Showing papers in "Nature Reviews Neuroscience in 2002"
TL;DR: Evidence for partially segregated networks of brain areas that carry out different attentional functions is reviewed, finding that one system is involved in preparing and applying goal-directed selection for stimuli and responses, and the other is specialized for the detection of behaviourally relevant stimuli.
Abstract: We review evidence for partially segregated networks of brain areas that carry out different attentional functions. One system, which includes parts of the intraparietal cortex and superior frontal cortex, is involved in preparing and applying goal-directed (top-down) selection for stimuli and responses. This system is also modulated by the detection of stimuli. The other system, which includes the temporoparietal cortex and inferior frontal cortex, and is largely lateralized to the right hemisphere, is not involved in top-down selection. Instead, this system is specialized for the detection of behaviourally relevant stimuli, particularly when they are salient or unexpected. This ventral frontoparietal network works as a 'circuit breaker' for the dorsal system, directing attention to salient events. Both attentional systems interact during normal vision, and both are disrupted in unilateral spatial neglect.
10,985 citations
TL;DR: Functional anatomical work has detailed an afferent neural system in primates and in humans that represents all aspects of the physiological condition of the physical body that might provide a foundation for subjective feelings, emotion and self-awareness.
Abstract: As humans, we perceive feelings from our bodies that relate our state of well-being, our energy and stress levels, our mood and disposition. How do we have these feelings? What neural processes do they represent? Recent functional anatomical work has detailed an afferent neural system in primates and in humans that represents all aspects of the physiological condition of the physical body. This system constitutes a representation of 'the material me', and might provide a foundation for subjective feelings, emotion and self-awareness.
4,673 citations
TL;DR: This work proposes that GABA becomes inhibitory by the delayed expression of a chloride exporter, leading to a negative shift in the reversal potential for choride ions, and provides a solution to the problem of how to excite developing neurons to promote growth and synapse formation.
Abstract: In the immature brain, GABA (gamma-aminobutyric acid) is excitatory, and GABA-releasing synapses are formed before glutamatergic contacts in a wide range of species and structures. GABA becomes inhibitory by the delayed expression of a chloride exporter, leading to a negative shift in the reversal potential for choride ions. I propose that this mechanism provides a solution to the problem of how to excite developing neurons to promote growth and synapse formation while avoiding the potentially toxic effects of a mismatch between GABA-mediated inhibition and glutamatergic excitation. As key elements of this cascade are activity dependent, the formation of inhibition adds an element of nurture to the construction of cortical networks.
2,275 citations
TL;DR: Genetic mutations that prevent persistent activation of CaMKII block LTP, experience-dependent plasticity and behavioural memory, making this kinase a leading candidate in the search for the molecular basis of memory.
Abstract: Long-term potentiation (LTP) in the CA1 region of the hippocampus has been the primary model by which to study the cellular and molecular basis of memory. Calcium/calmodulin-dependent protein kinase II (CaMKII) is necessary for LTP induction, is persistently activated by stimuli that elicit LTP, and can, by itself, enhance the efficacy of synaptic transmission. The analysis of CaMKII autophosphorylation and dephosphorylation indicates that this kinase could serve as a molecular switch that is capable of long-term memory storage. Consistent with such a role, mutations that prevent persistent activation of CaMKII block LTP, experience-dependent plasticity and behavioural memory. These results make CaMKII a leading candidate in the search for the molecular basis of memory.
1,864 citations
TL;DR: It is proposed that three such endophenotypes — a specific abnormality in reward-related circuitry that leads to shortened delay gradients, deficits in temporal processing that result in high intrasubject intertrial variability, and deficits in working memory — are most amenable to integrative collaborative approaches that aim to uncover the causes of ADHD.
