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Summary Recent advances in bioelectronics, such as skin-mounted electroencephalography sensors, multi-channel neural probes, and closed-loop deep brain stimulators, have enabled electrophysiological brain activities to be both monitored and modulated. Despite this remarkable progress, major challenges remain, which stem from the inherent mechanical, chemical, and electrical differences that exist between brain tissues and bioelectronics. New approaches are therefore required to address these mismatches between biotic and abiotic systems. Here, we review recent technological advances that minimize such mismatches by using unconventional soft materials, such as silicon/metal nanowires, functionalized hydrogels, and stretchable conductive nanocomposites, as well as customized fabrication processes and novel device designs. The resulting novel, soft bioelectronic devices provide new opportunities for brain research and clinical neuroengineering.

The human brain is often considered the most complex system known. It has a fantastic capacity to learn and remember, to recognize patterns in space and time, solve problems of all kinds, innovate tools and machines, create beautiful art and science. Is it reasonable to believe that we, in a foreseeable future, will be able to understand all the wonders of our own brain, enough to be able to mimic it and build artificial brains and minds that correspond to or even surpass the capacity of the human origin? Can we seriously believe that we (soon, or ever) will be able to build robots that know of and can reflect upon their own existence? This review of the book, The Brain and AI, deals with such issues, but in a very special way. It is written as a fascinating dialogue between the two authors, Chinese scientist Fanji Gu and German engineer Karl Schlagenhauf, where they discuss the development of neuroscience and artificial intelligence (AI) with a critical examination of given “truths” in these fields. The Brain and AI is indeed worth reading for many reasons, regardless if you are a student or researcher in any of the many fields of science discussed here (e.g. physics, computer science, neuroscience, cognitive science psychology, social science), or if you are just interested in the current and future development of brain research and artificial intelligence. The book is both educating and entertaining and can be strongly recommended.

Individuals of African ancestry have been starkly underrepresented in the pursuit of personalized medicine for brain illnesses. The African Ancestry Neuroscience Research Initiative will seek to generate much-needed brain gene and protein expression profiles for people of African ancestry.

Many studies in intact animals have shown that locally applied or synaptically released norepinephrine (NE) can enhance individual neuron and neural network responses to sensory inputs. However, a major unanswered question is how and when noradrenergically-mediated changes in sensory signal processing can influence downstream decision making, motor responding, and ultimately behavioral outcomes. Recent work using a variety of approaches in different sensory networks has started to consider this question. Evidence collected to date as reported in this Special Edition of Brain Research suggests that output from the brainstem locus coeruleus (LC)-NE system can modify task-related sensory signal processing and by so doing influence goal-directed behavioral responding. This report reviews the work leading to this most recent line of inquiry and at the same time identifies areas for future investigation.

The 21st century paradigm in toxicology, which emphasizes mechanistic understanding and species-relevant modeling of human biology and pathophysiology, is gaining traction in the wider biosciences through a global workshop series organized by the BioMed21 Collaboration. The second of this series, entitled Emerging Technology Toward Pathway-Based Human Brain Research, was held in Brazil in 2017, bringing together leading South American and international scientists, research funders and other stakeholders. The aims were to foster strategic scientific dialogue and identify actionable consensus recommendations as a first step toward a roadmap for 21st century, human-specific health research and funding in the region.

Urea cycle disorders (UCD) are inherited diseases resulting from deficiency in one of six enzymes or two carriers that are required to remove ammonia from the body. UCD may be associated with neurological damage encompassing a spectrum from asymptomatic/mild to severe encephalopathy, which results in most cases from Hyperammonemia (HA) and elevation of other neurotoxic intermediates of metabolism. Electroencephalography (EEG), Magnetic resonance imaging (MRI) and Proton Magnetic resonance spectroscopy (MRS) are noninvasive measures of brain function and structure that can be used during HA to guide management and provide prognostic information, in addition to being research tools to understand the pathophysiology of UCD associated brain injury. The Urea Cycle Rare disorders Consortium (UCDC) has been invested in research to understand the immediate and downstream effects of hyperammonemia (HA) on brain using electroencephalogram (EEG) and multimodal brain MRI to establish early patterns of brain injury and to track recovery and prognosis. This review highlights the evolving knowledge about the impact of UCD and HA in particular on neurological injury and recovery and use of EEG and MRI to study and evaluate prognostic factors for risk and recovery. It recognizes the work of others and discusses the UCDC's prior work and future research priorities.

