The restless brain: how intrinsic activity organizes brain function

Traditionally studies of brain function have focused on task-evoked responses. By their very nature such experiments tacitly encourage a reflexive view of brain function. While such an approach has been remarkably productive at all levels of neuroscience, it ignores the alternative possibility that brain functions are mainly intrinsic and ongoing, involving information processing for interpreting, responding to and predicting environmental demands. I suggest that the latter view best captures the essence of brain function, a position that accords well with the allocation of the brain''s energy resources, its limited access to sensory information and a dynamic, intrinsic functional organization. The nature of this intrinsic activity, which exhibits a surprising level of organization with dimensions of both space and time, is revealed in the ongoing activity of the brain and its metabolism. As we look to the future, understanding the nature of this intrinsic activity will require integrating knowledge from cognitive and systems neuroscience with cellular and molecular neuroscience where ion channels, receptors, components of signal transduction and metabolic pathways are all in a constant state of flux. The reward for doing so will be a much better understanding of human behaviour in health and disease.     

The impact of molecular biology on neuroscience

How our brains work is one of the major unsolved problems of biology. This paper describes some of the techniques of molecular biology that are already being used to study the brains of animals. Mainly as a result of the human genome project many new techniques will soon become available which could decisively influence the progress of neuroscience. I suggest that neuroscientists should tell molecular biologists what their difficulties are, in the hope that this will stimulate the production of useful new biological tools.     

Arthropod phylogeny: onychophoran brain organization suggests an archaic relationship with a chelicerate stem lineage

Neuroanatomical studies have demonstrated that the architecture and organization among neuropils are highly conserved within any order of arthropods. The shapes of nerve cells and their neuropilar arrangements provide robust characters for phylogenetic analyses. Such analyses so far have agreed with molecular phylogenies in demonstrating that entomostracans+malacostracans belong to a clade (Tetraconata) that includes the hexapods. However, relationships among what are considered to be paraphyletic groups or among the stem arthropods have not yet been satisfactorily resolved. The present parsimony analyses of independent neuroarchitectural characters from 27 arthropods and lobopods demonstrate relationships that are congruent with phylogenies derived from molecular studies, except for the status of the Onychophora. The present account describes the brain of the onychophoran Euperipatoides rowelli, demonstrating that the structure and arrangements of its neurons, cerebral neuropils and sensory centres are distinct from arrangements in the brains of mandibulates. Neuroanatomical evidence suggests that the organization of the onychophoran brain is similar to that of the brains of chelicerates.     

Encoding brain network response to free viewing of videos

A challenging goal for cognitive neuroscience researchers is to determine how mental representations are mapped onto the patterns of neural activity. To address this problem, functional magnetic resonance imaging (fMRI) researchers have developed a large number of encoding and decoding methods. However, previous studies typically used rather limited stimuli representation, like semantic labels and Wavelet Gabor filters, and largely focused on voxel-based brain patterns. Here, we present a new fMRI encoding model to predict the human brain’s responses to free viewing of video clips which aims to deal with this limitation. In this model, we represent the stimuli using a variety of representative visual features in the computer vision community, which can describe the global color distribution, local shape and spatial information and motion information contained in videos, and apply the functional connectivity to model the brain’s activity pattern evoked by these video clips. Our experimental results demonstrate that brain network responses during free viewing of videos can be robustly and accurately predicted across subjects by using visual features. Our study suggests the feasibility of exploring cognitive neuroscience studies by computational image/video analysis and provides a novel concept of using the brain encoding as a test-bed for evaluating visual feature extraction.     

