Human Brain Ebooks Catalog

Flash Brain Anatomy

This course gives you access to a full online course and software to learn more about the brain than you ever thought possible in a short amount of time. This software contains detailed, 3D brain models, animations to display concepts, hundreds of educational courses, a neuroanatomy atlas, and compatibility with most web browsers. You will also have access to a full online suite of tutors. Neuroanatomy is one of the hardest parts of anatomy to learn, and learning the brain will really be a lot easier if you had a detailed model to base your knowledge off. This software makes the brain as simple as possible, while also giving you a way to learn it throughly. This model simplifies a very complex subject that most people struggle with Don't be one of the people that doesn't know what to do with the brain model! This course is designed to teach you everything about the brain while keeping the lessons manageable and learning at your own pace. Read more here...

Flash Brain Anatomy Summary

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Highly Recommended

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Parallel Computation in Simulating Diffusion and Deformation in Human Brain

The purpose of this chapter is to survey some recent developments in the application of parallel and high-performance computation in simulating the diffusion process in the human brain and in modeling the deformation of the human brain. Computational neuroscience is a branch of biomedical science and engineering in which sophisticated high-performance computing techniques can make a huge difference in extracting brain anatomical information non-invasively and in assisting minimal invasive neurosurgical interventions. This chapter will demonstrate that there are lots of potential opportunities for computational scientists to work with biomedical scientists to develop high-performance computing tools for biomedical applications.

The contribution of neuroanatomy to psychiatry

The above is a necessarily abbreviated account of the anatomy of the central nervous system, centring on the organization and connections of the cortex including the limbic lobe. Topographical neuroanatomy has been ignored, despite its importance in the reading of modern images of the brain in living patients. For psychiatry, the importance of the connectionist view of the brain lies in the contribution it can make to the understanding of the normal and pathological functioning of the central nervous system. Present-day neuropsychology and cognitive neuroscience are aimed towards understanding the highest levels of central nervous system processing and function. It is these areas or systems that are commonly involved in the signs and symptoms of major psychiatric disease. It is to the pathways underlying cognition, perception, memory, mood, and attention that the psychiatrist interested in the pathophysiology of mental illness must turn his or her attention, and it is this area that...

Oligomers occur in human brain and are strikingly elevated in AD

Assays based on oligomer-selective antibodies have provided compelling evidence that oligomers are bona fide components of AD pathology oligomers occur in human brain and are strikingly elevated in AD oligomers from AD brain are structurally homologous to synthetic oligomers and hAPP mouse models of AD accumulate oligomers as predicted. Oligomers found in CSF, moreover, appear to provide a significant biomarker of AD that is potentially of value for future clinical diagnostics.

The Human Brain

The human brain has three major subdivisions brainstem, cerebellum, and the cerebrum. The central nervous system is first formed as a simple tube like structure in the embryo. The concentration of nervous tissues at one end of the human embryo to produce the brain and head is referred to as cephalization. When the embryo is about four weeks old, it is possible to identify the early forms of the brainstem, cerebellum, and the cerebrum, as well as the spinal cord. As development continues, the brain is located within the cranium in the cranial cavity. See Figure 5-5 for illustrations of the adult brain. Figure 5-5. Human brain A side view, B bottom view. Figure 5-5. Human brain A side view, B bottom view.

Anthropology Assessment

There is a new image of man emerging, an image that will dramatically contradict almost all traditional images man has made of himself in the course of his cultural history. For instance, to start with a rather trivial point, it will be strictly incompatible with the Christian image of man, as well as with many metaphysical conceptions developed in non-Western religions. Since about 1990 we have learned more about the human brain than in the three preceding centuries. Not only the cognitive neurosciences and consciousness research, but also a growing number of new disciplines like evolutionary psychology, artificial life, and cognitive robotics, are generating a flood of new insights into the foundations of mentality. Implicit in all these new data on the genetic, evolutionary, or neurocomputational roots of conscious human existence is a radically new understanding of what it means to be human. Although there is not yet a comprehensive formulation of a new anthropology, the...

What Should Be Modeled

Epilepsy accounts for a significant portion of the disease burden worldwide (Murray and Lopez, 1994). The economic, social, and personal costs of this disorder are due largely to uncontrolled seizures (Begley et al., 2000), which underscores the need for more research into new approaches for the diagnosis, treatment, and prevention of epilepsy and its consequences. Although one could argue that research on human epilepsy ideally should be carried out on humans with epilepsy, this approach is not always possible or practical (Engel, 1998). Obvious ethical constraints exist, particularly those associated with the invasive techniques often needed to pursue important investigative questions. It is difficult to control for clinical variables, and control data can be impossible to obtain. Statistical analysis frequently requires larger populations than can be obtained from most clinical practices. Finally, the cost of carrying out research projects on patients would be prohibitive....

Chapter References

Shepherd, G.M., Mirsky, J.S., Healy, M.D., et al. (1998). The Human Brain Project neuroinformatics tools for integrating, searching and modeling multidisciplinary neuroscience data. Trends in Neuroscience, 21, 460-8. 12. Holloway, R.L. (1995). Toward a synthetic theory of the human brain evolution. In Origins of the human brain (ed. J.P. Changeaux and J. Chavaillon), pp. 42-60. Clarendon Press, Oxford. 14. Tobias, P.V. (1995). The brain of the first hominids. In Origins of the human brain (ed. J.P. Changeaux and J. Chavaillon), pp. 61-83. Clarendon Press, Oxford.

Imaging 5hydroxytryptamine receptors

One recent success is the radioligand (11)C WAY 100635 for imaging 5-HT1A receptors in the human brain.(22) As many different antidepressant treatments alter 5-HT1A receptor function in rodents, this ligand will be useful investigating 5-HT 1A receptor populations in depressed patients before and after treatment especially. lack of selectivity, or the relatively low ratio of specific to non-specific signal obtained in the human brain, (23 although a few reports have appeared reporting reduced 5-HT2 receptor number in drug-free depressed patients. Further studies are needed using more selective ligands with higher signal to noise ratios, such as (11)C MDL 100907, a promising selective ligand for 5-HT2A receptors (Table 1).

Rationale for Labels and Abbreviations

No universally accepted way to identify specific features or structures in drawings or photographs exists. The variety of methods seen in currently available atlases reflects the personal preferences of the authors. Such is the case in the present endeavor. The goal of this atlas is to present basic functional and clinical neuroanatomy in an understandable and useful format. The abbreviations used in this atlas do not clutter the illustration they permit labeling of all relevant structures and are adequately informative while stimulating the thinking learning process. The abbreviations are, in a very real sense, mnemonics. When learning gyri and sulci of the occipital lobe, for example, one realizes that the abbreviation LinGy in the atlas could only mean lingual gyrus. It could not be confused with other structures in other parts of the nervous system. Regarding the pathways, RuSp could mean only rubrospinal tract and LenFas, the lenticular fasciculus. As the reader learns more and...

Driving intentionality back up

Humans, it seems, have 'exploited' the potential inherent in rule-bound processes, that events which can be viewed under one set can also be viewed under another. Furthermore they respond to numerous environmental stimuli not only but for a long time three of the traditional elements earth, fire and water, and more recently air, and a wide range of organisms other than those that they eat. Having created new uses for items in the environment they have then added to the range of stimuli that need to be discriminated, and to which responses are required. They seem to be well suited to this because of a capacity both to generate broad areas, or domains of interpretation, and specific subgroupings within these broad domains. These domains not only refer to features that objects have in common, but also to the actions associated with them. Thus the general characterization 'tool' does not so much refer to the physical characteristics of the object as to the use to which it is put. Having...

Motor and Premotor Pathways Controlling Eye Muscles

Injections of a simple retrograde tracer were placed in the muscle belly within the central endplate zone of the SIFs (fig. 2). The tracer was taken up by SIF endplates and some MIF endplates. There was retrograde filling of the classical motoneuron subgroups throughout III, or in IV or VI. Alternatively, when the injection was placed at the distal tip of the muscle the tracer involved only MIF 'en grappe' motor endplates. Thus, only the (global) MIF motoneurons were retrogradely filled. In fact, these experiments labeled mainly the global MIFs since the orbital MIFs did not extend into the distal tendon (fig. 1a) see also the chapter by Demer, this vol, pp 132-157 . The MIF motoneurons lay around the periphery of the classical III, IV and VI boundaries and did not intermingle with the SIF motoneurons. In VI, the LR MIFs surrounded the medial aspect of the nucleus the SO MIFs lay in a dorsal cap over IV in III the MIFs of MR and IR gathered into a small group on the...

Dopamine And Human Studies

The early work demonstrating that dopamine was a probable neurotransmitter in mammals and that a dopam-inergic nigrostriatal pathway appeared to be a major component of the extrapyramidal pathway led to investigations of human tissue. It was reasoned that a similar pathway existed in humans, analogous to that found in many other species. In addition, since it was known that Parkinson's disease was characterized by loss of nigral neurons and a primary feature was loss of motor control, it seemed likely that loss of dopamine neurons would be an important pathological feature of this disease. The presence of high concentrations of dopamine in the neostriatum and in the substantia nigra of human brain39-41 provided evidence for the existence of this pathway. The dramatic loss of dopamine in neostriatum and substantia nigra of Parkinson's patients demonstrated by Hornykiewicz and colleagues25,41 helped confirm the involvement of these neurons in the disease process. These findings were...

