Showing papers in "Nature Reviews Neuroscience in 2015"
TL;DR: Research over the past two decades broadly supports the claim that mindfulness meditation exerts beneficial effects on physical and mental health, and cognitive performance, but the underlying neural mechanisms remain unclear.
Abstract: Research over the past two decades broadly supports the claim that mindfulness meditation - practiced widely for the reduction of stress and promotion of health - exerts beneficial effects on physical and mental health, and cognitive performance. Recent neuroimaging studies have begun to uncover the brain areas and networks that mediate these positive effects. However, the underlying neural mechanisms remain unclear, and it is apparent that more methodologically rigorous studies are required if we are to gain a full understanding of the neuronal and molecular bases of the changes in the brain that accompany mindfulness meditation.
1,648 citations
TL;DR: As inflammation in AD primarily concerns the innate immune system — unlike in 'typical' neuroinflammatory diseases such as multiple sclerosis and encephalitides — the concept of neuroinflammation in AD may need refinement.
Abstract: The past two decades of research into the pathogenesis of Alzheimer disease (AD) have been driven largely by the amyloid hypothesis; the neuroinflammation that is associated with AD has been assumed to be merely a response to pathophysiological events. However, new data from preclinical and clinical studies have established that immune system-mediated actions in fact contribute to and drive AD pathogenesis. These insights have suggested both novel and well-defined potential therapeutic targets for AD, including microglia and several cytokines. In addition, as inflammation in AD primarily concerns the innate immune system - unlike in 'typical' neuroinflammatory diseases such as multiple sclerosis and encephalitides - the concept of neuroinflammation in AD may need refinement.
1,523 citations
TL;DR: Emerging evidence suggests that atypical engagement of specific subdivisions of the insula within the salience network is a feature of many neuropsychiatric disorders.
Abstract: The brain is constantly bombarded by stimuli, and the relative salience of these inputs determines which are more likely to capture attention. A brain system known as the 'salience network', with key nodes in the insular cortices, has a central role in the detection of behaviourally relevant stimuli and the coordination of neural resources. Emerging evidence suggests that atypical engagement of specific subdivisions of the insula within the salience network is a feature of many neuropsychiatric disorders.
1,484 citations
TL;DR: This work considers how brain-network topology shapes neural responses to damage, highlighting key maladaptive processes and the resources and processes that enable adaptation, and shows how knowledge of network topology allows for predictive models of the spread and functional consequences of brain disease.
Abstract: Pathological perturbations of the brain are rarely confined to a single locus; instead, they often spread via axonal pathways to influence other regions. Patterns of such disease propagation are constrained by the extraordinarily complex, yet highly organized, topology of the underlying neural architecture; the so-called connectome. Thus, network organization fundamentally influences brain disease, and a connectomic approach grounded in network science is integral to understanding neuropathology. Here, we consider how brain-network topology shapes neural responses to damage, highlighting key maladaptive processes (such as diaschisis, transneuronal degeneration and dedifferentiation), and the resources (including degeneracy and reserve) and processes (such as compensation) that enable adaptation. We then show how knowledge of network topology allows us not only to describe pathological processes but also to generate predictive models of the spread and functional consequences of brain disease.
1,297 citations
TL;DR: This Review focuses on studies that have used circuit-based approaches to gain a more detailed, and also more comprehensive and integrated, view on how the brain governs fear and anxiety and how it orchestrates adaptive defensive behaviours.
Abstract: Decades of research has identified the brain areas that are involved in fear, fear extinction, anxiety and related defensive behaviours. Newly developed genetic and viral tools, optogenetics and advanced in vivo imaging techniques have now made it possible to characterize the activity, connectivity and function of specific cell types within complex neuronal circuits. Recent findings that have been made using these tools and techniques have provided mechanistic insights into the exquisite organization of the circuitry underlying internal defensive states. This Review focuses on studies that have used circuit-based approaches to gain a more detailed, and also more comprehensive and integrated, view on how the brain governs fear and anxiety and how it orchestrates adaptive defensive behaviours.
1,223 citations
TL;DR: The Embodied Predictive Interoception Coding model is introduced, which integrates an anatomical model of corticocortical connections with Bayesian active inference principles, to propose that agranular visceromotor cortices contribute to interoception by issuing interoceptive predictions.
