Human Brain Software

Memory Improvement E-book

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Memory Improvement Ebook Summary


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Preface to the First Edition

The human brain is said to be the most complex object in our known universe, and the billions of cells and trillions of connections are truly wonders of enormous proportions. The study of the way that the cellular elements of the nervous system work to produce sensations, behaviours, and higher order mental processes has become a most productive area of science. However, neuroscientists have come to realize that they are studying a moving target growth and change are integral to brain function and form the very basis by which we can learn anything about it. As the behavioral embryologist George Coghill pointed out, Man is, indeed, a mechanism, but he is a mechanism which, within his limitations of life, sensitivity and growth, is creating and operating himself. To understand the brain, then, we need to understand how this mechanism arises and the ways in which it can change throughout a lifetime.

Preface to the Second Edition

The human brain perhaps the most complex object in our universe is composed of billions of cells and trillions of connections. It is truly a wonder of enormous proportions. Although we are far from a thorough understanding of our brains, study of the way that the cellular constituents of the nervous system, the neurons and glia, work to produce sensations, behaviors, and higher order mental processes has been a most productive area of science. However, more and more, neuroscientists are realizing that we are studying a moving target-growth and that changes are integral to brain function, forming the very basis for learning, perception, and performance. To comprehend brain function, then, we must understand how the circuits arise and the ways in which they are modified during maturation. Santiago Ram n y Cajal, one of the founders of modern neuroscience, was able to make his remarkable progress in studies of the cellular makeup of the nervous system in large part because of his work...

Development And Evolution Of Neurons

Almost as early as multicellular animals evolved, neurons have been part of their tissues. Metazoan nervous systems range in complexity from the simple nerve net of the jellyfish to the billions of specifically interconnected neuron assemblies of the human brain. Nevertheless, the neurons and nervous systems of all multicellular animals share many common features. Voltage-gated ion channels are responsible for action potentials in the neurons of hydras, as they are in people. Synaptic transmission between neurons in nerve nets is basically the same as that in the cerebral cortex in humans (Figure 1.1). This book describes the mechanisms responsible for the generation of these nervous systems, highlighting examples from a variety of organisms. Despite the great diversity in the nervous systems of various organisms, underlying principles of neural development have been maintained throughout evolution.

Norepinephrine transporter polymorphisms

At least 13 polymorphisms of NET have been identified,20 the functional significance of which is unknown. Alterations in the concentration of NE in the CNS have been hypothesized to cause, or contribute to, the development of psychiatric illnesses such as major depression and BPAD. Many studies have reported altered levels of NE and its metabolites NMN and dihydroxyphenylglycol (DHPG) in the CSF, plasma, and urine of depressed patients as compared with normal controls. These variances could reflect different underlying phenotypes of depressive disorders with varying effects on NE activity. The melancholic subtype of depression (with positive vegetative features, agitation, and increased hypothalamic-pituitary-adrenal (HPA) axis activity) is most often associated with increased NE. Alternatively, so-called atypical depression is associated with decreased NE and HPA axis hypoactivation. In one study, urinary NE and its metabolites were found to be significantly higher in unipolar and...

Patterning The Cerebral Cortex

The cerebral cortex, the largest region of the human brain by far, is not a homogeneous structure, but rather has many distinct regions, each of which has a dedicated function. It has been known for over one hundred years that there are significant variations in the cellular structure (cytoarchitecture) of the cortex from region to region. The different regions of the cerebral cortex were exhaustively classified into approximately 50 distinct areas by Brodmann (1909). Although all neocortical areas have six layers, the relative number of cells in each layer and the size of the cells are quite variable and specialized to the specific function of that area. For example, the visual cortex, a primary sensory area, has many cells in layer IV, the input layer, whereas the motor cortex has very large neurons in layer V, the output layer.

Tissue distribution and ontogenic development

Limited information is available on the ontogenic development of XOR and AOX, except that both enzymes are expressed in fetal tissues at levels similar to those found in adults. Regarding tissue distribution, most studies on XOR have been conducted in experimental animals rather than humans. In rodents the highest expression levels of mRNA and protein of XOR are observed in the liver, lung, kidney, and in the epithelial lining of the duodenum on the proximal side of the small intestine, decreasing steadily towards the distal portion of the small intestine. Similar expression patterns in the intestine have also been reported in humans. The mouse lung also expresses XOR, in contrast to human lung, where the enzyme is barely detectable. Other studies have also reported expression of XOR in the human brain and heart. Intracellularly, XOR is almost always localized exclusively to the cytoplasm. Interestingly, intact XOR is found in milk and other body fluids, including blood.

