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Neuroscience and the near-death experience: roles for the NMSA-PCP receptor, the sigma receptor and the endopsychosins.

The Near-Death Experience (NDE) is a dissociative mental state with characteristic features. These can be reproduced by ketamine which acts at sigma sites and blocks N-methyl-D-aspartate (NMDA) linked phencyclidine (PCP) receptors to reduce ischaemic damage. Endogenous ligands, alpha and beta-endopsychosin, have been detected for these receptors which suggests an explanation for some NDE's: the endopsychosins may be released in abnormal quantity to protect neurons from ischaemic and other excitotoxic damage, and the NDE is a side effect on consciousness with important psychological functions.

Consciousness↗

The cognitive neuroscience of response inhibition: relevance for genetic research in attention-deficit/hyperactivity disorder.

Psychological functions that are behaviorally and neurally well specified may serve as endophenotypes for attention-deficit/hyperactivity disorder (ADHD) research. Such endophenotypes, which lie between genes and symptoms, may relate more directly to relevant genetic variability than does the clinical ADHD syndrome itself. Here we review evidence in favor of response inhibition as an endophenotype for ADHD research. We show that response inhibition--operationalized by Go/NoGo or Stop-signal tasks--requires the prefrontal cortex (PFC), in particular the right inferior frontal cortex (IFC); that patients with ADHD have significant response inhibition deficits and show altered functional activation and gray matter volumes in right IFC; and that a number of studies indicate that response inhibition performance is heritable. Additionally, we review evidence concerning the role of the basal ganglia in response inhibition, as well as the role of neuromodulatory systems. All things considered, a combined right IFC structure/function/response inhibition phenotype is a particularly good candidate for future heritability and association studies. Moreover, a dissection of response inhibition into more basic components such as rule maintenance, vigilance, and target detection may provide yet better targets for association with genes for neuromodulation and brain development.

Animals↗

The mismatch negativity in cognitive and clinical neuroscience: theoretical and methodological considerations.

Mismatch negativity (MMN) component of the event-related brain potentials has become popular in cognitive and clinical brain research during the recent years. It is an early response to a violation of an auditory rule such as an infrequent change in the physical feature of a repetitive sound. There is a lot of evidence on the association of the MMN parameters and behavioral discrimination ability, although this relationship is not always straight-forward. Since the MMN reflects sound discrimination accuracy, it can be used for probing how well different groups of individuals perceive sound differences, and how training or remediation affects this ability. In the present review, we first introduce some of the essential MMN findings in probing sound discrimination, memory, and their deficits. Thereafter, issues which need to be taken into account in MMN investigations as well as new improved recording paradigms are discussed.

Auditory Perception↗

From electric patterns to drugs: perspectives of computational neuroscience in drug design.

A novel way of computational modeling by integrating compartmental neural techniques and detailed kinetic description of pharmacological modulation of transmitter-receptor interaction is offered as a method to test the electro-physiological and behavioral effects of potential drugs. Even more, an inverse method is suggested as a method for controlling a neural system to realize a prescribed temporal pattern. Generation and pharamcological modulation of theta rhythm in area CA1 of the hippocampus related to anxiety is analyzed. Integrative modeling might help to find positive allosteric modulators of alpha1 subunits as potential candidates for being selective anxyolitics.

Computer-Aided Design↗

The neuroscience of investing: fMRI of the reward system.

Functional magnetic resonance imaging (fMRI) has proven a useful tool for observing neural BOLD signal changes during complex cognitive and emotional tasks. Yet the meaning and applicability of the fMRI data being gathered is still largely unknown. The brain's reward system underlies the fundamental neural processes of goal evaluation, preference formation, positive motivation, and choice behavior. fMRI technology allows researchers to dynamically visualize reward system processes. Experimenters can then correlate reward system BOLD activations with experimental behavior from carefully controlled experiments. In the SPAN lab at Stanford University, directed by Brian Knutson Ph.D., researchers have been using financial tasks during fMRI scanning to correlate emotion, behavior, and cognition with the reward system's fundamental neural activations. One goal of the SPAN lab is the development of predictive models of behavior. In this paper we extrapolate our fMRI results toward understanding and predicting individual behavior in the uncertain and high-risk environment of the financial markets. The financial market price anomalies of "value versus glamour" and "momentum" may be real-world examples of reward system activation biasing collective behavior. On the individual level, the investor's bias of overconfidence may similarly be related to reward system activation. We attempt to understand selected "irrational" investor behaviors and anomalous financial market price patterns through correlations with findings from fMRI research of the reward system.