Element speciation offers deeper insight into the molecular mechanisms of disease by determining element species pattern. Thus, having great potential for investigating neurodegeneration in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and mild cognitive impairment, speciation is increasingly considered in epidemiological or clinical neurological studies. This review analyses recent speciation findings in neurodegeneration research, concentrating on measurements in cerebrospinal fluid and brain. Elements considered are aluminum, arsenic, copper, iron, mercury, manganese, selenium and zinc. Also interactions of trace element species are discussed briefly. Typically, hyphenated techniques are used in neurodegeneration speciation studies. The results allow sorting-out less important species from compounds significant for the disease, with subsequent use of molecular biology methods to uncover the exact mechanisms. This review indicates the trend of combining speciation and neuroscience and provides a sketch about data and outcomes. For brain research, we recommend using modern, powerful techniques throughout which provide advanced validity and information in a chemical sense.

Interest in the common marmoset (Callithrix jacchus) as a primate model animal has grown recently, in part due to the successful demonstration of transgenic marmosets. However, there is some debate as to the suitability of marmosets, compared to more widely used animal models, such as the macaque monkey and mouse. Especially, the usage of marmoset for animal models of human cognition and mental disorders, is still yet to be fully explored. To examine the prospects of the marmoset model for neuroscience research, the Marmoset Gene Atlas (https://gene-atlas.bminds.brain.riken.jp/) provides a whole brain gene expression atlas in the common marmoset. We employ in situ hybridization (ISH) to systematically analyze gene expression in neonate marmoset brains, which allows us to compare expression with other model animals such as mouse. We anticipate that these data will provide sufficient information to develop tools that enable us to reveal marmoset brain structure, function, cellular and molecular organization for primate brain research.

The mechanism of posttraumatic epilepsy (PTE) is complicated and the treatment and prognostic effects are not satisfactory. In this study, CiteSpace and VOSviewer are used to analyze the literature related to PTE (January 2000–June 2020). The aspects of the cooperative network (author, institution, and country), keywords co-occurrence, document co-citation clustering, and journal dual-map overlay were analyzed, and the atlas was constructed. The United States, Finland, and other research institutions have frequently published PTE-related articles, thus having richer research results. The relevant research was mostly published in journals, such as Journal of Neurotrauma, Journal of Neuroscience, Brain Research, Neurobiology of Disease. Quantitative diffusion MRI plays a critical role in PTE research. The study on the susceptibility to seizures and the underlying mechanism of PTE received different degrees of attention. The present study provided an in-depth understanding of the research foundation, relevant research results, the current research frontiers, and the main research focus in the PTE field. Herein, we briefly discussed relevant key articles and also provided ideas for future research directions.

I describe the origins of the British Neuroscience Association (BNA) based on new documents which I have discovered. The foundation of the Brain Research Association (BRA) on February 23rd 1968 was influenced by IBRO, notably its two UK Council members, and by many UK neuroscientists, especially the London-based Black Horse Group. The BRA changed its name to the BNA in 1996. The documents are in the Wellcome Trust Archives.

The relationship between structure and function is of interest in many research fields involving the study of complex biological processes. In neuroscience in particular, the fusion of structural and functional data can help understanding the underlying principles of the operational networks in the brain. To address this issue, this paper proposes a constrained autoregressive model leading to a representation of “effective” connectivity that can be used to better understand how the structure modulates the function. Or simply, it can be used to find novel biomarkers characterizing groups of subjects. In practice, an initial structural connectivity representation is re-weighted to explain the functional co-activations. This is obtained by minimizing the reconstruction error of an autoregressive model constrained by the structural connectivity prior. The model has been designed to also include indirect connections, allowing to split direct and indirect components in the functional connectivity, and it can be used with raw and deconvoluted BOLD signal.The derived representation of dependencies was compared to the well known dynamic causal model, giving results closer to known ground-truth. Further evaluation of the proposed effective network was performed on two typical tasks. In a first experiment the direct functional dependencies were tested on a community detection problem, where the brain was partitioned using the effective networks across multiple subjects. In a second experiment the model was validated in a case-control task, which aimed at differentiating healthy subjects from individuals with autism spectrum disorder. Results showed that using effective connectivity leads to clusters better describing the functional interactions in the community detection task, while maintaining the original structural organization, and obtaining a better discrimination in the case-control classification task.HighlightsA method to combine structural and functional connectivity by using autoregressive model is proposed.The autoregressive model is constrained by structural connectivity defining coefficients for Granger causality.The usefulness of the generated effective connections is tested on simulations, ground-truth default mode network experiments, a classification and clustering task.The method can be used for direct and indirect connections, and with raw and deconvoluted BOLD signal.

