Showing papers in "Nature Reviews Neuroscience in 2001"
TL;DR: It is argued that the most plausible candidate is the formation of dynamic links mediated by synchrony over multiple frequency bands.
Abstract: The emergence of a unified cognitive moment relies on the coordination of scattered mosaics of functionally specialized brain regions. Here we review the mechanisms of large-scale integration that counterbalance the distributed anatomical and functional organization of brain activity to enable the emergence of coherent behaviour and cognition. Although the mechanisms involved in large-scale integration are still largely unknown, we argue that the most plausible candidate is the formation of dynamic links mediated by synchrony over multiple frequency bands.
4,485 citations
TL;DR: Five important trends have emerged from recent work on computational models of focal visual attention that emphasize the bottom-up, image-based control of attentional deployment, providing a framework for a computational and neurobiological understanding of visual attention.
Abstract: Five important trends have emerged from recent work on computational models of focal visual attention that emphasize the bottom-up, image-based control of attentional deployment. First, the perceptual saliency of stimuli critically depends on the surrounding context. Second, a unique 'saliency map' that topographically encodes for stimulus conspicuity over the visual scene has proved to be an efficient and plausible bottom-up control strategy. Third, inhibition of return, the process by which the currently attended location is prevented from being attended again, is a crucial element of attentional deployment. Fourth, attention and eye movements tightly interplay, posing computational challenges with respect to the coordinate system used to control attention. And last, scene understanding and object recognition strongly constrain the selection of attended locations. Insights from these five key areas provide a framework for a computational and neurobiological understanding of visual attention.
4,485 citations
TL;DR: It is argued that coherence among subthreshold membrane potential fluctuations could be exploited to express selective functional relationships during states of expectancy or attention, and these dynamic patterns could allow the grouping and selection of distributed neuronal responses for further processing.
Abstract: Classical theories of sensory processing view the brain as a passive, stimulus-driven device. By contrast, more recent approaches emphasize the constructive nature of perception, viewing it as an active and highly selective process. Indeed, there is ample evidence that the processing of stimuli is controlled by top-down influences that strongly shape the intrinsic dynamics of thalamocortical networks and constantly create predictions about forthcoming sensory events. We discuss recent experiments indicating that such predictions might be embodied in the temporal structure of both stimulus-evoked and ongoing activity, and that synchronous oscillations are particularly important in this process. Coherence among subthreshold membrane potential fluctuations could be exploited to express selective functional relationships during states of expectancy or attention, and these dynamic patterns could allow the grouping and selection of distributed neuronal responses for further processing.
3,330 citations
TL;DR: This work explores the possibility that there might be a baseline or resting state of brain function involving a specific set of mental operations, including the manner in which a baseline is defined and the implications of such a baseline for the understanding ofbrain function.
Abstract: Functional brain imaging in humans has revealed task-specific increases in brain activity that are associated with various mental activities. In the same studies, mysterious, task-independent decreases have also frequently been encountered, especially when the tasks of interest have been compared with a passive state, such as simple fixation or eyes closed. These decreases have raised the possibility that there might be a baseline or resting state of brain function involving a specific set of mental operations. We explore this possibility, including the manner in which we might define a baseline and the implications of such a baseline for our understanding of brain function.
3,285 citations
TL;DR: Evidence for the existence of a system, the 'mirror system', that seems to serve this mapping function in primates and humans is discussed, and its implications for the understanding and imitation of action are explored.
Abstract: What are the neural bases of action understanding? Although this capacity could merely involve visual analysis of the action, it has been argued that we actually map this visual information onto its motor representation in our nervous system. Here we discuss evidence for the existence of a system, the 'mirror system', that seems to serve this mapping function in primates and humans, and explore its implications for the understanding and imitation of action.
2,995 citations
TL;DR: By this account, neurotrophins may participate in activity-dependent synaptic plasticity, linking synaptic activity with long-term functional and structural modification of synaptic connections.
Abstract: The role of neurotrophins as regulatory factors that mediate the differentiation and survival of neurons has been well described. More recent evidence indicates that neurotrophins may also act as synaptic modulators. Here, I review the evidence that synaptic activity regulates the synthesis, secretion and action of neurotrophins, which can in turn induce immediate changes in synaptic efficacy and morphology. By this account, neurotrophins may participate in activity-dependent synaptic plasticity, linking synaptic activity with long-term functional and structural modification of synaptic connections.
1,783 citations
TL;DR: It is argued that the overlap of these three domains is key to distinguishing the anterior cingulate cortex from other frontal regions, placing it in a unique position to translate intentions to actions.