Investment in higher order central processing regions is not constrained by brain size in social insects

The extent to which size constrains the evolution of brain organization and the genesis of complex behaviour is a central, unanswered question in evolutionary neuroscience. Advanced cognition has long been linked to the expansion of specific brain compartments, such as the neocortex in vertebrates and the mushroom bodies in insects. Scaling constraints that limit the size of these brain regions in small animals may therefore be particularly significant to behavioural evolution. Recent findings from studies of paper wasps suggest miniaturization constrains the size of central sensory processing brain centres (mushroom body calyces) in favour of peripheral, sensory input centres (antennal and optic lobes). We tested the generality of this hypothesis in diverse eusocial hymenopteran species (ants, bees and wasps) exhibiting striking variation in body size and thus brain size. Combining multiple neuroanatomical datasets from these three taxa, we found no universal size constraint on brain organization within or among species. In fact, small-bodied ants with miniscule brains had mushroom body calyces proportionally as large as or larger than those of wasps and bees with brains orders of magnitude larger. Our comparative analyses suggest that brain organization in ants is shaped more by natural selection imposed by visual demands than intrinsic design limitations.     

Central nervous system and computation

Computational systems are useful in neuroscience in many ways. For instance, they may be used to construct maps of brain structure and activation, or to describe brain processes mathematically. Furthermore, they inspired a powerful theory of brain function, in which the brain is viewed as a system characterized by intrinsic computational activities or as a "computational information processor. "Although many neuroscientists believe that neural systems really perform computations, some are more cautious about computationalism or reject it. Thus, does the brain really compute? Answering this question requires getting clear on a definition of computation that is able to draw a line between physical systems that compute and systems that do not, so that we can discern on which side of the line the brain (or parts of it) could fall. In order to shed some light on the role of computational processes in brain function, available neurobiological data will be summarized from the standpoint of a recently proposed taxonomy of notions of computation, with the aim of identifying which brain processes can be considered computational. The emerging picture shows the brain as a very peculiar system, in which genuine computational features act in concert with noncomputational dynamical processes, leading to continuous self-organization and remodeling under the action of external stimuli from the environment and from the rest of the organism.     

Consumer nueroscience: a new area of study for biomedical engineers

In scientific literature, the most accepted definition of consumer neuroscience or neuromarketing is that it is a field of study concerning the application of neuroscience methods to analyze and understand human behavior related to markets and marketing exchanges. First, it might seem strange that marketers would be interested in using neuroscience to understand consumer's preferences. Yet in practice, the basic goal of marketers is to guide the design and presentation of products in such a way that they are highly compatible with consumer preferences. To understand consumers preferences, several standard research tools are commonly used by marketers, such as personal interviews with the consumers, scoring questionnaries gathered from consumers, and focus groups. The reason marketing researchers are interested in using brain imaging tools instead of simply asking people for their preferences in front of marketing stimuli, arises from the assumption that people cannot (or do not want to) fully explain their preference when explicitly asked. Researchers in the field hypothesize that neuroimaging tools can access information within the consumer's brain during the generation of a preference or the observation of a commercial advertisement. The question of will this information be useful in further promoting the product is still up for debate in marketing literature. From the marketing researchers point of view, there is a hope that this body of brain imaging techniques will provide an efficient tradeoff between costs and benefits of the research. Currently, neuroscience methodology includes powerful brain imaging tools based on the gathering of hemodynamic or electromagnetic signals related to the human brain activity during the performance of a relevant task for marketing objectives. These tools are briefly reviewed in this article.     

