3D Brain Anatomy Models

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...

Flash Brain Anatomy Overview

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Highly Recommended

Some users might complain that the default interface is more complicated than it needs to be. If you just panicked grab a quick drink and relax because this baby has a full customizable interface.

However, Flash Brain Anatomy is a fairly good program considering the standard and depth of the material it provides. In addition to being effective and its great ease of use, this software makes worth every penny of its price.

Human Brain Tumor Xenograft Models

Xenografts of human brain tumors implanted intracranially or subcutaneously have proven useful as models for the study of human brain tumors. Nuclear magnetic resonance imaging (MRI) methods have been developed that can achieve volumetric comparison with histological methods and submillimeter resolution, improved by contrast enhancement with intravenous administration of a Gd agent 50-52 . Direct injection or convection-enhanced delivery of liposomes containing attached or encapsulated fluorochromes and or encapsulated gold particles were able to distribute throughout intracra-nially implanted U-87 glioma xenografts and into surrounding normal brain tissue by MRI scanning, thus demonstrating that convection-enhanced delivery of liposomes is feasible and may allow targeting of therapeutic agents to brain tumors 53 . MRI of murine brain tumors in different locations has been carried out with a 1.5 T MR system and a surface coil along with Gd injected via a tail vein to better delineate...

Computational Neuroanatomy Using Shape Transformations

The explosive growth of modern tomographic imaging methods has provided clinicians and scientists with the unique opportunity to study the structural and functional organization of the human brain, and to better understand how this organization is disturbed in many neurological diseases. Although the quest for understanding the anatomy and function of the brain has been very old, it has previously relied primarily on qualitative descriptions. The development of modern methods for image processing and analysis during the past 15 years has brought great promise for describing brain anatomy and function in quantitative ways, and for being able to characterize subtle yet important deviations from the norm, which might be associated with or lead to various kinds of diseases or disorders. Various methods for quantitative medical image analysis seem to be converging to the foundation of the emerging field of computational neuroanatomy, or more generally, computational anatomy. Despite the...

Assembling the Connectivity Matrix of the Human Brain

Since genetic approaches are not an option to chart the connectivity of the human brain how could we make progress here As the human brain is comparatively large we have the advantage of being able to use non-invasive imaging techniques to obtain structural and functional images with a resolution in the millimeter range. As defined above this would allow us to detect regional connectivity but not neuronal connectivity, and at present we have to rely on indirect measurements indicating anatomical connections. Creating the connectivity matrix of the human brain, however, is a worthwhile endeavour with great importance for cognitive neuroscience and neuropsychology. It would form a unique neuroinformatics resource for reference in a variety of fields, which would thereby make closer contact and maybe allow cross-linking of studies that were conceived with a very specific question in mind but have wider implications. As we suggested previously (Sporns et al. 2005) assembling the...

Bloodbrain Barrier In Human Brain Tumor Xenograft Models

Even though the blood-brain tumor barrier (BTB) is more permeable than the blood-brain barrier (BBB), the blood-brain tumor barrier still significantly restricts the delivery of anticancer drugs to brain tumors. Ningaraj et al., 15 were able to modulate the calcium-dependent potassium (K(Ca)) channel using a specific K(Ca) channel agonist, NS-1619, to obtain sustained enhancement of selective drug delivery in xenograft brain tumor models. NS-1619 administration was used to increase delivery of carboplatin, Her-2 monoclonal antibody and green fluorescence protein-adenoviral vectors to human brain tumor xenografts. P-glycoprotein (Pgp) in the blood-brain barrier limits the uptake of drugs such as paclitaxel into the brain. Kemper et al., 56 assessed the ability of several putative inhibitors of Pgp including cyclosporin A, PSC833, GF120918, and Cremophor EL, to improve the penetration of paclitaxel into mouse brain. Of the Pgp inhibitors tested, GF120918 was most effective in increasing...

Neuroanatomy

In recent years, much progress has been made in neuroanatomical research of eja-culatory processes. Most knowledge about the functional neuroanatomy of ejaculation is derived from male rat studies. With regard to male rat copulatory behavior, one has to distinguish among brain, brainstem, and spinal cord regions that become activated before and following ejaculation, when sensory information returns from the genitals (Fig. 9.1). The medial preoptic area (MPOA) in the rostral hypothalamus and the nucleus paragigantocellularis (nPGi) in the ventral medulla (6,7) are suggested as being important players in the process leading towards ejaculation. Electrical stimulation of the MPOA promotes ejaculation (8). It is hypothesized that ejaculation is tonically inhibited by serotonergic pathways descending from the nPGi to the lumbosacral motor nuclei. The present hypothesis is that the nPGi itself is inhibited by inhibitory stimuli from the MPOA. Disinhibition of the nPGi is supposed to lead...

The Human Brain

The human brain has three major subdivisions brainstem, cerebellum, and cerebrum. The CNS is first formed as a simple tubelike 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 cerebrum, as well as the spinal cord. As development continues, the brain is located within the cranium (para 4-13c(1)) in the cranial cavity. See figures 11-5A and 11-5B for illustrations of the adult brain. Figure 11-5A. Human brain (side view). Figure 11-5A. Human brain (side view). Figure 11-5B. Human brain (bottom view). Figure 11-5B. Human brain (bottom view).

Basic Principles Neurological Perspective

Acute, subacute, chronic) and to understand other coexisting factors that may be causing or influencing the patient's symptoms and signs. The neurologic examination is used to identify signs of neurologic dysfunction. This information is used along with knowledge of neuroanatomy and brain-behavior relationships to localize the area in the nervous system where there are signs of dysfunction. Information about the time course of disease and location within the nervous system is combined with knowledge of diseases of the nervous system to generate a differential diagnosis. This differential diagnosis helps dictate which diagnostic tests are ordered. The results of the diagnostic tests are used to refine or confirm the diagnosis or diagnoses.

Diane Pecher and Rolf A Zwaan

To fully understand why this idea is so exciting, we need to look at the history of cognitive science. One of the major ideas propelling the cognitive revolution was the computer metaphor, in which cognitive processes are likened to software computations (Turing, 1950). Just like software can run on different hardware systems, so can cognitive processes run independently from the hardware in which they happened to be implemented, the human brain and body. Furthermore, just as computer programs, the human mind was thought to manipulate abstract symbols in a rule-based manner. These symbols were abstract because they were not derived from interactions with the environment by way of sensory organs and effectors.

Sex determination and differentiation in C elegans

C. elegans is an androdioecious species. As shown in Fig. 1.1A, its two sexes are hermaphrodite and male. The hermaphrodite is essentially a modified female that produces and stores some sperm that can be used to self-fertilize its own oocytes. Animals of this sex lack male genital structures thus, C. elegans hermaphrodites are unable to cross-fertilize each other. In contrast, the male produces only sperm, and males can reproduce only by cross-fertilizing a hermaphrodite. Hermaphroditism is a recent evolutionary innovation in C. elegans, as its nearest phylogenetic neighbors are gonochoristic (i.e., malefemale) species (Kiontke et al., 2004), indicating that the hermaphrodite is generated from minor modification of an ancestral female developmental program. In self-fertilizing hermaphrodite populations, males arise very infrequently (< 0.3 ). Despite the relative rarity of the male, its developmental program is maintained in the genome, indicating that males may be required to...

The C elegans nervous system

The C. elegans nervous system simultaneously exhibits a minimalist simplicity and an astonishing complexity. The adult hermaphrodite nervous system comprises exactly 302 neurons, compared to 383 in the adult male. The identity and developmental history of each of these neurons have been completely described and are essentially identical between individuals. Moreover, through the painstaking work of John White and colleagues, the complete neuroanatomy of the adult hermaphrodite, including patterns of synaptic connectivity, has been reconstructed from serial electron micrographs (White et al., 1986). This wiring diagram for the C. elegans nervous system provides a substrate for understanding the neural control of behavior unrivaled in any system.

The Evolutionary Increase in the Size of the Main Areas of the Brain

The crucial change in the human brain in this million years or so has not been so much the increase in size by a factor of three, but the concentration of that increase in three or four main areas. The visual area has increased considerably, and, compared with the chimpanzee, the actual density of human brain cells is at least 50 percent greater.

Release Of Heat Shock Proteins In Vivo

It is well documented that specific cells within the brain can synthesise HSP72 in response to various cellular stresses, and, importantly, it has been shown that glial cells actively release HSP72 following stimulation (Guzhova et al, 2001). Therefore, we conducted a study to examine whether the human brain was capable of releasing HSP72 in response to exercise. HSP72 release was determined on the basis of the internal jugular venous to arterial balance and we were able to demonstrate that indeed the human brain is capable of releasing HSP72 in response to exercise (Lancaster et al, 2004).