Indirect Measures of Neuronal Output

This tomographic imaging technique samples the by-products of a chemical reaction generated by short-lived isotopes, or unstable radioactive substances. This method was first used in 1951 in order to image brain tumours in the human brain (Wrenn, Good & Handler, 1951). Ingvar and Lassen (1961) pioneered the inhalation of radioactive xenon gas (Xe133) to quantify of regional cerebral blood flow

Creation Art and the Brain

These first written traces testify to an activity that is fundamental to the human brain that of giving meaning to a physical makeup (in this case, randomly distributed line patterns) with the goal of mastering the evolution of time in a world that escapes us. The human brain proceeds in a direction opposite to the input-output mode long proposed by cybernetics. It always projects onto the world, in a spontaneous and internally generated fashion, mental representations that it tries to test against an external reality that is intrinsically devoid of meaning. This projection, as a generator of mental forms, represents an essential predisposition of the human brain toward creation (Changeux, 1983, 2004 Berthoz, 2002).

Action and mutations of molecular chaperones

In AD, several in vitro studies and animal models suggest direct interaction between chaperones (HSP 28, 70, 72, etc.) with Ap, which might regulate the formation of toxic Ap assemblies. Cross-talk between chaperones and the UPS might be pivotal in regulating the deposition and toxicity of tau. HSP 70 and others interact with hyperphosphorylated tau in human brain, facilitate tau ubiquitination, enhance the levels of insoluble tau (232), and in vitro suppresses tau-induced cell death (233).

Molecular Biology of aSynuclein

SNCA maps to chromosome 4q21.3-22 (45). The gene is composed of six exons encoding a 19 kDa, 140 amino acid protein. Alternative splicing leads to two minor transcripts, 128 amino acids, and 112 amino acids (46) that are poorly expressed relative to the full-length gene (47) (unpublished data). The amino terminus (1-67 amino acids) is composed of a consensus motif of 11 amino acids (XKTKEGVXXXX) conserved within synuclein homologues (48). Combined immunocytochemical and subcellular fractionation studies in human brain have shown a-, ft-, and -synuclein are abundant in the neuronal cytosol and present in enriched amounts at presynap-tic terminals (49). Early studies on the zebra finch suggest that a-synuclein has a role in development and in the regulation or support of synaptic plasticity (50). In vitro, both a- and ft-synucleins have been shown to selectively inhibit phosphatidylcholine specific phospholipase D2 (51) whose product, phosphatidic acid, mediates processes controlling...

Dysfunction of neurotrophines

There is growing evidence that reduced neurotrophic support is a significant factor in the pathogenesis of neurodegenerative diseases (240). Neurotrophines regulate development and the maintenance of the vertebrate nervous system. They affect neuronal survival influence synaptic function and plasticity, and are central to many aspects of the nervous system function. The neurotrophins are able to bind to different receptors, and bind to a common receptor p75wtr, and each of the neurotrophins also binds to one of the family of Trk receptors. By dimerization of the Trk receptors, and subsequent transphosphorylation of the intracellular kinase domain, signaling pathways are activated. Since NTFs in neurons are subject to retrograde and, in at least some cases, to anterograde transport from and to targeting neurons, their effects may be related to synthesis in local or remote sites or to changes in axonal transport. Observations in AD brain indicate increase in neurotrophic factor (NTF)...

Problem 4 The Methodological Problems with the Measurement Observation and Visualization of Consciousness

If consciousness literally resides in the brain, how should we expect it to reveal itself in the detailed computer-generated images of human brain function constructed from measurements made with PET, fMRI, EEG, and MEG To put it naively Why do we not see consciousness in functional brain images Or do we What is the relation between the neural correlates of consciousness and the actual neural constituents of consciousness

Basic organisation of nerve cells

Arthropod Circulatory System

The very title of this chapter would have been contentious in the nineteenth century, when detailed scientific study of the nervous system got underway. For it was then not generally agreed that the nervous system is composed of many individual nerve cells. This was mainly due to the fact that nerve cells are difficult to visualise with routine histological methods. Many cells are packed tightly together in nervous tissue (there are 100000 nerve cells in 1mm3 of human brain) and they give off fine, branched processes, so that it is almost impossible to determine the limits of a single cell. Many scientists therefore believed that nerve cells were fused together in a continuous network of branched processes, rather like the capillary beds that link small arteries and veins.

Neurophysiology of Periventricular and Periaqueductal Pain Modulation

Physiologically, stimulation-produced analgesia (SPA) is different for each of the sites selected. The best-understood, but perhaps most complex, is the mechanism for SPA produced by stimulation of the PVG and PAG. Initially, it was thought that stimulation of these sites produced direct effects on pain transmission, but when SPA produced by PVG stimulation was found by Akil and Liebeskind to be inhibited by naloxone, a specific opiate antagonist, understanding the physiology of pain modulation became more complex (4). Watson et al. have shown in the rodent that the cell bodies for the central opiate mechanism (mu system) are in the arcuate, infundibular, and periventricular nucleus of the hypothalamus, with axons extending from these nuclei anteriorly through the septal area and then superiorly and posteriorly through the septal area and medial to the thalamus in the PVG to the raphe nuclei in the ventral periaqueductal gray and inferior to the locus ceruleus, where this tract...

The Problem of the Measurement and the Functional Brain Imaging of Consciousness Can We Ever Discover Consciousness in

In fact, the phenomena reflected in our current measurements of brain activation are extremely indirect, far removed from the levels of organization likely to constitute consciousness. PET certainly produces beautiful color-coded images of activated brain areas, but we should remind ourselves what the actual phenomena reflected in those images are. How is a colorful PET image constructed PET detects gamma rays and thus directly images the sites of origin of those gamma rays in the brain. Those sites are the sites of positron annihilation. The positrons are generated when the radioactive isotope in the blood flow decays. Positron annihilation does not happen in the same location as positron formation does, so a PET image only indirectly depicts changes in local blood flow in the brain. And local blood flow is one step farther removed from any actual neural activity. The PET image is a shadow of changes in local blood flow, which is a rather pale shadow of changes in the level of neural...

Parallel Implementation

All the above-mentioned implementations of solving the anisotropic diffusion equation in a human brain with the measured DT-MRI data are done in a serial computing environment. To perform diffusion simulations over the whole brain with sufficient accuracy and acceptable computational time and memory cost, a parallel implementation of the solution is presented in Ref. 27 . The tensor data set used in the simulation is the same as that used in Ref. 22 , where the resolution of the data set is 128 x 128 x 16 with each voxel size being 2.5 mm x 2.5 mm x 7.5 mm defined on the Cartesian mesh. The 3D diffusion equation (5.2) is discretized on the Cartesian grid using finite difference approximation. The central difference in space and backward differentiation formula in time are applied to approximate the spatial and time derivative terms in Eq. (5.2), respectively. Kang et al. 27 apply the same boundary and initial condition as those used in Ref. 22 . The resulting coefficient matrix after...

Molecular Properties Of Dj1

The promoter region of DJ-1 and the regulation of expression has not been studied in detail but a Specificity Protein 1 (SP1)-binding site at position-100 from the transcription initiation site appears to contribute most of the promoter activity (25). SP1 is a general transcription factor that directs expression of genes in many tissues, and, indeed, expression of the DJ-1 transcripts can be detected in most body tissues, brain areas, and extracerebral tissues. Expression seems more abundant in subcortical than in cortical brain areas (2). A more detailed study on mouse brain largely confirmed these results but provided more details (32). Most structures involved in the regulation of motor activities (neurons in the motor cortex, caudate putamen, substantia nigra, red nucleus) were strongly labeled. Furthermore, cerebellum (granule cell layers and deep cerebellar nuclei, Purkinje cells) lateral globus pallidus and other nuclei such as hippocampus, piriform cortex, olfactory cortex,...

Physics Based Brain Deformation Models

Implementation of the model is carried out with two different materials being distinguished, namely brain tissue and skull bone. Instead of applying forces in the model, a set of manually determined correspondences is used to drive the deformation of the preoperative image. The finite element mesh is constructed by using four-node quadrilateral finite elements, in accordance with the underlying pixel grid of 2D images. The registration experiments are performed for the case of synthetic images and for real brain image data, with a preoperative MR image of the human brain and a corresponding postoperative image simulating an intraoperative image. The tests from both the cases yield physically plausible deformation results. The time cost to process an image with a size of 256 x 256 pixels is around 45 min on a Sun Ultra 2 1300 machine with a 300 MHz CPU. retraction and resection. This computational model, combined with the intraopera-tively acquired data, which is usually incomplete and...

