, older subjects with higher cognitive reserve showed decreased expression of the topography across tasks. This suggests some functional reorganization of the network used by the young subjects. Thus, for the old subjects this topography may represent an altered, compensatory network that is used to maintain function in the face of age-related physiological changes.

Adult↗
PubMed1987

Exact results for the average dynamic behavior of some non-linear neural networks.

We have studied the global dynamic behavior of neural-like networks of synchronous threshold elements by writing a master equation as a function of parameter values using statistical methods. Exact results for highly connected networks and no correlation are obtained, showing that in this case (contrary to previous results) the average activity can only display simple stable behaviour, the sole exception being special cases of a slow passage through a tangent bifurcation, and a limit cycle of length two. By introducing an appropriate probabilistic hypothesis, we also study the average activity and correlation for highly connected networks with the topology of a (Cayley) tree. In this case the dynamic is ruled by a pair of coupled equations linking activity and correlation, and the tendency is for the correlation to disappear over time. However, under reasonable biological conditions, this tendency will be extremely slow, giving rise to a region of pseudo-stability.

Animals↗
PubMed2005

Pathophysiology of stroke rehabilitation: temporal aspects of neuro-functional recovery.

Stroke almost always causes an impairment of motor activity and function. Clinical recovery, though usually incomplete, is often highly dynamic and reflects the ability of the neuronal network to adapt. Mechanisms that underlie neuro-functional plasticity are now beginning to be understood. Albeit the enormous efforts undertaken to support the natural course of re-convalescence through rehabilitation, little has been done to relate possible effects of these therapeutic approaches to mechanisms of adaptive pathophysiology. The review presented here focuses on these mechanisms during the course of recovery post stroke. Next to an unmasking of latent network representations, other adaptive processes, such as excitatory metabolic stress, an imbalance in activating and inhibiting transmission, leading to salient hyperexcitability or mechanisms that consolidate novel connections prime the system's plastic capabilities. These pathophysiological processes potentially interact with rehabilitative interventions. They therefore form the foundation of positive, but possibly also negative recuperation under therapy.

Brain↗
PubMed2000

Schizophrenia and the mechanisms of conscious integration.

This article considers the possibility that defective interactions among distributed brain areas may underlie certain dysfunctions of conscious integration such as those seen in schizophrenia. Recent experimental evidence obtained using whole-head magnetoencephalography during binocular rivalry is first reviewed. The results outline a cortical network that underlies conscious integration in the normal brain. This network is not localized to a small part of the brain but it is distributed over frontal, parietal, temporal, and occipital areas. Large-scale simulations of the dynamics of thalamocortical integration are then examined. These studies indicate that several factors can affect the rapid integration of the activity of distributed thalamocortical regions and the resulting behavioral performance. These simulations show that an altered dynamics of corticothalamic and corticocortical re-entrant circuits can result from increased conduction delays, blockade of voltage-dependent connections, reduced synaptic density, and disruptions of the local connectivity within a single cortical area. It can also result from alterations in the activity of diffuse ascending systems that lead to defective reinforcement of integrated activity patterns. Finally, the article briefly reviews theoretical measures of the integration of multiple brain areas, such as measures of functional clustering. These measures have been applied to PET data obtained from schizophrenic subjects and controls while performing cognitive tasks. The results show a change in the functional interactions among distributed brain areas in schizophrenics despite the absence of a change in activation patterns. The possibility is raised that disruption of re-entrant interactions among cortical areas may contribute to the pathophysiology of schizophrenia.

Brain↗
PubMed2004

Search for computational modules in the C. elegans brain.

BACKGROUND: Does the C. elegans nervous system contain multi-neuron computational modules that perform stereotypical functions? We attempt to answer this question by searching for recurring multi-neuron inter-connectivity patterns in the C. elegans nervous system's wiring diagram. RESULTS: Our statistical analysis reveals that some inter-connectivity patterns containing two, three and four (but not five) neurons are significantly over-represented relative to the expectations based on the statistics of smaller inter-connectivity patterns. CONCLUSIONS: Over-represented patterns (or motifs) are candidates for computational modules that may perform stereotypical functions in the C. elegans nervous system. These modules may appear in other species and need to be investigated further.

Animals↗
PubMed2003

Localization of function via lesion analysis.

This article presents a general approach for employing lesion analysis to address the fundamental challenge of localizing functions in a neural system. We describe functional contribution analysis (FCA), which assigns contribution values to the elements of the network such that the ability to predict the network's performance in response to multilesions is maximized. The approach is thoroughly examined on neurocontroller networks of evolved autonomous agents. The FCA portrays a stable set of neuronal contributions and accurate multilesion predictions that are significantly better than those obtained based on the classical single lesion approach. It is also used for a detailed synaptic analysis of the neurocontroller connectivity network, delineating its main functional backbone. The FCA provides a quantitative way of measuring how the network functions are localized and distributed among its elements. Our results question the adequacy of the classical single lesion analysis traditionally used in neuroscience and show that using lesioning experiments to decipher even simple neuronal systems requires a more rigorous multilesion analysis.