Comparison and Validation

In this section, we compared several methods based on their volumetric segmentation accuracy when applied to singlechannel as well as two-channel MR data. For that purpose, we employed digital MR phantoms of neuroanatomy 12 that simulated the appearance and image characteristics of the Tl-weighted images and double-echo images in elderly populations, which generally have lower contrast-to-noise ratio than younger subjects. Because tissue volumes are typically measured across a wide range of ages, this phantom provides a conservative measure of segmentation performance. There are many advantages for using digital phantoms rather than real image data for comparing segmentation methods. These advantages include prior knowledge of the true compartment volumes (i.e., WM, GM, and CSF volumes) and control over image parameters such as mean intensity values, noise, slice thickness, partial volume effects, and magnetic field intensity inhomogeneities.

Partial Volume Classification Approach Using Voxel Histograms

FIGURE 2 One slice of data from a human brain. (a) The original two-valued MRI data. (b) Four of the identified materials, white matter, gray matter, cerebrospinal fluid, and muscle, separated out into separate images. (c) Overlaid results of the new classification mapped to different colors. Note the smooth boundaries where materials meet and the much lower incidence of misclassified samples than in Fig. 5. See also Plate 16.

From Philosophy To Theory

Works of the turn of the century nosologist Emil Kraepelin In the ordinary course of clinical work, we find that every disorder seems to sort itself into ever finer subcategories, which rest on an a priori basis, but instead flow from cultural and social factors and their interaction with biological influences such as constitution, temperament, or perhaps even systematic neurological defects. Accordingly, if society were different, or if the neurotransmitters chosen by evolution to bathe the human brain were different, the subtypes would be different also. Such entities are the pristine product of clinical observation, and however sharp the classification boundaries may be drawn between them, they are, in fact, unusually soft.

Relevance for vertebrate systems

To link sexual karyotype to the development of sex-specific characteristics. Arnold has proposed that regulatory genes on the X (that escape dosage compensation) and Y chromosomes may directly organize sex-specific CNS characteristics (Arnold, 2004). Indeed, there is some evidence that the Y-chromosome sex-determining gene Sry has such a role in the nervous system (Dewing et al., 2006). However, such a model may capture only one aspect of this process. It is also quite possible that sexual karyotype controls much more complex regulatory networks, such as those characteristic of C. elegans and Drosophila sex determination, that read the sex-determining signal and set into motion a cascade of interactions that only very indirectly lead to sex-specific gene expression. The potential existence of such a pathway in the mammalian nervous system has intriguing implications for the mechanisms that bring about sex differences in neuroanatomy and neural function moreover, genes in such a...

Quantitative Comparison with Other Algorithms

Because of the lack of a gold standard'' against which classification algorithms can be measured, it is difficult to compare the technique described here with others. Each technique presents a set of results from some application area, and so anecdotal comparisons can be made, but quantitative comparisons require reimplementing other algorithms. Work in generating a standard would greatly assist in the search for effective and accurate classification techniques. The voxel histogram technique appears to achieve a given level of accuracy with fewer vector elements than the eigenimages of Windham et al. 12 or the classification results of Choi et al. 14 , which use three-valued data. Their results are visually similar to the voxel histogram results and underscore the need for quantitative comparison. Because neighboring sample values are interpolated, a given accuracy can be achieved with two-valued or even scalar data, while their technique is likely to require more vector components....

Expression Profile of HDAC8 Transcript Suggests That HDAC8 Is a Ubiquitous HDAC

It has been suggested that HDAC8 mRNA is ubiquitously expressed since this transcript could be detected in all normal human tissues examined (1-3). Intriguingly, different authors have observed HDAC8 transcript to be expressed at the highest levels in different organs, including normal human brain (1,3), pancreas (1,4), kidney (3,4), prostate (3), and liver (2). Nevertheless, the expression profile of HDAC8 mRNA has been found to be distinctly different from that of HDAC1 to 3 transcripts (3).

Descriptive Modeling Of The Molecular Pathology Of Brain Tumors

Malignant progression in cancer, comparative geno-mic hybridization (CGH) reveals even smaller portions of chromosomes that are gained or lost during malignant progression. From this closer look at the chromosomal aberrations in tumors, has emerged a description of brain tumors that includes foundational demarcations highlighting the roles of activated oncogenes and lost dysfunctional tumor suppressor genes. From these studies, a coherent model for the role of different genes and chromosomal regions in gliomagenesis has been developed which informs changes based on the age of tumor onset, the pattern of progression of the disease, and the histological subtype at diagnosis 1 . The histo-logical and molecular genetic descriptors of human brain tumors are maturing into routine applications in diagnostic and prognostic practices 2 . These cutting-edge developments are updated here.

Predictive Modeling Of Therapeutic Vulnerability Of Brain Tumors

Marker selection in glioma is rendered more intricate by recent findings from Singh and coworkers who presented evidence for stem cells as initiators and maintainers of glial tumors. Brain tumor stem cells were isolated from different human brain tumor specimens and expressed neural stem cell markers such as CD133. These cells exhibit clonogenic capacity and are capable of tumor propagation. In a xenograft model, isolated CD133 positive but not CD133 negative cells exhibited tumorigenicity and could be passaged through several animals while closely resembling the morphology of the original tumor 59 . The recognition of tumor stem cells may introduce an assortment of new therapeutic approaches

Synaptogenesis In Human Cerebral Cortex

Figure 2.3 Changes in the relative densities of synapses in the primary visual cortex (discontinuous line) and prefrontal cortex (continuous line) of human brain as a function of days after conception expressed on a log scale on the abscissae. Phases 3 and 4 are indicated with numbers 3 and 4. (This is a schematic representation of data published in Huttenlocher and Dabholkar, 1997, with permission from the authors and John Wiley and Sons, Inc.) Figure 2.3 Changes in the relative densities of synapses in the primary visual cortex (discontinuous line) and prefrontal cortex (continuous line) of human brain as a function of days after conception expressed on a log scale on the abscissae. Phases 3 and 4 are indicated with numbers 3 and 4. (This is a schematic representation of data published in Huttenlocher and Dabholkar, 1997, with permission from the authors and John Wiley and Sons, Inc.)

Effects of environment on diverse phases of synaptogenesis

We observed a true loss of synapses in neocortex of macaque monkey around puberty (Bourgeois, Goldman-Rakic, and Rakic, 1994 Bourgeois and Rakic, 1993). A similar loss of synapses near puberty was also observed, using quantitative synaptology, in the cortices of human brain (Huttenlocher and Dabholkar, 1997) and mouse brains (de Felipe et al., 1997). These observations are confirmed by brain imaging in the macaque (Jacobs et al., 1995) and human cortices (Chugani, 1999).

Nutrition and the brain

The human brain has high energy and nutrient needs. Changes in energy or nutrient intake can alter both brain chemistry and the functioning of nerves in the brain. Intake of energy and several different nutrients affect levels of chemicals in the brain called neurotransmitters. Neurotransmitters transmit nerve impulses from one nerve cell to another, and they influence mood, sleep patterns, and thinking. Deficiencies or excesses of certain vitamins or minerals can damage nerves in the brain, causing changes in memory, limiting problem-solving ability, and impairing brain function.

Energy intake and mental health

Energy, often referred to as the calorie content of a food, is derived from the carbohydrate, protein, fat, and alcohol found in foods and beverages. Although vitamins and minerals are essential to the body, they provide no energy. The human brain is metabolically very active and uses about 20 to 30 of a person's energy intake at rest. Individuals who do not eat adequate calories from food to meet their energy requirements will experience changes in mental functioning. Simply skipping breakfast is associated with lower fluency and problem-solving ability, especially in individuals who are already slightly malnourished. A hungry person may also experience lack of energy or motivation.

High Spatial Resolution Spectroscopy

A specific application requiring lower resolution is the MR spectroscopic study of small animals. These studies are usually performed on dedicated animal systems, which offer ideal conditions. However, given their increasing diffusion, researchers are interested in using whole-body high-field MR systems for animal studies both for reasons of cost reduction and to perform direct comparisons of animal and human data. This requires new techniques that allow to achieve the highest possible spatial resolution and obtain conclusive data from brain structures that are several orders of magnitude smaller than the human brain while keeping examination times short to minimize animal mortality 59 .

Measures of Brain Dynamics Functional Connectivity

As many of the structural studies reviewed in the previous section illustrate, brain networks (like other biological networks) are neither completely random nor completely regular. instead their local and global structure exhibits significant departures from randomness. A key question concerns how these nonrandom features of brain structural connectivity relate to brain function or dynamics. A consideration of brain evolution may guide our answer. In the course of evolution, brain connectivity is one of the prime substrates, the gradual modification of which in an adaptive context contributes to enhanced fitness and survival. Biological structure function relationship often become more comprehensible when viewed in the context of evolution, for example when we consider the structure and function of proteins, cellular organelles, or entire body plans. The evolutionary history of the primate and especially human brain may ultimately hold the key for understanding the structural basis of...