Abstract: Intuition suggests that perception follows sensation and therefore bodily feelings originate in the body. However, recent evidence goes against this logic: interoceptive experience may largely reflect limbic predictions about the expected state of the body that are constrained by ascending visceral sensations. In this Opinion article, we introduce the Embodied Predictive Interoception Coding model, which integrates an anatomical model of corticocortical connections with Bayesian active inference principles, to propose that agranular visceromotor cortices contribute to interoception by issuing interoceptive predictions. We then discuss how disruptions in interoceptive predictions could function as a common vulnerability for mental and physical illness.
996 citations
TL;DR: Empirical empathy is considered as an example of a complex social cognitive function that integrates several social processes and is impaired in schizophrenia, and interventions to improve social cognition in patients with this disorder are considered.
Abstract: Individuals with schizophrenia exhibit impaired social cognition, which manifests as difficulties in identifying emotions, feeing connected to others, inferring people's thoughts and reacting emotionally to others. These social cognitive impairments interfere with social connections and are strong determinants of the degree of impaired daily functioning in such individuals. Here, we review recent findings from the fields of social cognition and social neuroscience and identify the social processes that are impaired in schizophrenia. We also consider empathy as an example of a complex social cognitive function that integrates several social processes and is impaired in schizophrenia. This information may guide interventions to improve social cognition in patients with this disorder.
982 citations
TL;DR: Evidence that astrocytes have crucial roles in attracting and restricting CNS inflammation, with important implications for diverse CNS disorders is discussed.
Abstract: Astrocytes form borders (glia limitans) that separate neural from non-neural tissue along perivascular spaces, meninges and tissue lesions in the CNS. Transgenic loss-of-function studies reveal that astrocyte borders and scars serve as functional barriers that restrict the entry of inflammatory cells into CNS parenchyma in health and disease. Astrocytes also have powerful pro-inflammatory potential. Thus, astrocytes are emerging as pivotal regulators of CNS inflammatory responses. This Review discusses evidence that astrocytes have crucial roles in attracting and restricting CNS inflammation, with important implications for diverse CNS disorders.
823 citations
TL;DR: Drawing on computational approaches to value-based decision-making and reinforcement learning, this work proposes a unifying conceptual framework for understanding the neural bases of diverse forms of emotion regulation.
Abstract: Various brain regions have been implicated in emotion regulation, although this process remains poorly understood. In this Opinion article, Etkin and colleagues bring together neuroimaging findings and ideas from value-based decision-making and reinforcement learning to propose a conceptual framework for emotion regulation. Emotions are powerful determinants of behaviour, thought and experience, and they may be regulated in various ways. Neuroimaging studies have implicated several brain regions in emotion regulation, including the ventral anterior cingulate and ventromedial prefrontal cortices, as well as the lateral prefrontal and parietal cortices. Drawing on computational approaches to value-based decision-making and reinforcement learning, we propose a unifying conceptual framework for understanding the neural bases of diverse forms of emotion regulation.
743 citations
TL;DR: Genetics studies of autism spectrum disorder (ASD) have identified several risk genes that are key regulators of synaptic plasticity, and when deleterious mutations occur, inefficient genetic buffering and impaired synaptic homeostasis may increase an individual's risk for ASD.
Abstract: Genetics studies of autism spectrum disorder (ASD) have identified several risk genes that are key regulators of synaptic plasticity. Indeed, many of the risk genes that have been linked to these disorders encode synaptic scaffolding proteins, receptors, cell adhesion molecules or proteins that are involved in chromatin remodelling, transcription, protein synthesis or degradation, or actin cytoskeleton dynamics. Changes in any of these proteins can increase or decrease synaptic strength or number and, ultimately, neuronal connectivity in the brain. In addition, when deleterious mutations occur, inefficient genetic buffering and impaired synaptic homeostasis may increase an individual's risk for ASD.
730 citations
TL;DR: Progress has been made in understanding of how perturbations in autophagy are linked with neurodegenerative diseases and the potential therapeutic strategies resulting from the modulation of this process are summarized.
Abstract: Most neurodegenerative diseases that afflict humans are associated with the intracytoplasmic deposition of aggregate-prone proteins in neurons and with mitochondrial dysfunction. Autophagy is a powerful process for removing such proteins and for maintaining mitochondrial homeostasis. Over recent years, evidence has accumulated to demonstrate that upregulation of autophagy may protect against neurodegeneration. However, autophagy dysfunction has also been implicated in the pathogenesis of various diseases. This Review summarizes the progress that has been made in our understanding of how perturbations in autophagy are linked with neurodegenerative diseases and the potential therapeutic strategies resulting from the modulation of this process.
TL;DR: Recent evidence that supports the notion of neuron–neuron protein propagation is reviewed, with a focus on neuropathological and positron emission tomography imaging studies in humans.