The evolution of the folded cortical surface is an iconic feature of the human brain shared by a subset of mammals and considered pivotal for the emergence of higher-order cognitive functions. While our understanding of the neurodevelopmental processes involved in corticogenesis has greatly advanced over the past 70 years of brain research, the fundamental mechanisms that result in gyrification, along with its originating cytoarchitectural location, remain largely unknown. This review brings together numerous approaches to this basic neurodevelopmental problem, constructing a narrative of how various models, techniques and tools have been applied to the study of gyrification thus far. After a brief discussion of core concepts and challenges within the field, we provide an analysis of the significant discoveries derived from the parallel use of model organisms such as the mouse, ferret, sheep and non-human primates, particularly with regard to how they have shaped our understanding of cortical folding. We then focus on the latest developments in the field and the complementary application of newly emerging technologies, such as cerebral organoids, advanced neuroimaging techniques, and atomic force microscopy. Particular emphasis is placed upon the use of novel computational and physical models in regard to the interplay of biological and physical forces in cortical folding.

Electrocorticography (ECoG) neural signal recording has been widely used for recording brain electrical signals in brain research and clinical applications for disease diagnostic. In this work, we developed a flexible and re-pluggable ECoG electrode based on chromium-silver-chromium (Cr-Ag-Cr) structure which was deposited on 50 μm thick polymide (PI) foil. This electrode was used in neural signal recording tests and the results demonstrate, with low electrochemical impedance values of about 22.7 kΩ, can record the brain signals well. It can also be very nicely mounted on the curved surface of brain gyrus.

Building on the long history of neuroscience in Canada, Brain Canada is accelerating the funding of transformative brain research across Canada, primarily through an innovative $240-million CAN public-private partnership with the Government of Canada and numerous partners. This article describes Brain Canada's "One Brain One Community" approach and its views on international collaboration and the future of brain research.

The brainstem nucleus locus coeruleus (LC) is a major source of norepinephrine (NE) projections throughout the CNS. This important property was masked in very early studies by the inability to visualize endogenous monoamines. The development of monoamine histofluorescence methods by Swedish scientists led to a plethora of studies, including a paper published in Brain Research by Loizou in 1969. That paper was highly cited (making it a focal point for the 50th anniversary issue of this journal), and helped to spark a large and continuing set of investigations to further refine our understating of the LC-NE system and its contribution to brain function and behavior. This paper very briefly reviews the ensuing advances in anatomical, physiological and behavioral aspects of the LC-NE system. Although its projections are ubiquitously present throughout the CNS, recent studies find surprising specificity within the organizational and operational domains of LC neurons. These and other findings lead us to expect that future work will unmask additional features of the LC-NE system and its roles in normative and pathological brain and behavioral processes. This article is part of a Special Issue entitled SI:50th Anniversary Issue.

Quantitative Susceptibility Mapping (QSM) is an emerging area of brain research with clear application to brain iron studies in deep gray matter. However, acquisition of standard whole brain QSM can be time-consuming. One means to reduce scan time is to use a focal acquisition restricted only to the regions of interest such as deep gray matter. However, the non-local dipole field necessary for QSM reconstruction extends far beyond the structure of interest. We demonstrate the practical implications of these non-local fields on the choice of brain volume for QSM. In an illustrative numerical simulation and then in human brain experiments, we examine the effect on QSM of volume reduction in each dimension. For the globus pallidus, as an example of iron-rich deep gray matter, we demonstrate that substantial errors can arise even when the field-of-view far exceeds the physical structural boundaries. Thus, QSM reconstruction requires a non-local field-of-view prescription to ensure minimal errors. An axial QSM acquisition, centered on the globus pallidus, should encompass at least 76mm in the superior-inferior direction to conserve susceptibility values from the globus pallidus. This dimension exceeds the physical coronal extent of this structure by at least five-fold. As QSM sees wider use in the neuroscience community, its unique requirement for an extended field-of-view needs to be considered.

Summary A revolution is taking place in the life and associated sciences. Nowhere is this clearer than in neuroscience where a number of State-level brain research projects have been initiated to investigate the operations of our central nervous system (CNS). This benignly-intended work is much to be welcomed as it will undoubtedly help people suffering from brain illnesses and injuries. However, there is a substantial history of advances in the life and associated sciences being used in the development of novel weapons – the problem of dual use. So, care needs to be taken to guard this welcome research from such misuse. This paper investigates how the brain projects are dealing with dual use and concludes that there will be a continuing need for neuroethical analyses to help scientists find ways to protect their work from such misuse.