Algorithms↗
PubMed1997

Path integration and cognitive mapping in a continuous attractor neural network model.

A minimal synaptic architecture is proposed for how the brain might perform path integration by computing the next internal representation of self-location from the current representation and from the perceived velocity of motion. In the model, a place-cell assembly called a "chart" contains a two-dimensional attractor set called an "attractor map" that can be used to represent coordinates in any arbitrary environment, once associative binding has occurred between chart locations and sensory inputs. In hippocampus, there are different spatial relations among place fields in different environments and behavioral contexts. Thus, the same units may participate in many charts, and it is shown that the number of uncorrelated charts that can be encoded in the same recurrent network is potentially quite large. According to this theory, the firing of a given place cell is primarily a cooperative effect of the activity of its neighbors on the currently active chart. Therefore, it is not particularly useful to think of place cells as encoding any particular external object or event. Because of its recurrent connections, hippocampal field CA3 is proposed as a possible location for this "multichart" architecture; however, other implementations in anatomy would not invalidate the main concepts. The model is implemented numerically both as a network of integrate-and-fire units and as a "macroscopic" (with respect to the space of states) description of the system, based on a continuous approximation defined by a system of stochastic differential equations. It provides an explanation for a number of hitherto perplexing observations on hippocampal place fields, including doubling, vanishing, reshaping in distorted environments, acquiring directionality in a two-goal shuttling task, rapid formation in a novel environment, and slow rotation after disorientation. The model makes several new predictions about the expected properties of hippocampal place cells and other cells of the proposed network.

Animals↗
PubMed1997

Invariant association of ecdysis with increases in cyclic 3',5'-guanosine monophosphate immunoreactivity in a small network of peptidergic neurons in the hornworm, Manduca sexta.

At the end of each molt insects shed their old cuticle by performing the stereotyped behavior of ecdysis. In the moth, Manduca sexta, this behavior is triggered by the neuropeptide eclosion hormone (EH). Insights into the mechanism of action of EH have come from the identification of a small network of peptidergic neurons that shows increased cyclic 3',5'-guanosine monophosphate (cGMP) immunoreactivity at ecdysis in insects from many different orders. Here we present further evidence that strengthens the association between ecdysis and the occurrence of this cGMP response in Manduca. We found that the cGMP increases occurred at every ecdysis, although some of the neurons that showed a response at larval ecdysis did not participate at pupal and adult ecdysis. Both ecdysis and the cGMP increases only required an intact connection with the brain for the first 30 min after EH injection. Interestingly, ecdysis in debrained animals only occurred if the cGMP response had been initiated, suggesting that the onset of this response marks the time at which the central nervous system is first able to drive ecdysis. Finally, we found that the appearance of sensitivity to EH for triggering the cGMP response coincided with the time at which EH first triggers ecdysis.

Animals↗
PubMed2006

Auditory motion perception activates visual motion areas in early blind subjects.

We have previously shown that some visual motion areas can be specifically recruited by auditory motion processing in blindfolded sighted subjects [Poirier, C., Collignon, O., De Volder, A.G., Renier, L., Vanlierde, A., Tranduy, D., Scheiber, C., 2005. Specific activation of V5 brain area by auditory motion processing: an fMRI study. Brain Res. Cogn. Brain Res. 25, 650-658]. The present fMRI study investigated whether auditory motion processing may recruit the same brain areas in early blind subjects. The task consisted of simultaneously determining both the nature of a sound stimulus (pure tone or complex sound) and the presence or absence of its movement. When a movement was present, blind subjects had to identify its direction. Auditory motion processing, as compared to static sound processing, activated the brain network of auditory and visual motion processing classically observed in sighted subjects. Accordingly, brain areas previously considered as specific to visual motion processing could be specifically recruited in blind people by motion stimuli presented through the auditory modality. This indicates that the occipital cortex of blind people could be organized in a modular way, as in sighted people. The similarity of these results with those we previously observed in sighted subjects suggests that occipital recruitment in blind people could be mediated by the same anatomical connections as in sighted subjects.

Adolescent↗
PubMed2006

Separating respiratory-variation-related fluctuations from neuronal-activity-related fluctuations in fMRI.