Abstract: The progression of many neurodegenerative diseases is thought to be driven by the template-directed misfolding, seeded aggregation and cell-cell transmission of characteristic disease-related proteins, leading to the sequential dissemination of pathological protein aggregates. Recent evidence strongly suggests that the anatomical connections made by neurons - in addition to the intrinsic characteristics of neurons, such as morphology and gene expression profile - determine whether they are vulnerable to degeneration in these disorders. Notably, this common pathogenic principle opens up opportunities for pursuing novel targets for therapeutic interventions for these neurodegenerative disorders. We review recent evidence that supports the notion of neuron-neuron protein propagation, with a focus on neuropathological and positron emission tomography imaging studies in humans.
TL;DR: As a new paradigm for neuroscience, neural network models have the potential to incorporate knowledge acquired with single-neuron approaches to help us understand how emergent functional states generate behaviour, cognition and mental disease.
Abstract: For over a century, the neuron doctrine--which states that the neuron is the structural and functional unit of the nervous system--has provided a conceptual foundation for neuroscience This viewpoint reflects its origins in a time when the use of single-neuron anatomical and physiological techniques was prominent However, newer multineuronal recording methods have revealed that ensembles of neurons, rather than individual cells, can form physiological units and generate emergent functional properties and states As a new paradigm for neuroscience, neural network models have the potential to incorporate knowledge acquired with single-neuron approaches to help us understand how emergent functional states generate behaviour, cognition and mental disease
TL;DR: The new research on activity-dependent myelination is summarized, the possible implications of these studies are explored, and the potential for new research is outlined.
Abstract: The precise timing of impulse transmission along axons is crucial for synaptic plasticity and brain oscillations, and is partly determined by myelin thickness. In this Opinion article, R. Douglas Fields discusses how electrical activity influences myelin thickness and thus conduction velocity and circuit properties.
TL;DR: An empirical review of the brain systems that are involved in placebo effects and a conceptual framework linking these findings to the mind–brain processes that mediate them suggest that the neuropsychological processes thatMediate placebo effects may be crucial for a wide array of therapeutic approaches, including many drugs.
Abstract: Placebo effects are positive effects on health that arise from the response of the brain to the contextual information that accompanies the delivery of a treatment. In this Review, Wager and Atlas examine the neural mechanisms that underlie such effects, focusing on placebo analgesia.
TL;DR: The brain regulates information flow by balancing the segregation and integration of incoming stimuli to facilitate flexible cognition and behaviour and recent whole-brain computational modelling approaches have enabled us to start assessing the effect of input perturbations on brain dynamics in silico.
Abstract: The brain regulates information flow by balancing the segregation and integration of incoming stimuli to facilitate flexible cognition and behaviour. The topological features of brain networks--in particular, network communities and hubs--support this segregation and integration but do not provide information about how external inputs are processed dynamically (that is, over time). Experiments in which the consequences of selective inputs on brain activity are controlled and traced with great precision could provide such information. However, such strategies have thus far had limited success. By contrast, recent whole-brain computational modelling approaches have enabled us to start assessing the effect of input perturbations on brain dynamics in silico.
TL;DR: Literacy acquisition provides a remarkable example of how the brain reorganizes to accommodate a novel cultural skill.
Abstract: The acquisition of literacy transforms the human brain. By reviewing studies of illiterate subjects, we propose specific hypotheses on how the functions of core brain systems are partially reoriented or 'recycled' when learning to read. Literacy acquisition improves early visual processing and reorganizes the ventral occipito-temporal pathway: responses to written characters are increased in the left occipito-temporal sulcus, whereas responses to faces shift towards the right hemisphere. Literacy also modifies phonological coding and strengthens the functional and anatomical link between phonemic and graphemic representations. Literacy acquisition therefore provides a remarkable example of how the brain reorganizes to accommodate a novel cultural skill.
TL;DR: There is good evidence that striatal dopamine receptor availability and dopamine release are diminished in individuals with stimulant or alcohol dependence but not in Individuals with opiate, nicotine or cannabis dependence, which has implications for understanding reward and treatment responses in various addictions.
Abstract: For several decades, addiction has come to be viewed as a disorder of the dopamine neurotransmitter system; however, this view has not led to new treatments. In this Opinion article, we review the origins of the dopamine theory of addiction and discuss the ability of addictive drugs to elicit the release of dopamine in the human striatum. There is robust evidence that stimulants increase striatal dopamine levels and some evidence that alcohol may have such an effect, but little evidence, if any, that cannabis and opiates increase dopamine levels. Moreover, there is good evidence that striatal dopamine receptor availability and dopamine release are diminished in individuals with stimulant or alcohol dependence but not in individuals with opiate, nicotine or cannabis dependence. These observations have implications for understanding reward and treatment responses in various addictions.