Nanostructured neural interfaces, comprising nanotubes or nanowires, have the potential to overcome the present hurdles of achieving stable communication with neuronal networks for long periods of time. This would have a strong impact on brain research. However, little information is available on the brain response to implanted high-aspect-ratio nanoparticles, which share morphological similarities with asbestos fibres. Here, we investigated the glial response and neuronal loss in the rat brain after implantation of biostable and structurally controlled nanowires of different lengths for a period up to one year post-surgery. Our results show that, as for lung and abdominal tissue, the brain is subject to a sustained, local inflammation when biostable and high-aspect-ratio nanoparticles of 5 μm or longer are present in the brain tissue. In addition, a significant loss of neurons was observed adjacent to the 10 μm nanowires after one year. Notably, the inflammatory response was restricted to a narrow zone around the nanowires and did not escalate between 12 weeks and one year. Furthermore, 2 μm nanowires did not cause significant inflammatory response nor significant loss of neurons nearby. The present results provide key information for the design of future neural implants based on nanomaterials.

The use of psychotropic drugs in clinical and translational brain research continues to grow, and the need for novel experimental models and screens is becoming widely recognized. Mounting evidence supports the utility of zebrafish (Danio rerio) for studying various pharmacological manipulations, as an alternative model complementing the existing rodent paradigms in this field. Here, we explore the effects of acute 20-min exposure to two commonly abused psychotropic compounds, Δ(9)-tetrahydrocannabinol (THC) and heroin, on adult zebrafish behavior in the novel tank test. Overall, THC administration (30 and 50 mg/L) produces an anxiogenic-like reduction of top swimming, paralleled with a slower, continuous bottom swimming. In contrast, heroin exposure (15 and 25 mg/L) evoked a hyperlocomotor response (with rapid bouts of bottom swimming and frequent 'bouncing' motions) without altering anxiety-sensitive top/bottom endpoints. The behavioral effects of these two compounds in zebrafish seem to parallel the respective rodent and human findings. Collectively, this emphasizes the growing significance of novel emerging aquatic models in translational drug abuse research and small molecule screening.

Background Researchers routinely cite neuromyths and neurorealism as barriers preventing teachers from effectively applying brain research to practice. A primary goal within educational neuroscience (EN), is to provide teachers with professional development that allows them to overcome these barriers and gain agency in developing the field. Yet, the EN literature does not provide a tangible framework for developing teachers' philosophical perspectives regarding neuroscience in education. Purpose Here, we review the history of teacher neuroscience professional development and identify challenges in developing EN teacher learning programs. Next, we present ‘learning study’, a form of collaborative action research, as a framework for addressing these challenges. Conclusion We highlight how learning study could be used as an appropriate model for exploring future classroom applications of theoretical neuroscience.

Brain donation has helped researchers and doctors to better understand the pathophysiology of disease, and it is also a key procedure in the research on treatment and prevention of brain diseases. However, it is known that various factors such as personal environment, social cognition, and attitude affect the brain donation decision. The purpose of this study is to investigate perception about brain donation and to figure out affecting factors of the brain donation in Korean community. From October to November 2017, 411 community residents were enrolled in this study. A designed questionnaire was used to analyze the perception and affecting factors of brain donation. Among the 411 participants, only 31 participants (7.5%) were aware of brain donation. After providing the correct information through the questionnaire, we were able to observe a positive change in the recognition of brain donation. In addition, factors including ‘for helping others’, ‘social contribution by promoting brain research’, and ‘for medical development’ have been found to affect positive attitude. This study found education and providing detailed information about brain donation was insufficient. And it also figured out accurate information would contribute to a positive change of the recognition about brain donation. Therefore, in order to invigorate culture of brain donation, it is necessary to provide more detailed information and education related to the results on positive and negative perception about brain donation.

At early neonatal ages, SOD1 G83R spinal MNs appear to undergo a period of maladaptation, with reduced dendritic arbor lengths (Amendola and Durand, 2008; Amendola et al., 2007; Filipchuk and Durand, 2012). At early neonatal ages, SOD1 G85R spinal MNs appear to undergo a period of maladaptation, with increased dendritic arbor lengths (Amendola and Durand, 2008; Amendola et al., 2007; Filipchuk and Durand, 2012). The authors would like to apologize for any inconvenience caused.

Optogenetics with microbial opsin genes, and pharmacogenetics with designer receptors, represent potent and versatile experimental modalities that can be integrated with each other as well as with a rich diversity of synergistic methods to provide fundamental opportunities in neuroscience research. Since initial steps were taken with these approaches less than 10 years ago, we are witnessing a rapid rise in publications (Fig. 1). The 7th Annual Brain Research Meeting in New Orleans in October 2012, Optogenetics and Pharmacogenetics in Neuronal Function and Dysfunction, brought together leading researchers that have developed and used these tools to explore a wide range of questions in nervous system function and dysfunction. This special issue of Brain Research includes articles by speakers in this meeting and others, which together synthesize and summarize the state of the art for optogenetics and designer receptors.