The Effect of DJ1 Mutations

In addition to having a low steady-state level, the subcellular localization of the mutant DJ-1L166P protein in transfection experiments is changed in comparison with the pattern seen with the wild type DJ-1. While the wild type DJ-1 shows uniform localization in the cytosol and nucleus, the DJ-1L166P mutant retains the nuclear localization but has lost the uniform cytosolic distribution in a fraction of the cells (between 10 and 50 of the cells depending on the study) and colocalizes with mitochondria (2,43,44,46). However, due to the high levels of expression in cell systems analyzed, it cannot be excluded that a fraction of wild type DJ-1 also localizes to mitochondria, and in fact there is evidence to indicate this (44). However, the mitochondrial localization has not yet been confirmed for endogenous protein in human brain tissue or primary mouse neurons. The observation that the mutant (or perhaps also the wild type) DJ-1 can colocalize with mitochondria suggests links to the...

Addressing Cognitive Problems

Multiple sclerosis (MS) is a disease that affects both the body and the mind. It causes damage to tissue in both the brain and the spinal cord. When it affects the brain, MS is highly likely to affect cognition. Cognition includes high-level functions carried out by the human brain, including comprehension and use of speech, visual perception and construction, calculation ability, attention (information processing), memory, and executive functions such as planning, problem-solving, and self-monitoring.

Using Localization To Help Identify Operations Heuristic Identity Theory

So far I have focused on attempts in cognitive science to identify operations in the mind using purely behavioral tools. I noted that, largely for pragmatic reasons, cognitive science had developed without neuroscience playing much of a role. A major reason was that few tools existed for studying brain activity as humans perform cognitive tasks. This situation changed dramatically when positron emission tomography (PET), and later functional magnetic resonance imaging (fMRI), became available to noninvasively determine which human brain regions were most active for different cognitive tasks. My contention in this section is that this does not obviate the need to perform the hard conceptual work of figuring out what the operations are, but it does provide valuable constraints that can assist in this endeavor.

Upregulated Expression of Nav18 in MS and Its Models

The increased expression of Nav1.8 within Purkinje cells is not limited to animal models of MS. Study of postmortem human brain tissue (Black et al., 2000) has demonstrated up-regulation of Nav1.8 mRNA and protein within Purkinje cells in patients with disabling progressive MS with cerebellar deficits on neurological examination (Fig. 9).

Pathophysiology of ischaemic stroke

(neuroprotection) the combination of reperfusion and neuroprotection would seem a logical conclusion.86 Although there is evidence that the concept of the ischaemic penumbra is valid,87,88 it remains unclear how long ischaemic human brain might survive in other words, the time window for intervention is unknown. It seems likely that the duration of any time window will vary between individuals and it will be increasingly important to identify the factors which influence it.

HDL2 Pathogenesis Three Hypotheses 51 Poly Amino Acid Toxicity

Alternatively, HDL2 neurotoxicity could arise from expression of long tracts of polyalanine or polyleucine. Long tracts of these amino acids are toxic to cells in culture, and at least one neurodegenerative disease results from an alanine expansion 1 . However, while exon 2A from alleles with normal length repeats is expressed in human brain, to date we have not found evidence for expression of the expanded repeat (Rudnicki, unpublished observations).

Structural and Biochemical Properties of the P450aro

The identity of the structure of the P450aro in the different tissues does not correspond to an analogous identity of the mRNAs coding for the protein. In some tissues (e.g., the human placenta, mouse and rat ovaries) the use of alternative splicing during the mRNA processing gives rise to P450aro transcripts of different length. In particular, three different mRNA species have been demonstrated in the rat ovary (49) among these, only the largest one seems to be able to produce a functional protein, because the two smaller species lack the heme-binding domain coding region, and contain an unspliced intron. However, these two transcripts have not been identified in brain structures (31). A high degree of heterogeneity has been demonstrated in the 5'-untranslated region of exon I. Exon I presents several subtypes (named exon I.a, I.b, and so forth, or, alternatively, I.1, I.2, and so forth) (47,50-52) which can be alternatively utilized for the synthesis of the different mRNA species in...

Experimental modeling of traumatic CNS injury

In vivo animal models preserve much of the complexity associated with human traumatic CNS injury while allowing the investigator to experimentally manipulate certain parameters (e.g., treatment variables, time of sacrifice) that are not possible in humans. In the study of injury biome-chanics, in vivo models provide a more complete representation of the human brain and spinal cord

Integrating Cells Into Tissues

The adult form of the roundworm Caenorhabditis elegans contains a mere 959 cells, yet these cells fall into 12 different general cell types and many distinct subtypes. Vertebrates have hundreds of different cell types, including leukocytes (white blood cells), erythrocytes, and macrophages in the blood photoreceptors in the retina adipocytes that store fat secretory a and p cells in the pancreas fibroblasts in connective tissue and hundreds of different subtypes of neurons in the human brain. Despite their diverse forms and functions, all animal cells can be classified as being components of just five main classes of tissue epithelial tissue, connective tissue, muscular tissue, nervous tissue, and blood. Various cell types are arranged in precise patterns of staggering complexity to generate the different tissues and organs. The costs of such complexity include increased requirements for information,

Conclusions and Outlook

Why do Ml agonists exhibit such a plethora of valuable effects, some expected and a few not envisaged before The answer to this question may be found in the pivotal and physiological role of Ml mAChR-mediated PKC-and MAPK-signaling that mediate a multitude of effects. This allows the Ml mAChR to cross-talk with the Wnt signaling at PKC, and neurotrophin-mediated signaling at MAPK (Fig. l). The Ml mAChR-mediated pathway can be regarded as a physiological imitation of the effects of ACh on this receptor but without the interference of the other mAChR and nicotinic receptor subtypes that may control, limit, or even antagonize these effects. In this context, the Ml agonist therapeutic strategy, in addition to its unique effects on the major hallmarks of AD, restores beneficially those kinases and secretases that are affected in AD (Caccamo et al., 2006 Table l). Notably, PKC and a-secretase are decreased, while GSK-3P and BACE-l are elevated, respectively in AD human brain (Kurumatani et...

Regulation of iron brain homeostasis

Transferrin, a bilobal glycoprotein of approximately 88kDa with its two homologous domains both containing one high-affinity Fe(III)-binding site (Ponka, 1999) is the most important iron transport protein in the human brain. Most studies on transferrin within the brain focus upon its role in iron uptake via the transferrin receptor, although it is also involved in intracellular iron processing and possibly in iron efflux (Aisen et al., 1999 Ponka, 1999). In addition, it has been suggested that lactotransferrin (synonym lactoferrin) have a role in the transport of iron into dopaminer-gic neurons in the SN. Lactotransferrin is an 80kDa glycoprotein belonging to the transferring family with a transferrin-similar structure (Anderson et al., 1989) that has been localized in the human brain to neurons, glial cells and microvasculature (Aisen and

Aspartoacylase Deficiency In Cd

The central nervous system contains high level of NAA (36). The concentration of NAA in the human fetus brain in utero is approximately 2.5 ol g (36), while in the normal adult human brain the level varies 8-10 ol g (36-39). The accumulation in the brain of NAA due to ASPA deficiency, and the efflux of this compound form the brain, leads to elevated urinary NAA. Thus, in Canavan disease, patients had urine NAA 1440.5 873.3 mol mmol Cr in contrast to 23.5 16.1 ol mmol Cr in normal subjects (3,14). Therefore, urinary NAA is one of the markers to determine CD. However, mild elevation of NAA with macrocephaly must not be predicted as Canavan disease, unless spongy degeneration of the brain is confirmed (30).

Some Important Facts from the Neuropsychological Investigation of Consciousness

The ideas surveyed in this paper were inspired largely by observations of neurological patients with disorders of mind and behavior, and by findings from the experimental neuropsycholog-ical investigation of those disorders. The results of such studies, along with evidence from general biology, neuroanatomy, and neurophysiology, were used to construct a theory and to design testable hypotheses regarding the neuroanatom-ical underpinnings of consciousness. The detailed analysis of the pertinent evidence is presented in my book The Feeling of What Happens, which lists the supporting references and outlines an ongoing research program in this area.1 In the pages that follow, I summarize the theoretical framework, the hypotheses, and the available evidence. The first fact is that some aspects of the processes of consciousness can be related to the operation of specific brain regions and systems. In the case of the problem of self, the regions and systems are located in a restricted set of...

Introduction Puzzling Changes In Cell Numbers In Huntingtons Disease Brain

Brain disorders with uniquely human manifestations such as HD may benefit from being examined within a conceptual framework that is based on the unique biology of the human brain (reviewed in 3 ). We believe that the unique pattern and timing of human brain myelination can help explain many phenotypic aspects of neuropsychiatric disease as well as the striking patterns of spread of their pathognomonic lesions across the brain in predictable symmetric bilateral patterns (reviewed in 25 ) (see Section 2.2). We will therefore examine HD as well as other age-related neuropsychiatry diseases in the context of a myelin-centered model of the human brain. The model's central premise is that the trajectory of myelin development and breakdown is essential to our very uniqueness as a species (reviewed in 3,25,26 ). In its widest perspective, the model primarily delineates a myelin hypothesis of human brain evolution and normal development and is 'secondarily' useful in conceptualizing a wide...