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TL;DR: This Review develops four defining criteria that enable us to critically assess the recent progress that has been made towards finding the engram, and proposes that findings from 'capture' studies represent considerable progress in allowing us to observe, erase and express the engrams.
Abstract: Many attempts have been made to localize the physical trace of a memory, or engram, in the brain However, until recently, engrams have remained largely elusive In this Review, we develop four defining criteria that enable us to critically assess the recent progress that has been made towards finding the engram Recent 'capture' studies use novel approaches to tag populations of neurons that are active during memory encoding, thereby allowing these engram-associated neurons to be manipulated at later times We propose that findings from these capture studies represent considerable progress in allowing us to observe, erase and express the engram
TL;DR: It is suggested that imbalance between goal-directed and habitual action and inhibition contributes to some manifestations of Parkinson's disease, Tourette syndrome and obsessive–compulsive disorder and is proposed that basal ganglia surgery improves these disorders by restoring a functional balance between facilitation and inhibition.
Abstract: Classically, the basal ganglia have been considered to have a role in producing habitual and goal-directed behaviours. In this article, we review recent evidence that expands this role, indicating that the basal ganglia are also involved in neural and behavioural inhibition in the motor and non-motor domains. We then distinguish between goal-directed and habitual (also known as automatic) inhibition mediated by fronto-striato-subthalamic-pallido-thalamo-cortical networks. We also suggest that imbalance between goal-directed and habitual action and inhibition contributes to some manifestations of Parkinson's disease, Tourette syndrome and obsessive-compulsive disorder. Finally, we propose that basal ganglia surgery improves these disorders by restoring a functional balance between facilitation and inhibition.
TL;DR: Research in animals and humans has revealed some of the structural, functional and molecular changes in the brain that underlie the effects of stress on social behaviour and will have implications both for the clinic and for society.
Abstract: Early-life stress can contribute to predispositions to antisocial behaviour in adulthood. Similarly, acute or chronic stress during adulthood can alter our social behaviour. Sandi and Haller emphasize the importance of timing of stress for its effects on social behaviour and describe current understanding of the underlying mechanisms.
TL;DR: Down syndrome, which arises in individuals carrying an extra copy of chromosome 21, is associated with a greatly increased risk of early-onset Alzheimer disease, and the presence of three copies of the gene encoding amyloid precursor protein is thought to play a part.
Abstract: Down syndrome, which arises in individuals carrying an extra copy of chromosome 21, is associated with a greatly increased risk of early-onset Alzheimer disease. It is thought that this risk is conferred by the presence of three copies of the gene encoding amyloid precursor protein (APP)--an Alzheimer disease risk factor--although the possession of extra copies of other chromosome 21 genes may also play a part. Further study of the mechanisms underlying the development of Alzheimer disease in people with Down syndrome could provide insights into the mechanisms that cause dementia in the general population.
TL;DR: Epigenetic processes have the ability to reprogramme the epigenome in response to environmental challenges, such as maternal stress, making the organism more or less adaptive depending on the future challenges presented.
Abstract: Neurodevelopmental programming - the implementation of the genetic and epigenetic blueprints that guide and coordinate normal brain development - requires tight regulation of transcriptional processes. During prenatal and postnatal time periods, epigenetic processes fine-tune neurodevelopment towards an end product that determines how an organism interacts with and responds to exposures and experiences throughout life. Epigenetic processes also have the ability to reprogramme the epigenome in response to environmental challenges, such as maternal stress, making the organism more or less adaptive depending on the future challenges presented. Epigenetic marks generated within germ cells as a result of environmental influences throughout life can also shape future generations long before conception occurs.
TL;DR: Intervention studies which suggest that the restoration of insulin activity in the hippocampus may be an effective strategy to alleviate the cognitive decline associated with T2DM and AD are discussed.
Abstract: Clinical studies suggest a link between type 2 diabetes mellitus (T2DM) and insulin resistance (IR) and cognitive dysfunction, but there are significant gaps in our knowledge of the mechanisms underlying this relationship. Animal models of IR help to bridge these gaps and point to hippocampal IR as a potential mediator of cognitive dysfunction in T2DM, as well as in Alzheimer disease (AD). This Review highlights these observations and discusses intervention studies which suggest that the restoration of insulin activity in the hippocampus may be an effective strategy to alleviate the cognitive decline associated with T2DM and AD.