The aim of this essay is to identify the significance of animal research, and how such research can help us to understand the functioning of the human brain. Although techniques such as Electroencephalography (EEG), Transcranial Magnetic Stimulation (TMS), and Functional Magnetic Resonance Imaging (fMRI) uniquely contributes to brain research, this essay will focus on the advantages of conducting research using animal models, a brief historical perspective, and ethical issues and limitations surrounding this technique. Overall it will evaluate how such research technique has contributed to improve our knowledge of the human brain functioning.

Much scholarship in the history of cybernetics has focused on the far-reaching cultural dimensions of the movement. What has garnered less attention are efforts by cyberneticians such as Warren McCulloch and Norbert Wiener to transform scientific practice in an array of disciplines in the biomedical sciences, and the complex ways these efforts were received by members of traditional disciplines. In a quest for scientific unity that had a decidedly imperialistic flavour, cyberneticians sought to apply practices common in the exact sciences—mainly theoretical modeling—to problems in disciplines that were traditionally defined by highly empirical practices, such as neurophysiology and neuroanatomy. Their efforts were met with mixed, often critical responses. This paper attempts to make sense of such dynamics by exploring the notion of a scientific style and its usefulness in accounting for the contrasts in scientific practice in brain research and in cybernetics during the 1940s. Focusing on two key institutional contexts of brain research and the role of the Rockefeller and Macy Foundations in directing brain research and cybernetics, the paper argues that the conflicts between these fields were not simply about experiment vs. theory but turned more closely on the questions that defined each area and the language used to elaborate answers.

There can be little doubt that genetics has transformed our understanding of mechanisms mediating brain disorders. The last two decades have brought tremendous progress in terms of accurate molecular diagnoses and knowledge of the genes and pathways that are involved in a large number of neurological and psychiatric disorders. Likewise, new methods and analytical approaches, including genome array studies and “next-generation” sequencing technologies, are bringing us deeper insights into the subtle complexities of the genetic architecture that determines our risks for these disorders. As we now seek to translate these discoveries back to clinical applications, a major challenge for the field will be in bridging the gap between genes and biology. In this Overview of Neuron's special review issue on neurogenetics, we reflect on progress made over the last two decades and highlight the challenges as well as the exciting opportunities for the future.PaperClip

Stuttering is present in all cultures with a prevalence of around 1%. While there has been extensive brain and behavioral research into stuttering over the last 50 years, its cause remains unknown. Brain imaging research has shown anomalous activations during stuttered speech and, more recently, has identified structural anomalies in the speech language areas of the brain. A recent meta-analysis concluded that these aberrant neural activations are a consequence of stuttering rather than a cause, and that stuttering is a disorder of the initiation of speech motor plans. Expanding on this hypothesis we propose that this disorder comprises the initiation of syllables. We provide evidence that this is underpinned by a disturbance of neural function in SMA. Our syllable initiation (SI) theory has evolved from our working model, the variability or Vmodel. SI theory draws not only on brain research in stuttering but also on research into speech production deficits after brain damage. SI theory locates stuttering at the interface of speech and language and we suggest that it provides a plausible and parsimonious explanation of the cause and critical phenomena of stuttering.

Constantin von Monakow (1853-1930), director of the Brain Anatomy Institute in Zurich, was a pioneer in the early history of interdisciplinary brain sciences. The elucidation of connectivity in sensory and motor pathways was richly illustrated in two landmark monographs: Pathologie du cerveau (1897) and La localisation de l'encephale et la dégradation fonctionelle par des lésions circonscrites du cortex cérébral (1914). His special merit was to conceptualize his accumulating results. As to his term 'diaschisis': (1) neurological lesion are rarely restricted to a histologically defined neural structure; (2) any brain focus is interconnected with remote structures - thus, dependent structures are deafferented from the lesioned territory (= 'diaschisis') -; (3) dependent structures, however, gradually regain some autonomy, as reflected in partial behavioral recovery. His term 'chronogenic localization' was used for the brain's fundamental organization in time-dependent network constellations. Monakow attracted many researchers, particularly from Japan. He was an engaged member of the International Brain Commission until its dissolution during World War I.

In biomedical research the distributions of physiologically or pathologically active elements around or in a certain structure (e.g. tangles, plaques or different cell types) are often of great interest. Therefore, μPIXE analyses are applied to yield quantitative and spatially resolved concentration images of the elements of interest. However, the localisation of the structures to be examined is sometimes scarcely practicable or even impossible. This paper proposes a method of localising the areas of interest for μPIXE analysis. The method is based on the application of a suitable antibody tagged with a single elemental marker (e.g. Ni, Co, Cd, Ag or Au). The antibody then binds selectively to the structures of interest. The elemental marker is detectable via μPIXE, thus, showing finally the structure of interest via the bound antibody. The versatility of the antibodies in combination with the easily applied marker facilitates the localisation of a variety of structures in both light microscopy and μPIXE-imaging. The method is demonstrated on several cellular and subcellular structures in the brain. The elemental concentrations of two consecutive slices, one stained with Ni-enhanced antibody, the other unstained control, are compared to show the feasibility of trace elemental analysis for particular elements in spite if immunohistochemical structure identification. It has to be stated that the proposed technique will not work for free diffusing elements (like Na, Cl, K and Ca) whose concentrations can be altered by wet sample preparation.