Ricardo C Sampaio And Charles L Truwit

Myelination in the human central nervous system (CNS) is a complex but orderly process, occurring in predictable topographical and chronological sequences. The sequence of myelination in the human brain has been carefully defined by histochemical (Kinney et al., 1994 Yakovlev and Lecours, 1967) as well as imaging (Barkovich et al., 1988 Bird et al., 1989 Martin et al., 1991 Nakagawa et al., 1998 Staudt et al., 1993 van der Knaap and Valk, 1990) methods. Histochemi-cally, the CNS myelination begins as early as 12-14

MR of postnatal brain development

Myelination of the human brain has been studied in vivo by means of magnetic resonance (MR) imaging (Barkovich et al., 1988 Bird et al., 1989 Martin et al., 1991 Nakagawa et al., 1998 Staudt et al., 1993 van der Knaap and Valk, 1990). The fundamental work in this domain was done by Barkovich and colleagues (1988), later complemented by others (Bird et al., 1989 Huppi et al., 1998 Koenig et al., 1990 Martin et al., 1991 Nakagawa et al., 1998 Staudt et al., 1993 Takeda et al., 1997 van der Knaap and Valk, 1990). To better understand the following description, a brief review of MR terminology may be helpful. Most MR images used to assess myelination are based on the concept of T1 or T2 weighting (table 3.1), which reflect differences in tissue water. Tl-weighted images are typically more anatomic, whereas T2-weighted images typically show subtle abnormalities reflected in changes in water, or edema. More importantly, images can be Tl- or T2-weighted to optimize tissue characteristics.

Artificial Neural Networks

An ANN is a computational structure inspired by the study of biological neural processing. It has some capability for simulating the human brain and learning or recognizing a pattern based on partial (incomplete) information. Although there are many types of ANN topologies (e.g., from a relatively simple perceptron to a very complex recurrent network), by far the most popular network architecture is a multilayer feedforward ANN trained using the back-propagation method. Because it has been proved that only one hidden layer is enough to approximate any continuous function 10 , most ANNs used in medical image processing are three-layer networks. In this chapter, we only discuss three-layer feedforward ANNs, but the conclusion also should be applicable to other types of ANNs. Once the topology of an ANN (the number of neurons in each layer) is decided, the ANN needs to be trained either in supervised or unsupervised mode using a set of training samples. In the supervised training the...

Synaptic Transmission

Synapses provide the informational potential of the nervous system, as billions of neurons make many trillions of connections. The human brain at birth contains 60 to 100 billion neurons. If that number is equated to the number of trees in the Amazon rain forest, then the number of synapses can be compared to the number of leaves on those 60 to 100 billion trees.

Regional Connectivity

Moving from connections between individual neurons to connections between brain regions, the most widespread and valuable method delivering detailed information about directed long distance connections is neuroanatomical tract tracing (for reviews see Sawchenko and Swanson 1981 Kobbert et al., 2000 Wouterlood et al. 2002). The general approach comprises now a vast range of substances with the common feature that they are taken up by neurons and spread along their projections, where the label then can be visualized. Some substances are directly inserted intracellularly and therefore suitable for tracing of individual neurons. Most of the tracer substances, however, are applied extracellularly to the living tissue by pressure injection, iontophoresis or mechanical insertion. Most of them are actively incorporated through the neuronal membrane and transported in the cytoplasm to reveal the distant location of cell bodies (fast retrograde transport) or axonal terminals (fast and slow...

Assembling Connectivity Matrices

While macaques are a well investigated genus with particular relevance to the human brain, the wide availability of rodents has resulted in more detailed investigations at the columnar and cellular levels. This bears the promise to bridge levels and to understand the relationship between them. Unfortunately, not much corresponding efforts have been made to match investigations at the different levels.

Materials 21 Tissue Culture

Human brain-derived neurotrophic factor (R& D Systems, Minneapolis, MN cat. no. 248-BD). 7. Media for neural progenitor differentiation Neural progenitor differentiation media is comprised of Neurobasal media supplemented with B27, 10 ng mL human neurotrophin 3, and 10 ng mL human brain-derived neurotrophic factor. For 100 mL 89 mL Neurobasal, 1 mL B27, and 100 L of each human neurotrophin 3 (10 g mL) and human brain-derived neurotrophic factor (10 g mL).

Regulation of Expression of the FMR1 Gene in the Normal and Premutation Ranges

The FMR1 gene (L29074) spans approximately 38 kb of genomic DNA, and contains 17 exons and an unusually large (9.9-kb) first intron such introns have been implicated in both transcriptional and splicing regulation (Liu et al. 2000 Morishita et al. 2001). The gene is widely expressed in both neural and nonneural tissues, although at different levels in different tissues. High expression of a 4.4-kb transcript is observed by Northern blot analysis in brain, placenta, testis, lung, and kidney (Hinds et al. 1993). Lower expression is observed in liver, skeletal muscle, and pancreas. Multiple truncated transcripts of 1.4 kb have been observed in human heart (Hinds et al. 1993). In fetal human brain, FMR1 expression has been observed early in the development in proliferating and migrating cells of the nervous system, while in older brain tissues higher expression levels were detected in cholinergic and pyramidal neurons (Abitbol et al. 1993).

The Hypoxic Tumor Microenvironment And Hif Activation

Leading to a tumor microenvironment characterized by low oxygen tension, low glucose levels, and an acidic pH. Hypoxia is a common feature of solid tumor growth. Reduced pO2 levels have been found in the majority of human tumors analyzed as compared to normal tissue of the corresponding organ 2,3 . A wide range of genes known to be involved in adaptive mechanisms to hypoxia such as angiogenic growth factors, enzymes of glucose metabolism, and pH regulation have classically been associated with tumors. Many of these genes have subsequently been shown to be regulated by HIF function (see below). To date, more than 60 genes have been identified as potential HIF-target genes providing further evidence for HIF as a key regulatory system of adaptive mechanisms 4,5 . HIF activation is a frequent finding in human tumors. Indirect experimental evidence for the induction of HIF activity by the hypoxic tumor environment came from studies showing perinecrotic expression patterns of HIF target...

Melanin Concentrating Hormone Receptors

A second receptor, MCHR2, with similarly high affinity for MCH has been identified in the human brain.61-64 MCHR2 is distributed throughout the brain, especially in cortical areas expression levels in the feeding centers of the hypothalamus are low relative to other brain regions. Due to differences in expression pattern from MCHR1, it has been suggested that MCHR2 may be involved in physiological effects of MCH other than feeding behavior and neuroendocrine modulation. Because rodent genomes do not encode MCHR2, it will be difficult to determine a role for this receptor subtype in the human brain.

Aged Rodents for Biogerontology Research

Human aging is the result of a complex interaction between biological changes and environmental social influences. Healthcare throughout life, diet, and habits such as smoking, alcohol consumption and physical activity can all impact the rate of biological aging and complicate the study of the biology of aging in human populations. The rodent provides a venue for modeling the biological changes with age and investigating the genetic and physiological basis of aging and age-related diseases while controlling intrinsic and extrinsic influences. The genetic background, diet, environment, and health status of the rodent can be strictly controlled. Rodents are similar to humans in much of their physiology, cellular function, and to a lesser degree, even their anatomy. The musculoskeletal system, immune and endocrine systems, and gastrointestinal tract are very similar in both function and architecture between rodents and humans. Cardiac function has been modeled in rodents, as have...

Lymphatic and hematopoietic system see also chapters 14 and

HHV-6 replicates with low efficiency in neuroglial cells (Luppi et al., 1995). Viral DNA and antigen have been successfully demonstrated in human brain tissue, both in healthy organs and in diseased tissues, with subtype A being about three times more frequent than subtype B (Fig. 2 Luppi et al., 1995 Hall et al., 1998 Cuomo et al., 2001). There are increasing reports of HHV-6-associated meningitis, encephalitis in children with febrile seizures (Caserta et al., 1994 Wilborn et al., 1994 Knox and Carrigan, 1995 Bonthius and Karacay, 2002 Eeg-Olofsson, 2003), acute necrotizing or hemorrhagic encephalitis and demyelinating brain diseases in immune-deficient patients and in persons suffering from multiple sclerosis (Challoner et al., 1995 Wagner et al., 1997 Solldan et al., 2000 An et al., 2002 Cirone et al., 2002 Chapenko et al., 2003 Tejada-Simon et al., 2003). CNS infections with HHV-6 appear more frequent in patients with T-cell immune deficiency (Pruitt, 2003).

Implications Beyond The Formal Mtmm Approach

Considered in this light, it also becomes necessary to expand the MTMM approach to include data from other species. Specifically, most techniques that allow us to look at the causative effects of manipulating brain regions can only ethically be carried out in nonhuman populations. These animal studies typically proceed on the assumption that (a) there are homologous brain regions across species, (b) these regions perform the same tasks, and (c) the regions perform the tasks in the same way. However, despite many features that are conserved across species, even a cursory study of neuroanatomy reveals substantial interspecies differences. Given these potential cross-species differences, we need evidence of convergence and divergence across methods used in different species. It thus may prove useful to take a multitrait-multi-method-multispecies approach to evaluating brain-behavior relationships. In summary, the core logic articulated by Campbell and Fiske provides an extremely useful...

