Neuroanatomy Software

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. Continue reading...

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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...

Finally Some Glimmering Of Success

Billie had been working hard for months trying to improve cultures of PHFG cells. It was slow going. Initially the cultures consisted of astrocytes that would form a monolayer, but spongioblasts were either sparse or absent. We thought it important to have good cultures of spongioblasts because neurobiologists considered spongioblasts to be precursors of oligodendrocytes, the cells in which the virus was found in human brain.

Questions For Future Studies

In conclusion, during the late stage, production of progeny virions is regulated in multiple steps, including transcription, splicing, translation, nuclear transport, and maturation of virions (Fig. 8.9). We have shown in this chapter that JCV has distinctive regulatory mechanism from SV40 and murine polyoma virus. Studies on the underlying molecular mechanisms in the production of progeny virions and their structures can contribute to understanding the nature of JCV and the pathogenesis of PML. Inhibition of critical regulatory steps in the production of progeny virions may provide an efficient therapy for progressive demyelination in the JCV-infected human brain.

The Start Of A Collaboration

After obtaining the New Jersey tissue, we had enough virus-containing tissue to begin serious work. We began what turned into a long and frustrating series of efforts to cultivate the virus from the diseased tissue. We tried explants of the fresh brain tissue, but after many weeks of coaxing and coddling only a few fibroblasts and astrocytes grew. We made 10 extracts of diseased brain tissue and clarified it by centrifugation and then used the supernatant fluid to inoculate cell cultures. A similar extract of normal human brain tissue was used on control cultures. Monolayer cultures of primary and secondary human embryonic kidney cells, Hep-2 cells, and human fibroblasts were inoculated. None of these cell cultures showed any evidence of being infected even after weeks of cultivation and medium changes and subculturing. Mice, newborn mice, and hamsters were inoculated by the intracerebral and peritoneal routes and were observed for many months without showing signs of disease or...

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 (

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.

Elements of Functional Neuroimaging

There has been explosive interest in the use of brain imaging to study cognitive and affective processes in recent years. Examine Figure 2.1, for example, to see the dramatic rise in numbers of publications using positron emission tomography (PET) and functional Magnetic Resonance Imaging (fMRI) from 1985 to 2004. A recent surge in inte-grative empirical work that combines data from human performance, neuroimaging, neuropsychology, and psy-chophysiology provides a more comprehensive, but more complex, view of the human brain-mind than ever before. Because the palette of evidence from which researchers draw is larger, there is an increasing need to for cross-disciplinary integration and education. Our goal in this chapter is to provide an introduction to the growing field of neuroimaging research, including a brief survey of important issues and new directions.

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).

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...

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).

Astrocyte glutamate transporters

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.

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

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 schemadc 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 schemadc representation of data published in Huttenlocher and Dabholkar, 1997, with permission from the authors and John Wiley and Sons, Inc.)

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...

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).

Is the wafl dpi gene altered in cancer

Reported in colorectal cancer and somatic mutations have not been found in codons 9 through 139 that were screened (Li YJ et al, 1995). Multiple polymorphisms were seen in human brain tumours, most frequently of codon 31 - again there were no somatic mutations (Koopmann et al, 1995). Codon 31 polymorphism occurs also in normal individuals (Li YJ et al, 1995 Marchetti et al., 1995c) and, in the brain tumour study, the polymorphisms did not relate to histological type (Koopmann et al, 1995). Jung et al (1995b) also investigated gliomas for wafl cipl abnormalities. Surprisingly, wafl cipl protein levels were low in normal brain tissue and in reactive gliosis, but were highly elevated in gliomas irrespective of grade. Glioblastoma multiforme showed elevated protein levels, in tumour samples carrying either wild-type or mutated p53- No elevation of protein occurred in anaplastic astrocytomas carrying mutant p53-Jung et al (1995b) also stated that wafl cipl gene is not deleted in gliomas....

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.