Genesis and Migration

The human brain is made up of an enormous number of neurons and glial cells. The sources of all these neurons and glia are the cells of the neural tube, described in the previous chapters. Neurogenesis and gliogenesis, the generation of neurons and glia during development, occurs in many different ways in the various regions of the embryo. Part of the complex process of making the brain includes the proper migration of neurons and glia from their site of origin to their final position in the adult brain. Precisely orchestrated cell movements or migrations are an integral part of what is collectively known as histogenesis in the brain. This chapter describes the cellular and molecular principles by which the appropriate numbers of neurons and glia are generated from the neural precursors, and gives an overview of some of the complex cellular migration processes involved in the construction of the brain.

Important biological features

Female Rat Clitorid Gland

Today's laboratory rats are the domesticated descendants of Rattus norvegicus. Albino animals were held and used for rat shows, and frequent handling is thought to have tamed these animals. By the 1800s these animals were used for breeding and neuroanatomy studies in the United States and Europe. It was in the late 1800s and early 1900s that individual stocks and strains had their beginnings.

Knowledge Links Connect Pairs of Cooccurring Symbols

Tesla Car Power Systems

Billions of pairs of symbols are connected via knowledge links. The set of all knowledge links joining symbols belonging to one specific source module to symbols belonging to one specific target module is termed a knowledge base. In the human brain, knowledge bases take the form of huge bundles of axons termed fascicles, which together make up a large portion of each cerebral hemisphere's ipsilateral white matter. Each module also typically has a knowledge base to its contralateral twin module (and perhaps to a few others near its twin) - which together constitute the corpus callosum fascicle linking the two cerebral hemispheres. Here, reciprocal knowledge links (red arrows), only some of which are shown, connect each expressed symbol representing an attribute of an apple pairwise with other such symbols. When an apple is currently present in the mental world, it is its collection of knowledge-link-connected symbols which are currently being expressed. There is no binding...

Interleukin1 and neurodegeneration

In vitro by gp120 led to the induction of IL-1P and the activation of caspase-1 and COX-2 expression, culminating in neuronal death. Using recombinant IL-1P in primary cultures of human neurons and glia, we and others have found that IL-1 is toxic to neurons 68,69 . The IL-1-induced neurotoxicity was enhanced by the Th1 cytokine IFN but reduced by inhibitors of TNFa or nitric oxide (NO) synthase. These studies support the idea that NO alone is a weak neurotoxin and that the conditions in which both NO and a proinflammatory cytokine (TNFa) are coex-pressed lead to significant damage to the CNS 70 . Importantly, these studies have delineated striking species differences in the cytokine-induced neurotoxicity cascade. Whereas LPS, IL-1, or TNFa can all trigger neurotoxicity in rodent cultures, the induction of neurotoxicity in human brain cell cultures appears to be dependent on the presence of IL-1 68,69,71,72 . Furthermore, IL-1-activated astrocytes are an important mediator of...

Apolipoprotein E Immunolocalization

Intraneuronal localization of apoE has also been reported in several studies that examined human brain specimens. The occurrence of apoE in cortical and hippocampal neurons without neurofibrillary changes was demonstrated in brains of nondemented elderly indi-viduals.84,85 As seen in primates, numerous apoE-immunoreactive neurons were found in the CA1-2 subfields of the hippocampal formation, whereas the granule cell layer did not stain.84 ApoE ICC also revealed staining of hippocampal glial cells (astrocytes and ependy-mal cells), although the intensity varied widely between cases.84 In the frontal cortex, apoE immunoreactivity was intense in some neuronal cell bodies and their processes.85 Most of these cells have been identified as small pyramidal neurons in layer III and some as large

Cognitive Brain Hardware and Software

In effect, the human brain thinks by maneuvering subsets of 4,000 digital processors (the thalamocortical modules) through smooth, graceful, thought maneuvers. These thought processes are learned, stored, and recalled just as movement processes are learned, stored, and recalled. At higher hierarchical levels, closely related movement processes and thought processes are often stored mixed together in the same knowledge links.

Neuronal Implementation of Knowledge Links

In summary, Model A shows that human cortical implementation of billions of knowledge links by two-stage synfire chains (Abeles 1991) may be possible. This crude model now needs to be followed up by more detailed models that take detailed neuroanatomy and neuronal behavior into account.