Neuroscientists from across the country gathered at the University of Wisconsin, Madison in September to honor Ray Guillery and his seminal work on the thalamus. The meeting focused on three timely research topics, each of which inspired new thinking about thalamic function. Presentations on the organization and dynamic nature of thalamocortical pathways, the role of the thalamus in communication between cortical areas, and the relationship between sensory and motor pathways of the brain, including cognitive aspects of thalamocortical processing, made for lively discussions. The meeting revealed that communication between thalamus and cortex is so rich that we should no longer consider the operations of either structure separately from the other. Proceedings of the meeting will be published in Progress in Brain Research in 2005. In this report, we provide a general overview of the main themes of the meeting.

Department of Neurology, Kanazawa Medical University, Ishikawa, Japan Division of Nephrology, Kanazawa Medical University, Ishikawa, Japan Department of Virology I, National Institute of Infectious Disease, Tokyo, Japan Department of Neurosurgery, Brain Research Institute, University of Niigata, Niigata, Japan Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan

Head movement during positron emission tomography (PET) studies causes loss of image quality and quantity and is problematic for brain PET study. During the PET scan, the head of the subject is often fixed by a head holder. However, the head holder is not perfect and it is sometimes difficult to use the head holder for a less cooperative patient. Moreover, head fixation might generate unwanted signals in neural activation studies. There are several software packages, such as AIR and SPM, offering software tools to correct head motion between two scans. These tools, however, cannot correct head motions during scanning. We developed a system to correct the head motion during PET scanning using list-mode acquisition and an optical tracking system. To compensate for escaped photon from the FOV of the PET scanner, the concept of a “virtual ring” was introduced. The present system has the potential to do real-time motion correction during PET scanning and makes it possible to scan a subject without any head fixation, which provides a new aspect of brain research using PET.

First, the major steps in the progress of molecular biology of a single cell are summarized starting from the 1940s. This is followed by mentioning the major unsolved problems in this field. Afterwards, already existing applications of the main ingredients of a theory of a single cell (quantum theory, statistical mechanics in the most general sense, information theory and theory of regulation of non-linear systems) are briefly described. The further probable developments in these fields which will make it possible to solve the, until now unresolved, important problems of molecular biology (especially the regulation of reaction ensembles in the cell and the self-regulation of a cell) are briefly described. Finally, the possibilities of until now in biology unused other mathematical methods are mentioned. It is pointed out that all these theories most probably will grow to provide a general theoretical description of a single cell. In the conclusion, one has tried to describe the probable extension of the theory of a cell to cell ensembles, organs and organism. In the last case, the importance of the development of brain research is pointed out.

High-field magnetic resonance imaging scanners with a static magnetic field of 3 Tesla or higher are becoming ubiquitous in clinical and basic neurosciences. Given the high cost and complexity of operation, it is important to ask whether or not and how the use of high-field magnets can be beneficial for the neurosciences. What new questions can be addressed? Which new insights can we expect from these new tools? In addition, what are the limitations of these new techniques? This review discusses the three most important applications of the high-field magnetic resonance techniques for the neuroscience community: first, functional magnetic resonance imaging, second, in vivo spectroscopy, and third, in vivo fiber tracking on the basis of diffusion tensor imaging.

Positron Emission Tomography (PET) is a functional imaging modality used in brain research to map in vivo neurotransmitter and receptor activity and to investigate glucose utilization or blood flow patterns both in healthy and disease states. Such research is made possible by the wealth of radiotracers available for PET, by the fact that metabolic and kinetic parameters of particular processes can be extracted from PET data and by the continuous development of imaging techniques. In recent years great advancements have been made in the areas of PET instrumentation, data quantification and image reconstruction that allow for more detailed and accurate biological information to be extracted from PET data. It is now possible to quantitatively compare data obtained either with different tracers or with the same tracer under different scanning conditions. These sophisticated imaging approaches enable detailed investigation of disease mechanisms and system response to disease and/or therapy.

The Decade of the Brain is now over, but the most important discoveries are still to come. Given that in the United States and elsewhere in the world the population is aging, the impact of high-quality brain research over the next 2 decades could be tremendous. It is important to improve stroke prevention and acute stroke treatment and also to find the means to eliminate stroke-related disability for those who live each day with motor and other neurologic impairments.