The smallest number of coordinates needed to specify uniquely a point in space

Brains are considered to have evolved in evolution under pressures that were supposed to lead to the selection of faculties beneficial for survival in a limited niche of the universe.2 It is therefore likely, in spite of occasional sparks of unjustified hubris that claim otherwise, that the individual human brain perceives only limited dimensions of nature, in terms of both properties and magnitude. That segment of our physical ambience that is directly accessible to our senses and has shaped our intuition3 can be dubbed, based on its dimensions, as the 'mesoworld'. It refers to properties such as size, number, and location in a four-dimensional space to scales of millimetres to kilometres, milligrams to kilograms, seconds to years and to complexities that are subserved by processing a few chunks of information at a time. Whatever transcends the aforementioned properties, scales, or complexities, requires culturally derived technical and conceptual tools for detection, qualification,...

Developmental Underpinnings of Degenerative Brain Diseases

The human brain is unique in its extensive and pervasive myelination process that supports its high information processing capacity ( 3 , reviewed in 26-28 ). Myelination increases axonal transmission speed, reduces action potential refractory time, and improves synchrony of high-frequency bursts of signals across the distributed neural networks of the brain. Thus, if the brain were to be compared to the Internet 29 , myelination not only increases its speed (transforming it from a telephone-line based system to a T1-line based system) but also its 'bandwidth' increasing the actual amount of information that can be transmitted per unit time. Human behavior and cognitive function is dependent on high-throughput information processing, which in turn depends on the uniquely extensive myeli-nation of our brain and the maintenance of its functional integrity over our lifespan (reviewed in 3,26,28,30 ). This myelin-centered model of the human brain is not intended to diminish the importance...

Neurobiology of normal emotion

Any account of function in the human brain must start with its anatomy. Indeed, the most influential modern theory of how emotion is represented within the brain was an essentially anatomical speculation.(l) Building on the observation that decorticate animals could express 'sham rage', Papez argued that areas projecting to the hypothalamus would be essential for the experience of emotion. Movement, thought, and emotion were identified with sensory projections to the striatum, neocortex and limbic system respectively. The limbic cortex had been observed by neuropathologists to be a particular locus for infection with the rabies virus, and the association of early stages of disease expression with psychiatric symptoms was well established. The particular symptoms seen most floridly in rabies are intermittent outbursts of fury or terror.

Mathematical Reasoning

And psychologists have made similar moves in their theorizing about how humans think. Some modules of the brain appear to handle unexpectedly specialized functions, such as recognition of familiar human faces (Desimone 1991 Bruce 1991). When we understand everything our specialized modules do, it is not at all clear what will remain. It's true that it's hard to imagine how Mozart's mind could be the result of the interaction of ordinary human brain modules, but perhaps most of what the average person does could be.

Specialized Regions of Neurons Carry Out Different Functions

Axons, whose diameter varies from a micrometer in certain nerves of the human brain to a millimeter in the giant fiber of the squid, are specialized for conduction of action potentials. An action potential is a series of sudden changes in the voltage, or equivalently the electric potential, across the plasma membrane. When a neuron is in the resting (nonstim-ulated) state, the electric potential across the axonal membrane is approximately 60 mV (the inside negative relative to the outside) this resting potential is similar to that of the membrane potential in most non-neuronal cells. At the peak of an action potential, the membrane potential can be as much as +50 mV (inside positive), a net change of 110 mV.

The Architecture of the Mind

It might seem as if my bias toward modularity in this chapter has been extreme. Other discussions of cognitive science, such as Jackendoff (1987), have argued, often cogently, for the existence of certain kinds of representation in the human brain, based purely on the fact that people can grasp a certain kind of distinction. The typical result of such an argument is a suggested representational structure that is expressive enough to make the distinctions people make. When such an exercise is taken to its logical end, we wind up with elaborate systems of knowledge representation in which anything at all can represented (Davis 1990 Lenat and Guha 1990). The problem with these arguments is that they don't say much about how the knowledge is manipulated. Indeed, the more expressive the notation systems, the less tractable the problem of making

Tests of the Hypothesis That Protein Synthesis Is Required for Memory Storage

By what processes do enriched experience or formal training lead to plastic changes in cerebral neurochemistry and neuroanatomy We found early on that enriched experience causcs increased rates of protein synthesis and increased amounts of protein in the cortex (Bennett, Diamond, Krech, & Rosenzweig, 1964). Later, training (imprinting) was reported to increase the rates of incorporation of precur

Question And Answer Session

I presume since we can measure all of these osmolytes with MR spectroscopy in the human brain, that you now routinely use spectroscopy in your patients. DR. VERBALIS You presume wrong, but it has been done. The same kind of decreases in osmolytes shown in the animal models has also been documented in human brains at UCLA using magnetic resonance spectroscopy. But it's not being used routinely for therapeutic purposes at this time.

Hemispheric Asymmetry In Creativity

Kurup and Kurup (2003) have proposed a biochemical model to explain asymmetric differences between creative and less-creative individuals. Central to this model is the glycoside Digoxin, produced by the hypothalamus. Digoxin is an endogenous membrane Na+ - K+ ATPase inhibitor that is involved in the modulation of several neurotransmitter systems throughout the human brain (Hisaka, Kasamatsu, Takenaga, & Ohtawa, 1990). Kurup and Kurup (2003) measured differences in blood serum levels of digoxin and neurotransmitters between both left and right hemisphere-dominant and creative (poets) versus less-creative individuals. Digoxin levels were found to be significantly higher in the creative compared to the less-creative individuals and in the right-hemisphere dominant compared to left-hemisphere dominant individuals, as was serotoninegic, strychninergic, and nicotinergic transmission. In contrast, the less creative and the left-hemisphere dominant individuals were found to display higher...

XK Expression XK mRNA

In caudate putamen, nucleus lateralis thalami and cerebral cortex. Northern blots of samples from different regions of the human brain support the in situ hybridization results of mouse brain. Large amounts of mouse Kell (mKell) mRNA expression were noted only in spleen, bone marrow and newborn mouse liver, but RT-PCR analysis detected small amounts of mRNA in testis and placenta.

The Generality of Synchronicity

Found in a large number of different functional systems. Thus, it seems justified to generalize the results obtained in the visual cortex and to suggest that temporal coordination of discharges may be of general relevance for neural information processing. Importantly, there is increasing evidence that dynamic synchronization, in particular at frequencies in the gamma band, also occurs in the human brain. EEG studies have provided evidence for precise synchronization of activity in the gamma-frequency range in human visual cortex that is related to perception and reflects the subjective coherence of stimulus arrangements (Tallon-Baudry et al. 1996, 1997, 1998 Rodriguez et al. 1999 Miltner et al. 1999).

Polymethodological Study Of Creativity

Perhaps the most comprehensive study of the neurophysiology of creative processes has been conducted by researchers at the institute of the human brain at the Russian Academy of Science. Four tasks of varying creative content were specifically developed for EEG and PET analysis. The first task (D Difficult) consisted of composing a mental story from words spanning several different semantic areas (e.g. to begin, glass, to want, roof, mountain, to keep silence), which was designed to induce subjects to give up stereotyped ways of thinking. The second task (E Easy) consisted of composing a mental story from words from the same semantic area (e.g. school, to understand, task, to learn, lesson), which was considered to involve more stereotyped thinking than the first task. While the first and second tasks involved making a story out of as many of the listed words as possible, in any order, the third task (R Reconstruction) consisted of making a mental story out of the listed words without...

The immediate future of remote memory

How are remote memories stored in the brain Are they distributed throughout the brain or are they stored close to the primary areas that initially processed them Which regions store information, which regions organize retrieval, and more importantly, which circuits oversee the integration of new information into pre-established semantic structures These are just a small sample of the vast array of cognitive neuroscience questions that need to be addressed concerning the neuroanatomy and processing of remote memory. In these studies, it will be important to not only image these processes but also to take full advantage of opportunities to study the impact of disruptions of these processes. Although often plagued with pleiotropic problems, human genetic disorders that affect cognitive function, from neurological to psychiatric conditions, offer precious opportunities to study brains with molecular and developmental dysfunction that may aid the cognitive neuroscience of memory, including...

S Miksys and R F Tyndale

Disease have been identified, as have some toxins that can cause a Parkinson's diseaselike syndrome, such as catecholamines, amphetamine, pesticides, tetrahydroisoquinoline (TIQ) and (MPTP). Since 1985, efforts have been made to elucidate the role of drug-metabolizing CYPs in the development of Parkinson's disease, as these enzymes, in particular CYP2D6, are able to inactivate or activate many of these neurotoxins. CYP-mediated reactions can also create neurotoxic free oxygen radicals, and the balance of the neuroprotective and neurotoxic roles of specific brain CYPs requires elucidation for Parkinson's disease and other CNS disorders. Parkinson's-inducing toxins, or their neurotoxic metabolites, can be taken up into dopaminergic neurons by the dopamine transporter, where they cause oxidative stress, mitochondrial dysfunction, and eventually cell death. CYPs are expressed in neurons in human brain (Miksys and Tyndale, 2002, 2004), including dopaminergic neurons of substantia nigra and...