The scale of the problem

How many neurons must be included in a realistic network model is far from clear. The human brain is commonly estimated to contain about 2 x 1010 neurons, but a rat gets by with perhaps 107 neurons the major source of this discrepancy is of course in the size of the neocortex. The neocortex, however, is one of the parts of the brain about which we understand least, substantially because the functions that we think it is principally involved in are, in general, not very amenable to reductionist experimental testing at the single cell level. In the rat brain, prob

John Tooby and Leda Cosmides

The human brain is a biological system produced by the evolutionary process, and thus, cognitive neuroscience is itself a branch of evolutionary biology. Accordingly, cognitive neuro-scientists can benefit by learning about and applying the technical advances made in modern evolutionary biology. Among other things, evolutionary biology can supply researchers with (2) a growing list of the specialized functions the human brain evolved to perform, and (3) the ability to distinguish the narrowly functional aspects of the neural and cognitive architecture that are responsible for its organization from the much larger set of properties that are byproducts or noise. With these and other tools, researchers can construct experimental stimuli and tasks that activate and are meaningful to functionally dedicated subunits of the brain. The brain is comprised of many such subunits evolutionarily meaningful stimuli and tasks are far more likely than arbitrary ones to elicit responses that can...

Seeing with New Eyes Toward an Evolutionarily Informed Cognitive Neuroscience

The task of cognitive neuroscience is to map the information-processing structure of the human mind and to discover how this computational organization is implemented in the physical organization of the brain. The central impediment to progress is obvious The human brain is, by many orders of magnitude, the most complex system that humans have yet investigated. Purely as a physical system, the vast intricacy of

Naturally Occurring Neuron Death

Nervous system differentiation is accompanied by tremendous growth neuron cell bodies and dendrites expand, glial cells and myelin are added, blood vessels arborize, and extracellular matrix is secreted. Even after the period of neurogenesis has largely ended, the human brain continues to increase in size from approximately 400 grams at birth to 1400 grams in adulthood (Dekaban and Sadowsky, 1978). Surprisingly, neuro-genesis and this later period of growth overlap with a tremendous loss of neurons and glia, both of which die from natural causes. Depending on the brain region, 20 to 80 of differentiated cells degenerate during development (Oppenheim, 1991 Oppenheim and Johnson, 2003).

Vascular Adhesion Molecules In The

In both the acute and chronic relapsing forms of EAE an increase in leucocyte infiltration is associated with an upregulation of ICAM-1 on CNS vessels.2677-79 This adhesion molecule is reported to be present on most microvessels isolated from MS brain80 and on a third of blood vessels in active MS plaques.81 Blood vessels expressing ICAM-1 may not necessarily indicate sites of lymphocyte extravasation since ICAM-1-positive cerebral vessels appear in normal human brain,81 and in the active clinical disease of EAE the molecule is expressed on several vessels in uninvolved CNS tissue.26 By inference, other factors are required to support lymphocyte extravasation and hence disease progression. Human cerebral blood vessels normally express very little VCAM-1, but in MS high levels appear within lesions,80 especially in older, active plaques where there is concomitant expression of VLA-4 on nearby lymphocytes.82 The expression of ICAM-1 and VCAM-1 on nonendo-thelial cells of CNS blood...

Neuronal Implementation of Confabulation

Model 5 is successfully able to deal with starting mixtures of hundreds of partially excited symbols, and its inhibitory elements fit within the confines of known cortical neuroanatomy and neurophysiology (e.g., the gap junctions used in the model are known to exist). However, Model 5's convergence speed is still far too slow.

The Subventricular Zone

Medial Ganglionic Eminence Sagittal

The SVZ was first recognized by Schaper and Cohen (1905) by the presence of mitotic figures in a location distant from the lateral ventricles. It was first shown definitively to have proliferating cells using 3H-thymidine label in vitro using slabs of human brain (Rakic and Sidman, 1968). The proliferating cells of the SVZ differ in two major ways from those of the VZ (Fig. 4). First, the nuclei of proliferating cells of the SVZ do not move during the cell cycle, but reflecting the fact that cells of the SVZ, in contrast to those of the VZ, are not attached to each other as a pseudostratified epithelium, this population does not undergo interkinetic nuclear migration in the course of the cell cycle (Boulder Committee, 1970 Smart, 1972 Altman and Bayer, 1990). Second, the cell bodies of the SVZ cells do not have long

Introduction Brain Science and Information Technology Do They Add Up

It is, then, understandable that throughout the 1990s, while some scientists tried to straddle the disciplines, there was little systematic dialogue between researchers in IT and brain scientists. The Foresight Cognitive Systems Project was perhaps the first sustained initiative to bring the two fields together to see if they have anything productive to say to one another. Cognitive systems - natural and artificial - sense, act, think, feel, communicate, learn and evolve. We see these capabilities in many forms in living organisms. The natural world shows us how systems as different as a colony of ants or a human brain achieve sophisticated adaptive

