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Soul, mind, brain: Greek philosophy and the birth of neuroscience.

The nature of "soul" and the source of "psychic life", the anatomical seat of cognitive, motor and sensory functions, and the origin of neural diseases were broadly debated by ancient Greek scientists since the earliest times. Within the space of few centuries, speculation of philosophers and medical thinkers laid the foundations of modern experimental and clinical neuroscience. This review provides a brief history of the leading doctrines on the essence of soul and the properties of mind professed by Greek philosophers and physicians as well as the early attempts to localize brain faculties and to explain neural disorders.

Brain↗

Systems biology in neuroscience: bridging genes to cognition.

Systems biology is a new branch of biology aimed at understanding biological complexity. Genomic and proteomic methods integrated with cellular and organismal analyses allow modelling of physiological processes. Progress in understanding synapse composition and new experimental and bioinformatics methods indicate the synapse is an excellent starting point for global systems biology of the brain. A neuroscience systems biology programme, organized as a consortium, is proposed.

Animals↗

Generalist genes and cognitive neuroscience.

Multivariate genetic research suggests that a single set of genes affects most cognitive abilities and disabilities. This finding already has far-reaching implications for cognitive neuroscience, and will become even more revealing when this - presumably large - set of generalist genes is identified. Similar to other complex disorders and dimensions, molecular genetic research on cognitive abilities and disabilities is adopting genome-wide association strategies. These strategies involve very large samples to detect DNA associations of small effect size using microarrays that simultaneously assess hundreds of thousands of DNA markers. When this set of generalist genes is identified, it can be used to provide solid footholds in the climb towards a systems-level understanding of how genetically driven brain processes work together to affect diverse cognitive abilities and disabilities.

Chromosome Mapping↗

Cognitive neuroscience and the law.

Advances in cognitive neuroscience now allow us to use physiological techniques to measure and assess mental states under a growing set of circumstances. The implication of this growing ability has not been lost on the western legal community. If biologists can accurately measure mental state, then legal conflicts that turn on the true mental states of individuals might well be resolvable with techniques ranging from electroencephalography to functional magnetic resonance imaging. Therefore, legal practitioners have increasingly sought to employ cognitive neuroscientific methods and data as evidence to influence legal proceedings. This poses a risk, because these scientific methodologies have largely been designed and validated for experimental use only. Their subsequent use in legal proceedings is an application for which they were not intended, and for which those methods are inadequately tested. We propose that neurobiologists, who might inadvertently contribute to this situation, should be aware of how their papers will be read by the legal community and should play a more active role in educating and engaging with that community.

Cognitive Science↗

The cognitive neuroscience of remote episodic, semantic and spatial memory.

The processes and mechanisms implicated in retention and retrieval of memories as they age is an enduring problem in cognitive neuroscience. Research from lesion and functional neuroimaging studies on remote episodic, semantic and spatial memory in humans is crucial for evaluating three theories of hippocampal and/or medial temporal lobe-neocortical interaction in memory retention and retrieval: cognitive map theory, standard consolidation theory and multiple trace theory. Each theory makes different predictions regarding first, the severity and extent of retrograde amnesia following lesions to some or all of the structures mentioned; second, the extent of activation of these structures to retrieval of memory across time; and third, the type of memory being retrieved. Each of these theories has strengths and weaknesses, and there are various unresolved issues. We propose a unified account based on multiple trace theory. This theory states that the hippocampus is needed for re-experiencing detailed episodic and spatial memories no matter how old they are, and that it contributes to the formation and assimilation of semantic memories and schematic spatial maps.

Amnesia, Retrograde↗

Language bias in neuroscience--is the Tower of Babel located in Germany?

In internal medicine German authors tend to publish randomized controlled trials (RCTs) with non-significant findings in German journals, RCTs with significant findings in international journals. In the neurosciences a similar trend was seen but the findings were not statistically significant. The reason for this inconclusive finding might be the low number of RCTs published in German.