Other Non Erythroid Tissues

Adult brain ISHH showed the presence of mXK mRNA in many different regions such as cerebellum, pons, hippocampus, hypothalamus, cerebral cortex, caudate-putamen and olfactory lobe. The magnocellular neurons in the pontine region, cerebellar Purkinje cells, Cornu Ammonis fields of hippocampus, nucleus lateralis thalami and mitral cell layer of olfactory lobe were noticeably stained. Northern blot analyses of various regions of human brain confirmed the findings of mouse brain ISHH except that the corpus callosum, which showed low expression in human, did not yield a positive signal in mouse by ISHH. mKell mRNA ISHH of a newborn sagittal section, adult testis and brain did not give a distinct positive signal in non-erythroid tissues 15 . mKell was not detected in brain, even in the caudate-putamen or pons, where mXK expression was moderate to high. RT-PCR of mouse cerebellum showed a very weak mKell band, but GPA was also detected, indicating that the mKell band may be the result of...

Roles Of Representation And Processing Of Reinforcement And Motivation By Dopamine Neurons And Striatal Neurons

Forebrain bundle containing ascending axons of dopamine neurons and the cell area of dopamine neurons. Certain major drugs of abuse are related intimately to dopaminergic transmission. Finally, in the human brain, regions belonging to a mesostriatal and mesolimbic dopamine system respond to reinforcement (Mar-tin-Soelch et al. 2001 Thut et al. 1997).

Tau Normal Biology And Dysfunction In Disease

Tau is a microtubule-binding protein that stabilizes microtubules and promotes their polymerization in neurons (15,24,30). Six isoforms of tau are present in the adult human brain. These isoforms are generated by alternative mRNA splicing of the tau gene on chromosome 17 (15). Significantly, in the carboxy-terminal half of the molecule, alternative splicing of exon 10 results in the presence of either three or four microtubule-binding motifs, yielding 3R-tau and 4R-tau isoforms, respectively (Fig. 1).

Cindy Van Rooy John Song and Con Stough

Biological intelligence is the kind of concept Galton was concerned with it refers to the structure of the human brain, its physiology, biochemistry, and genetics which are responsible for the possibility of intelligent action on the part of human beings. The human brain is a highly complex organ that consists of several billion cells that are connected by 150,000 km of neural fibres. Ultimately, it is the properties of these cells and neural fibres, which work endlessly in complex neural firing patterns, that are responsible for our behaviours and thoughts (Chen & Buckley, 1988). Researchers have utilized a range of brain imaging techniques to investigate the properties of these cells and neural fibres in their search for the biological basis of intelligence. For example, some researchers have utilised electroencephalography (EEG) and evoked potentials (EPs) to investigate the relationship between brain electrical activity and intelligence, while other researchers have used...

Cerebral Localization Of Learning And Memory Processes Using Dissociation Designs

Knowlton, Mangels, and Squire (1996) start their review article by stating, Students of brain and behavior have long recognized that double dissociations references to Teuber (1955) and later authors provide the strongest evidence for separating the functions of brain systems (p. 1399). They present evidence for a double dissociation between human brain regions and kinds of memory amnesic patients, with damage to the limbic-diencephalic regions, show impaired formation of declarative but not of nondeclarative memories, whereas patients with Parkinson's disease, who have damage to the neostriatum (caudate nucleus and putamen), show impaired formation of habits but not of declarative memories. Kesner, in a series of studies summarized in Chapter 10, has found evidence of double and triple dissociations between brain regions involved in working memory for different attributes of the learning situation. A similar research project in another laboratory also found a triple dissociation,...

Experimental models for bloodCNSbarrier observations

The best-studied system so far is a human brain microvascular endo-thelial cell line (HBMEC) that has been derived from a brain biopsy of an adult female with epilepsy. The HBMEC were immortalized by transfection with simian virus 40 large-T antigen 90 . This cell line has proven invaluable in multiple experiments on bacterial interaction with the BBB. Many different bacterial species have been examined, e.g. S. agalactiae 91 , S. suis 92 , S. pneumoniae 83 , N. meningitidis 93 , Staphylococcus aureus 94 , and H. influenzae 95 .

Spontaneous Eeg And Intelligence

The majority of studies investigating the relationship between spontaneous EEG and intelligence have focussed their attention on measures of the alpha rhythm (AR), and to a lesser extent the slower theta and delta rhythms. The alpha rhythm has a frequency range of approximately 8-13 Hz, and is the dominant frequency in the EEG recorded from the scalp of adult humans (Pilgreen, 1995 Anokhin & Vogel, 1996 Klimesch, 1999). It is maximal over the occipital lobe when relaxed, but awake and alert, with eyes closed (Steriade, Gloor, Llinas, Lopes da Silva, & Mesulam, 1990 Pilgreen, 1995). There is multiple evidence that AR recorded from the scalp represents neurophysiological mechanisms directly related to individual differences in information processing in the human brain (Klimesch, Schimke& Pfurtscheller, 1993 Lebedev, 1990). The delta (1.5-4.5 Hz) and theta (4.5-7.0 Hz) rhythms are sometimes referred to as 'slow wave' activity, and research has indicated that these slow wave frequencies...

Candidates For The Ncc Ii Vision

Based on work by Vorberg et al. (in prep.), Thomas Schmidt presents data that demonstrate the possibility of color processing without awareness. He shows the existence of response priming by color, which implies that response control is not functionally isolated from the flow of color information in the human brain. On the other hand, it is not critical whether or not the primes used are phenomenally available, if they actually form the content of visual awareness. The functional profile of our cognitive architecture sets limits to what is accessible to conscious experience. This has interesting methodological implications, but simultaneously generates questions possessing a typically philosophical flavor, such as Could something like invisible colors actually exist

Organization Of The Visual Processing Mechanism

Framework to provide an overall macro-level organizational perspective on visual processing (see Figure 3.9). As a basis for their account they appealed to established neuroanatomy indicating two fiber bundles from the occipital lobe the superior longitudinal fasciculus follows a dorsal path traversing the posterior parietal region before reaching the frontal lobe whereas the inferior longitudinal fasciculus follows a ventral route into the temporal lobe (Flechsig, 1896 1920). Ungerleider and Mishkin's strategy was then to dissociate the contributions of these two pathways. In the first study from their laboratory, Pohl (1973) found a dissociation between monkeys with ventral pathway lesions who manifested a deficit on object discrimination tasks, but not on discriminations that required assessing proximity to a landmark, and monkeys with dorsal pathway lesions that exhibited the opposite pattern of deficits. From this and successive studies, Ungerleider and Mishkin arrived at a...

Mechanism of Action

Monoamine oxidase exists in the human body in two molecular forms, known as type A and type B. Each of these isozymes has selective substrate and inhibitor characteristics. Neurotransmitter amines, such as norep-inephrine and serotonin, are preferentially metabolized by MAO-A in the brain. MAO-B is more likely to be involved in the catabolism of human brain dopamine, although dopamine is also a substrate for MAO-A.

Studies Using Noninvasive Brain Imaging

Black and Greenough in Chapter 2 cite FRMI studies that demonstrate structural changes in the human brain caused by learning, changes that may reflect synaptogenesis. Gershberg and Shimamura in Chapter 9 cite findings from imaging studies in their review of roles of different brain regions in different memory processes.

Substrates and Interacting Proteins

Toward the identification of substrates of PARKIN E3 ligase activity, a number of groups utilized yeast two-hybrid technology with human brain libraries to attempt identify proteins that directly bind to PARKIN. The simplest model of PARKIN-linked disease might involve the accumulation of a toxic substance in human cells that PARKIN normally degrades. The first test is usually whether PARKIN ubiquitinates a target and whether this ubiquitination promotes degradation. The first PARKIN substrate identified, CDCrel-1, belongs to a family of GTPases called septins and is robustly expressed in the nervous system where it associates with synaptic vesicles, although mice deficient in CDCrel-1 do not display a phenotype (71,77). Overexpression of CDCrel-1 in neurons by adeno-associated viral transfer induced neurodegeneration, although there is limited evidence that CDCrel-1 accumulates in the absence of PARKIN and that PARKIN modulates CDCrel-1 levels in vivo (78,79).

Proton Magnetic Resonance Spectroscopy

Water-suppressed, proton MR spectra of normal human brain at long echo times reveal four major resonances one at 3.2 ppm from tetramethylamines (mainly from choline-containing phospholipids Cho ), one at 3.0 ppm from creatine and phosphocreatine (Cr), one at 2.0 ppm from -acetyl groups (mainly NAA), and one at 1.3 ppm from the methyl resonance of lactate (Lac). NAA is a marker of axonal integrity Cho and Lac are considered as chemical correlates of acute inflammatory demyelinating changes (Filippi et al., 2001). 1H-MRS studies with shorter echo times can detect additional metabolites, such as lipids and myoinositol (mI), which are also regarded as markers of ongoing myelin damage.