Generation of Control Commands by a Cognitive

With gradual learning and self-adaptation 5 , the cognitive memory in human brain builds up a control model for muscle movements and determines the valuation space of the control signals for the execution of a task. For The human brain receives composite signals from different receptors, which in turn generates control commands for actuating the motor nerves and muscles. Let the control commands generated by brain or spinal chord be Xj for j 1 to n, while the driving signal for the actuators is yi for i 1 to m, where

Cerebral Cortex and Thalamus The Seat of Cognition

North Plan For Photoshop

The two main human neuroanatomical structures postulated by confabulation theory to be involved in the implementation of thought are thalamocortical modules (Fig. 1.1) and knowledge bases (Fig. 1.2). These structures, which constitute the information-processing hardware used to carry out thought, exist within the cerebral cortex and thalamus. The human brain possesses roughly 4,000 thalamocortical modules and roughly 40,000 knowledge bases2. All vertebrates (and even invertebrates such as bees and octopi) are postulated to possess functionally analogous structures, albeit in smaller quantities. Fig. 1.1. A thalamocortical module (one of roughly 4,000 in the human brain). Each thalamocortical module is comprised of a small patch of cerebral cortex and a uniquely paired small zone of thalamus. The cortical patch of each module is reciprocally axonally connected with the thalamic zone of the module. The cortical patches of different modules are largely disjoint (partial overlaps do...

Implications of Confabulation Theory

With one relatively small exception, the axonal connectivity between the tha-lamocortical modules in the human brain seems to roughly resemble that of other great apes. That one exception is the modules of the human language faculty - which seem to connect widely to modules in many other faculties. In this sense, language is the hub of human cognition. It seems likely that this (along with having a brain which is, overall, over three times larger) can explain some of the commanding power of human thought in comparison with that of other apes. As we learn more about cetaceans, it may well be that some of them (and perhaps other species as well, such as jays, ravens, and parrots) also have this language hub cognitive architecture characteristic to some degree. A large-scale human brain modeling project of this sort will surely require a widely knowledgeable and exceptionally well educated team of hundreds of mathematical neurobiologists and computer scientists operating as willing and...

Modularity and Connectivity

Each hemisphere has four major lobes frontal, temporal, parietal, and occipital (see Figure 1.1). Because most knowledge is stored in the cerebral cortex, it is important to have a large cortex. One way of increasing the relative size of the cortex without increasing the overall size of the brain is to have convolutions, and the human brain is more convoluted than the brain of any other organism. A convoluted brain has mountains called gyri, valleys called sulci, and gorges called fissures. Some of the major gyri of the brain that we will be discussing are diagrammed in Figure 3.5.

Tgfp Expression In Cns Wounds

To the damaged neuropil posthaemorrhage, both via the CSF as well as by local synthesis within the wound. In accordance with the observations in rodent experimental models, TGF-P 1 levels have also been investigated in a preliminary study of the cerebrospinal fluid of humans with severe traumatic brain injury 54 levels are dramatically raised, with the highest values observed in the first few days postinjury. TGF-P1 levels also rise in human brain tissue damaged by hypoxic ischaemic insults,55 suggesting a neuroprotective role as well as stimulating angiogenesis and scarring.

Three Dimensional Finite Element Models

Later, Ward et al. (1978) proposed two brain models representing the baboon and the small primate (rhesus or cynomolgus monkey) brains in addition to the early human brain model (Ward and Thompson, 1975). The models included the internal folds of the falx and tentorium. Each model was subjected to the same skull acceleration in an attempt to establish response relationships between species. Model responses were compared with experimentally derived head injury data and correlated well with test results. It showed that the location and magnitude of the maximum stresses were different in humans and animals. This finding led to a conclusion that scaling the response between specimens is inadvisable. Also, the viscoelastic response of the human brain to impact has been investigated by Ruan et al. (1993a) using a 3-D finite element human head model. The model was developed based on their previous model (Ruan et al., 1992, 1994) by the addition of the scalp, dura mater, and falx partition....

Summary of the Theory

All of cognition is built from the above-discussed elements modules, knowledge bases, and the action commands associated with the individual symbols of each module. The following sections of this chapter discuss more details of how these elements are implemented in the human brain. See Chaps. 3 and 5 for some citations of past research that influenced this theory's development.