Subtle changes in a subject's breathing rate or depth, which occur naturally during rest at low frequencies (<0.1 Hz), have been shown to be significantly correlated with fMRI signal changes throughout gray matter and near large vessels. The goal of this study was to investigate the impact of these low-frequency respiration variations on both task activation fMRI studies and resting-state functional connectivity analysis. Unlike MR signal changes correlated with the breathing motion ( approximately 0.3 Hz), BOLD signal changes correlated with across-breath variations in respiratory volume ( approximately 0.03 Hz) appear localized to blood vessels and regions with high blood volume, such as gray matter, similar to changes seen in response to a breath-hold challenge. In addition, the respiration-variation-induced signal changes were found to coincide with many of the areas identified as part of the 'default mode' network, a set of brain regions hypothesized to be more active at rest. Regions could therefore be classified as being part of a resting network based on their similar respiration-induced changes rather than their synchronized neuronal activity. Monitoring and removing these respiration variations led to a significant improvement in the identification of task-related activation and deactivation and only slight differences in regions correlated with the posterior cingulate at rest. Regressing out global signal changes or cueing the subject to breathe at a constant rate and depth resulted in an improved spatial overlap between deactivations and resting-state correlations among areas that showed deactivation.

Adult↗
PubMed2000

Three types of putative presympathetic neurons in the rostral ventrolateral medulla studied with rat brainstem-spinal cord preparation.

To study the electrophysiological properties of presympathetic neurons in the rostral ventrolateral medulla (RVLM), intracellular recordings were performed by the whole-cell patch-clamp technique. We utilized the neonatal rat brainstem-spinal cord preparation, in which the sympathetic neuronal network is thought to be preserved, unlike in slice preparation. In response to stimulation in the ipsilateral Th2 spinal segment including intermediolateral cell column (IML), 33 of 151 non-respiratory RVLM neurons showed antidromic action potentials with a constant latency of 45 ms, and can be considered as presympathetic neurons. We classified and characterized the RVLM presympathetic neurons into three types: 'regularly firing neurons (n=7)', which showed ramp depolarization and frequent action potentials (4.2+/-0.9 spikes/s) with rare excitatory postsynaptic potentials (EPSPs); 'irregularly firing neurons (n=21)', which exhibited many EPSPs that modulated the firing rate; and 'silent-type neurons (n=5)', which discharged action potentials only during current-induced depolarization. Lucifer-Yellow staining showed that the irregularly firing neurons were significantly larger and had more dendrites than the regularly firing neurons. All regularly firing neurons retained their discharges during low-Ca2+ -high-Mg2+ superfusion that blocks synaptic input, whereas the discharges in 11 of 16 irregularly firing neurons were abolished, suggesting that the regularly firing neurons discharged independently of synaptic input. Seven of 31 RVLM neurons were hyperpolarized by stimulation of vagal afferent nerves. In summary, three types of RVLM presympathetic neurons were characterized by the patch-clamp technique in the brainstem-spinal cord preparation, in which the connection was preserved from vagal afferent to the Th2 spinal segment through the RVLM. Since antidromic action potentials were demonstrated by stimulation in the Th2 spinal segment in 33 neurons of all three types, all types of RVLM neurons constitute a part of the sympathetic neuronal network.

Action Potentials↗
PubMed2001

Enhanced CREB phosphorylation in immature dentate gyrus granule cells precedes neurotrophin expression and indicates a specific role of CREB in granule cell differentiation.

Differentiation and maturation of dentate gyrus granule cells requires coordinated interactions of numerous processes. These must be regulated by protein factors capable of integrating signals mediated through diverse signalling pathways. Such integrators of inter and intracellular physiological stimuli include the cAMP-response element binding protein (CREB), a leucine-zipper class transcription factor that is activated through phosphorylation. Neuronal activity and neurotrophic factors, known to be involved in granule cell differentiation, are major physiologic regulators of CREB function. To examine whether CREB may play a role in governing coordinated gene transcription during granule cell differentiation, we determined the spatial and temporal profiles of phosphorylated (activated) CREB throughout postnatal development in immature rat hippocampus. We demonstrate that CREB activation is confined to discrete, early stages of granule cell differentiation. In addition, CREB phosphorylation occurs prior to expression of the neurotrophins BDNF and NT-3. These data indicate that in a signal transduction cascade connecting CREB and neurotrophins in the process of granule cell maturation, CREB is located upstream of neurotrophins. Importantly, CREB may be a critical component of the machinery regulating the coordinated transcription of genes contributing to the differentiation of granule cells and their integration into the dentate gyrus network.

Animals↗
PubMed2006

Neural correlates of epigenesis.