Developmental genetic evidence for a monophyletic origin of the bilaterian brain

The widely held notion of an independent evolutionary origin of invertebrate and vertebrate brains is based on classical phylogenetic, neuroanatomical and embryological data. The interpretation of these data in favour of a polyphyletic origin of animals brains is currently being challenged by three fundamental findings that derive from comparative molecular, genetic and developmental analyses. First, modern molecular systematics indicates that none of the extant animals correspond to evolutionary intermediates between the protostomes and the deuterostomes, thus making it impossible to deduce the morphological organization of the ancestral bilaterian or its brain from living species. Second, recent molecular genetic evidence for the body axis inversion hypothesis now supports the idea that the basic body plan of vertebrates and invertebrates is similar but inverted, suggesting that the ventral nerve chord of protostome invertebrates is homologous to the dorsal nerve cord of deuterostome chordates. Third, a developmental genetic analysis of the molecular control elements involved in early embryonic brain patterning is uncovering the existence of structurally and functionally homologous genes that have comparable and interchangeable functions in key aspects of brain development in invertebrate and vertebrate model systems. All three of these findings are compatible with the hypothesis of a monophyletic origin of the bilaterian brain. Here we review these findings and consider their significance and implications for current thinking on the evolutionary origin of bilaterian brains. We also preview the impact of comparative functional genomic analyses on our understanding of brain evolution.     

Introduction to ‘Homology and convergence in nervous system evolution’

The origin of brains and central nervous systems (CNSs) is thought to have occurred before the Palaeozoic era 540 Ma. Yet in the absence of tangible evidence, there has been continued debate whether today''s brains and nervous systems derive from one ancestral origin or whether similarities among them are due to convergent evolution. With the advent of molecular developmental genetics and genomics, it has become clear that homology is a concept that applies not only to morphologies, but also to genes, developmental processes, as well as to behaviours. Comparative studies in phyla ranging from annelids and arthropods to mammals are providing evidence that corresponding developmental genetic mechanisms act not only in dorso–ventral and anterior–posterior axis specification but also in segmentation, neurogenesis, axogenesis and eye/photoreceptor cell formation that appear to be conserved throughout the animal kingdom. These data are supported by recent studies which identified Mid-Cambrian fossils with preserved soft body parts that present segmental arrangements in brains typical of modern arthropods, and similarly organized brain centres and circuits across phyla that may reflect genealogical correspondence and control similar behavioural manifestations. Moreover, congruence between genetic and geological fossil records support the notion that by the ‘Cambrian explosion’ arthropods and chordates shared similarities in brain and nervous system organization. However, these similarities are strikingly absent in several sister- and outgroups of arthropods and chordates which raises several questions, foremost among them: what kind of natural laws and mechanisms underlie the convergent evolution of such similarities? And, vice versa: what are the selection pressures and genetic mechanisms underlying the possible loss or reduction of brains and CNSs in multiple lineages during the course of evolution? These questions were addressed at a Royal Society meeting to discuss homology and convergence in nervous system evolution. By integrating knowledge ranging from evolutionary theory and palaeontology to comparative developmental genetics and phylogenomics, the meeting covered disparities in nervous system origins as well as correspondences of neural circuit organization and behaviours, all of which allow evidence-based debates for and against the proposition that the nervous systems and brains of animals might derive from a common ancestor.     

Neuroecology of cartilaginous fishes: the functional implications of brain scaling

It is a widely accepted view that neural development can reflect morphological adaptations and sensory specializations. The aim of this review is to give a broad overview of the current status of brain data available for cartilaginous fishes and examine how perspectives on allometric scaling of brain size across this group of fishes has changed within the last 50 years with the addition of new data and more rigorous statistical analyses. The current knowledge of neuroanatomy in cartilaginous fishes is reviewed and data on brain size (encephalization, n = 151) and interspecific variation in brain organization (n = 84) has been explored to ascertain scaling relationships across this clade. It is determined whether similar patterns of brain organization, termed cerebrotypes, exist in species that share certain lifestyle characteristics. Clear patterns of brain organization exist across cartilaginous fishes, irrespective of phylogenetic grouping and, although this study was not a functional analysis, it provides further evidence that chondrichthyan brain structures might have developed in conjunction with specific behaviours or enhanced cognitive capabilities. Larger brains, with well-developed telencephala and large, highly foliated cerebella are reported in species that occupy complex reef or oceanic habitats, potentially identifying a reef-associated cerebrotype. In contrast, benthic and benthopelagic demersal species comprise the group with the smallest brains, with a relatively reduced telencephalon and a smooth cerebellar corpus. There is also evidence herein of a bathyal cerebrotype; deep-sea benthopelagic sharks possess relatively small brains and show a clear relative hypertrophy of the medulla oblongata. Despite the patterns observed and documented, significant gaps in the literature have been highlighted. Brain mass data are only currently available on c. 16% of all chondrichthyan species, and only 8% of species have data available on their brain organization, with far less on subsections of major brain areas that receive distinct sensory input. The interspecific variability in brain organization further stresses the importance of performing functional studies on a greater range of species. Only an expansive data set, comprised of species that span a variety of habitats and taxonomic groups, with widely disparate behavioural repertoires, combined with further functional analyses, will help shed light on the extent to which chondrichthyan brains have evolved as a consequence of behaviour, habitat and lifestyle in addition to phylogeny.     