Clusterin Expression and Localization in the Brain

After its identification in bovine neural tissue1 clusterin was identified in the CNS as a mRNA species with increased abundance in AD hippocampus7,8 and scrapie-infected hamster brain.9 Clusterin mRNA has a similar regional distribution in normal rat and human brain, being widely found in astrocytes throughout the brain, with regional selectivity for neurons.10 Immunohistological localization of clusterin reveals similar selectivity for neurons but few clusterin-positive astrocytes in normal embryonic and postnatal rodent brains.11,12 Three different clusterin immunostaining patterns exist diffuse, cytoplasmic punctate, and granules without visible cell membranes.11 Unlike apoE, clusterin (apoJ) does not appear to be made by microglia.13 In vitro studies using primary neurons or astrocytes

Response of the Brain to Sagittal Angular Acceleration

Shear deformation of the brain due to head rotation has long been postulated as a major cause of brain injury because of the very low shear stiffness of brain tissue (Holbourn, 1943). Animal, physical, and finite element models have been used to investigate brain response due to rotational impacts. But three-dimensional finite element simulations of rotational impacts are rare, and little information on the distribution of shear stress strain of the human brain due to rotational impact is available. In this section, the brain injury model version 95 was exercised to investigate elastic and viscoelastic responses of the brain to an impulsive sagittal plane rotation of the head. An angular acceleration pulse taken from Abel's monkey test data (1978) was scaled to provide input for the human brain. The scaling method used maintained an approximately equal shear strain level in the brain and equal displacement of the head.

Drug Induced Changes in Calcium Channel Function

Building upon previous findings, David Dooley and colleagues (Pfizer Ann Arbor) showed that gabapentin reduces calcium influx and neurotransmitter release from rat and human brain tissues.72-78 Alexander McKnight and YP Maneuf (Parke-Davis Cambridge) found that gabapentin reduced glutamate release in a manner suggesting relevance for analgesia.79,80 Electrophysiologists in Cambridge and at Aberdeen University in the UK demonstrated changes in calcium channel and synaptic function that were presumed to be caused by gabapentin action at the a2-S site.81-85 These findings together with SAR described in Sections provided a strong circumstantial argument that binding at to the a2-S site was important to the pharmacology of gabapentin and pregabalin.

Cytotoxic Edema in Status Epilepticus

Cytotoxic Edema

The parts of the human brain that are most vulnerable include parts of the hippocampus (the CA1and CA3 segments, and the hilus), amygdala, pyriform cortex, thalamus, cerebellum, and cerebral cortex. NMDA receptors are predominantly located in the CA1 of the hippocampus and layers 3 and 4 in the cerebral cortex 32,33 . The Purkinje cell loss of the cerebellum, seen in severe epilepsy, may be explained by an increased demand for inhibition, re-suiting in GABA depletion and subsequent influx of calcium into neurons 34 . Unilateral hemispheric involvement is occasionally seen in status epilepticus.

Substantia Nigra Neurons

Leslie Iversen

The rat and human brain contain approximately the same concentrations of dopamine in the substantia nigra, in the order of 0.40 (ig g of wet tissue (Sourkes and Poirier, 1965 Hornykiewicz, 1972 Cuello and Iversen, 1978). At the time we developed a highly sensitive radioenzymatic technique (Cuello et al., 1973) which permitted us to determine monoamine concentrations in minute, separate, microdissected regions of the rat substantia nigra. We observed relatively high concentrations (1.52 Hg gi of dopamine in the SN pars compacta where the dopaminergic elements are densely concentrated in cell bodies and short dendrites, while smaller amounts (0.28 Hg g,) were found in the pars reticulata where the long-branched dopaminergic dendrites are present (Cuello and Iversen, 1978). As the weight of the pars reticulata is almost 3 times that of the compacta, it can be concluded that the pars reticulata contributes significantly to the total dopamine content of the substantia nigra.

Blood Brain Partitioning

Subsequent unpublished work has extended the range of applicability of the BB model. To deal with the nonlinear nature of the property-structure relation, an ANN model was developed for 103 compounds, and tested by the prediction of an external validation test set.33 Figure 7 shows the predictions for this external test set. One significant aspect of the new validation test set is that it consists of data on human brain and human cerebrospinal fluid (CSF) as well as data on rat and monkey. Data in the training set are entirely based on rat brain, but the external validation test set includes human brain data as well as CSF data in addition to monkey brain. The validation test results are statistically satisfactory, rpress 0.62 and MAE 0.39, even though the experimental nature of the test data arises from different sources than the training set. To provide a different view of the predictions, the data were divided into three bins, corresponding to low, medium, and high partitioning....