Abstract: Controversy surrounds the function of the anterior cingulate cortex. Recent discussions about its role in behavioural control have centred on three main issues: its involvement in motor control, its proposed role in cognition and its relationship with the arousal/drive state of the organism. I argue that the overlap of these three domains is key to distinguishing the anterior cingulate cortex from other frontal regions, placing it in a unique position to translate intentions to actions.
1,688 citations
TL;DR: There has been considerable progress in identifying the mechanisms that contribute to long-lived neural and behavioural plasticity related to addiction, including drug-induced changes in gene transcription, in RNA and protein processing, and in synaptic structure.
Abstract: Studies of human addicts and behavioural studies in rodent models of addiction indicate that key behavioural abnormalities associated with addiction are extremely long lived. So, chronic drug exposure causes stable changes in the brain at the molecular and cellular levels that underlie these behavioural abnormalities. There has been considerable progress in identifying the mechanisms that contribute to long-lived neural and behavioural plasticity related to addiction, including drug-induced changes in gene transcription, in RNA and protein processing, and in synaptic structure. Although the specific changes identified so far are not sufficiently long lasting to account for the nearly permanent changes in behaviour associated with addiction, recent work has pointed to the types of mechanism that could be involved.
1,688 citations
TL;DR: This work focuses on the central issue in this dispute — the relative contributions of the hippocampus and the perirhinal cortex to recognition memory.
Abstract: The hallmark of medial temporal lobe amnesia is a loss of episodic memory such that patients fail to remember new events that are set in an autobiographical context (an episode). A further symptom is a loss of recognition memory. The relationship between these two features has recently become contentious. Here, we focus on the central issue in this dispute — the relative contributions of the hippocampus and the perirhinal cortex to recognition memory. A resolution is vital not only for uncovering the neural substrates of these key aspects of memory, but also for understanding the processes disrupted in medial temporal lobe amnesia and the validity of animal models of this syndrome.
1,560 citations
TL;DR: Neuroimaging studies, combined with other methods, are revealing the ways in which imagery draws on mechanisms used in other activities, such as perception and motor control.
Abstract: Mental imagery has, until recently, fallen within the purview of philosophy and cognitive psychology. Both enterprises have raised important questions about imagery, but have not made substantial progress in answering them. With the advent of cognitive neuroscience, these questions have become empirically tractable. Neuroimaging studies, combined with other methods (such as studies of brain-damaged patients and of the effects of transcranial magnetic stimulation), are revealing the ways in which imagery draws on mechanisms used in other activities, such as perception and motor control. Because of its close relation to these basic processes, imagery is now becoming one of the best understood 'higher' cognitive functions.
1,521 citations
TL;DR: It is no longer appropriate to consider solely neuron–neuron connections; it is also necessary to develop a view of the intricate web of active connections among glial cells, and between glia and neurons.
Abstract: Glial cells are emerging from the background to become more prominent in our thinking about integration in the nervous system. Given that glial cells associated with synapses integrate neuronal inputs and can release transmitters that modulate synaptic activity, it is time to rethink our understanding of the wiring diagram of the nervous system. It is no longer appropriate to consider solely neuron–neuron connections; we also need to develop a view of the intricate web of active connections among glial cells, and between glia and neurons. Without such a view, it might be impossible to decode the language of the brain.
TL;DR: Insights into abnormalities in two genes, together with errors in the handling of synaptic glutamate and the potential excitotoxic response that this alteration provokes, have provided leads for the development of new strategies to identify an as yet elusive remedy for this progressive, fatal disorder.
Abstract: Since its description by Charcot more than 130 years ago, the mechanism underlying the characteristic selective degeneration and death of motor neurons in amyotrophic lateral sclerosis has remained a mystery. Modern genetics has now identified mutations in two genes — SOD1 and ALS2 — as primary causes of the disease, and has implicated others as potential contributors. Insights into these abnormalities, together with errors in the handling of synaptic glutamate and the potential excitotoxic response that this alteration provokes, have provided leads for the development of new strategies to identify an as yet elusive remedy for this progressive, fatal disorder.
TL;DR: Experimental and theoretical results indicate that correlated fluctuations might be important for cortical processes, such as attention, that control the flow of information in the brain.
Abstract: For years we have known that cortical neurons collectively have synchronous or oscillatory patterns of activity, the frequencies and temporal dynamics of which are associated with distinct behavioural states. Although the function of these oscillations has remained obscure, recent experimental and theoretical results indicate that correlated fluctuations might be important for cortical processes, such as attention, that control the flow of information in the brain.