Germany↗

A microarray platform comparison for neuroscience applications.

To address the need for high sensitivity in gene expression profiling of small neural tissue samples ( approximately 100 ng total RNA), we compared a novel RT-PCR-IVT protocol using fluor-reverse pairs on inkjet oligonucleotide microarrays and an RT-IVT protocol using 33P labeling on nylon cDNA arrays. The comparison protocol was designed to evaluate these systems for sensitivity, specificity, reproducibility, and linearity. We developed parameters, thresholds, and testing conditions that could be used to differentiate various systems that spanned detection chemistry and instrumentation; probe number and selection criteria; and sample processing protocols. We concluded that the inkjet system had better performance in sensitivity, specificity, and reproducibility than the nylon system, and similar performance in linearity. Between these two platforms, the data indicates that the inkjet system would perform better for the transcriptional profiling of 100 ng total RNA samples for neuroscience studies.

Animals↗

Plasticity imbalance in mental disorders the neuroscience of psychiatry: implications for diagnosis and research.

In 1895 Freud tried to explain mental disorders using the neurophysiological knowledge of his time. He soon abandoned this attempt realizing it was immature considering the neuroscientific knowledge available to him. For the rest of his career he limited himself to psychological formulations. Along the same lines, lacking etiology for mental disorders, the diagnostic system of psychiatry is exclusively descriptive. The need for a brain related diagnosis of mental disorders is important for developing better treatments and more reliable diagnosis. Today with the development of neuroscience it is time to go back to Freud's initial attempts and explain mental disorders as altered neuronal organizations in the brain. The neural network level is chosen as the relevant description level for mental functions. Plasticity is chosen as a general concept for neuronal dynamics explaining neuropathology of psychiatric disorders. Plasticity is divided according to timescales into "fast plasticity," "slow plasticity" and "stable plasticity". It is proposed that normal mental functions require optimal balance among all the plasticity timescales. Mental disorders arise when such balance is disturbed, thus mental disorders could be reformulated as deficiencies of the different plasticity processes. Changes in coherence synchrony and phase-locking membrane potentials in cortically spread neuronal ensembles are all expressions of fast plasticity. Synaptogenic and neurogenic processes, such as brain derived neurotrophic factor-dependent processes, are defined as slow plasticity. Finally those synaptic and neuronal pathways that consolidated into long lasting circuits are referred to as stable plasticity. With the aid of a neural network model simulating the plasticity imbalance, a mathematical formulation could be realized for mental disorders. Once achieved this mathematical formulation could form a guiding framework for interpreting brain-imaging data collected from psychiatric patients. Such a model is realized using interconnected "modules" each simulating the relevant plasticity dynamics relevant for the model. Diagnosing plasticity imbalance has some advantages over current descriptive psychiatric diagnosis. It is brain-related thus less stigmatising in the sense that mental disorders are brain disorders and not "person" disorders. The diagnostic system is much more flexible allowing for a high degree of variations and combinations in the description of the disorders thus naturally accounting for comorbidities. Most importantly, this diagnostic model is brain-related offering research targets for intervention and a theoretical framework guiding such interventions.

Biomedical Research↗

RNA interference in neuroscience.

One of the most exciting findings in recent years has been the discovery of RNA interference (RNAi). RNAi is an important system that allows sequence-specific gene silencing through targeted degradation of mRNA by cognate double-stranded RNA (dsRNA). RNAi plays a role in endogenous cellular processes, such as developmental control and heterochromatin formation, and serves as an antiviral defense mechanism. Recent findings suggest that RNAi and related pathways are involved in protecting the genome against instabilities caused by transposons and repetitive sequences. Several rapidly developing RNAi methodologies provide a new approach for elucidation of gene functions. RNAi technology is also currently being evaluated as a potentially useful method to develop highly specific dsRNA-based gene-silencing therapeutics. In this paper, we review the use of RNAi in neuroscience research and as a possible therapeutic tool for treatment of neurological diseases.