Developmental objections to evolutionary modularity

Evolutionary psychologists argue that selective pressures in our ancestral environment yield a highly specialized set of modular cognitive capacities. However, recent papers in developmental psychology and neuroscience claim that evolutionary accounts of modularity are incompatible with the flexibility and plasticity of the developing brain. Instead, they propose cortical and neuronal brain structures are fixed through interactions with our developmental environment. Buller and Gray Hardcastle contend that evolutionary accounts of cognitive development are unacceptably rigid in light of evidence of cortical plasticity. The developing structure of the brain is both too random and too sensitive to external stimuli to be the product of a fixed genetic mechanism. They also claim that the complexity of the human brain cannot be explained in terms of our meager genetic endowment. There simply are not enough genes to program the intricate neuronal structures that are essential to cognition. I argue that neither of these arguments are persuasive. Small numbers of genes can function to determine diverse phenotypical outcomes through evolutionarily selected developmental systems. Similarly, theories of modularity do not rule out the possibility that innate cognitive systems exploit environmental regularities to guide the developing structure of the brain. Consequently, the anti-adaptionist consequences of these positions should be rejected.     

Exploring Memory Representations with Activity-Based Genetics

The brain is thought to represent specific memories through the activity of sparse and distributed neural ensembles. In this review, we examine the use of immediate early genes (IEGs), genes that are induced by neural activity, to specifically identify and genetically modify neurons activated naturally by environmental experience. Recent studies using this approach have identified cellular and molecular changes specific to neurons activated during learning relative to their inactive neighbors. By using opto- and chemogenetic regulators of neural activity, the neurons naturally recruited during learning can be artificially reactivated to directly test their role in coding external information. In contextual fear conditioning, artificial reactivation of learning-induced neural ensembles in the hippocampus or neocortex can substitute for the context itself. That is, artificial stimulation of these neurons can apparently cause the animals to “think” they are in the context. This represents a powerful approach to testing the principles by which the brain codes for the external world and how these circuits are modified with learning.A central feature of nervous systems is that, to function properly, specific neurons must become active in response to specific stimuli. The nature of this selective activation and its modification with experience is the focus of much neuroscience research, ranging from studies of sensory processing in experimental animals to disorders of thought such as schizophrenia in humans. The central dogma of neuroscience is that perceptions, memories, thoughts, and higher mental functions arise from the pattern and timing of the activity in neural ensembles in specific parts of the brain at specific points in time. Until quite recently, the investigation of these “circuit”-based questions has primarily been limited to observational techniques, such as single unit recording, functional magnetic resonance imagery (fMRI), and calcium imaging, to document the patterns of neural activity evoked by sensory experience or even complex psychological contingencies in human fMRI studies. These techniques have been enormously successful and created a framework for understanding information processing in the brain. For example, recordings in the visual system have indicated that, in the primary visual cortex, neurons are tuned to the orientation of linear stimuli (Hubel and Wiesel 1962). In contrast, neurons in higher brain areas can respond to discrete items. The most striking example of this specificity comes from in vivo recording in the human medial temporal lobe in which single units have been identified that respond to photos of the actress Halle Berry as well as her written name (Quiroga et al. 2005). This highly selective tuning of neural activity is suggestive of function, but how can this be directly tested? What would be the effect of stimulating just this rare population of neurons, a memory of the actress, a sensory illusion of her image? How does this type of specific firing arise? Do these neurons differ from their nonresponsive neighbors in terms of biochemistry, cell biology, or connectivity? Do they undergo molecular alterations when new information is learned about this individual and are these changes required for the learning? These types of questions have recently become accessible to study in mice through the use of activity-based genetic manipulation, in which neurons that are activated by a specific sensory stimulus can be altered to express any gene of experimental interest. These studies and approaches will be the focus of this work.     