Abstract: Research on attention-deficit/hyperactivity disorder (ADHD), a highly prevalent and controversial condition, has, for the most part, been descriptive and atheoretical. The imperative to discover the genetic and environmental risk factors for ADHD is motivating the search for quantifiable intermediate constructs, termed endophenotypes. In this selective review, we conclude that such endophenotypes should be solidly grounded in the neurosciences. We propose that three such endophenotypes — a specific abnormality in reward-related circuitry that leads to shortened delay gradients, deficits in temporal processing that result in high intrasubject intertrial variability, and deficits in working memory — are most amenable to integrative collaborative approaches that aim to uncover the causes of ADHD.
1,723 citations
TL;DR: Members of the nerve growth factor and glial cell line-derived neurotrophic factor families — comprising neurotrophins and GDNF-family ligands (GFLs) — are crucial for the development and maintenance of distinct sets of central and peripheral neurons.
Abstract: Members of the nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) families — comprising neurotrophins and GDNF-family ligands (GFLs), respectively — are crucial for the development and maintenance of distinct sets of central and peripheral neurons. Knockout studies in the mouse have revealed that members of these two families might collaborate or act sequentially in a given neuron. Although neurotrophins and GFLs activate common intracellular signalling pathways through their receptor tyrosine kinases, several clear differences exist between these families of trophic factors.
1,711 citations
TL;DR: Parallel studies in Drosophila and vertebrates have revealed that proneural genes are key regulators of neurogenesis, coordinating the acquisition of a generic neuronal fate and of specific subtype identities that are appropriate for the location and time of neuronal generation.
Abstract: Certain morphological, physiological and molecular characteristics are shared by all neurons. However, despite these similarities, neurons constitute the most diverse cell population of any organism. Recently, considerable attention has been focused on identifying the molecular mechanisms that underlie this cellular diversity. Parallel studies in Drosophila and vertebrates have revealed that proneural genes are key regulators of neurogenesis, coordinating the acquisition of a generic neuronal fate and of specific subtype identities that are appropriate for the location and time of neuronal generation. These studies reveal that, in spite of differences between invertebrate and vertebrate neural lineages, Drosophila and vertebrate proneural genes have remarkably similar roles.
1,450 citations
TL;DR: An overview of the neurobiology of stress–memory interactions is provided, and a neural–endocrine model is presented to explain how stress modifies hippocampal functioning.
Abstract: Stress is a biologically significant factor that, by altering brain cell properties, can disturb cognitive processes such as learning and memory, and consequently limit the quality of human life. Extensive rodent and human research has shown that the hippocampus is not only crucially involved in memory formation, but is also highly sensitive to stress. So, the study of stress-induced cognitive and neurobiological sequelae in animal models might provide valuable insight into the mnemonic mechanisms that are vulnerable to stress. Here, we provide an overview of the neurobiology of stress memory interactions, and present a neural endocrine model to explain how stress modifies hippocampal functioning.
1,403 citations
TL;DR: Methods for reporting location in functional imaging are reviewed and the problems that arise from the great variability in brain anatomy between individuals are discussed.
Abstract: Functional imaging gives us increasingly detailed information about the location of brain activity. To use this information, we need a clear conception of the meaning of location data. Here, we review methods for reporting location in functional imaging and discuss the problems that arise from the great variability in brain anatomy between individuals. These problems cause uncertainty in localization, which limits the effective resolution of functional imaging, especially for brain areas involved in higher cognitive function.
1,194 citations
TL;DR: Evidence supports a role for the amygdala in processing positive emotions as well as negative ones, including learning about the beneficial biological value of stimuli.
Abstract: The amygdala -- an almond-shaped group of nuclei at the heart of the telencephalon -- has been associated with a range of cognitive functions, including emotion, learning, memory, attention and perception. Most current views of amygdala function emphasize its role in negative emotions, such as fear, and in linking negative emotions with other aspects of cognition, such as learning and memory. However, recent evidence supports a role for the amygdala in processing positive emotions as well as negative ones, including learning about the beneficial biological value of stimuli. Indeed, the amygdala's role in stimulus-reward learning might be just as important as its role in processing negative affect and fear conditioning.