The effect of life stress on depression is moderated by a repeat length variation in the transcriptional control region of the serotonin transporter gene, which renders carriers of the short variant vulnerable for depression. We investigated the underlying neural mechanisms of these epigenetic processes in individuals with no history of psychopathology by using multimodal magnetic resonance-based imaging (functional, perfusion, and structural), genotyping, and self-reported life stress and rumination. Based on functional MRI and perfusion data, we found support for a model by which life stress interacts with the effect of serotonin transporter genotype on amygdala and hippocampal resting activation, two regions involved in depression and stress. Life stress also differentially affected, as a function of serotonin transporter genotype, functional connectivity of the amygdala and hippocampus with a wide network of other regions, as well as gray matter structural features, and affected individuals' level of rumination. These interactions may constitute a neural mechanism for epigenetic vulnerability toward, or protection against, depression.

Adult↗
PubMed2002

Effects of verbal working memory load on corticocortical connectivity modeled by path analysis of functional magnetic resonance imaging data.

We investigated the hypothesis that there are load-related changes in the integrated function of frontoparietal working memory networks. Functional magnetic resonance imaging time-series data from 10 healthy volunteers performing a graded n-back verbal working memory task were modeled using path analysis. Seven generically activated regions were included in the model: left/right middle frontal gyri (L/R MFG), left/right inferior frontal gyri (L/R IFG), left/right posterior parietal cortex (L/R PPC), and supplementary motor area (SMA). The model provided a good fit to the 1-back (chi(2) = 7.04, df = 8, P = 0.53) and 2-back conditions (chi(2) = 9.35, df = 8, P = 0.31) but not for the 3-back condition (chi(2) = 20.60, df = 8, P = 0.008). Model parameter estimates were compared overall among conditions: there was a significant difference overall between 1-back and 2-back conditions (chi(2)(diff) = 74.77, df = 20, P < 0.001) and also between 2-back and 3-back conditions (chi(2)(diff) = 96.28, df = 20, P < 0.001). Path coefficients between LIFG and LPPC were significantly different from zero in both 1-back and 2-back conditions; in the 2-back condition, additional paths from LIFG to LPPC via SMA and to RMFG from LMFG and LPPC were also nonzero. This study demonstrated a significant change in functional integration of a neurocognitive network for working memory as a correlate of increased load. Enhanced inferior frontoparietal and prefrontoprefrontal connectivity was observed as a correlate of increasing memory load, which may reflect greater demand for maintenance and executive processes, respectively.

Adult↗
PubMed1989

[Morphologic characteristics of the vascular network of the dentate nucleus during development].

The development of the blood network of the dentate nucleus was studied on 20 human fetal brains of different crown-rump length (CRL). In the stage of 17 to 20 weeks, the blood network of the dentate nucleus consisted of moderate spiral blood vessels. They anastomosed each other and made irregular elongated polyhedral meshes. From this meshwork, blood vessels of a greater volume arose and extended to the hilum of the nucleus. Between 23 and 25 weeks, a clear segmental vascular pattern was noticed. The capillary network was very dense. Along the outer surface of the nucleus the blood vessels which connected two secondary wrinkles of the gray matter were observed. In all the stages investigated the blood vessels were moderately spiral.

Blood Vessels↗
PubMed2026

Neurocorrelates of nocturnal enuresis in pre-adolescent children.

INTRODUCTION: Nocturnal enuresis (NE) is a common neurodevelopmental condition, yet its underlying neural mechanisms remain unclear. This study leverages the large-scale Adolescent Brain Cognitive Development (ABCD) dataset to identify structural and functional brain correlates associated with active symptoms and the resolution of bedwetting. METHODS: Using cross-sectional data from 3472 participants aged 9-10 years, children were categorized into three groups: active nocturnal enuresis (ANE, n = 225), history of nocturnal enuresis (HNE, n = 1171), and healthy control groups (CG, n = 2076). Multimodal neuroimaging protocol evaluated macrostructural properties via structural MRI (sMRI), microstructural white matter integrity via diffusion MRI (dMRI), and functional connectivity via resting-state fMRI (fMRI). Group differences were evaluated using linear models within an ANCOVA framework, adjusting for intracranial volume and handedness with False Discovery Rate (FDR) correction. RESULTS: Compared to controls, the ANE group exhibited a significant volume deficit in the right caudate, decreased sulcal depth in the left insula, and lower internal correlation within the Cingulo-Opercular Network (CON). Conversely, the dry HNE group demonstrated significant structural adaptations, including bilaterally larger putamen volumes and increased right caudate volume compared to the ANE group. The HNE group also showed increased microstructural density (decreased mean diffusivity) in the bilateral hippocampus and an increased cortical surface area in the left insula. Both NE groups demonstrated persistently reduced functional coupling within the CON. CONCLUSIONS: Nocturnal enuresis appears to be associated with a potential complex central signaling deficits. Reduced internal correlation within the CON across both active and former bedwetters indicates a potential for impairment in processing internal homeostatic bladder signals during sleep.

Humans↗