Brains Are Composed Primarily of Adaptive Problem Solving Devices

Adapted to the past The human brain, to the extent that it is organized to do anything functional at all, is organized to construct information, make decisions, and generate behavior that would have tended to promote inclusive fitness in the ancestral environments and behavioral contexts of Pleistocene hunter-gatherers and before. (The preagricultural world of hunter-gatherers is the appropriate ancestral context because natural selection operates far too slowly to have built complex information-processing adaptations to the post-hunter-gatherer world of the last few thousand years.) 6. Ruling out and ruling in Evolutionary biology gives specific and rigorous content to the concept of function, imposing strict rules on its use (Williams, 1966 Dawkins, 1982, 1986). This allows one to rule out certain hypotheses about the proposed function of a given cognitive mechanism. But the problem is not just that cognitive neuroscientists sometimes impute functions that they ought not to. An even...

Two Dimensional Finite Element Models

Several two-dimensional finite element models have been reported to simulate the human brain, animal brain, and physical surrogates. The model geometry ranged from midsagittal to coronal sections of the human and animal brains. Both elastic and viscoelastic materials have been considered to simulate the brain tissues. The loading conditions included direct and indirect or rotational impacts. Brain pressures and strains have been used as parameters for injury-potential assessment. Ueno et al. (1989) used a 2-D finite element model of a human brain based on a photograph of a sagittal section of the brain in conjunction with Lee et al.'s rhesus monkey model to scale experimental animal data (Abel et al., 1978) to the human level by a scaling law based on the mass of two models. Ueno et al. (1991) developed a 2-D ferret brain model subjected to a direct impact to the brain at a controlled velocity and stroke. A fairly good agreement between simulated and experimental pressure-time...

Transport Across the Cell Membrane

These mediate uptake of iodothyronines and their sulphonated derivatives and they are members of the Na+ taurocholate cotransporting polypeptide (NTCP) and the Na+-independent organic anion transporting polypeptide (OATP) families 23, 24 . NTCP is only expressed on hepatocytes and is the major transporter of conjugated bile acids in the liver. The OATPs are a large family responsible for transmembrane transport of a number of compounds including TH. The most interesting OATP superfamily members in terms of TH transport are OATP1C1 and OATP14. The former has been demonstrated to be widely expressed both in human brain and the Leydig cells of testis 25 . In the brain they seem to participate in maintaining the T3 concentration along with parallel changes in D2 expression. It has been demonstrated that the thyroid state modulates OATP1C1, and by doing so counteracts the effects of alterations in circulating T4 levels on brain T4 uptake 26, 27 . In humans, OATP1C1 is also expressed in the...

Clusterin Immunoreactivity and Its Colocalization with Clusterin mRNA

In contrast to aged rats, either light staining of some temporal cortex neurons and the neuropil or no clusterin immunoreactivity at all was observed in the hippocampus, as well as in several cortical regions of the brain, in elderly humans, using a monoclonal antibody against human clusterin.19,44,45 It should be specified that in these studies, the antibody strongly stained brain tissues of Alzheimer's disease patients. Unfortunately, data regarding clusterin's distribution in other regions of the normal human brain are lacking and therefore comparison with the rat brain is not possible.

Series Preface

Each volume in the series consists of a few substantial chapters on a particular topic. In some cases, the topics will be ones of traditional interest for which there is a substantial body of data and theory, such as auditory neuroanatomy (Vol. 1) and neurophysiology (Vol. 2). Other volumes in the series deal with topics that have begun to mature more recently, such as development, plasticity, and computational models of neural processing. In many cases, the series editors are joined by a co-editor having special expertise in the topic of the volume.

In the Beginning

The set of all knowledge links connecting the symbols of one module with the symbols of a second module are collectively termed a knowledge base or cortical knowledge fascicle. In humans, the set of all cortical knowledge fascicles is, by far, the most massive single brain structure. The capacity for accumulating a vast number of knowledge links is the single most important attribute of the human brain (at an average rate, for most people, exceeding one new knowledge link per second of life) followed by the large symbol capacities of human modules.


There are several people who deserve my special thanks. The first is Eric Clarke who goaded me into action in 1992 and who has been a constant source of encouragement and practical help. The second is Dr Gordon Wright MA, MD, Fellow of Clare College, Cambridge, who in 1970-1971 taught me neuroanatomy with great wit and style, and who responded to my request for constructive criticism of an earlier version of the text. Of course, I bear sole responsibility for errors. I look forward to receiving constructive criticism from others. And finally, I thank Pauline Graham and her colleagues at Cambridge University Press.