1,153 citations
TL;DR: It is proposed that defective sequestration of dopamine into vesicles, leading to the generation of reactive oxygen species in the cytoplasm, is a key event in the demise of dopaminergic neurons in Parkinson's disease and might represent a common pathway that underlies both genetic and sporadic forms of the disorder.
Abstract: Parkinson's disease is a devastating neurological condition that affects at least four million people. A striking feature of this disorder is the preferential loss of dopamine-producing neurons in the midbrain. Several aetiological triggers have been linked to Parkinson's disease, including genetic mutations and environmental toxins, but the pathway that leads to cell death is unknown. Recent developments have shed light on the pathogenic mechanisms that underlie the degeneration of these cells. We propose that defective sequestration of dopamine into vesicles, leading to the generation of reactive oxygen species in the cytoplasm, is a key event in the demise of dopaminergic neurons in Parkinson's disease, and might represent a common pathway that underlies both genetic and sporadic forms of the disorder.
TL;DR: The unique features of the early-appearing GABA signalling systems might help to explain how GABA acts as a developmental signal in the immature brain.
Abstract: In the mature brain, GABA (gamma-aminobutyric acid) functions primarily as an inhibitory neurotransmitter. But it can also act as a trophic factor during nervous system development to influence events such as proliferation, migration, differentiation, synapse maturation and cell death. GABA mediates these processes by the activation of traditional ionotropic and metabotropic receptors, and probably by both synaptic and non-synaptic mechanisms. However, the functional properties of GABA receptor signalling in the immature brain are significantly different from, and in some ways opposite to, those found in the adult brain. The unique features of the early-appearing GABA signalling systems might help to explain how GABA acts as a developmental signal.
TL;DR: It is argued that imaging provides a useful way to define functional fingerprints because it is possible to compare activations across many cortical areas and across a wide range of tasks.
Abstract: The functions of a cortical area are determined by its extrinsic connections and intrinsic properties. Using the database CoCoMac, we show that each cortical area has a unique pattern of corticocortical connections — a ‘connectional fingerprint’. We present examples of such fingerprints and use statistical analysis to show that no two areas share identical patterns. We suggest that the connectional fingerprint underlies the observed cell-firing differences between areas during different tasks. We refer to this pattern as a ‘functional fingerprint’ and present examples of such fingerprints. In addition to electrophysiological analysis, functional fingerprints can be determined by functional brain imaging. We argue that imaging provides a useful way to define such fingerprints because it is possible to compare activations across many cortical areas and across a wide range of tasks.
TL;DR: Cognitive neuroscientists have taken great advantage of functional magnetic resonance imaging as a non-invasive method of measuring neuronal activity in the human brain, but what exactly does fMRI tell us?
Abstract: In recent years, cognitive neuroscientists have taken great advantage of functional magnetic resonance imaging (fMRI) as a non-invasive method of measuring neuronal activity in the human brain. But what exactly does fMRI tell us? We know that its signals arise from changes in local haemodynamics that, in turn, result from alterations in neuronal activity, but exactly how neuronal activity, haemodynamics and fMRI signals are related is unclear. It has been assumed that the fMRI signal is proportional to the local average neuronal activity, but many factors can influence the relationship between the two. A clearer understanding of how neuronal activity influences the fMRI signal is needed if we are correctly to interpret functional imaging data.
TL;DR: Destabilization of calcium signalling seems to be central to the pathogenesis of Alzheimer's disease, and targeting this process might be therapeutically beneficial.