Other Action Of Gh In The

The classic hippocampal electrophysiological paradigm for learning and memory is long-term potentiation (LTP), but preliminary results suggest that no obvious defects are seen in the ability to induce LTP in GH-deficient dwarf rats (M. L. Errington and I. C. A. F. Robinson, unpublished). This does not exclude the possibility of local GH effects, or that these animals might show some deficits when tested in behavioral paradigms of learning and memory. Further experiments of this type are clearly warranted in view of the increasing evidence from clinical studies that GH administration to GH-deficient adults may be associated with positive effects on mood and mental performance (56,108). Although it is always difficult to exclude secondary effects of GH treatment (increased muscle strength, loss of fat, increased energy), direct effects of GH on the metabolism or protein synthesis of neural tissue have been demonstrated (109,110). Thus, the presence of central...

Neurofibrillary Tangles

In humans, abnormal hyperphosphorylation of the micro-tubule protein tau leads to the development of neuro-fibrillary tangles (NFTs), which are linked to cognitive decline in aging (Duyckaerts et al., 1997). In the dog, the role of neurofibrillary tangle formation is unclear. Although dogs exhibit early stages of tangle formation characterized by tau phosphorylation and an intracellular punctuate distribution, the morphology is distinct from the human brain and does not progress into thioflavine-S or silver positive NFTs (Cummings et al., 1996). Using AT8, a marker for early neurofibrillary tangle formation, Head et al. (2001) observed hyperphosphorylated tau in select neuronal populations in middle-aged but not old dogs. This is consistent with earlier studies of cytoskeletal abnormalities (Cumming et al., 1996), distended neurites (Wisniewski et al., 1970), and tau positive neurons (Uchida et al., 1993) in the dog.

Synapse formation in the human hippocampus

Light microscopic studies of the development of dendrites, and the early appearance of first spines, suggest that synapse formation starts early in the human hippocampal formation. It is extremely difficult to achieve adequate preservation of postmortem fetal or child brains for electron microscopy. Data relating to the synaptic development of the human hippocampal formation are rare. In accord with expectations based on studies of monkey brains (Berger, Alvarez, and Goldman-Rakic, 1993), the first synapses have been observed in the marginal zone and in the cortical subplate of Ammon's horn in a 15-week-old fetus (Kostovic et al., 1989). The axodendritic asymmetric synapses in the marginal zone suggest that entorhinal axons have already reached the hippocampus at that age, since those are the sole excitatory afferents in that zone. Recent findings using anterograde and retrograde tracers indicate that reciprocal entorhinal-hippocampal projections may be among the first corticocortical...

Brain Imaging In The

An alternate method of assessing volumetric brain changes in aging is VBM. VBM permits rapid voxel-by-voxel comparisons of local gray and white matter brain regions without the need for a priori selection of ROIs and is highly sensitive to volumetric differences in normal and pathological aging (Tisserand et al., 2004). Despite its popularity in human brain imaging, application of VBM for mapping brain aging in animal models is less common. We recently developed a VBM procedure for analyzing regional brain aging in the dog (Tapp et al., 2005b). The initial steps of this procedure are time consuming and require the creation of standardized dog brain templates and a priori probability maps but once

Error Correction Methods

Tractography may yield anatomical reconstruction errors with any technique. These errors can be minimized using one of two methods of result analysis, one based on functional brain anatomy and one, a probabilistic method, using a standard space of brain coordinates. The first consists of using the anatomical data a priori by requiring a fibre tract to pass through at least two manually selected regions of interest (ROIs) 34, 42 . Using a single ROI, the reconstructed tract is more likely to contain different fibres, some representing trajectories belonging to the tract being studied and others generated by partial volume effects or noise. The latter can be eliminated by selecting multiple ROIs along the fibre tract being reconstructed so as to avoid an erroneous deviation of the reconstruction algorithm from the actual trajectory (Fig. 8.7). This method makes it possible to track simply and non-invasively the position of several tracts with a high level of confidence 34 . Its main...

What Are the Limitations to Place Cell Research

Electrophysiological recording of single-cells is not the only means of studying neuronal activity. For example, the fMRI technique is a noninvasive way to study activation over the entire human brain, while the subject thinks about a computer screen (for applications relevant to aging, see Chapter 12 by Small). However, the spatial precision of fMRI is far from individual neurons, the trials must be averaged, which reduces temporal precision, and the subjects are restricted in behavior. Recently in animal research, gene activation studies have proved capable of studying the activity of single neurons simultaneously across many brain regions. cFos, Arc, and Homer are genes whose expression is induced immediately following neuronal activity. Through immunostaining, these genes provide a marker for which neurons have been activated during a particular time period prior to sacrifice of the rat. A drawback of the immediate-early gene technique to study neuronal activation is that the rat...

Ontogeny And Tissue Distribution Of Iodothyronine Sulfotransferases

The expression of the different sulfotransferases is tissue- and developmental stage-dependent. Richard et al. (2001) studied the ontogeny of SULT1A1 and 1A3 in human tissues. They found high but variable hSULT1A1 expression in the fetal and postnatal human liver, which reached half the expression level of adult liver. hSULT1A3 is differently regulated highest hSULT1A3 expression in the liver was found early in development, decreasing in the late fetal and early neonatal period, being absent in the adult liver (Richard et al., 2001). hSULT1A1 expression was also found in the fetal human brain, especially in the choroid plexus. In contrast, hSULT1A3 expression was low in the developing brain, with relatively the highest expression in cerebellum and germinal eminence (Richard et al., 2001).

Neurobiology of the Aging Brain

Different anatomical, histological, cellular, and sub-cellular alterations occur in the human brain during aging. Because of this wide variety of changes, often masked by compensating reactions, the identification of clear-cut decays due to age may constitute a difficult task. In the elderly, brain volume and weight decrease because of an insignificant loss of neurons, dendritic atrophy, and glial cells degeneration. Damage of blood vessels, due to atherosclerosis and amyloid angiopathy, by reducing brain blood perfusion, may play a role in neuronal, glial, and dendritic degenerative phenomena. Impaired cellular membrane turnover leads to accumulation of age pigments or lipofuscin. Loss of synapses, paired with an imbalance of neurotransmitter systems, occurs in physiological and, to a higher degree, pathological aging. Brain energy metabolism also declines in aging, which involves a decay in the mitochondrial metabolic competence that can be considered an unfavorable condition...

Energy Metabolism The Critical Role of Mitochondrial Function Decay

The human brain, representing less than 2 of the body weight, receives about 16 to 17 of the cardiac output and accounts for about 20 of the total oxygen consumption in resting conditions. From these data it can easily be inferred that routine brain functions are critically dependent on the synthesis of high energy intermediates by neurons and glia, although these two types of nerve cells have different energy requirements and, of course, there are marked differences between their energy demands. cognitive functions. Other areas of the old human brain appear to be differently affected by a decrease in CBF, but the most commonly observed age-related impairment has been found in the frontal lobes bilaterally. Moreover it has been found that in aging there is a decrease of CBF in gray, but not in white, matter (Leenders et al., 1990). The quantitative estimations of CBF may easily be affected by physiological, psychological, and environmental factors. However, the regional values...

Quick And Incomplete Tour Of Animal And Plant Development

Here we consider general characteristics of multicellular organization, and in Chapter 9 we will consider the genetic mechanisms that bring this structure about. First, we should repeat what has been noted by countless other biologists the range of multicellular organization cannot be arrayed in a hierarchical Great Chain of Being graded from worst to best. The simplest organisms are still with us and, if anything, seem far less likely to become extinct than most complex organisms (who may, in fact, be at an overall disadvantage and more vulnerable to extinction in the long run). If there is one multicellular structure that is better in this sense, it might be the human brain because it is the only structure that seems to make it possible to exterminate so many others, around the globe, at least in the short run.

Chemical Shift Effects

FIGURE 6 Diffusion weighted images collected in the human brain without (a) and with (b) navigator echo correction for microscopic bulk motions of the patient. A gradient b-value of 900 s mm2 was used in the anterior-posterior direction. Note the substantial correction made by the navigator echo information. FIGURE 6 Diffusion weighted images collected in the human brain without (a) and with (b) navigator echo correction for microscopic bulk motions of the patient. A gradient b-value of 900 s mm2 was used in the anterior-posterior direction. Note the substantial correction made by the navigator echo information.

Models of Brain Aging and Agerelated Pathologies

The studies on aging of the human brain are hampered by the obvious difficulties of carrying out investigations on fresh samples. On the other hand, post-mortem material may provide erroneous information because of the different circumstances and factors that can affect the reliability of the data obtained. These include, first of all, the agonal state of the patient and the post-mortem delay in performing autopsy. Neurobiological, genetic, and molecular studies conducted in laboratory rodents or in vitro systems, have documented the vulnerability of selected pools of neurons and the changes occurring in several neural systems and molecular processing with advancing age. However, in order to get results matching as much as possible those that potentially can be found in the old human brain, some animal models have been developed. These models, though constituting abundant sources of fresh brain samples to be investigated, may be helpful in better delineating the mechanisms of

Aged Nonhuman Primates

Nonhuman primates, for example, different monkey strains, develop age-related behavioral and brain alterations similar to those found in humans. Monkeys (e.g., Macaca mulatta) have an estimated lifespan of more than 35 years and are the best available model to study AD pathology. Behavioral testing has shown that memory and cognition decline in the second decade of the monkey life and are particularly evident in the mid- to late twenties. In old monkeys, dystrophic neurites, amyloid deposition, and alterations of specific neurotransmitter systems are similar, although less severe, than those reported in the old human brain and AD patients. Namely, slightly enlarged neurites and pre-amyloid deposits constitute the earliest lesions found in the parenchyma of the cortex of the animals around 20 years of age. In addition to the classical alterations found in the human brain (i.e., neurites containing membranous elements, degenerating mitochondria, lysosomes, APP, phosphorylated...