经颅磁刺激在大脑皮质研究中的应用和进展

经颅磁刺激（TMS）是一种能够在脑中感应聚焦电流,瞬间调制大脑皮质的无创方法,在临床研究、基础神经学和诊治疾病等方面有许多应用。通过记录运动皮质诱发电位（MEPs),TMS已经或将成为探测脑下运动路径传导、评价皮质兴奋性、皮质映射和研究皮质塑性的常规工具。TMS能够主动干预脑功能,这种特性使它成为研究正常人脑－行为关系的独特技术,可以建立脑活动与任务完成之间的因果关系,探索脑功能连接。近年来的许多实验又表明,TMS在运动紊乱和精神疾病方面有潜在的治疗作用,但达到临床应用还有一定距离。     

Meta level concept versus classic reflex concept for the control of posture and movement

Postural reflexes are replaced soon after birth by automatic reactions that allow for volition and cognition. It is still an enigma how this change in postural control is achieved. We suggest that the change involves the formation of a sensory processing level (meta level) that becomes interleaved in between the tight sensor-actuator coupling of the classic reflexes. We assume that the brain applies at this level intersensory interactions to reconstruct the physical stimuli which are causing the physiological stimuli and sensory signals. The thus derived estimates of the physical stimuli are then used as feedback signals in the posture control system. We present this concept on the background of the classic reflex concept and earlier attempts in the literature to overcome it. The earlier attempts were often motivated by the question how the brain prevents voluntary movements from being hampered by reflexive stabilisation of posture (so-called posture-movement problem). We compare our new concept with the classic reflex concept in a theoretical approach, by implementing both concepts into simple postural control models. In simulations of the two models we superimpose external perturbations (the physical stimuli) and a voluntary body lean movement. We show that it is possible to achieve successful stimulus compensation and unperturbed lean movement with both, the model derived from the new concept and the one of the classic reflex concept. With both approaches, the posture-movement problem does not arise. Based on preliminary considerations that include experimental findings from the literature, however, we conclude that the new concept provides more explanatory power than the classic reflex concept.     

For the law, neuroscience changes nothing and everything

The rapidly growing field of cognitive neuroscience holds the promise of explaining the operations of the mind in terms of the physical operations of the brain. Some suggest that our emerging understanding of the physical causes of human (mis)behaviour will have a transformative effect on the law. Others argue that new neuroscience will provide only new details and that existing legal doctrine can accommodate whatever new information neuroscience will provide. We argue that neuroscience will probably have a transformative effect on the law, despite the fact that existing legal doctrine can, in principle, accommodate whatever neuroscience will tell us. New neuroscience will change the law, not by undermining its current assumptions, but by transforming people's moral intuitions about free will and responsibility. This change in moral outlook will result not from the discovery of crucial new facts or clever new arguments, but from a new appreciation of old arguments, bolstered by vivid new illustrations provided by cognitive neuroscience. We foresee, and recommend, a shift away from punishment aimed at retribution in favour of a more progressive, consequentialist approach to the criminal law.     