Abstract: Calcium modulates many neural processes, including synaptic plasticity and apoptosis. Dysregulation of intracellular calcium signalling has been implicated in the pathogenesis of Alzheimer's disease. Increased intracellular calcium elicits the characteristic lesions of this disorder, including the accumulation of amyloid-β, the hyperphosphorylation of TAU and neuronal death. Conversely, neurodegeneration that is induced by amyloid-β or TAU is probably mediated by changes in calcium homeostasis. Disruption of calcium regulation in the endoplasmic reticulum mediates the most significant signal-transduction cascades that are associated with Alzheimer's disease. Moreover, mutations that cause familial Alzheimer's disease have been linked to intracellular calcium signalling pathways. Destabilization of calcium signalling seems to be central to the pathogenesis of Alzheimer's disease, and targeting this process might be therapeutically beneficial.
TL;DR: This work has shown that plastic changes across brain systems and related behaviours vary as a function of the timing and the nature of changes in experience, and this specificity must be understood in the context of differences in the maturation rates and timing of the associated critical periods.
Abstract: Animal studies have shown that sensory deprivation in one modality can have striking effects on the development of the remaining modalities. Although recent studies of deaf and blind humans have also provided convincing behavioural, electrophysiological and neuroimaging evidence of increased capabilities and altered organization of spared modalities, there is still much debate about the identity of the brain systems that are changed and the mechanisms that mediate these changes. Plastic changes across brain systems and related behaviours vary as a function of the timing and the nature of changes in experience. This specificity must be understood in the context of differences in the maturation rates and timing of the associated critical periods, differences in patterns of transiently existing connections, and differences in molecular factors across brain systems.
TL;DR: To appreciate the neural underpinnings of sleep, it is important to view this universal mammalian behaviour at multiple levels of its biological organization.
Abstract: To appreciate the neural underpinnings of sleep, it is important to view this universal mammalian behaviour at multiple levels of its biological organization. Molecularly, the circadian rhythm of sleep involves interlocking positive- and negative-feedback mechanisms of circadian genes and their protein products in cells of the suprachiasmatic nucleus that are entrained to ambient conditions by light. Circadian information is integrated with information on homeostatic sleep need in nuclei of the anterior hypothalamus. These nuclei interact with arousal systems in the posterior hypothalamus, basal forebrain and brainstem to control sleep onset. During sleep, an ultradian oscillator in the mesopontine junction controls the regular alternation of rapid eye movement (REM) and non-REM sleep. Sleep cycles are accompanied by neuromodulatory influences on forebrain structures that influence behaviour, consciousness and cognition.
TL;DR: The conversion of acetylcholine binding into ion conduction across the membrane is becoming more clearly understood in terms of the structure of the receptor and its transitions.
Abstract: The conversion of acetylcholine binding into ion conduction across the membrane is becoming more clearly understood in terms of the structure of the receptor and its transitions. A high-resolution structure of a protein that is homologous to the extracellular domain of the receptor has revealed the binding sites and subunit interfaces in great detail. Although the structures of the membrane and cytoplasmic domains are less well determined, the channel lining and the determinants of selectivity have been mapped. The location and structure of the gates, and the coupling between binding sites and gates, remain to be established.
TL;DR: Here, this work focuses on the functional and anatomical differences that have been detected in musicians by modern neuroimaging methods.
Abstract: Studies of experience-driven neuroplasticity at the behavioural, ensemble, cellular and molecular levels have shown that the structure and significance of the eliciting stimulus can determine the neural changes that result. Studying such effects in humans is difficult, but professional musicians represent an ideal model in which to investigate plastic changes in the human brain. There are two advantages to studying plasticity in musicians: the complexity of the eliciting stimulus — music — and the extent of their exposure to this stimulus. Here, we focus on the functional and anatomical differences that have been detected in musicians by modern neuroimaging methods.
TL;DR: Why remyelination fails is crucial for devising effective methods by which to enhance it, and as the disease progresses, the numbers of lesions in which demyelinations persists increases, significantly contributing to clinical deterioration.