Animals↗

Psychobiology and Neuroscience at the Florida State University: a history.

In the 1950s, young faculty in Psychology and Physiology/Biology at the newly established Florida State University recognized common interests in the study of sensory systems. They spontaneously formed one of this country's earliest interdisciplinary research cohorts in the emerging field of "psychobiology". In the 1960s, this group established a formal graduate program in Psychobiology, acquired resources for building a new laboratory and for supporting pre- and post-doctoral students, and began the expansion of faculty and research focuses that continues to this day. In 1991, FSU's Psychobiology Program was re-branded as a Program in Neuroscience that awards a doctoral degree. It now encompasses faculty and students from four academic departments in the Colleges of Arts and Sciences, Human Sciences, and Medicine. This paper traces some main developments in our 50-year history of these research and training efforts.

Behavioral Sciences↗

Gompertzian growth and decay: a powerful descriptive tool for neuroscience.

First-order kinetics is based on simple exponential decay, usually expressed in base e (Naperian) notation. "Nonexponential" processes, for example, S-shaped functions, are frequently modeled as sums of that elemental construct, and the number of rate constants increases with the number of such terms. A powerful descriptive alternative to sums of simple exponentials is the Gompertz function. In Gompertz kinetics, the rate coefficient of an exponential process is assumed to change exponentially with the independent variable. Nonexponential processes are easily modeled, more efficiently and more accurately than is possible with standard kinetics. Application of Gompertz kinetics to neuroscience research topics ranging from cognitive to molecular is presented to illustrate the power of the model: distribution of nerve fiber diameters, conditioning-testing responses of excitable nerve, psychophysical estimates of taste intensity magnitude, time course of synaptic current, and behavior of membrane conductance during voltage clamp of squid axon.

Animals↗

Two hands, one brain: cognitive neuroscience of bimanual skill.

Bimanual coordination, a prototype of a complex motor skill, has recently become the subject of intensive investigation. Whereas past research focused mainly on the identification of the elementary coordination constraints that limit performance, the focus is now shifting towards overcoming these coordination constraints by means of task symbolization or perceptual transformation rules that promote the integration of the task components into a meaningful "gestalt". The study of these cognitive penetrations into action will narrow the brain-mind gap and will facilitate the development of a cognitive neuroscience perspective on bimanual movement control.

Attention↗

Developmental cognitive neuroscience: progress and potential.

Developmental cognitive neuroscience is an evolving field that investigates the relations between neural and cognitive development. Lying at the intersection of diverse disciplines, work in this area promises to shed light on classic developmental questions, mechanisms subserving developmental change, diagnosis and treatment of developmental disorders, and cognitive and neuroscientific topics traditionally considered outside the domain of development. Fundamental questions include: What are the interrelations between developmental changes in the brain (e.g. in connectivity, chemistry, morphology) and developmental changes in children's behavior and cognitive abilities (e.g. representational complexity, ability to sustain selective attention, speed of processing)? Why, and how, is learning enhanced during certain periods in development? How is our knowledge organized, and how does this change with development? We discuss preliminary investigations of such questions and directions for future work.

Aptitude↗

Consciousness: converging insights from connectionist modeling and neuroscience.

Over the past decade, many findings in cognitive neuroscience have resulted in the view that selective attention, working memory and cognitive control involve competition between widely distributed representations. This competition is biased by top-down projections (notably from prefrontal cortex), which can selectively enhance some representations over others. This view has now been implemented in several connectionist models. In this review, we emphasize the relevance of these models to understanding consciousness. Interestingly, the models we review have striking similarities to others directly aimed at implementing 'global workspace theory'. All of these models embody a fundamental principle that has been used in many connectionist models over the past twenty years: global constraint satisfaction.

Consciousness↗

Modeling developmental cognitive neuroscience.