The Grete Lundbeck European Brain Research Foundation awarded the inaugural Brain Prize 2011 to Peter Somogyi, Tamas Freund and Gyorgy Buzsaki ‘for their wide-ranging, technically and conceptually brilliant research on the functional organization of neuronal circuits in the cerebral cortex, especially in the hippocampus, a region that is crucial for certain forms of memory’. The present article highlights key findings and major conceptual contributions by these three scientists that were recognized by the award.

International associations of scientists, set up to organize cooperative scientific investigations in an international scope and to lay down global binding standards of research, are of great and still growing importance for the advancement of science. This was also recognized at the beginning of the 20th century by the community of researchers in basic and clinical neurological sciences, who created their first international organization following the trend initiated by scholars in astronomy and geophysics. Thus, the so-called “Brain Commission” of the International Association of Academies was founded in 1903 and was active until the outbreak of the First World War. The Brain Commission had no successor for nearly half a century, until the “International Brain Research Organization” (IBRO) was founded in 1961. Although the Brain Commission could exert an impact on neurosciences only for one decade, this international scientific association inspired and promoted the foundation of a series of Brain Research Institutes, which in part still exist in Europe, and long-lasting innovations in the neurosciences.

The brain is a highly sophisticated assembly of neuronal networks for interaction with the internal and external environment. Fundamentally, the neuronal communication process is analogous structurally and functionally to the electrical (wire-mediated) network. In particular, both have coupled information-processing and conduction properties. We suggest that the electrical system can be used as a learning paradigm in brain research and clinical practice. Our model shows how the study of wire-mediated networks may be of benefit in tracing overt psychiatric manifestations to intrinsic biological faults in brain circuitry.

The first real breakthrough in the research of brain organization and thinking in the 20th century was made in neurophysiological investigations performed in direct contact with different sites of the brain, which became possible in diagnosis and treatment. The second breakthrough is happening at present. It is based on the opportunities provided by the non-invasive technique. The theory of the unique character of the brain system consisting of rigid and flexible elements maintaining thinking was created as well as concepts on the reliability in the system, of the error detector and intrinsic protective mechanisms of the brain. In the clinic these data enabled us to help patients who had lost various functions due to stroke. In confirmation with the above theory it was revealed that the same task could be solved in the brain by systems consisting of different elements due to environmental changes or even direction of attention. Data on the functional properties or every zone of the cortex and subcortex as well as cerebellum are rapidly increasing in number. The first priority lies in neurophysiologically penetrating into the physiological character and micromosaic of the activation sites of PET. The main aim of future brain research lies in the investigation of the fine physiological rearrangements which underlie thinking, i.e. deciphering its brain code. This is going to be the basis for the third, extremely valid breakthrough in the research on brain organization of thinking.

The stated goal of this Special Issue (namely, addressing a key issue for the study of language and the brain in the next century) would seem to call for some type of linkage of behavioral research issues with brain research issues. Thus, dealing with concerns such as the contribution of the right hemisphere to language processing; the nature of the integration of LH and RH language information into a final ‘‘percept’’ during comprehension; the true underlying role of Broca’s area in language processing; or, linking human genetic description to potential language and/or language–brain functions, would be critical and obviously meritorious goals for new millennium research. However, while research on the brain–behavior link is of obvious and central importance, a far more fundamental issue requires resolution before behavior–brain relationships can be fruitfully examined. Simply put, we need to understand, precisely, how our behavioral methodologies reflect on, and interact with, the language processes we are attempting to study and define. While this issue may not appear at first blush to be as ‘‘new-age’’ as, for example, providing brain imaging maps of putative language functions, it is ever-current and arguably far more fundamental. The reason is simple: our behavioral research forms the basis upon which we define and select the inventory of language functions and properties we take to constitute comprehension and production. Our entire behavioral classification and description of language functions is thus dependent on knowing how well the methods by which we examine such putative functions