Dissociation and dissociative disorders

Moderate or severe forms of dissociation are caused by such traumatic experiences as childhood abuse, combat, criminal attacks, brainwashing in hostage situations, or involvement in a natural or transportation disaster. Patients with acute stress disorder, post-traumatic stress disorder (PTSD), conversion disorder, or somatization disorder may develop dissociative symptoms. Recent studies of trauma indicate that the human brain stores traumatic memories in a different way than normal memories. Traumatic memories are not processed or integrated into a person's ongoing life in the same fashion as normal memories. Instead they are dissociated, or split off, and may erupt into consciousness from time to time without warning. The affected person cannot control or edit these memories. Over a period of time, these two sets of memories, the normal and the traumatic, may coexist as parallel sets without being combined or blended. In extreme cases, different sets of dissociated memories may...

Inosine Monophosphate Imp Is Synthesized From Amphibolic Intermediates

Liver, the major site of purine nucleotide biosynthesis, provides purines and purine nucleosides for salvage and utilization by tissues incapable of their biosynthesis. For example, human brain has a low level of PRPP amidotransferase (reaction 2, Figure 34-2) and hence depends in part on exogenous purines. Erythrocytes and polymorphonuclear leukocytes cannot synthesize 5-phosphoribosylamine (structure III, Figure 34-2)

Cerebral Anatomy at the Macroscopic Level

In fact, most of the knowledge concerning the macroscopic architecture of the human brain came from the work of anatomists working at the end of the 19th century. At that time, these investigators had at their disposal only a few cadaver brains and no method of resectioning a brain in a different direction after an initial dissection. Therefore, they had to describe the coronal views using one hemisphere, the axial using another, and needed a second brain to describe the sagittal views. Additionally, removal of the brain from the skull resulted in deformations, and there was no formally standardized way to cut the brain into slices. Despite all these limitations, these anatomists did pioneering work and established the basis of modern brain anatomic labeling 2 . The human brain is a relatively small organ (around 1400 g) sitting within the skull and protected by membranes called the meninges, which include an external dense outer layer, called the dura mater, a thin inner layer,...

Models in Immature Animals

Precise correlations with human brain development are difficult, in particular because of the fact that rodents present an arrhinencephalic brain. However, brains of 7-day-old rats and 10-day-old mice are similar to third-trimester (34 to 35 weeks of gestation) human fetuses (and thus premature human newborns), in terms of cellular proliferation, cortical organization, synapse number, neurochemical indices such as neurotransmitter synthetic enzymes, and electrophysiology (Hagberg et al., 1994 Marret et al., 1995). Cortex of the 10- to 12-day-old rats (18-35 g) could correspond to term newborn with myelination of the fiber tract beginning on approximately day 11 in the rat (Rice et al., 1981). Based on these considerations, postnatal day 1 (P1) could be equivalent to 18 to 20 weeks gestation and P3 of 24 to 28 weeks gestation in humans.

Cytoarchitectural maturation of the cortex

The ontogenesis of all cortical regions follows a carefully timed sequence of events (Poliakov, 1965 Sidman and Rakic, 1973). All cortical neurons are generated along the ventricular surface in the so-called marginal zone and migrate toward the surface after undergoing several mitotic divisions. Poliakov (1965) described five stages of cortical development in human brain, beginning with Stage I at approximately the seventh fetal week when postmitotic cells begin to move upward. Stage V, the longest period, occurs between the sixteenth fetal week and the early postnatal period. During Stage V, postmitotic neuronal cells continue migrating and reach their final destination within the cortical plate. As neurons enter the cortical plate, those destined for more superficial layers arrive later than those that occupy deeper layers and show an inside-out progression (Rakic, 1974). Studies of motor cortex in humans have shown that by 7 months of gestation, layers V and VI have attained a more...

Developmental changes in specific neurotransmitter systems

The maturation of the prefrontal cortex must involve obligatory changes in both the intrinsic and extrinsic neurotransmitter systems that mediate its activity. Although there is a dearth of specific information regarding their development in human brain, the discussion that follows considers data obtained from studies in rodents where developmental changes of cortical neurotransmitters have been extensively characterized. It is true that the specific timing of developmental changes can vary considerably from one species to another nevertheless, some general principles can be formulated from the studies of rodent and, to a lesser extent, primate brain. In this regard, it is useful to point out that the equivalent of adolescence in rats occurs between postnatal weeks 3 and 8, while the early adult period begins at approximately postnatal day 60. Where available, studies in the developing human brain are also described. The amount of GABA and benzodiazepine receptor activity does not...

Average Density of GABAimmunoreactive Punctae per Ceil in Rat Medial Prefrontal Cortex

Serotonin The timing of developmental changes in the serotonin (5-hydroxytryptamine, or 5-HT) system is similar to that observed for the noradrenergic system (Hamon and Bourgoin, 1977 Hedner and Lundberg, 1980). Serotonin-containing neurons of the raphe nuclei in rat brain (Descarries, Beaudet, and Watkins, 1975) are first visualized between gestational days 13 and 17 when some of their axons have already grown toward the pyriform cortex (Wallace and Lauder, 1983). As seen with other transmitter systems in rat brain (see Dopamine below), 5-HT levels increase steadily between birth and the fourth postnatal week (Johnston, 1988). The synthesizing enzyme for 5-HT, tryptophan hydroxylase, is 10 of adult levels by birth, but rises to adult levels by postnatal day 30 (Deguchi and Barchas, 1972). During the perinatal period, high-affinity 5-HT receptor binding activity is approximately a third of that seen in adults, but does not attain adult levels until the sixth postnatal week (Uphouse...

Institutional Oversight of hES Cell Research

The second role of the ESCRO committee is to review research proposals that involve particularly sensitive kinds of research. It is important to note that the vast majority of in vitro experiments using already derived hES cell lines are unlikely to raise serious ethical issues and will require minimal review. However, proposals to generate additional hES cell lines by any means will require more extensive review. Some other experiments will also warrant careful consideration, including research in which the identity of the donors of the blastocysts or gametes from which the hES cells were derived is readily ascertainable by the investigator and experiments involving implantation of hES cells or human brain cells into nonhuman animals. Because of the sensitive nature of some aspects of hES cell research, it is critical that the scientific community propose and implement limits on what is to be allowed and provide clear guidance on which research activities require greater scrutiny....

Supranuclear Eye Movements

Transverse section of caudal pons. AbdNu, abducens nucleus AbdNr, abducens nerve AMV, anterior medullary velum CSp, corticospinal tract FacG, internal genu of facial nerve FacNr, facial nerve FacNu, facial nucleus LVN, lateral vestibular nucleus ML, medial lemniscus MLF, medial longitudinal fasciculus MVN, medial vestibular nucleus RetF, paramedian pontine reticular formation SCP, superior cerebellar peduncle SpTNu, spinal trigeminal nucleus SpTT, spinal trigeminal tract SVN, superior vestibular nucleus. (Adapted from Haines DE. Neuroanatomy an atlas of structures, sections, and systems. Baltimore Urban & Schwarzenberg, 1983, with permission.) FIGURE 5-4. Transverse section of caudal pons. AbdNu, abducens nucleus AbdNr, abducens nerve AMV, anterior medullary velum CSp, corticospinal tract FacG, internal genu of facial nerve FacNr, facial nerve FacNu, facial nucleus LVN, lateral vestibular nucleus ML, medial lemniscus MLF, medial longitudinal fasciculus MVN, medial...

Developmental similarities among transmitter systems

Regarding human brain, available evidence suggests that postnatal maturation of both the cholinergic and serotonergic systems may continue throughout childhood and adolescence, and may, in some cases, persist throughout the lifespan of the normal individual. Based on observations in rats, however, it seems likely that changes in the dopamine system are also occurring until the early adult period.

Nonlinear Spatial Transformation Models

More often, nonlinear spatial transformation models are used for intersubject registration. As discussed in the chapter Biological Underpinnings of Anatomic Consistency and Variability in the Human Brain, biological intersubject variability is highly unconstrained and varied. Nonlinear models are used to improve upon the results traditionally achieved with linear approaches such as the Talairach transformation discussed in the chapter Talairach Space as a Tool for Intersubject Standardization in the Brain, but it is implicitly understood that the spatial transformation model that is being used is only an approximation that may simultaneously overly constrain certain types of distortions while inadequately constraining others. In most cases, the

Wavelet Edge Detection and Segmentation

Figure 6.23 Sample results using multiscale texture segmentation. (a) Synthetic texture image. (b) Segmentation result for image (a) with a 2-class labeling. (c) MRI T1 image of a human brain. (d) Segmentation result for image (c) with a 4-class labeling. Figure 6.23 Sample results using multiscale texture segmentation. (a) Synthetic texture image. (b) Segmentation result for image (a) with a 2-class labeling. (c) MRI T1 image of a human brain. (d) Segmentation result for image (c) with a 4-class labeling.