In the past few years connectionist models have greatly contributed to formulating theories of cognitive development. Some of these models follow the approach of developmental cognitive neuroscience in exploring interactions between brain development and cognitive development by integrating structural change into learning. We describe two classes of these models. The first focuses on experience-dependent structural elaboration within a brain region by adding or deleting units and connections during learning. The second models the gradual integration of different brain areas based on combinations of experience-dependent and maturational factors. These models provide new theories of the mechanisms of cognitive change in various domains and they offer an integrated framework to study normal and abnormal development, and normal and impaired adult processing.

Algorithms↗

Towards a cognitive neuroscience of consciousness: basic evidence and a workspace framework.

This introductory chapter attempts to clarify the philosophical, empirical, and theoretical bases on which a cognitive neuroscience approach to consciousness can be founded. We isolate three major empirical observations that any theory of consciousness should incorporate, namely (1) a considerable amount of processing is possible without consciousness, (2) attention is a prerequisite of consciousness, and (3) consciousness is required for some specific cognitive tasks, including those that require durable information maintenance, novel combinations of operations, or the spontaneous generation of intentional behavior. We then propose a theoretical framework that synthesizes those facts: the hypothesis of a global neuronal workspace. This framework postulates that, at any given time, many modular cerebral networks are active in parallel and process information in an unconscious manner. An information becomes conscious, however, if the neural population that represents it is mobilized by top-down attentional amplification into a brain-scale state of coherent activity that involves many neurons distributed throughout the brain. The long-distance connectivity of these 'workspace neurons' can, when they are active for a minimal duration, make the information available to a variety of processes including perceptual categorization, long-term memorization, evaluation, and intentional action. We postulate that this global availability of information through the workspace is what we subjectively experience as a conscious state. A complete theory of consciousness should explain why some cognitive and cerebral representations can be permanently or temporarily inaccessible to consciousness, what is the range of possible conscious contents, how they map onto specific cerebral circuits, and whether a generic neuronal mechanism underlies all of them. We confront the workspace model with those issues and identify novel experimental predictions. Neurophysiological, anatomical, and brain-imaging data strongly argue for a major role of prefrontal cortex, anterior cingulate, and the areas that connect to them, in creating the postulated brain-scale workspace.

Brain↗

Fuzzy-trace theory: dual processes in memory, reasoning, and cognitive neuroscience.