TL;DR: The choroid plexus is the principal source of cerebrospinal fluid, which has accepted roles as a fluid cushion and a sink for nervous system waste in vertebrates and uncovered new, active roles for this dynamic system in the regulation of neural stem cells, critical periods and the overall health of the nervous system.
Abstract: The health of the vertebrate brain is dependent on appropriate levels of cerebrospinal fluid (CSF), which is secreted by the choroid plexus (ChP). In this Review, Lehtinen and colleagues examine ChP structure and development and explore recently discovered functions of the ChP–CSF system.
TL;DR: Findings indicate that spontaneous neurotransmission has an autonomous role in interneuronal communication that is distinct from that of evoked release, challenging current assumptions about neuronal signalling and neurotransmission.
Abstract: Fast synaptic communication in the brain requires synchronous vesicle fusion that is evoked by action potential-induced Ca(2+) influx. However, synaptic terminals also release neurotransmitters by spontaneous vesicle fusion, which is independent of presynaptic action potentials. A functional role for spontaneous neurotransmitter release events in the regulation of synaptic plasticity and homeostasis, as well as the regulation of certain behaviours, has been reported. In addition, there is evidence that the presynaptic mechanisms underlying spontaneous release of neurotransmitters and their postsynaptic targets are segregated from those of evoked neurotransmission. These findings challenge current assumptions about neuronal signalling and neurotransmission, as they indicate that spontaneous neurotransmission has an autonomous role in interneuronal communication that is distinct from that of evoked release.
TL;DR: Findings indicate that the immune system is a point of convergence for multiple ASD-related genetic and environmental risk factors.
Abstract: Various lines of evidence suggest that immune system dysregulation has a key role in autism spectrum disorder (ASD). Estes and McAllister review this evidence, covering genetic and maternal immune system-related risk factors, chronic immune system changes in individuals with ASD and in animal models, and potential pathophysiological mechanisms. Increasing evidence points to a central role for immune dysregulation in autism spectrum disorder (ASD). Several ASD risk genes encode components of the immune system and many maternal immune system-related risk factors — including autoimmunity, infection and fetal reactive antibodies — are associated with ASD. In addition, there is evidence of ongoing immune dysregulation in individuals with ASD and in animal models of this disorder. Recently, several molecular signalling pathways — including pathways downstream of cytokines, the receptor MET, major histocompatibility complex class I molecules, microglia and complement factors — have been identified that link immune activation to ASD phenotypes. Together, these findings indicate that the immune system is a point of convergence for multiple ASD-related genetic and environmental risk factors.
TL;DR: Understanding the contributions of eCB disruptions to behavioural and physiological traits provides insight into the eCB influence on addiction vulnerability.
Abstract: Brain endocannabinoid (eCB) signalling influences the motivation for natural rewards (such as palatable food, sexual activity and social interaction) and modulates the rewarding effects of addictive drugs. Pathological forms of natural and drug-induced reward are associated with dysregulated eCB signalling that may derive from pre-existing genetic factors or from prolonged drug exposure. Impaired eCB signalling contributes to dysregulated synaptic plasticity, increased stress responsivity, negative emotional states and cravings that propel addiction. Understanding the contributions of eCB disruptions to behavioural and physiological traits provides insight into the eCB influence on addiction vulnerability.
TL;DR: It is suggested that longitudinal studies of sensory processing, beginning in infancy, are required to successfully identify the neural basis of developmental dyslexia and have a powerful impact on remediation.
Abstract: Recent years have seen the publication of a range of new theories suggesting that the basis of dyslexia might be sensory dysfunction. In this Opinion article, the evidence for and against several prominent sensory theories of dyslexia is closely scrutinized. Contrary to the causal claims being made, my analysis suggests that many proposed sensory deficits might result from the effects of reduced reading experience on the dyslexic brain. I therefore suggest that longitudinal studies of sensory processing, beginning in infancy, are required to successfully identify the neural basis of developmental dyslexia. Such studies could have a powerful impact on remediation.
TL;DR: Recent discoveries have shown that oestradiol is not only a reproductive hormone but also a brain-derived neuroprotective factor in males and females and that ERs coordinate multiple signalling mechanisms that protect the brain from neurodegenerative diseases, affective disorders and cognitive decline.
Abstract: Recent discoveries have shown that both hormonal and brain-derived oestradiol have neuroprotective effects. This Review provides a comprehensive review of the multiple cell types, receptors and signalling cascades that underlie oestradiol-mediated neuroprotection.