TL;DR: The molecular properties of the synucleins, the different diseases characterized by the accumulation of α-synuclein, and the possible mechanisms by which dysfunction ofα- synuclein might lead to neurodegeneration are reviewed.
Abstract: In recent years, two developments have imparted a new direction to research on the aetiology and pathogenesis of Parkinson's disease. First, the discovery that a missense mutation in the α-synuclein gene is a rare genetic cause of Parkinson's disease. Second, the identification of the α-synuclein protein as the main component of Lewy bodies and Lewy neurites, the defining neuropathological characteristics of all cases of Parkinson's and several other diseases. The filamentous inclusions of multiple system atrophy are also made of α-synuclein. These findings have placed α-synuclein dysfunction at the centre of several common neurodegenerative diseases. Here, I review the molecular properties of the synucleins, the different diseases characterized by the accumulation of α-synuclein, and the possible mechanisms by which dysfunction of α-synuclein might lead to neurodegeneration.
TL;DR: Evidence is reviewed for the possibility that compulsion and its persistence are based on a pathological usurpation of molecular mechanisms that are normally involved in memory, which is often initiated by exposure to drug-related cues.
Abstract: People take addictive drugs to elevate mood, but with repeated use these drugs produce serious unwanted effects, which can include tolerance to some drug effects, sensitization to others, and an adapted state - dependence - which sets the stage for withdrawal symptoms when drug use stops. The most serious consequence of repetitive drug taking, however, is addiction: a persistent state in which compulsive drug use escapes control, even when serious negative consequences ensue. Addiction is characterized by a long-lasting risk of relapse, which is often initiated by exposure to drug-related cues. Substantial progress has been made in understanding the molecular and cellular mechanisms of tolerance, dependence and withdrawal, but as yet we understand little of the neural substrates of compulsive drug use and its remarkable persistence. Here we review evidence for the possibility that compulsion and its persistence are based on a pathological usurpation of molecular mechanisms that are normally involved in memory.
TL;DR: The time is ripe to summarize the evidence on a remarkable diversity of acetylcholinesterase functions, as well as some of the long-suspected 'non-classical' actions of this enzyme, which have more recently driven a profound revolution in research.
Abstract: The discovery of the first neurotransmitter — acetylcholine — was soon followed by the discovery of its hydrolysing enzyme, acetylcholinesterase. The role of acetylcholinesterase in terminating acetylcholine-mediated neurotransmission made it the focus of intense research for much of the past century. But the complexity of acetylcholinesterase gene regulation and recent evidence for some of the long-suspected 'non-classical' actions of this enzyme have more recently driven a profound revolution in acetylcholinesterase research. Although our understanding of the additional roles of acetylcholinesterase is incomplete, the time is ripe to summarize the evidence on a remarkable diversity of acetylcholinesterase functions.
TL;DR: Three subgroups comprise the TRP channel family; the best understood of these mediates responses to painful stimuli, and other proposed functions include repletion of intracellular calcium stores, receptor-mediated excitation and modulation of the cell cycle.
Abstract: Mammalian homologues of the Drosophila transient receptor potential (TRP) channel gene encode a family of at least 20 ion channel proteins. They are widely distributed in mammalian tissues, but their specific physiological functions are largely unknown. A common theme that links the TRP channels is their activation or modulation by phosphatidylinositol signal transduction pathways. The channel subunits have six transmembrane domains that most probably assemble into tetramers to form non-selective cationic channels, which allow for the influx of calcium ions into cells. Three subgroups comprise the TRP channel family; the best understood of these mediates responses to painful stimuli. Other proposed functions include repletion of intracellular calcium stores, receptor-mediated excitation and modulation of the cell cycle.
TL;DR: Over the past decade, studies in a range of vertebrates, including humans, have begun to address the neural basis of attachment at a molecular, cellular and systems level.
Abstract: It is difficult to think of any behavioural process that is more intrinsically important to us than attachment. Feeding, sleeping and locomotion are all necessary for survival, but humans are, as Baruch Spinoza famously noted, "a social animal" and it is our social attachments that we live for. Over the past decade, studies in a range of vertebrates, including humans, have begun to address the neural basis of attachment at a molecular, cellular and systems level. This review describes some of the important insights from this work.
TL;DR: Some of the beneficial functions of MMPs during neural development are considered and their roles in repair after brain injury are speculated, as well as a family of proteins known as ADAMs, as some of the properties previously ascribed to M MPs are possibly the result of ADAM activity.
Abstract: Matrix metalloproteinases (MMPs) have been implicated in several diseases of the nervous system. Here we review the evidence that supports this idea and discuss the possible mechanisms of MMP action. We then consider some of the beneficial functions of MMPs during neural development and speculate on their roles in repair after brain injury. We also introduce a family of proteins known as ADAMs (a disintegrin and metalloproteinase), as some of the properties previously ascribed to MMPs are possibly the result of ADAM activity.