Abstract: Multiple sclerosis is a common cause of neurological disability in young adults. The disease is complex — its aetiology is multifactorial and largely unknown; its pathology is heterogeneous; and, clinically, it is difficult to diagnose, manage and treat. However, perhaps its most frustrating aspect is the inadequacy of the healing response of remyelination. This regenerative process generally occurs with great efficiency in experimental models, and sometimes proceeds to completion in multiple sclerosis. But as the disease progresses, the numbers of lesions in which demyelination persists increases, significantly contributing to clinical deterioration. Understanding why remyelination fails is crucial for devising effective methods by which to enhance it.
TL;DR: This work discusses neuronal-network and regional forebrain activity during sleep, and its consequences for consciousness and cognition, and indicates possible roles for sleep in neuroplasticity.
Abstract: Sleep can be addressed across the entire hierarchy of biological organization. We discuss neuronal-network and regional forebrain activity during sleep, and its consequences for consciousness and cognition. Complex interactions in thalamocortical circuits maintain the electroencephalographic oscillations of non-rapid eye movement (NREM) sleep. Functional neuroimaging affords views of the human brain in both NREM and REM sleep, and has informed new concepts of the neural basis of dreaming during REM sleep — a state that is characterized by illogic, hallucinosis and emotionality compared with waking. Replay of waking neuronal activity during sleep in the rodent hippocampus and in functional images of human brains indicates possible roles for sleep in neuroplasticity. Different forms and stages of learning and memory might benefit from different stages of sleep and be subserved by different forebrain regions.
TL;DR: Research carried out in the intervening years has made it possible to provide a detailed description of the saccadic command signals that are generated by motor neurons and the formation of these signals in premotor brainstem regions.
Abstract: The modern era of oculomotor research began with the advent of the chronic single-unit recording method in the late 1960s. Research carried out in the intervening years has made it possible to provide a detailed description of the saccadic command signals that are generated by motor neurons and the formation of these signals in premotor brainstem regions. These findings have been assimilated in control-systems models that simulate important behavioural features of saccades. Despite these great advances, key issues, such as the nature of the feedback signal and the location of the comparator, are unresolved and some of the factors that have impeded progress can be identified.
TL;DR: A distributed network that governs the processes of neural synchronization and desynchronization that underlie the rich variety of coordinated functions accounts for disruptions of interlimb coordination across various movement disorders.
Abstract: Locomotion in vertebrates and invertebrates has a long history in research as the most prominent example of interlimb coordination However, the evolution towards upright stance and gait has paved the way for a bewildering variety of functions in which the upper limbs interact with each other in a context-specific manner The neural basis of these bimanual interactions has been investigated in recent years on different scales, ranging from the single-cell level to the analysis of neuronal assemblies Although the prevailing viewpoint has been to assign bimanual coordination to a single brain locus, more recent evidence points to a distributed network that governs the processes of neural synchronization and desynchronization that underlie the rich variety of coordinated functions The distributed nature of this network accounts for disruptions of interlimb coordination across various movement disorders
TL;DR: According to this hypothesis, the olfactory system actively creates a large coding space in which to place odour representations and simultaneously optimizes their distribution within it, using both oscillatory and non-periodic dynamic processes with complementary functions.
Abstract: The brain faces many complex problems when dealing with odorant signals. Odours are multidimensional objects, which we usually experience as unitary percepts. They are also noisy and variable, but we can classify and identify them well. This means that the olfactory system must solve complicated pattern-learning and pattern-recognition problems. I propose that part of the solution relies on a particular architecture that imposes a dynamic format on odour codes. According to this hypothesis, the olfactory system actively creates a large coding space in which to place odour representations and simultaneously optimizes their distribution within it. This process uses both oscillatory and non-periodic dynamic processes with complementary functions: slow non-periodic processes underlie decorrelation, whereas fast oscillations allow sparsening and feature binding.
TL;DR: The long-term induction of the innate immune response and its transition to an adaptive form might be central to the pathophysiology and aetiology of neurodegenerative disorders.