Behavioral Sciences↗

Neuron theory, the cornerstone of neuroscience, on the centenary of the Nobel Prize award to Santiago Ramón y Cajal.

Exactly 100 years ago, the Nobel Prize for Physiology and Medicine was awarded to Santiago Ramón y Cajal, "in recognition of his meritorious work on the structure of the nervous system". Cajal's great contribution to the history of science is undoubtedly the postulate of neuron theory. The present work makes a historical analysis of the circumstances in which Cajal formulated his theory, considering the authors and works that influenced his postulate, the difficulties he encountered for its dissemination, and the way it finally became established. At the time when Cajal began his neurohistological studies, in 1887, Gerlach's reticular theory (a diffuse protoplasmic network of the grey matter of the nerve centres), also defended by Golgi, prevailed among the scientific community. In the first issue of the Revista Trimestral de Histología Normal y Patológica (May, 1888), Cajal presented the definitive evidence underpinning neuron theory, thanks to staining of the axon of the small, star-shaped cells of the molecular layer of the cerebellum of birds, whose collaterals end up surrounding the Purkinje cell bodies, in the form of baskets or nests. He thus demonstrated once and for all that the relationship between nerve cells was not one of continuity, but rather of contiguity. Neuron theory is one of the principal scientific conquests of the 20th century, and which has withstood, with scarcely any modifications, the passage of more than a 100 years, being reaffirmed by new technologies, as the electron microscopy. Today, no neuroscientific discipline could be understood without recourse to the concept of neuronal individuality and nervous transmission at a synaptic level, as basic units of the nervous system.

Animals↗

The novelty value of the combined use of electroencephalography and transcranial magnetic stimulation for neuroscience research.

Electroencephalographic (EEG) responses measured simultaneously with transcranial magnetic stimulation (TMS) have opened a new window into the human nervous system. The combined use of TMS and EEG (TMS-EEG) provides a means for the detailed study of the reactivity of any cortical region in the intact brain; also the reactivities of non-motor cortical areas related with higher-order functions are now appreciable. A recent epochal finding concerning cortical reactivity is that neuronal activation is induced with remarkably low stimulation intensities. This knowledge is significant when optimizing experimental set-ups for maximal patient safety. Stimulation of different cortical areas evokes different patterns of remote EEG activity, confirming the viability of TMS-EEG for the study of corticocortical connections. In this review, we expand on these and other notable findings related with TMS-EEG. We discuss the possibilities of the technique for the study of cortical reactivity and connectivity. We show that TMS-EEG allows the study of interhemispheric connections with high spatiotemporal specificity and the assessment of cortical reactivity with excellent sensitivity.

Biomedical Research↗

Neuroscience and architecture: seeking common ground.

As these paired Commentaries discuss, neuroscientists and architects are just beginning to collaborate, each bringing what they know about their respective fields to the task of improving the environment of research buildings and laboratories.

Architecture↗

Intracellular applications of fluorescence correlation spectroscopy: prospects for neuroscience.

Based on time-averaging fluctuation analysis of small fluorescent molecular ensembles in equilibrium, fluorescence correlation spectroscopy has recently been applied to investigate processes in the intracellular milieu. The exquisite sensitivity of fluorescence correlation spectroscopy provides access to a multitude of measurement parameters (rates of diffusion, local concentration, states of aggregation and molecular interactions) in real time with fast temporal and high spatial resolution. The introduction of dual-color cross-correlation, imaging, two-photon excitation, and coincidence analysis coupled with fluorescence correlation spectroscopy has expanded the utility of the technique to encompass a wide range of promising applications in living cells that may provide unprecedented insight into understanding the molecular mechanisms of intracellular neurobiological processes.

Animals↗

Manipulating proteins for neuroscience.