Quantifying Anatomy via Shape Transformations

However, this approach has its roots in the early century's seminal work by D'Arcy Thompson 7 , who visualized the differences between various species by looking at transformations of Cartesian grids, which were attached to images of samples from the species. Although D'Arcy Thompson, with his insightful analysis, placed the roots for modern computational anatomy, his vision came short of realizing that this technique can be far more powerful than merely quantifying gross morphological differences across species. This is because modern image analysis techniques have made it possible to morph one anatomy to another with much higher accuracy than D'Arcy Thompson's transformations. We will see some examples later in this chapter. Placing this analogy in the context of computational neuroanatomy, we need three steps in order to construct a representation of an individual's anatomy. First, we must choose a unit. Here, the unit is a template of anatomy, perhaps an...

Causes and symptoms

The cause of Rett's disorder is a genetic mutation on the long arm of the X chromosome (Xq28) at a locus known as MECP2. The gene was discovered in 1999, and it produces a protein known as MeCP2, which is essential to life and crucial to the normal development of the human brain. The mutation that causes Rett's disorder allows other genes to become or remain active at inappropriate points in the brain's development. These activated genes interfere with the normal pattern of development and maturation of the brain's functions. Although Rett's disorder was previously thought to result from degeneration or deterioration of brain tissue, the discov-

Functional Imaging of Brain Activity and Connectivity with MEG

Magnetoencephalography (MEG) measures non-invasively the magnetic fields produced by electrical activity in the human brain at a millisecond temporal resolution. The generators of these magnetic fields are dendritic currents in the pyramidal cells of the cerebral cortex. Since the currents produced by individual neurons are exceedingly weak, thousands of neurons have to be coherently active to produce a field that can be measured by MEG. The macroscopic fields generated by such ensembles of coherent neurons have strengths on the order of a few picotesla and are still one billion times smaller than the magnetic field of the earth. The inverse problem is to find the neuronal activity, i.e. the location and strength of the associated ECDs, on the cerebral cortex or throughout the brain volume from noninvasive measurements of the magnetic fields produced outside the head. Likewise, if electroencephalographic (EEG) measurements are recorded, the change in scalp potentials due to the ECD...

Mechanisms Of Action

MAOs are intracellular enzymes found throughout the body, with most bound tightly to the outer mitochondrial membrane (11,12). The MAOs oxidatively deam-inate monoamines in the presence of oxygen (13). MAO-A is the primary form in the intestine, pancreas, and spleen, and the sole form in human placenta (14-16). MAO-B predominates in skin and skeletal muscle, and is the sole form in platelets. Although the human liver contains both forms, MAO is absent in plasma and red blood cells (17). Human brain MAO is 70 to 80 type B (18), whereas MAO-A predominates in rodent brain (19). MAO-A in the brain is found in the locus ceruleus, nucleus subceruleus, periventricular regions of the hypothalamus, and striatal dopaminergic neurons (20,21). MAO-A content of primate substantia nigra is low, relative to the number of tyrosine hydroxylase positive cells (21). Astrocytes are the main repository of brain MAO-B (21). With increasing age, human brain MAO-B but not MAO-A activity increases (22). The...

Positron Emission Tomography Scan Studies in Humans

Although male rat studies are of utmost importance for a better understanding of the neurobiology of ejaculation, brain imaging studies in humans are the tools which provide a better understanding of how the human brain mediates ejaculation and orgasm. Brain imaging studies will probably lead to a deeper insight into which parts of the brain mediate ejaculation and which parts are involved in the mechanism of orgasm, how these neural areas are linked to each other, and which parts are disturbed in the different ejaculatory and orgasm disturbances. The first Positron Emission Tomography (PET)-scan study during ejaculation has recently been conducted by Holstege et al. (14). Eleven healthy male volunteers were brought to ejaculation by manual stimulation of their female partner. The PET technique using radioactive water (H 5O) shows increases or decreases in blood flow in distinct parts of the brain, representing increases or decreases of activation of neurons in these areas. It was...

Learning and Memory Assessment

A second learning and memory task that highly complements the Morris water test is the cued and contextual conditioning test. This trial is much easier to perform in terms of less elaborate equipment needed, less time for investigator and mouse, and less laboratory space required. The test takes only 2 days with 10 min per mouse per day. Cued and contextual conditioning is based on fear conditioning in that it measures the ability of a mouse to learn and remember an association between an aversive experience and certain environmental cues. This type of fear conditioning is highly intuitive to mice as a species, because it is in their nature to freeze at the hint of danger. Conditioning training occurs on Day 1, when a mouse is placed in a chamber and allowed to explore for 2 min. After the timed exploration period, the animal is subjected to 30 sec of an auditory cue, white noise from an 80 dB broad-band auditory clicker. Following cessation of the white noise, the unconditioned...

Relative brain size and intelligence

Humans have the largest brain to body size ratio among terrestrial mammals, rivaled only by the smaller odontocete whales. The modern human brain has nearly tripled in size since the origins of the subfamily Homininae. The brain reaches its modern size relative to body size at approximately 300,000 years ago, which is late in human evolutionary history. Brain size reaches its apogee among the Neanderthals, where the average cranial capacity was about 300 cc more than that of the average for living humans (1,200 cc). Using other primates for comparison, many researchers argue that human brain size increase is associated with social intelligence, driven by complex social interactions and the ability to predict and manipulate the behavior of other members of the social group (Machiavellian intelligence). However, tool behavior also must be a factor that contributes to human technical intelligence and innovation. Furthermore, humans have an ability to understand and manipulate the...

Structure And Function Of The Human Sult1a Subfamily

SULT1E1 suggested that sulfonate transfer follows a random Bi Bi mechanism with two dead-end complexes (Zhang, 1998). These same authors also reported that the binding of -estradiol (E2) to human SULT1E1 resulted in two E2-binding sites catalytic subunit, suggesting that the enzyme contains an allosteric E2-binding site. In contrast to the random Bi Bi mechanism discussed above, two studies using purified SULTs from human brain (Whittemore et al., 1986) and rhesus monkey liver (Barnes et al., 1986) concluded that the sulfonation reaction proceeds via a sequentially ordered Bi Bi reaction. Varin and Ibrahim (1992) have also reported a similar mechanism for a plant flavonol SULT. When the crystal structure of mouse SULT1E1 complexed with PAP and E2 was solved, it became clear that the core structure resembles the uridine kinase enzyme, indicating a similar mechanism to phosphoryl transfer (i.e., SN2 in-line displacement Kakuta et al., 1997, 1998). The active site and the transition...

Challenges in 3D Brain Imaging

The complexity of human brain structure mandates the use of engineering approaches drawn from computer vision, image analysis, computer graphics, and artificial intelligence research fields to manipulate, analyze, and communicate brain data. The rapid growth in brain imaging technologies has also been matched by an extraordinary increase in the number of investigations analyzing brain structure and function in clinical and research settings.

Gene Structure And Regulation

Weinshilboum, 1995 Her et al., 1996 Raftogianis et al., 1996). The SULT1A1 and SULT1A2 genes are arranged head to tail, approximately 10 kbp apart. SULT1A1 is located most centromeric and SULT1A3 most telomeric of the three SULT1A genes, the latter being separated from the SULT1A2 gene by approximately 1.7 Mbp. All three genes contain seven coding exons and alternate untranslated first exons. Two alternatively transcribed exons have been identified for SULT1A1 and SULT1A2 mRNA species and three for SULT1A3 (Aksoy and Weinshilboum, 1995 Bernier et al., 1994a Raftogianis et al., 1996 Zhu et al., 1993a, 1993b). Our laboratory was the first to identify this phenomenon, which does not influence the coding exons but is limited to the 5'-untranslated region and could potentially be a tissue-specific mechanism. We found that the SULT1A1 cDNA isolated from a human brain library contains 41 bp of untranslated region found immediately upstream of the ATG start codon on the SULT1A1 gene, whereas...

Neurogenetic Syndromes

As with DS, research into the underlying neuroanatomical features of WMS reveals patterns of alteration concordant with our current understanding of functional neuroanatomy and the behavioral phenotype of WMS. Although both autopsy and MRI studies have shown that the overall brain size of persons with WMS is substantially decreased relative to typically developing controls, certain regions are relatively spared (24-26). As expected from the observation of preserved language and musical abilities in this condition, the temporal lobe, specifically the superior temporal gyrus (STG), is relatively preserved in volume. In addition, the cerebellum is preserved in volume, and, on average, is of similar size compared to typically developing individuals (25-27). Given recent studies implicating the cerebellum in higher cognitive and social abilities (28,29), disproportionately increased cerebellum may be related to the hypersociability seen in this condition. In contrast, regions of the brain...