Abstract: Innate immunity was previously thought to be a nonspecific immunological programme that was engaged by peripheral organs to maintain homeostasis after stress and injury. Emerging evidence indicates that this highly organized response also takes place in the central nervous system. Through the recognition of neuronal fingerprints, the long-term induction of the innate immune response and its transition to an adaptive form might be central to the pathophysiology and aetiology of neurodegenerative disorders. Paradoxically, this response also protects neurons by favouring remyelination and trophic support afforded by glial cells.
TL;DR: Recent work indicates that a significant proportion of parietal neurons in two cortical areas transforms the sensory signals that are used to guide movements into a common reference frame, an eye-centred representation that is modulated by eye-, head-, body- or limb-position signals.
Abstract: Orchestrating a movement towards a sensory target requires many computational processes, including a transformation between reference frames. This transformation is important because the reference frames in which sensory stimuli are encoded often differ from those of motor effectors. The posterior parietal cortex has an important role in these transformations. Recent work indicates that a significant proportion of parietal neurons in two cortical areas transforms the sensory signals that are used to guide movements into a common reference frame. This common reference frame is an eye-centred representation that is modulated by eye-, head-, body- or limb-position signals. A common reference frame might facilitate communication between different areas that are involved in coordinating the movements of different effectors. It might also be an efficient way to represent the locations of different sensory targets in the world.
TL;DR: Functional neuroimaging in humans and electrophysiology in awake mokeys indicate that there are important differences between striate and extrastriate visual cortex in how well neural activity correlates with consciousness.
Abstract: The directness and vivid quality of conscious experience belies the complexity of the underlying neural mechanisms, which remain incompletely understood. Recent work has focused on identifying the brain structures and patterns of neural activity within the primate visual system that are correlated with the content of visual consciousness. Functional neuroimaging in humans and electrophysiology in awake mokeys indicate that there are important differences between striate and extrastriate visual cortex in how well neural activity correlates with consciousness. Moreover, recent neuroimaging studies indicate that, in addition to these ventral areas of visual cortex, dorsal prefrontal and parietal areas might contribute to conscious visual experience.
TL;DR: Evidence is reviewed for two modes of radial movement: somal translocation, which is adopted by the early-generated neurons; and glia-guided locomotion, which was used predominantly by pyramidal cells.
Abstract: The conventional scheme of cortical formation shows that postmitotic neurons migrate away from the germinal ventricular zone to their positions in the developing cortex, guided by the processes of radial glial cells. However, recent studies indicate that different neuronal types adopt distinct modes of migration in the developing cortex. Here, we review evidence for two modes of radial movement: somal translocation, which is adopted by the early-generated neurons; and glia-guided locomotion, which is used predominantly by pyramidal cells. Cortical interneurons, which originate in the ventral telencephalon, use a third mode of migration. They migrate tangentially into the cortex, then seek the ventricular zone before moving radially to take up their positions in the cortical anlage.
TL;DR: Recent observations indicate that calcium signalling in neurons can regulate dendritic growth and remodelling by several mechanisms, and these mechanisms are likely to be key mediators of structural plasticity in the developing brain.
Abstract: One of the most remarkable features of the developing brain is its ability to undergo structural change in response to experience. Among the cellular elements that show this kind of plasticity are dendrites, which are the components that receive and process synaptic information. Recent observations indicate that calcium signalling in neurons can regulate dendritic growth and remodelling by several mechanisms, and these mechanisms are likely to be key mediators of structural plasticity in the developing brain.
TL;DR: H.M. became amnesic in 1953 and since that time, nearly 100 investigators, first at the Montreal Neurological Institute and since 1966 at the Massachusetts Institute of Technology, have participated in studying him.
Abstract: H.M. became amnesic in 1953. Since that time, nearly 100 investigators, first at the Montreal Neurological Institute and since 1966 at the Massachusetts Institute of Technology, have participated in studying him. We all understand the rare opportunity we have had to work with him, and we are grateful for his dedication to research. He has taught us a great deal about the cognitive and neural organization of memory. We are in his debt.