The future trends in the development of drugs for the treatment affective disorders have followed the high degree of anatomical overlap in the distribution and coexistence of monoamine and neuropeptide neurons in limbic regions of the human brain. The intimacy of the relationship between monoamines and neuropeptides suggests a common downstream effect on neural systems that mediate stress. The relationship between stress-related interactions among glutamate, CRF, galanin, NPY, SP, and vasopressin V1B and monoamines in the brain is well documented. However, the role of neuropeptides in depression is still in its infancy and it is premature to speculate on whether and how these systems might exert common downstream effects on brain pathways that mediate stress and emotion. Thus, although SP, CRF, vasopressin, NPY, MCH, and galanin demonstrate important functional interactions with monoamines implicated in the etiology and treatment of stress-related disorders, their effects almost...


Structural and functional neuroimaging studies have been used to investigate the human neuroanatomy and neurocircuitry of specific anxiety disorders.11'15 Structural neuroimaging techniques include morphometric magnetic resonance imaging (mMRI), which allows for accurate assessment of brain structure volumes, and magnetic resonance diffusion tensor imaging, which allows for determination of white matter tract orientations. Functional imaging techniques focus on acquisition of data that reflect regional brain activity. These include positron emission tomography (PET) with tracers that measure blood flow (15O-carbon dioxide or water) or glucose metabolism (18F-fluorodeoxyglucose), single photon emission computed tomography (SPECT) with tracers that measure correlates of blood flow, and functional magnetic resonance imaging (fMRI), which measures blood oxygenation level-dependent (BOLD) signal changes. Functional imaging studies can be performed using several paradigms.11 Neutral state...

Brain Slices

More recently, improvements in techniques for isolation and maintenance of brain slices with well-preserved extracellular space,52 together with new imaging techniques (such as 2-photon confocal microscopy) allowing examination of structures within the slice, have allowed studies of cell-cell interaction within the neurovascular unit, including influences of astrocytes on blood vessels.6 However, as the vessels within the slice are unperfused, these preparations are not suitable for examining BBB permeability and transport. For studies of gene and protein expression, the powerful technique of laser capture microdissection (LCM) can be used not only to sample from individual blood vessels in defined regions of brain slices, but also to separate relatively cleanly the endothelial and perivascular cells.53 This tool has significant applications in determining changes in phenotype of blood vessels in pathological human brain material (resectioned, biopsy, or post-mortem), to guide drug...

Primary Cultures

It is important to characterize the culture produced to demonstrate that important features of the in vivo BBB relevant to the study planned are expressed. A number of suitable biomarkers are available, to assess endothelial phenotype (e.g., von Willebrand factor, platelet endothelial adhesion molecule PECAM-1, alkaline phosphatase),79-82 presence of tight junction proteins (e.g., occludin, claudins, zonula occludens protein-1 (ZO-1)) and apical-basal transport polarity (e.g., apical transferrin receptor, basolateral Na+, K+-ATPase).83 The best established primary cultures of brain microvessel endothelial cells have been generated and characterized from bovine,61 porcine,59 rat,76,77 mouse,81 and human brain,84 and methods have also been reported for ovine, goat, and monkey brain.

Associative Memory

The models of associative memory pioneered by Kosko 14 is a by-product of his research in fuzzy systems. Associative memory to some eXtent has resemblance with the human brain, where from one set of given input output pattern, the brain can determine analogously the output (input) pattern when the input (output) pattern is known. In Kosko's model, he assumed the fuzzy membership distribution of the output patterns for a given input pattern and

The Neuron

A huge number of neuronal cells form the nervous system that regulates all aspects of body functions. The human brain contains about 1012 neurons (nerve cells) with each neuron forming thousands of connections to other neurons so that a large network of electrical connections with massively parallel information processing characteristics results. The nervous system also contains glial cells that occupy the spaces between neurons and modulate their function. They surround the soma and axons of the neurons and are metabolically coupled to the neurons. The output of a nervous system is the result of its inputs and its circuit properties, that is, of the wiring or interconnections (synapses) between the single neurons, and of the strength of these interconnections. The synaptic connections between neurons can be reorganized, which is known as synaptic plasticity, and is believed to be the mechanism of learning in our brain. Basically, three different types of neurons can be distinguished...

Cognitive Maps

The hippocampus region 2 of the human brain contains a specialized structure, responsible for reasoning, recognition and control of the cognitive activities in the biological brain. This structure is usually called the cognitive map. The biological cognitive map stores spatial, temporal, incidental and factual relationship among events. The cognitive maps are generally represented by graphs, where the nodes denote the events and the directed arcs denote the causal dependence of the events. The graph may include cycles as well. Generally, a token representing the belief of the fact is assigned at the corresponding node, describing the fact. The directed arcs in a cognitive map are weighted. The weight associated with an arc in a cognitive map represents the degree by which the effect node is influenced for a unit change in the causal node . Sometimes, a plus (+) or a minus (-) sign 15 is attached with a directed arc to describe whether the cause has a growing or decreasing effect on...