TL;DR: It is proposed that the stem cells in the central nervous system are contained within the neuroepithelial → radial glia → astrocyte lineage.
Abstract: For many years, it was assumed that neurons and glia in the central nervous system were produced from two distinct precursor pools that diverged early during embryonic development This theory was partially based on the idea that neurogenesis and gliogenesis occurred during different periods of development, and that neurogenesis ceased perinatally However, there is now abundant evidence that neural stem cells persist in the adult brain and support ongoing neurogenesis in restricted regions of the central nervous system Surprisingly, these stem cells have the characteristics of fully differentiated glia Neuroepithelial stem cells in the embryonic neural tube do not show glial characteristics, raising questions about the putative lineage from embryonic to adult stem cells In the developing brain, radial glia have long been known to produce cortical astrocytes, but recent data indicate that radial glia might also divide asymmetrically to produce cortical neurons Here we review these new developments and propose that the stem cells in the central nervous system are contained within the neuroepithelial → radial glia → astrocyte lineage
TL;DR: Evidence for the contribution of cytokines to acute neurodegeneration is reviewed, focusing primarily on interleukin 1, tumour necrosis factor-α (TNFα) and transforming growth factor-β (TGFβ).
Abstract: Cytokines have been implicated as mediators and inhibitors of diverse forms of neurodegeneration. They are induced in response to brain injury and have diverse actions that can cause, exacerbate, mediate and/or inhibit cellular injury and repair. Here we review evidence for the contribution of cytokines to acute neurodegeneration, focusing primarily on interleukin 1 (IL-1), tumour necrosis factor-α (TNFα) and transforming growth factor-β (TGFβ). TGFβ seems to exert primarily neuroprotective actions, whereas TNFα might contribute to neuronal injury and exert protective effects. IL-1 mediates ischaemic, excitotoxic and traumatic brain injury, probably through multiple actions on glia, neurons and the vasculature. Understanding cytokine action in acute neurodegeneration could lead to novel and effective therapeutic strategies, some of which are already in clinical trials.
TL;DR: The molecular and cellular mechanisms that govern each of these stages are now being elucidated by a combination of microscopic and genetic methods, allowing the neuromuscular junction to serve as a model for smaller and less-accessible central synapses.
Abstract: The postsynaptic apparatus of the skeletal neuromuscular junction, like that of other synapses, contains a high-density patch of neurotransmitter receptors that is closely associated with a variety of extracellular, transmembrane and cytoplasmic proteins that have adhesive, structural and signalling roles. The postsynaptic apparatus is organized by signals from the presynaptic nerve terminal. It changes in shape, size and molecular architecture as it matures. Once mature, it can be maintained for the life of the organism, but has the capacity for remodelling in response to altered input. The molecular and cellular mechanisms that govern each of these stages are now being elucidated by a combination of microscopic and genetic methods, allowing the neuromuscular junction to serve as a model for smaller and less-accessible central synapses.
TL;DR: A model for vertebrate cell-fate determination has been proposed that combines findings on the relative roles of extrinsic and intrinsic regulators in controlling cell- fate choices and proposes that progenitors pass through intrinsically determined competence states.
Abstract: Postmitotic neurons are produced from a pool of cycling progenitors in an orderly fashion during development. Studies of cell-fate determination in the vertebrate retina have uncovered several fundamental principles by which this is achieved. Most notably, a model for vertebrate cell-fate determination has been proposed that combines findings on the relative roles of extrinsic and intrinsic regulators in controlling cell-fate choices. At the heart of the model is the proposal that progenitors pass through intrinsically determined competence states, during which they are capable of giving rise to a limited subset of cell types under the influence of extrinsic signals.
TL;DR: New insights into the molecular mechanisms that regulate spine morphogenesis offer potential ways to manipulate dendritic spines in vivo and to explore their physiological roles in the brain.
Abstract: Dendritic spines are tiny protrusions that receive excitatory synaptic input and compartmentalize postsynaptic responses. Heterogeneous in size and shape, and modifiable by activity and experience, dendritic spines have long been thought to provide a morphological basis for synaptic plasticity. Although advanced imaging techniques have highlighted the rapid and regulated motility of spines in living neurons, the functional significance of spine plasticity remains elusive. Recent insights into the molecular mechanisms that regulate spine morphogenesis offer potential ways to manipulate dendritic spines in vivo and to explore their physiological roles in the brain.