Modifiers of Parkin Function

As with the above interacting proteins, a number of post-translational modifications that serve to down regulate PARKIN function have been identified. Phosphorylated PARKIN has been described in a number of cell lines, associated with a decrease in autoubiquitination activity (121). S-nitrosylation of PARKIN was demonstrated in vivo in mouse and human brain, where S-nitrosylation serves to inhibit PARKIN E3 ligase and neuroprotection activity (110,122). S-nitrosylated protein generally appears increased in PD brains so that the impact of nitrosylation on other proteins and pathways important in PD warrants further examination (110).

Disease and pathogenesis

The clinical signs and symptoms are a consequence of the extent and frequency of infection, larval migration, and the host response. VLM or visceral toxocarosis seems to be associated with the host immune response to a large number of larvae migrating in the tissue. It is characterized by high eosinophilia, usually more than 30 , fever, hepatosplenomegaly, lymphadenopathy, hypergammaglobulinemia, respiratory signs, abdominal pain, and elevated titres of blood group isohaemagglutinins. Neurological manifestations have also been observed, such as convulsions, and larvae have been found in brains of patients at postmortem (Hill et al. 1985 Nelson et al. 1990). However, the results in a case-control study by Magnaval et al. (1997) suggest that migration of the larvae in human brain does not frequently induce a recognizable neurological syndrome.

Localization Within the Central Nervous System

FGF-12 and FGF-13 are expressed in the embryonic nervous system, but they seem also to occur in the adult brain. By Northern hybridization analysis, a prominent expression of FGF-13 in the adult human brain, particularly in the cerebellum and cortex, has been demonstrated. However, as in case for many other members of the FGF-family, data from detailed analyses of the distribution pattern of mRNAs or proteins are not available.

Evidence from Neuroimaging Studies in Humans

Functional neuroimaging studies also provide some support for the idea that egocentric spatial encoding for action is carried out by mechanisms in the parietal cortex and that different actions depend on spatial encoding in different anatomical sites. Thus, different areas in and around the intraparietal sulcus are activated when subjects make saccadic eye movements as opposed to manual pointing movements toward the same visual targets (e.g., Anderson et al. 1994 Kawa-shima et al. 1996 Pierrot-Deseilligny and M uri 1997 ). Similarly, a region in the human brain that appears to correspond to the part of the

Overlapping resonances in the lipid lactate region

With localized 2D J-resolved MRS, Thomas et al. 100 were able to identify and quantify the lactate peak in the presence of overlapping lipid in a patient with glioblastoma. They conclude in vivo J-resolved plots of human brain tumors indicate the exciting potential of this technique in extracting additional information from the conventional MR spectrum (p. 459). The content of the resonances at 0.9 and 1.3 ppm is further clarified by in vitro MRS. The ratios between the 0.93 and 1.3 ppm peaks have been highly variable with in vivo MRS 101 . High-resolution studies of tumor cells show that the CH3 signal at 0.9 ppm arises from protein residues at 0.92 ppm and from lipids at 0.88 ppm. This is due to a nonlipid contribution super-imposed on the 0.9 ppm resonance. The large lipid content of the normal human brain is not visible with in vivo MRS. When lipid peaks are seen, this is clinically important, reflecting necrosis from any cause. Identification of specific lipids has heretofore...

Ca Channels May Promote Influx and Trigger Release from Internal Stores

Pathological states such as inflammatory demyelination may promote inappropriate ectopic insertion of channels into the axon membrane. Lassmann and co-workers showed an excess of N-type Ca channel subunit accumulation at the axolemma in areas of spheroid formation within actively demyelinating lesions in both human brain and EAE animals (Kornek et al., 2001). This raises the interesting possibility that normal axons (at least those not previously exposed to a chronic insult such and inflammatory demyelination) may have very low densities of Ca channels, but chronic pathological states may increase channel densities, thus promoting Ca influx and Ca-dependent injury. What is not yet clear is whether these accumulated channels are functionally inserted into the axolemma of pathological axons where they can impart an increased Ca permeability.

The Role Of Genetics

Beyond behavioral analysis, studies of learning and memory must also include information about the neuroanatomy of the brain regions required for the particular behaviors studied. Neuroanatomical results have often provided hints about the kinds of computations that a specific brain region could support. For example, the interconnective pattern of CA3 suggests that it can be used as an association matrix. Neuroanatomy has placed Purkinje cells in the central stage of cerebellar computational models, because these cells not only receive inputs from prominent pathways in the cerebellum but their axons are also the principal outputs of this structure (for review, see Raymond, Lisberger, & Mark, 1996). Insights into the neuroanatomical structure of a brain region can also be extremely important in guiding physiological studies. For example, modeling considerations led to the discovery of LTD in the cerebellum and to intensive study of LTP in the hippocampus.

The origin of modern human consciousness

Thus at this point in our knowledge we have thin grounds for identifying the key factor(s) possessed by the human brain that account(s) for our unique reasoning abilities. However, whatever this key factor was, since any evolutionary novelty must already exist (for random genetic reasons) before natural selection can begin to work on it, it cannot, as we so often tend to assume, have been propelled into existence by natural selection. Natural selection is simply not a propulsive force, for in essence it works by elimination, not by creation. And the necessary neural constituent for symbolic thought must, obviously, have been in existence before it could be exploited for cognitive purposes. As a working hypothesis, then, it seems reasonable to view the acquisition of human consciousness as an emergent event, one that was unrelated to adaptation, but was rather due to a chance coincidence of elements. What those elements were, exactly, must for the time being remain a mystery, although...

A memory system in which new patterns are stored on top of previous ones

'Palimpsest' has been used as a metaphor for brain and mind by Romantic writers. 'What else than a natural and mighty palimpsest is the human brain Everlasting layers of ideas, images, feelings, have fallen upon your brain softly as light. Each succession has seemed to bury all that went before. And yet not one has been extinguished Yes, reader, countless are the mysterious hand-writing of grief or joy which have inscribed themselves successively upon the palimpsest of your brain' (De Quincey 1866). Postulated palimpsestic properties of biological memory systems were also contemplated by Freud (1925). Similarly, Gestalt psychologists have proposed that new memory records are inscribed on top of old ones (Koffka 1935).1 'Palimpsest' resurfaced in modern neurosciences with the introduction of models of artificial neural networks (Nadal et al. 1986 Amit 1989 Amit and Fusi 1994). In subclasses of such model networks, which keep a permanent capacity for learning, new patterns are stored on...

Mechanism of Neurofibrillary Degeneration

In AD brain, there is as much normal tau as in age-matched control human brain, but, in addition, the diseased brain contains four- to eight-fold of abnormally hyperphosphorylated tau (Khatoon, Grundke-Iqbal, & Iqbal, 1992, 1994). As much as 40 of the abnormally hyperphosphorylated tau is present in the cytosol and not polymerized into PHFs NFTs (Kopke et al., 1993).

Why do we make reasoning errors

So, thanks to neuroimaging, it is now possible to know what happens in the human brain when a logic error is made. We can thus assert that there is a biological reality behind irrationality, as the philosopher Stephen Stich hypothesized in his book, The Fragmentation ofReason (Stich 1990), or, ifwe wish to avoid speaking of irrationality, we can say, as Evans (2003) stated, that there are two minds or two rationalities in one brain (p. 458).

Clinical substantiation that AD pathology includes neurologically active Ap oligomers

If soluble Ap oligomers are to be valid targets for AD therapeutics, they must be present in human brain and manifest a strong AD-dependent accumulation. All the evidence reviewed so far comes from experimental models and oligomeric toxins generated in vitro. The critical question is whether AD-affected brains contain identical neurologically active Ap oligomers.

Multiple O2aopc Populations With Different Properties

One of the striking aspects of CNS development is that different regions of this tissue develop according to different schedules, with great variations seen in the timing of both neurogenesis and gliogenesis. For example, neuron production in the rat spinal cord is largely complete by the time of birth, is still ongoing in the rat cerebellum for at least several days after birth, and continues in the olfactory system and in some regions of the hippocampus of multiple species throughout life. Similarly, myelination has long been known to progress in a rostral-caudal direction, beginning in the spinal cord significantly earlier than in the brain (e.g., refs. 127-129). Even within a single CNS region, myelination is not synchronous. In the rat optic nerve, for example, myelino-genesis occurs with a retinal-to-chiasmal gradient, with regions of the nerve nearest the retina becoming myelinated first (127,130). The cortex itself shows the widest range of timing for myelination, both...