<Emphasis Type="SmallCaps">A</Emphasis> contextualist approach to functional localization in the brain

Functional localization has historically been one of the primary goals of neuroscience. There is still debate, however, about whether it is possible, and if so what kind of theories succeed at localization. I argue for a contextualist approach to localization. Most theorists assume that widespread contextual variability in function is fundamentally incompatible with functional decomposition in the brain, because contextualist accounts will fail to be generalizable and projectable. I argue that this assumption is misplaced. A properly articulated contextualism can ground successful theories of localization even without positing completely generalizable accounts. Via a case study from perceptual neuroscience, I suggest that there is strong evidence for contextual variation in the function of perceptual brain areas. I then outline a version of contextualism that is empirically adequate with respect to this data, and claim that it can still distinguish brain areas from each other according to their functional properties. Finally, I claim that the view does not fail the norms for good theory in the way that anticontextualists suppose. It is true that, on a contextualist view, we will not have theories that are completely generalizable and predictive. We can, however, have successful partial generalizations that structure ongoing investigation and lead to novel functional insight, and this success is sufficient to ground the project of functional localization.     

Three brain collections for comparative neuroanatomy and neuroimaging

In the context of increasing extinction rates and the potential loss of essential evolutionary biological and anthropological information, it is an important task to support efforts to prepare, preserve, and curate collections of histological brain sections; to disseminate information on such collections in the neuroscience community; and to make the collections publicly available. This review emphasizes the importance of complete, serially sectioned human brains of different ontogenetic stages as well as those of adult and old human individuals for neurobiological and medical research. Such histological sections enable microstructural analyses and anatomical evaluations of functional and structural neuroimaging data, for example, based on magnetic resonance imaging. Here, this review provides the first detailed and updated account of the content of the Stephan, Zilles, and Zilles-Amunts collections, which consist of serially sectioned and cell body- and myelin-stained histological preparations. Finally, this review will give an overview of past and recent research using these collections to increase our understanding of the detailed patterns of divergent brain evolution in primates as well as of the structural organization of the human brain.     

Order in spontaneous behavior

Brains are usually described as input/output systems: they transform sensory input into motor output. However, the motor output of brains (behavior) is notoriously variable, even under identical sensory conditions. The question of whether this behavioral variability merely reflects residual deviations due to extrinsic random noise in such otherwise deterministic systems or an intrinsic, adaptive indeterminacy trait is central for the basic understanding of brain function. Instead of random noise, we find a fractal order (resembling Lévy flights) in the temporal structure of spontaneous flight maneuvers in tethered Drosophila fruit flies. Lévy-like probabilistic behavior patterns are evolutionarily conserved, suggesting a general neural mechanism underlying spontaneous behavior. Drosophila can produce these patterns endogenously, without any external cues. The fly's behavior is controlled by brain circuits which operate as a nonlinear system with unstable dynamics far from equilibrium. These findings suggest that both general models of brain function and autonomous agents ought to include biologically relevant nonlinear, endogenous behavior-initiating mechanisms if they strive to realistically simulate biological brains or out-compete other agents.     

On the Neurobiology of Truth

The concept of truth arises from puzzling over distinctions between the real and the apparent, while the origin of these distinctions lies in the neurobiology of mammalian cerebral lateralization, that is, in the evolution of brains that can address the world both indicatively and subjunctively; brains that represent the world both categorically and hypothetically. After some 2,500 years of thinking about it, the Western philosophical tradition has come up with three major theories of truth: correspondence, coherence, and pragmatist. Traditional philosophy has nevertheless failed to arbitrate much among these views; certainly no clear winner has emerged. I argue, however, that contemporary neuroscience provides adequate theoretical grounds for a unified theory of truth. More specifically, I contend that the correspondence, the coherence, and the pragmatic utility of symbols are each biological features of our neurophysiological information processing systems—that is to say, our brains. On my view, the traditional trifurcation of philosophical accounts of the predicate, “is true”, stems from a trifurcation of focus on the information latent in sensory, motor, and somatosensory cortices of the human brain.