TL;DR: Evidence that supports the existence of several tangential migration pathways in the telencephalon is reviewed, and recent findings that describe their regulation are summarized.
Abstract: Recent studies on the origin of cell populations in rodent and chicken embryonic brains provide evidence for extensive tangential migration within the developing telencephalon. On the basis of these findings, a new concept of corticogenesis has emerged, which proposes that two distinct neuronal populations cooperate in the formation of the cortex. One population consists of radially migrating neurons that originate in the ventricular zone of the pallium (cortex) and give rise to the glutamatergic pyramidal neurons. The second population consists of tangentially migrating neurons that originate in the ventricular zone of the subpallium (subcortical telencephalon) and give rise to GABA (γ-aminobutyric acid)-producing local circuit neurons. The subpallium is also the origin of other cell types that follow distinct tangential trajectories to migrate to structures such as the olfactory bulb and the striatum. Here, we review evidence that supports the existence of several tangential migration pathways in the telencephalon, and summarize recent findings that describe their regulation.
TL;DR: Evidence that biological motion is processed as a special category, to which humans from an early age attribute mental states such as intention is reviewed, to support the idea that the brain is a powerful simulating machine, designed to extract intentions from the motion and to predict the future actions of other animate beings.
Abstract: Humans have an inherent tendency to infer other people's intentions from their actions. Here we review psychophysical and functional neuroimaging evidence that biological motion is processed as a special category, from which we automatically infer mental states such as intention. The mechanism underlying the attribution of intentions to actions might rely on simulating the observed action and mapping it onto representations of our own intentions. There is accumulating neurophysiological evidence to support a role for action simulation in the brain.
TL;DR: The amygdala is involved in processing facial signals of fear and in fear conditioning, and this conclusion has emerged from evidence converging from the analysis of animals with amygdala lesions, from patients with bilateral amygdala damage and from functional imaging experiments in healthy individuals.
Abstract: For over 60 years, ideas about emotion in neuroscience and psychology have been dominated by a debate on whether emotion can be encompassed within a single, unifying model. In neuroscience, this approach is epitomized by the limbic system theory and, in psychology, by dimensional models of emotion. Comparative research has gradually eroded the limbic model, and some scientists have proposed that certain individual emotions are represented separately in the brain. Evidence from humans consistent with this approach has recently been obtained by studies indicating that signals of fear and disgust are processed by distinct neural substrates. We review this research and its implications for theories of emotion.
TL;DR: The infant's interaction with its environment helps to sculpt inter- and intraregional connections within the cortex, eventually resulting in the highly specialized adult brain.
Abstract: There is a continuing debate in developmental neuroscience about the importance of activity-dependent processes. The relatively delayed rate of development of the human brain, compared with that of other mammals, might make it more susceptible to the influence of postnatal experience. The human infant is well adapted to capitalize on this opportunity through primitive biases to attend to relevant stimuli in its environment. The infant's interaction with its environment helps to sculpt inter- and intraregional connections within the cortex, eventually resulting in the highly specialized adult brain.
TL;DR: An adaptive coding model of prefrontal function is proposed, implying that, within the prefrontal cortex, regional specializations will be statistical rather than absolute, and suggesting that conclusions concerning regional specialization will depend on criteria for assessing selectivity and on experimental demand and power.
Abstract: The prefrontal cortex has a vital role in effective, organized behaviour Both functional neuroimaging in humans and electrophysiology in awake monkeys indicate that a fundamental principle of prefrontal function might be adaptive neural coding — in large regions of the prefrontal cortex, neurons adapt their properties to carry specifically information that is relevant to current concerns, producing a dense, distributed representation of related inputs, actions, rewards and other information A model based on such adaptive coding integrates the role of the prefrontal cortex in working memory, attention and control Adaptive coding points to new perspectives on several basic questions, including mapping of cognitive to neurophysiological functions, the influences of task content and difficulty, and the nature of frontal lobe specializations
TL;DR: It is argued that the declarative/procedural model provides a new framework for the study of lexicon and grammar.
Abstract: What are the psychological, computational and neural underpinnings of language? Are these neurocognitive correlates dedicated to language? Do different parts of language depend on distinct neurocognitive systems? Here I address these and other issues that are crucial for our understanding of two fundamental language capacities: the memorization of words in the mental lexicon, and the rule-governed combination of words by the mental grammar. According to the declarative/procedural model, the mental lexicon depends on declarative memory and is rooted in the temporal lobe, whereas the mental grammar involves procedural memory and is rooted in the frontal cortex and basal ganglia. I argue that the declarative/procedural model provides a new framework for the study of lexicon and grammar.