The design and manipulation of proteins has created many tools that have become popular in neurobiological studies, and new developments in protein science will be the fuel for future research. Genetically encoded protein-based biosensors have been developed with a wider range of sensing moieties, enabling detection of changes in localized protein synthesis, voltage, glutamate and/or glucose levels. Existing sensors, such as cameleon, have been modified and improved. Heterologous expression of Channelrhodopsin-2 and other light-gated methods for controlling cellular polarization enable action potentials to be non-invasively evoked, facilitating the study and modulation of behavior in intact animals. Finally, new methods in protein manipulation, including the site-specific incorporation of unnatural amino acids in vivo and the directed evolution of proteins, show promise in elucidating neural function with greater precision and flexibility.

Amino Acids↗

Auditory neuroscience: activating the cortex without sound.

Sensory brain areas are usually characterized by their responses to external stimuli; however, neuroimaging studies have now shown that activation of auditory cortex occurs spontaneously and can be induced during silence by stimulus expectancy or mental imagery.

Acoustic Stimulation↗

Form and function in systems neuroscience.

'Form follows function' is an architectural philosophy attributed to the great American architect Louis Sullivan, and later taken up by the Bauhaus movement. It stresses that the form of a building should reflect its function. Neuroscientists have used the converse of this dictum to learn the functions of neural circuits, believing that if we study neural architecture, it will lead us to an understanding of how neural systems function. New tools for studying the structure of neural circuits are being developed, so it is important to discuss what the old techniques have taught us about how to derive function from the form of a neural circuit.

Animals↗

A breakthrough in neuroscience needs a "Nebulous Cartesian System" Oscillations, quantum dynamics and chaos in the brain and vegetative system.

The Cartesian System is a fundamental conceptual and analytical framework related and interwoven with the concept and applications of Newtonian Dynamics. In order to analyze quantum processes physicist moved to a Probabilistic Cartesian System in which the causality principle became a probabilistic one. This means the trajectories of particles (obeying quantum rules) can be described only with the concept of cloudy wave packets. The approach to the brain-body-mind problem requires more than the prerequisite of modern physics and quantum dynamics. In the analysis of the brain-body-mind construct we have to include uncertain causalities and consequently multiple uncertain causalities. These multiple causalities originate from (1) nonlinear properties of the vegetative system (e.g. irregularities in biochemical transmitters, cardiac output, turbulences in the vascular system, respiratory apnea, nonlinear oscillatory interactions in peristalsis); (2) nonlinear behavior of the neuronal electricity (e.g. chaotic behavior measured by EEG), (3) genetic modulations, and (4) additional to these physiological entities nonlinear properties of physical processes in the body. The brain shows deterministic chaos with a correlation dimension of approx. D(2)=6, the smooth muscles approx. D(2)=3. According to these facts we propose a hyper-probabilistic approach or a hyper-probabilistic Cartesian System to describe and analyze the processes in the brain-body-mind system. If we add aspects as our sentiments, emotions and creativity to this construct, better said to this already hyper-probabilistic construct, this "New Cartesian System" is more than hyper-probabilistic, it is a nebulous system, we can predict the future only in a nebulous way; however, despite this chain of reasoning we can still provide predictions on brain-body-mind incorporations. We tentatively assume that the processes or mechanisms of the brain-body-mind system can be analyzed and predicted similar to the metaphor of "finding the walking path in a cloudy or foggy day". This is meant by stating "The Nebulous Cartesian System" (NCS). Descartes, at his time undertaking his genius step, did not possess the knowledge of today's physiology and modern physics; we think that the time has come to consider such a New Cartesian System. To deal with this, we propose the utilization of the Heisenberg S-Matrix and a modified version of the Feynman Diagrams which we call "Brain Feynman Diagrams". Another metaphor to consider within the oscillatory approach of the NCS is the "string theory". We also emphasize that fundamental steps should be undertaken in order to create the own dynamical framework of the brain-body-mind incorporation; suggestions or metaphors from physics and mathematics are useful; however, the grammar of the brains intrinsic language must be understood with the help of a new biologically founded, adaptive-probabilistic Cartesian system. This new Cartesian System will undergo mutations and transcend to the philosophy of Henri Bergson in parallel to the Evolution theory of Charles Darwin to open gateways for approaching the brain-body-mind problem.

Brain↗