Multiple Modalities and Dimensions

As noted earlier, because of pronounced anatomic variability between individual human brains, any atlas or clinical diagnostic system based on a single subject's anatomy cannot succeed fully. A deformable brain atlas counteracts some of the limitations of a fixed atlas by using mathematically flexible transformations. Nonetheless, its success is still based on the premise that brains resemble a prototypical template of anatomy and can be produced by continuously deforming it. Atlasing considerations suggest that a statistical confidence limit, rather than an absolute representation of neuroanatomy, may be more appropriate for representing particular subpopulations. Methods to create probabilistic brain atlases currently fall into three major categories, each differing slightly in its conceptual foundations. The three methods are density-based, label-based, and deformation-based approaches.

Dynamic Brain Atlases

Current atlases of fetal development 29,73 use collections of labeled data from multiple imaging modalities to characterize specific developmental stages. The first comprehensive MRI atlas of pediatric cranial anatomy 86 incorporates 180 MRI scans acquired parallel to the orbito-meatal anatomical plane, and 360 explanatory diagrams depicting functional neuroanatomy from birth through 16 years of age. In this collection, 3D horizontal and sagittal images facilitate identification of sulci and gyri. However, stereotaxic coordinate systems were not applied to the atlas data because of difficulties in using them to reference embryonic and pediatric data. In the spirit of the deformable atlas methods described earlier, extreme deformations could be imposed to fit all stages of development into a standardized atlas, but this would hardly meet the primary requirement of atlasing, which is to provide a natural coordinate framework in which to localize and classify structures present in...

Applications of Magnetic Resonance Imaging to the Study of Development

Abstract Recent methodological advances in magnetic resonance imaging (MRI) have revolutionized our ability to study the developing human brain. This chapter examines the use and promise of MRI in addressing key developmental questions, including how the healthy normal brain develops and how such development is related to behavior. This methodology can also help us understand the biological substrates of childhood disorders. Examples of studies that examine the biological progression of developmental disorders following treatment and remediation are provided. Used effectively, this methodology could shed light on an array of developmental questions with respect to both healthy and pathological development. Magnetic resonance imaging (MRI), with its lack of ionizing radiation and capacity to provide exquisite anatomical detail, has revolutionized the study of human brain development. Other imaging modalities, such as conventional radiography, computerized tomography (CT), positron...

Intracerebral Drug Infusion Glial Cell Line Derived Neurotrophic Factor

The first, large, randomized trial of intraventricular GDNF was published in 2003. In this trial, 50 patients underwent placement of pumps and intraventricular catheters. The patients were randomized to receive either carrier alone or one of several concentrations of recombinant GDNF. At six to eight months, none of the GDNF groups had demonstrated improvements over placebo and several of the groups had worsened (39). Additionally, adverse effects were noted in 100 of patients receiving GDNF. These included nausea, anorexia, and shock-like sensory symptoms resembling Lhermitte's phenomena. It was suggested that the relative size of the human brain makes the transependymal diffusion of GDNF insufficient to create the necessary concentrations to produce an effect (40).

Anatomy And Cell Biology

FIGURE 18-4 Medial surface of the right hemisphere of the human brain. Abbreviations C, cerebellum H, hypophysis He, haben-ular commissure P, pineal gland Pc, posterior commissure S, splen-ium of the corpus callosum SC, superior colliculus Ssc, superior subarachnoid cistern III, third ventricle. Scale in the bottom half shows 1-mm divisions. Reproduced with permission from Shafii, M., and Shafii, S. L. (eds.) (1990). Biological Rhythms, Mood Disorders, Light, Therapy, and the Pineal Gland. American Psychiatric Press, Inc., Washington, D.C. FIGURE 18-4 Medial surface of the right hemisphere of the human brain. Abbreviations C, cerebellum H, hypophysis He, haben-ular commissure P, pineal gland Pc, posterior commissure S, splen-ium of the corpus callosum SC, superior colliculus Ssc, superior subarachnoid cistern III, third ventricle. Scale in the bottom half shows 1-mm divisions. Reproduced with permission from Shafii, M., and Shafii, S. L. (eds.) (1990). Biological Rhythms, Mood...

Xcongenital Malformations Of The

Craniopharyngioma Infundibulum

Amold-Chiari malformation. Midsagittal section. (A) Normal cerebellum, fourth ventricle, and brain stem. (B) Abnormal cerebellum, fourth ventricle, and brain stem showing the common congenital anomalies (1) beaking ol the rectal plate, (2) aqucductal stenosis, (3) kinking and rranstoraminal herniation of the medulla into the vertebral canal, and herniation and unrolling of the cerebellar vermis into the vertebral canal. An accompanying meningomyelocele is common. (Reprinted with permission from Fix JD BRS Neuroanatomy. Baltimore, Williams Si Wilkins, 1996, p. 72.) Figure 4-7. Amold-Chiari malformation. Midsagittal section. (A) Normal cerebellum, fourth ventricle, and brain stem. (B) Abnormal cerebellum, fourth ventricle, and brain stem showing the common congenital anomalies (1) beaking ol the rectal plate, (2) aqucductal stenosis, (3) kinking and rranstoraminal herniation of the medulla into the vertebral canal, and herniation and unrolling of the cerebellar vermis into...

Ocn Ad P10 P5 R1 E18 Group

Because neural generation is most intense during the second trimester in humans and is largely complete by the third trimester, the second trimester is probably most similar to the last week of gestation in the rat. Similarly, because the third trimester in humans is a time of active cell migration and the beginning of differentiation, the third trimester of humans parallels the first week of life in the infant rat. From these observations, we would predict that the worst time for injury in the human brain would likely be the third trimester, whereas there should be relatively good compensation for injuries during the second trimester. It is interesting in this regard that one of the most common causes of epilepsy is now thought to be abnormalities of neural migration, which would occur in the third trimester.

Solutions To Exercises Lesson

The three major subdivisions of the human brain are the brainstem, the cerebellum, and the cerebrum. The brainstem is that part of the brain remaining after removal of the cerebrum and cerebellum. It is the basal portion. Together with the spinal cord, it is known as the neuraxis. (para 11 -9a)

Model For The Ageimpaired Medial Temporal System

Difference Rat Human Hippocampus

Figure 32.1 Schematic of the medial temporal lobe system, including the hippocampus and associated structures in human and rat brain. The top left diagram shows a mid-sagittal view of the human brain. The general area of the medial temporal lobe is identified and the hippocampal formation is shaded dark gray. The top right panel shows a circuit diagram, and demonstrates the flow of information within this system. Structures that are part of the medial temporal lobe in this system are seen in light gray boxes. Generally, the neocortex sends afferent projections to the hippocampus from the entorhinal cortex via parahippocampal structures. Other subcortical structures (e.g., cholinergic projections from the basal forebrain) also project to hippocampus and entorhinal cortex. The lower diagram shows the rat brain, with the hippocampus highlighted in dark gray. An enlarged coronal section through hippocampus illustrates the basic cellular circuitry within this region. Projections from...

Astrocyte glutamate transporters

Astrocyte Transporter

There are five types of glutamate transporters in the human brain, classified as EAAT1 to EAAT5 (where EAAT stands for Excitatory Amino Acid Transporter), out of which EAAT1 and EAAT2 are expressed in astrocytes, and the remaining three types are expressed in various types of neurones. Analogues of EAAT1 and EAAT 2 expressed in rat brain are known as GLAST (glutamate aspartate transporter) and GLT-1 (glutamate transporter-1), respectively. Functional properties of all transporters are similar, although they differ slightly in their binding affinities for glutamate.

The Psychobiology Of Stress

Balancing internal and external demands is reflected not only in CRH activity at the level of the hypothalamus, but also in CRH activity at extra-hypothalamic sites (Nemeroff, 1996). CRH is produced in many brain structures that are involved in associating fear and anxiety with activation of the stress system, including the amygdala and prefrontal cortex. In addition, one subtype of the CRH receptor, CRH1, appears specifically to mediate fear-related functions, whereas increasing evidence suggests that CRH2 receptors are more involved in anxiety states (Steckler & Holsboer, 1999). The neuroanatomy of the CRH system has lead to the (likely overly simplistic) view of CRH as the central orchestrator of the stress system, both in terms of endocrine and behavioral responses.

Schwann Cells Electrically Excitable

Glial Cells The Brain

There are two major classes of cells in the brain - neurones and glia (Figure 1.1). The fundamental difference between these lies in their electrical excitability -neurones are electrically excitable cells whereas glia represent nonexcitable neural cells. Neurones are able to respond to external stimulation by generation of a plasmalemmal 'all-or-none' action potential, capable of propagating through the neuronal network, although not all neurones generate action potentials. Glia are unable to generate an action potential in their plasma membrane (although they are able to express voltage-gated channels). Glial cells are populous (as they account for 90 per cent of all cells in the human brain) and diverse. In the central nervous system (CNS) they are represented by three types of cells of neural (i.e. ectodermal) origin, often referred to as 'macroglial cells' (which may also be properly called 'neuroglial cells'). These are the astrocytes, the oligodendrocytes and the ependymal...