Cellular mechanism oligomers specifically target synapses and disrupt the molecular cell biology of memory

Oligomers block synaptic information storage in electrophysiological experiments. They trigger AD-type pathology in transgenic models and likely instigate memory loss. Furthermore, in human brain, oligomers show a striking accumulation around neurons that begins in very early stages of AD. There clearly is a need to understand how oligomers act in terms of molecular mechanisms. How is it that oligomers attack neurons, and what memory-relevant molecular changes are triggered An appealing hypothesis is suggested by the putative association of oligomers with dendritic arbors in situ perhaps oligomers attack and disrupt signaling pathways specifically at sites critical to memory formation, in essence acting as pathogenic ligands.

The causal variety Some framework remarks

Even though any suitable, physically implemented, simulation of a system, with its internal and external causal interactions, is another system governed by no less causal laws, it is possible that there is no point-to-point or step-by-step correspondence between the two causal sequences. (After all, some interference in the hardware can produce a wrong result, as well as a right result in contrast with a badly designed algorithm.) Be that as it may, the human brain has an architecture that is very different from a Turing machine. Nevertheless, ever since information was linked to negative entropy, the information processing metaphor has become so pervasive that one might still say that the brain, though not a Turing machine, carries out computations (such as that of the squaring function), processes information and so on. No doubt, it is a sort of computation very different from those carried out by the liver. The brain's computations support representations, while those of the liver...

Ischemic Stroke Pathophysiology

Although the human brain accounts for 2 of the total body weight, it utilizes 20 of the cardiac output to supply the required oxygen and glucose necessary for its incessant metabolic needs. Because the brain does not store or produce these substances, any interruption in their delivery results in some kind of dysfunction. Blood-flow alterations or limitations can, at times, be tolerated, because of compensatory mechanisms such as collateral circulation. Progressive ischemia can lead to brain infarction which, in turn, leads to local vasodilatation, edema, stasis of the blood column and segmentation of the red blood cells and, eventually, brain tissue necrosis. The local vasodilatation leads to an increase in cerebral blood volume and enhanced oxygen extraction from the capillaries.

Reviving Liquid Computing

High-level cognitive functions in the human brain involve the activation of processes (from the activation of the ACh receptor to memory) with time constants covering 13 orders of magnitude (from microseconds to years). These microcircuits implement massively parallel computations, where the inputs consist of multimodal input streams stemming from a rapidly changing environment, and results of computations have to be provided at any time. In contrast, nearly all of the previous theoretical approaches to understand how such systems can possibly provide the basis for cognition and learning (e.g., Dayan and Abbott 2001) have been based on highly simplified and homogenized neurons and synapses as well as on simplified connection patterns, and they result in simple dynamics converging towards a set of point attractors. New paradigms of computation that depart significantly from this concept are needed, where the complexity expressed in the recurrent ongoing activity of the network is the...

Genetics of dystonia S Bressman

May impair protein handling they also point to involvement of the pedunculopontine nucleus and other brainstem structures, which have extensive connections to the basal ganglia. Recent transgenic mouse model results support these findings as pathological for DYT1. Shashidharan and colleagues reported that 40 of four overexpressing transgenic lines developed hyperkinesias those with hyperkinesias were found to have decreased striatal dopamine compared to increased dopa-mine levels in transgenic mice without hy-perkinesias. Immunohistochemistry revealed perinuclear brainstem inclusions similar to those identified in DYT1 human brains (Shashidharan, 2005). Augood SJ, Penney JB Jr, Friberg IK, Breakefield XO, Young AB, Ozelius LJ, Standaert DG (1998) Expression of the early-onset torsion dystonia gene (DYT1) in human brain. Ann Neurol 43 669-673 Augood SJ, Hollingsworth Z, et al. (2002) Dopamine transmission in DYT1 dystonia a biochemical and autoradiographical study. Neurology 59(3)...

Ravindranath R P Kommaddi and H V

Cytochromes P450 is a family of heme proteins that metabolize xenobiotics including drugs. Unique human brain cyto-chrome P450 enzymes metabolize xenobiotics including drugs to active inactive metabolites through biotransformation pathways that are different from the well-characterized ones in liver. We have identified an alternate spliced functional transcript of CYP2D7 containing partial inclusion of intron 6 in human brain but not in liver or kidney from the same individual. Genotyping revealed the presence of the frame-shift mutation 138delT only in those subjects who expressed the brain variant CYP2D7, which metabolizes codeine exclusively to morphine unlike hepatic CYP2D6 that metabolizes codeine to nor codeine and morphine. CYP1A1 bioactivates polycyclic aromatic hydrocarbons to reactive DNA binding metabolites and initiates carcinogenesis. We have identified a unique splice variant of CYP1A1 having deletion of 87 bp of exon 6 which is present in human brain but not in...

Dendritic Spine Structure

The Different Dendritic Spine Structures and Morphologies. Dendritic spine morphology can be observed in a hippocampal neuron transfected with GFP as shown in the top left panel. A more detailed analysis of spine shape has been observed by a 3D reconstruction of serial electron microscopy (EM) images as shown in the top right panel. In panels A-C are represented examples of different dendritic spine shapes viewed at EM level (spines labeled with asterisks). Similar images have been used for the 3D reconstruction. EM and 3D-recontruction images were adapted from Synapse Web, Atlas of Ultrastructural Neurocytology Josef Spacek MUDr DrSc, John C. Fiala PhD, Kristen M. Harris PhD, Funded by the Human Brain Project, NIH grant R01 MH DA 57351, http synapses.mcg.edu and from Fiala, J. C., Spacek, J., and Harris, K. M. (2002) Brain Res Brain Res Rev 39, 29-54, with permission from Elsevier. Figure 18.1. The Different Dendritic Spine Structures and Morphologies. Dendritic spine...

Toxicokinetics and Mechanism of Action

Lead has also been suggested to possibly perturb glucocorticoid-mediated events in the central nervous system hormonal target tissues 78 . Glucocorticoid receptors are widespread in neurons and glial cells and are known to modulate glial cell functions such as synthesis of myelin phosphatide precursors by glyc-erol phosphate dehydrogenase, amidation of the neurotransmitter glutamate, and detoxification of ammonia by glutamine synthetase. Tonner and Heiman 78 found that addition of lead acetate to C6 glioma cells in vitro resulted in a significant reduction of the binding affinity of glucocorticoids for cytosolic receptors. High-affinity cytosolic lead-binding proteins have been identified in the brain (and kidneys) of rats. These high-affinity zinc- and lead-binding proteins are thought to moderate lead inhibition of 8-aminolevulinic acid hydratase (ALAD) through lead chelation and zinc donation, and to translocate lead to the nucleus, where it may influence gene expression. Similar...

The Role Of Oxidative Stress In Radiationinduced Late Effects

A number of factors contribute to the inherent vulnerability of the brain and neural tissue to oxidative stress. The brain represents one of the most metabolically active organs in the body, consuming an inordinate fraction (20 ) of the total O2 consumption for its relatively small weight (2 ) (134). This leads to a relatively high intracellular production of O2- and other ROS 2-5 of the O2 consumed in mitochondrial electron transport is converted to O2-. In addition, studies using isolated brain mitochondria indicate that H2O2 production represents about 2 of the total O2 consumed when NADH supplies the reducing equivalents (135). The brain is rich in the more readily oxidizable polyunsat-urated fatty acids such as docosahexaenoic acid and eicosapentaenoic acid, while myelin membrane is a preferential target of ROS due to its composition and high lipid to protein ratio (136). The human brain has high iron content in some brain regions and cells, particularly in oligodendrocytes (137)...

A small mammal of the genus Rattus family Muridea order Rodentia rodents

The advantages of the rat for the science of memory are numerous. Some of these advantages pertain directly to the rat's ability to learn quickly in tasks which are convenient for use in the laboratory. It is especially shrewd in spatial, olfactory, and taste learning (Tolman 1948 Slotnick 1994 Biegler and Morris 1996 Schul et al. 1996). Other advantages of the rat relate to its size (not too big, not too small). But probably must important at this stage is the immense body of knowledge that has accumulated over the years on the rat's neuroanatomy, neuropharmacology, neurophysiology, and behaviour. This combination turns the rat into a prime choice for the cross- level study of certain types of mammalian learning.

Advantages And Limitations Of The Zebrafish Model

seizure resistant zebrafish mutants. This research program is based on a fundamental question of how to identify genes that prevent, or protect, an individual from developing epilepsy. Because larval zebrafish are a pediatric epilepsy model, perhaps these types of studies could lead to new therapies for the large number of children suffering with medically intractable forms of epilepsy. Although it is too early to speculate on how data from zebrafish will be extrapolated to human pediatric epilepsy disorders, especially considering the vast complexity of the human brain in relation to the relative simplicity of the zebrafish CNS, it is safe to predict that the process of discovery will lead to novel insights.