Harris A Gelbard

(Petito et al., 1995) noted the presence of apoptotic astrocytes in 2 7 brains of patients with HIVE. This finding was only observed with a DNA poly-merase technique, not the TUNEL technique. Interestingly, only one in vitro study has demonstrated apoptosis of astrocytes after HIV-1 infection of primary human brain cultures.25


SCF and c-kit are expressed throughout the CNS of developing rodents, and the pattern of expression suggests a role in growth, migration, and differentiation of neuroectodermal cells. Expression of both receptor and ligand have also been reported in the adult brain (Hamel and Westphal, 1997). Expression of c-kit has also been observed in normal human brain tissue (Tada et al., 1994). Glioblastoma and astrocytoma, which define the majority of intracranial tumors, arise from neoplastic transformation of astrocytes (Levin et al., 1997). Expression of c-kit has been observed in glioblastoma cell lines and tissues (Berdel et al., 1992 Tada et al., 1994 Stanulla et al., 1995). However, exogenous addition of SCF to glioblastoma cell lines appears to be mitogenic in only a minority of cases (Berdel et al., 1992 Stanulla et al., 1995), and antibodies that block the interaction of SCF with c-kit did not inhibit the proliferation of cells with an autocrine loop (Stanulla et al., 1995). The...

Singing In The Brain

One of the most striking correlations between sexual behavior and brain anatomy is found among several species of songbirds. Male birds attract a mate of the same species with vocalizations, or songs, that are commonly learned during juvenile development (see below). Zebra finches learn one song during the first 80 days after hatching, while canaries add new phrases to their song each breeding season. When scientists first looked at the brains of these animals, they were startled to find brain regions of remarkably different size in each sex (Nottebohm and Arnold, 1976). The sexual dimorphism occurs in brain nuclei that are known to participate in song production (RA, HVc),

T1t2 R1R2 M1M21379

In this study, the scaling was done according to the above equations, assuming that R 68 mm for the human brain and R 26 mm for the rhesus monkey brain. The angular acceleration pulse was taken from Abel et al. (1978). The input angular acceleration impulse scaled from Abel's tests data is shown in Fig. 7.22. A peak angular acceleration of 7030 rad s2 occurred at about 4 ms, and the peak angular deceleration of 9192 rad s2 was reached at about 32 ms. These values are well within the common range

Mechanism of Action

In recent years, a specific receptor in the mammalian and hence the human brain has been discovered and, in fact, cloned (Sugiura & Waku, 2002). There are at least two subtypes of this receptor. Along with it, a natural ligand in marijuana, anandamide, has been identified. Substances of abuse mimic molecules that naturally occur in the brain. Such compounds (the naturally occurring ones), called ligands, have an effect on the receptors to which they have an affinity. This effect may be to stimulate, to inhibit, or a variety of in-between effects. The natural ligand for marijuana is called anandamide, and its receptor is the anandamide receptor. Interestingly, the term anandamide is derived from the Hindi word for bless. At present, pharmaceutical companies have synthesized both agonists and antagonists to the receptor. Much research has been conducted to identify the properties of these compounds, but it is still unclear what function they serve in mammalian and human brains....

Apoptosis References

Giulian, D., Wendt, E., Vaca, K., and Noonan, C.A. 1993a. The envelope glyco-protein of human immunodeficiency virus type 1 stimulates release of neurotoxins from monocytes. Proc. Natl. Acad. Sci. U.S.A. 90 2769-2773. Giulian, D., Vaca, K., and Corpuz, M. 1993b. Brain glia release factors with opposing actions upon neuronal survival. J. Neurosci. 13 29-37. Giulian, D., Yu, J.H., Li, X., Tom, D., Wendt, E., Lin, S.N., Schwarcz, R., and Noonan, C. 1996. Study of receptor-mediated neurotoxins released by HIV-1 infected mononuclear phagocytes found in human brain. J. Neurosci. 16 3139-3153. Koka, P., He, K., Zack, J.A., Kitchen, S., Peacock, W., Fried, I., Tran, T., Yashar, S.S., and Merrill, J.E. 1995. Human immunodeficiency virus 1 envelope proteins induce interleukin 1, tumor necrosis factor alpha, nitric oxide in glial cultures derived from fetal, neonatal and adult human brain. J. Exp. Med. 182 941-952. Krajewski, S., James, H.J., Ross, J., Blumberg, B.M., Epstein, L.G., Gendelman,...

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