Fuzzy-trace theory has evolved in response to counterintuitive data on how memory development influences the development of reasoning. The two traditional perspectives on memory-reasoning relations--the necessity and constructivist hypotheses--stipulate that the accuracy of children's memory for problem information and the accuracy of their reasoning are closely intertwined, albeit for different reasons. However, contrary to necessity, correlational and experimental dissociations have been found between children's memory for problem information that is determinative in solving certain problems and their solutions of those problems. In these same tasks, age changes in memory for problem information appear to be dissociated from age changes in reasoning. Contrary to constructivism, correlational and experimental dissociations also have been found between children's performance on memory tests for actual experience and memory tests for the meaning of experience. As in memory-reasoning studies, age changes in one type of memory performance do not seem to be closely connected to age changes in the other type of performance. Subsequent experiments have led to dual-process accounts in both the memory and reasoning spheres. The account of memory development features four other principles: parallel verbatim-gist storage, dissociated verbatim-gist retrieval, memorial bases of conscious recollection, and identity/similarity processes. The account of the development of reasoning features three principles: gist extraction, fuzzy-to-verbatim continua, and fuzzy-processing preferences. The fuzzy-processing preference is a particularly important notion because it implies that gist-based intuitive reasoning often suffices to deliver "logical" solutions and that such reasoning confers multiple cognitive advantages that enhance accuracy. The explanation of memory-reasoning dissociations in cognitive development then falls out of fuzzy-trace theory's dual-process models of memory and reasoning. More explicitly, in childhood reasoning tasks, it is assumed that both verbatim and gist traces of problem information are stored. Responding accurately to memory tests for presented problem information depends primarily on verbatim memory abilities (preserving traces of that information and accessing them when the appropriate memory probes are administered). However, accurate solutions to reasoning problems depend primarily on gist-memory abilities (extracting the correct gist from problem information, focusing on that gist during reasoning, and accessing reasoning operations that process that gist). Because verbatim and gist memories exhibit considerable dissociation, both during storage and when they are subsequently accessed on memory tests, dissociations of verbatim-based memory performance from gist-based reasoning are predictable. Conversely, associations are predicted in situations in which memory and reasoning are based on the same verbatim traces (Brainerd & Reyna, 1988) and in situations in which memory and reasoning are based on the same gist traces (Reyna & Kiernan, 1994). Fuzzy-trace theory's memory and reasoning principles have been applied in other research domains. Four such domains are developmental cognitive neuroscience studies of false memory, studies of false memory in brain-damaged patients, studies of reasoning errors in judgment and decision making, and studies of retrieval mechanisms in recall. In the first domain, the principles of parallel verbatim-gist storage, dissociated verbatim-gist retrieval, and identity/similarity processes have been used to explain both spontaneous and implanted false reports in children and in the elderly. These explanations have produced some surprising predictions that have been verified: false reports do not merely decline with age during childhood but increase under theoretically specified conditions; reports of events that were not experienced can nevertheless be highly persistent over time; and false reports can be suppressed by retrieving verbatim traces of corresponding true events. In the second domain, the same principles have been invoked to explain why some forms of brain damage lead to elevated levels of false memory and other forms lead to reduced levels of false memory. In the third domain, the principles of gist extraction, fuzzy-to-verbatim continua, and fuzzy-processing preferences have been exploited to formulate a general theory of loci of processing failures in judgment and decision making, cluminating in a developmental account of degrees of rationality that distinguishes more and less advanced reasoning. This theory has in turn been used to formulate local models, such as the inclusion illusions model, that explain the characteristic reasoning errors that are observed on specific judgment and decision-making tasks. Finally, in the fourth domain, a dual-process conception of recall has been derived from the principles of parallel verbatim-gist storage and dissociated verbatim-gist retrieval. In this conception, which has been used to explain cognitive triage effects in recall and robust false recall, targets are recalled either by directly accessing their verbatim traces and reading the retrieved information out of consciousness or by reconstructively processing their gist traces.

Aging↗

Methods for proteomics in neuroscience.

Proteomics reveals complex protein expression, function, interactions and localization in different phenotypes of neuron. As proteomics, regarded as a highly complex screening technology, moves from a theoretical approach to practical reality, neuroscientists have to determine the most-appropriate applications for this technology. Even though proteomics compliments genomics, it is in sheer contrast to the basically constant genome due to its dynamic nature. Neuroscientists have to surmount difficulties particular to the research in neuroscience; such as limited sample amounts, heterogeneous cellular compositions in samples and the fact that many proteins of interest are hydrophobic proteins. The necessity of exclusive technology, sophisticated software and skilled manpower tops the challenge. This review examines subcellular organelle isolation, protein fractionation and separation using two-dimensional gel electrophoresis (2-DGE) as well as multi-dimensional liquid chromatography (LC) followed by mass spectrometry (MS). The methods for quantifying relative gene product expression between samples (e.g., two-dimensional difference in gel electrophoresis (2D-DIGE), isotope-coded affinity tag (ICAT) and iTRAQ) are elaborated. An overview of the techniques used currently to assign post-translational modification status on a proteomics scale is also evaluated. The feasible coverage of the proteome, ability to detect unique cell components such as post-synaptic densities and membrane proteins, resource requirements and quantitative as well as qualitative reliability of different approaches is also discussed. While there are many challenges in neuroproteomics, this field promises many returns in the future.

Animals↗