Essential Fatty Acid Requirements

As human brain gray matter and retinal membranes contain significant amounts of C22 6n-3, the requirement for n-3 EFA may be more critical during the last trimester of gestation and first months of life, when rapid accretion of these FA occurs in the central nervous system (125, 131). Brain PL acquires only long-chain derivatives of EFA, not their 18-carbon precursors, and C22 6n-3 is the predominant PUFA in PL in synaptosomal membranes and photoreceptors (131). C22 6n-3 also accounts for approximately 50 to 60 of FA in the PL of the photoreceptor disks that contain rhodopsin and the G-protein. Much of the C22 6n-3 acquired by the brain is accrued during the suckling period, when the brain undergoes rapid development. A number of animal studies have demonstrated an impairment in the visual process, altered learning behavior, and low brain C22 6n-3 content because of a deficiency in C18 3n-3 and its metabolites C20 5n-3 and C22 6n-3 ( 125, 131). Permanent learning defects and...

Decreased Ferritin In Substantia Nigra Parkinson

Connor JR, Menzies SL, Martin SM, Mufson EJ (1990) Cellular distribution of transferrin, ferritin and iron in normal and aged human brains. J Neurosci Res 27 595-611 pathogenesis of Parkinson's disease. Ann NY Acad Sci 1012 193-208 Hallgren B, Sourander P (1958) The effect of age on non-haem iron in the human brain. J Neurochem 3 41-51 Halliwell B, Gutteridge JM (1986) Iron and free radical reactions two aspects of antioxidant protection. Trends Biochem Sci 11 1372-1375 He Y, Thong PS, Lee T, Leong SK, Mao BY, Dong F, Watt F (2003) Dopaminergic cell death precedes iron elevation in MPTP-injected monkeys. Free Rad Biol Med 35 540-547 Hirsch E, Graybiel A, Agid Y (1988) Melanized dopamine neurons are differentially susceptible to degeneration in Parkinson's disease. Nature 334 345-348 Hu J, Connor J (1996) Demonstration and characterisation of the iron regulatory protein in human brain. J Neurochem 67 838-844 Jellinger K (1989) Pathology of Parkinson's syndrome. In Calne DB (eds)...

Did Evolution Fix Human Values

Primate Characteristics Evolution

What had happened to the human brain by that time Katherine Semendeferi and Hanna Damasio (2000) proved that no extra-allometric expansion exists in the frontal area of humans. In relative terms, we have the same parieto-occipital, temporal and frontal volumes corresponding to any ape. Only the overall large capacity of our brain makes a volumetric difference. However, the human brain is not just bigger than that of any other simian. Let us consider the cortical gyrifica-tion, measured by tracing an inner contour of the complete surface of the brain and by tracing an outer contour with tangential lines connecting the crests of gyral curvatures of the cortex. James Rilling and Thomas Insel (1999) studied the gyrification index of the primate cortex, showing that gyrification is allometric the bigger the brain is, the more gyrificated the cortex is. However, an extra-al-lometric gyrification does exist, precisely in the prefrontal cortex ofhumans.

Unanticipated contradiction between percepts or thoughts and the predictions of organized knowledge

Recording the electrical activity of the human brain in action by electroencephalography (EEG, functional neuroimaging), has identified brain waves that appear only under 'surprising' situations. The EEG of individuals that respond to a rare stimulus occurring randomly in a sequence of frequent stimuli, or to an omission of an expected stimulus, shows a characteristic wave about 300 ms after the surprising event ('P300 wave' Sutton et al. 1965). Similarly, a characteristic evoked-response brain wave about 400 ms after the stimulus is detected in individuals that encounter an out-of-context word in a sentence reading task ('N400 wave' Kutas and Hillyard 1980). These are striking physiological correlates that differentiate fast cognitive responses by time and type.

Parallels Between the Spread of Myelination and Huntingtons Disease Neurotoxicity

The normal lifelong trajectory of human brain myelination has a quadratic-like (inverted U) shape with increasing myelin content that peaks in middle-age and subsequently breaks down and declines in older age (reviewed in 25,28,36 ). The myelin-centered view of the human brain defines our entire lifespan and especially the first six decades as a period of development as myelinated white matter volume increases 29,37 .

Sources Of Increased Iron In Parkinsons Disease

Area Notch Plate

At the post-transcriptional level cellular iron uptake and storage are regulated by cytoplasmic factors, iron-regulatory protein 1 and 2 (IRP-1 and IRP-2). When intracellular iron levels fall, IRPs bind to iron-responsive elements (IREs) in the 5'-untranslated region of ferritin mRNA and the 3'-untranslated region of the transferrin receptor mRNA, inhibiting the translation of ferritin RNA to decrease iron storage capacity and stimulates the translation of the transferrin receptor mRNA by stabilization of the mRNA to up-regulate iron uptake. When sufficient intracellular iron is present the opposite situation develops to down-regulate intracellular iron levels (reviewed in 69 ). These proteins have received recent attention because of the observation that IRPs can be regulated by ROS (reviewed in 70 ), suggesting that these proteins may represent an oxidant-mediated mechanism by which iron regulation can be altered. Of particular interest is the fact that the activation of IRP...

Factors Associated with Increased Risk for Parkinsons Disease

Lifetime cigarette smoking.9699100 Although not all studies confirmed the inverse association,101102 and a clearly defined biological basis for this finding has yet to be defined. One hypothesis is that smoking protects against the development of Parkinson's disease because of its effect on the enzyme monoamine oxidase (MAO) B. Cigarette smoke reduces MAO B activity in the animal and human brain.103 104 MAO B activates the neurotoxin MPTP, and a MAO B inhibitor, cigarette smoke, may offer neuroprotection in Parkinson's disease.61,105 Another hypothesis is that nicotine itself is neuroprotective,92 given that it has antioxidant properties.106 The nicotine in cigarette smoke may inhibit free radical formation and offer associated neuronal protection. An alternative hypothesis is that some inherent, perhaps life-long characteristic of those destined to develop Parkinson's disease also determines a constitutional lack of interest in smoking cigarettes. The relationship between...

Basal Cisterns Cisternogram

Brain Death Scan Vasc Flow Study

The full scope of nuclear medicine's role in the clinical evaluation of brain disorders is still evolving. Some applications have emerged as clearly useful, but others must be used in a prudent manner until there is additional documentation of their efficacy. Research in psychiatry, neurology and nuclear imaging should help us to characterise diseases affecting the human brain at their most fundamental, molecular level. Nuclear medicine imaging techniques are uniquely suited to the in vivo, non invasive measurement of such parameters. Neuropsychiatric nuclear medicine is probably at the threshold of an explosion in its clinical use.

The Il6 Response To Exercise

Muscle but we did detect IL-6 in the post-exercise samples. The observation that intramuscular IL-6 gene expression increases in skeletal muscle in response to exercise, was confirmed in a rat exercise model using the quantitative competitive RT-PCR method 56 . In this model, rats were subjected to electrically-stimulated eccentric or concentric contractions of one hind leg, while the other leg remained at rest. Both the eccentric and concentric contractions resulted in elevated levels of IL-6 mRNA in the exercised muscle, whereas the level in the resting leg was not elevated. It appears, therefore, that the local IL-6 production is connected with contracting muscle, and is not due to a systemic effect, because IL-6 mRNA was elevated only in the muscle from the exercising leg and not in the resting leg. As discussed, in these previous studies, we were unable to detect IL-6 mRNA in resting skeletal muscle. Of note, the finding of similar levels of IL-6 mRNA in both concentric and...

About Abt 695 Medicine Made By Frog Poison

Boksa, P. and Quirion, R., 3H N-methyl-carbamylcholine, a new radioligand specific for nicotinic acetylcholine receptors in brain, Eur. J. Pharmacol., 139, 323-333, 1987. Harfstrand, A., Adem, A., Fuxe, K., Agnati, L., Anderson, K., and Nordberg, A., Distribution of nicotinic cholinergic receptors in the rat tel- and diencephalon a quantitative receptor autoradiographical study using 3H acetylcholine, 125I -a-bun-garotoxin and 3H nicotine, Acta. Physiol. Scand., 132, 1-14, 1988. Houghtling, R., Davila-Garcia, M., and Kellar, K., Characterization of (+)- 3H Epi-batidine binding to nicotinic cholinergic receptors in rat and human brain, Mol. Pharmacol., 48, 280-287, 1995.

Melatonin Receptors As Therapeutic Targets

Molecular and pharmacological studies suggest the presence of melatonin receptors in the human central nervous system. Melatonin receptors were localized to the human suprachiasmatic nucleus and to the molecular layer of the cerebellum by receptor autoradiography with 2- 125I -iodomelatonin (19,21). In postmortem human cerebellar membranes 2- 125I -iodomelatonin binds to a site showing pharmacological characteristics similar to those of the human mt1 melatonin receptor (24,39). Both mt1 and MT2 mRNAs have been amplified from human tissues using reverse transcription polymerase chain reaction. The mt, mRNA was localized to the suprachiasmatic nucleus and retina and the MT2 to the retina, hippocampus and whole brain (8,21,23). Using in situ hybridization histochemistry, the mt1 melatonin receptor was localized to the suprachiasmatic nucleus and to the granule cell layer of the cerebellum of human postmortem brain (21,48). Recently, we demonstrated the localization of MT2 mRNA to human...

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