McGovern Institute for Brain Research and Department of Brain and Cognitive Science, Massachusetts Institute of Technology,Cambridge, MA, USA*Correspondence: jritt@mit.edu (J.T.R.), cim@mit.edu (C.I.M.)DOI 10.1016/j.neuron.2008.11.022Sensorysignalsgeneratedduringfreebe-havior areshaped by objects in the world,the animal’s active sensing choices, andthe innate construction, or embodiment,of the sensory system. Together theseconstitute the ‘‘natural scene’’ of sensoryinputs. Our study (Ritt et al., 2008) wasthe first to measure the fine-scale signalstransmitted through vibrissae whileanimals freely explored textured surfaces.Specifically, we quantified ‘‘micromo-tions,’’ small-amplitude, high-velocity sig-nals thought by most researchers in thefield (Carvell and Simons, 1990, 1995;Mehta and Kleinfeld, 2004; Neimarket al., 2003), including Diamond and col-leagues (Arabzadeh et al., 2005; Hippet al., 2006; von Heimendahl et al., 2007),to play a key role in texture perception.In their letter, Diamond et al. suggestthat our characterization of an embodiedproperty of perception—resonant tuningof vibrissae—is inappropriate. They pre-dict that resonance will not shape trans-ductioninaninitialcontactwindow,whichthey claim is the relevant period in texturetasks, the only time when the brain is ‘‘lis-tening.’’ We directly address this factualconcern below by reanalyzing our data,and observe resonance tuning within theinitial contact window. We also addressconceptual issues raised by their letter,in the hopes that this discussion will helpmove the field forward.We first provide brief historical contextanddescribewhatwebelievetobeamis-understanding about resonance. Despitewidespread study of the vibrissa sensorysystem as a model, consideration of thepossibleroleofitsembodimenthasarisenonlyrecently.Aninitialobservationinvitrowas that vibrissae express mechanicalfrequency tuning related to their length,much as harp string length determinespitch (Andermann et al., 2004; Hartmannet al., 2003; Mehta and Kleinfeld, 2004;Moore and Andermann, 2005; Neimarket al., 2003), leading to the ‘‘resonancehypothesis.’’ The central idea was thatvibrissae might filter sensory informationrather than veridically transmit surfaceprofile. A suggestive further point wasthat stereotyped differences in vibrissalengths across the face, providing differ-ences in frequency tuning, might lead toa ‘‘preneural’’ organization and process-ing of sensory inputs.Onthebasisofinvitroandexvivostud-ies in which they swept real and metallicvibrissae over textures at a single velocity(Arabzadehetal.,2005;Hippetal.,2006),Diamond and colleagues questionedwhether resonance would shape trans-duction in freely behaving animals andappeared to favor the idea instead thatvibrissae are largely interchangeabledespitevariationsintheirphysicalproper-ties. Addressing this question requiredmeasurement in freely behaving animals,in part because sensing choices (forexample, speed at which vibrissae areswept over a surface) should be a strongdeterminant of contact-induced micro-motions. We showed (Ritt et al., 2008)that vibrissa length is correlated withmicromotion mean frequency in freelybehaving animals exploring surfaces,resolving the original concern raised byDiamond and colleagues (a finding repli-cated in Wolfe et al., 2008).To understand this finding, it is impor-tanttoconsiderthenatureoftransductionfromcomplexsurfaces.Micromotionsareoftenfarfromperiodicoscillations,yetav-erage micromotion frequencies may stillexhibit a biomechanical, vibrissa-specificbias, which is the definition of resonance.For example, the amplitude of a given mi-cromotion could depend on where it fallswithin a temporal pattern of micromo-tions. Sustained oscillations on smoothsurfaces, due to friction, also demon-strate an impact of biomechanics beyondsimple transmission of surface profile(e.g., Figure 5 in Ritt et al., 2008). Assuch, an absence of isolated oscillations(e.g., ‘‘rings’’) is not in itself evidencethat resonance plays no role. Diamondet al. appear to equate resonance withrings only (for a similar view, see Wolfeet al., 2008). This view is also indicatedby their incorrect attribution of the term‘‘microvibration’’ to us, a word that ap-pears nowhere in our manuscript, andthat they define as distinct from all othermotions.Instead,weusetheterm‘‘micro-motion’’ to refer to all small-amplitude,high-velocity motions, including frictionalstick/slips as well as rings. In this termi-nology (derived from Brecht et al., 1997;Carvell and Simons, 1995), the ‘‘kineticsignature’’hypothesisof(Arabzadehetal.,2005; Hipp et al., 2006) is the statementthat different surfaces generate distinctpatternsofmicromotions.Thesepatterns,transduced by vibrissae, should be sub-ject to biomechanical filtering (e.g., reso-nance), including variation as a functionof vibrissa identity.In their letter, Diamond et al. expressa new concern, that resonance mayshape transduction, but not during theright window. In their recent paper (vonHeimendahl et al., 2007), they found ratsmade texture judgments quickly, withshort vibrissa contacts, and suggest thatif resonance shapes transduction only af-terward,itisperceptuallymoot.Todirectlyaddress this question, we reanalyzed theNeuron 60, December 11, 2008 a2008 Elsevier Inc. 745

This research was supported by a grant(M103KV010021-07K2201-02110) from Brain Research Center of the 21st Century Froniter Research Program(I.K.L.).