Nonmyelinating Schwann Cells

Schwann Cell

4.1 Phylogeny of glia and evolutionary specificity of glial cells in human brain In human brain, glial cells are certainly the most numerous as it is generally believed that glial cells outnumber neurones in human brain by a factor of 10 to 50 although the precise number of cells in the brain of Homo sapiens remains unknown. Early estimates put a total number of neurones at 85 billion however, now we know that this number should be substantially larger as a cerebellum alone contains 105 billion neurones. Therefore, the human brain as a whole may contain several hundred billions of neurones and probably several trillions (or thousand billions) of astrocytes. Morphological data for the cortex are more reliable and they show that human brain has the highest glia to neurone ratio among all species (this ratio is 0.3 1 in mice and about 1.65 1 in human brain - see Figure 4.1). Interestingly, however, the overall volume of the glial compartment remains more or less constant as they occupy...

Biological Basis of EEG 21 Cortical Anatomy

It is estimated that there are roughly 1011 neurons in the human brain, and 1010 of these in the cortex. Of these, approximately 85 are pyramidal cells (Braitenberg and Schuz 1991), whose dendritic trees have a distinctive, elongated geometry that makes possible the generation of extracellular fields at large distances. The remaining 15 may be broadly classified as stellate cells, whose dendritic trees are approximately spherical, and make little or no contribution to distant fields. Of course, both cells types are interconnected to form a single dynamical network, but it is believed that the fields at large distances are dominated by pyramidal cells.

Brief Review Of Basic Aspects Of Nonconventional Mr Techniques

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 (Cr) and phosphocreatine, one at 2.0 ppm from N-acetyl groups (mainly NAA), and one at 1.3 ppm from the methyl resonance of lactate (Lac). NAA is a marker of axonal integrity, while Cho and Lac are considered as chemical correlates of acute inflammatory demyelinating changes (30). An immunopathologic study of MS (31) has indeed shown that a decrease in NAA levels is correlated with axonal loss, and an increase in Cho correlates with the presence of active demyelination and gliosis. 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. Therefore, 1H-MRS can complement conventional MRI in the assessment of MS patients by defining simultaneously...

Astrocytes as cellular substrate of memory and consciousness

Glial Cells The Brain

Contemporary neuroscience regards neuronal networks, and neuronal networks only, as the substrate of memory and consciousness. More than that, current understanding, in essence, denies the existence of special cells or cellular groups which can be the residence of memory, consciousness and other high cognitive functions. At the same time, information processing in the neuronal networks relies entirely on a simple binary code, which might not necessarily offer sophistication sufficient enough to explain how the human brain thinks and becomes

Age Related Hippocampa Dysfunction Early Alzheimers Disease vs Normal Aging

As we age, all of us will experience an inexorable slide into forgetfulness. Age-related memory decline localizes, in part, to the hippocampal formation, a brain circuit made up of separate but interconnected hippocampal subregions. Human studies have established that Alzheimer's disease targets the hippocampal circuit early in its course, and since Alzheimer's disease affects older individuals it is one cause of age-related hippocampal dysfunction. Animal studies, however, have established that the aging process itself targets the hippocampal circuit, contributing to age-related hippo-campal dysfunction observed in all mammalian species. These independent observations have led to a continued debate among investigators of the aging human brain, summarized by the following questions Is age-related hippocampal dysfunction in humans etiologically homogeneous, or is age-related hippocampal dysfunction caused by both AD and by normal aging If age-related hippocampal dysfunction is caused...

And L Judson Chandler PhD

Alcohol-induced changes in the brain have been studied in both humans and rodents. A variety of postmortem histological analyses as well as supporting imaging analyses suggest that chronic alcohol exposure changes brain structure (2,3). Computed tomography (CT) and magnetic resonance imaging (MRI) studies of the human brain have repeatedly shown enlargement of the cerebral ventricles and sulci in most alcoholics. The enlargement of the ventricles and sulci essentially reflect a shrinking of the brain mass. This is consistent with studies on postmortem brain tissue, which show that alcoholics have a reduction in total brain weight relative to controls. Particularly severe alcoholics have significant reductions in global cerebral hemisphere and cerebellar mass compared to controls and moderate drinkers (8). Some of this loss of brain mass is likely the result of actual loss of neurons and the resulting loss of myelin sheath white matter, which normally envelops neuronal extensions....

Anatomical and Functional Variability

Brain, as determined by intraoperative cortical electrical stimulation 39 . Finally, neuroimaging studies have observed that functional areas as fundamental as primary motor cortex for mouth may bear no relation to any detectable sulcal or gyral feature'' 29,45,52 . This lack of correspondence between functional areas and gross anatomical features is a clear indication that an alternative to the gross anatomical space'' is needed for functional mapping ofthe human brain. For those mapping cortical areas in the macaque monkey and other non human primates, the alternative that has been developed and adopted is a surface-flattened, planar reporting space 51 . For a large and rapidly growing segment of the human neuroscience community, the alternative to the gross anatomical space'' is a 3D volumetric space, the Talairach space 19 .

Humoral Immunity As Indirect Evidence For Autoimmunity In Ms

Several groups of investigators have performed these studies with very consistent results. For example, in one study, IgG VH sequences from two acute MS plaques from a single patient were examined and compared with IgG VH sequences in subacute sclerosing panencephalitis (SSPE) brain and normal human brain. As expected, IgG purified from both the SSPE and MS brains displayed OCBs, whereas the normal human brain displayed a more heterogeneous Ig pattern. When the VH regions were cloned and sequenced, VH4 usage predominated within MS lesions, although the majority of sequences at the two sites from the one MS patient were different. All CDR sequences from the acute MS plaques displayed mutations compared to the germline (105). The same group later reported on studies of two additional MS brains where, once again, genes encoding Ig within MS plaques were more restricted in gene segment usage than germline, displayed multiple mutations, and had a high percentage of replacement mutations in...

Aging And Longevity Of Species

A relationship between the level of chaperone expression and the longevity of species can be assumed from the observation that the constitutional expression of Hsp70 in human pancreatic islets is about five times higher than in the islets of mice or rats. Also, the basal level of expression of Hsp70 in the human brain has been observed to be about 50 fold higher than in rat brain. Modifications of chaperone expression caused by hormonal factors may also influence life span. Thus, in humans, the estrogen-induced higher levels of expression of Hsp72 and Hsp90 alpha might contribute to the difference in longevity between genders. Concerning the circulating levels of chaperones, regression analysis has revealed a progressive decline with age in the serum levels of Hsp60 and Hsp70, probably a consequence of the age-related reduced ability to respond to stress (Krall, 2005).

Sexual differentiation

Sex differences in phenotype are also analyzed at the level of the supporting neuroanatomy (Madeira and Lieberman, 1995 Simerly, 2002). The medial preoptic area (MPOA) of the rat is essential for the expression of male sexual behavior. Studies of Gorski et al. (1980) reveal a sexually dimorphic region of the MPOA that is significantly larger in male than in female rats. The gender difference in the size of the sexually dimorphic nucleus of the MPOA is androgen sensitive. The nucleus is significantly smaller in males castrated at birth, and equivalent in size in females treated with androgens in late fetal and early postnatal life (Gorski, 1984). The gender difference in the MPOA is apparent in early postnatal life and is associated with an increase in neurogenesis in the males (Jacobson et al., 1985) as well as an increased rate of neuron death in the females (Davis et al., 1996 McCarthy et al., 1997). In mice, ablation of bax, a member of the Bcl-2 family of proteins that is required...

Molecular Genetics of Brain TumorsAn Overview

ABSTRACT Human brain tumors continue to benefit from ongoing investigation of the molecular genetic changes that explain gliomagenesis, malignant progression, patient outcome, and possibly therapeutic responsiveness. Optimal utilization of current therapies may be gained by using molecular genetic markers of glial tumors, but meaningful advances in improved patient treatment will emerge from new therapies matched to the specific chemo-vulnerabilities of these tumors as addressed by small-molecule agents specifically targeting the points of vulnerability.

Segregation and Integration

Anatomical and functional segregation refers to the existence of specialized neurons and brain areas, organized into distinct neuronal populations grouped together to form segregated cortical areas (Shipp and Zeki, 1985 Zeki, 1993). The concept of anatomical segregation is rooted in the notion that specific brain processes or functions can be localized to specific anatomical regions of the human brain, an idea that is central to the history of neurology and cognitive neuroscience (Phillips et al., 1984). Maps of cortical regions, such as those assembled by Ungerleider and Mishkin (1982), Van Essen and Maunsell (1983), Zeki and Shipp (1988), and Felleman and Van Essen (1991) have provided increasingly refined network diagrams of multiple anatomically

Springer Complexity

Complex Systems are systems that comprise many interacting parts with the ability to generate a new quality of macroscopic collective behavior the manifestations of which are the spontaneous formation of distinctive temporal, spatial or functional structures. Models of such systems can be successfully mapped onto quite diverse real-life situations like the climate, the coherent emission of light from lasers, chemical reaction-diffusion systems, biological cellular networks, the dynamics of stock markets and of the internet, earthquake statistics and prediction, freeway traffic, the human brain, or the formation of opinions in social systems, to name just some of the popular applications.

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