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

Neuropathological Findings in the PostHAART

In the adult human brain, six isoforms of Tau are expressed by alternative mRNA splicing from a single gene. Abnormalities in Tau mRNA splicing are linked with frontotemporal dementia and parkinsonism linked to chromosome 17, and similar alterations are suggested in sporadic tauopathies, such as progressive supranuclear palsy or corticobasal degeneration (85). Alterations in Tau mRNA have also been linked with alterations in neurofilament gene expression, suggesting that these structural support proteins of the neuron are intrinsically linked to the degenerative process (85). In vitro studies have shown altered neurofilament gene expression in neuronal co-cultures exposed to supernatant from HAART-treated macrophages (77). Changes in neural cell signalling proteins as well as structural and functional proteins may represent subtle forms of cellular dysfunction rather than frank cell death (77).

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.

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).

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.

Prion proteins and prion diseases

Similar observations were made with kuru, a disease prevalent in the Fore people of Papua New Guinea. Kuru was spread by cannibalism (ritual eating of infected human brain), until the colonial power (Australia) stomped out this habit in 1957. New cases are still reported from time to time, but only in older people who probably became infected while cannibalism was still rife. This points to a very long incubation period which can exceed 40 years. Victims first giggle and tremble uncontrollably (kuru actually means the laughing death ), later they lose all awareness and control over body functions and finally die.

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).

Model For The Ageimpaired Medial Temporal System

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...

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...

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...

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.

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

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...

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...

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...

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

Astrocytes as cellular substrate of memory and consciousness

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

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...

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...

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).

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...

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.

The Inverse Problem in MEGEEG

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...

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...

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...

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...

Overview of Neuroimaging Methods

Neuroimaging permits the in vivo (and largely non-invasive) study of the human brain through quantification of functional neurochemical, metabolic, and micro- (e.g., white matter tracts) and macro-structural (localized volume and density of gray and white matter) features. In particular, using magnetic resonance imaging (MRI), the same scanner can generate a range of quantifiable biological measurements within the same individual to give convergent multivariate information about functional and structural integrity of brain processes. Among MRI methods, functional MRI (fMRI) of brain (measuring regional hemodynamic changes contingent on local neural activity) now represents a leading human neuroscientific tool, having developed rapidly from positron emission tomography (PET) techniques for measuring regional cerebral blood flow and metabolism. By labeling specific molecules with radioisotopes, PET uses the source localization of radioactive decay to provide three-dimensional, absolute...

Functional Brain Changes in MDD

Functional neuroimaging studies have contributed greatly to the widely held view that MDD is a brain disorder affecting an integrated system of cortical, subcortical, and limbic structures (Mayberg, 1997). To fully appreciate the complexity of the functional neuroanatomy of MDD, it is useful to consider at least two types of studies. The first are studies in which functional activity in specific brain regions at one point in time differs in MDD relative to non-depressed control subjects. The second are fMRI studies of antidepressant treatment response. Studies using different methodologies provide converging results, which support the conceptualization of MDD as a disorder associated with increased functional activity in reciprocally connected (Mesulam and Mufson, 1982) structures such as the amygdala, subgenual ACC, and insula, which are critically involved in emotion processing, and with decreased activity in the PFC and ACC, which are involved in emotion regulation. Debate remains...

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).

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...

Pros and Cons of the Accumulator Model of PD Timing Effects

While the most important outcome from these simulations is the light it sheds on the manner in which limitations of SET can be overcome to account for migration, this model has certain features that interest us with respect to modeling timing in the basal ganglia. An important aspect of basal ganglia anatomy is the dichotomy between the direct and indirect pathways from the striatum to the globus pallidus. Both of these pathways originate in the striatum (Bejjani et al., 1997 Benabid et al., 1991, 1998 Limousin et al., 1995a, 1995b, 1998 Mitchell et al., 1986, 1995 Molinuevo et al., 2000 Pollak et al., 2002 Yelnik et al., 2000), rely on dopaminergic function (Young and Penney, 1984), and terminate at the globus pallidus (Albin et al., 1989 Crossman, 1989 DeLong, 1990 Filion et al., 1991 Miller and DeLong, 1987 Robertson et al., 1990, 1991 Tronnier et al., 1997). The net influence of activity in these pathways is opposite in that the direct pathway upregulates pallidal activity, while...

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.

The great areal expansion of the association cortices

The development of the immensely convoluted human cortex begins in the second trimester of pregnancy, and is mediated by extraordinarily complex, yet precise, molecular events (for a recent review, see Rakic (2009)). Recent whole-genome, exon-level expression characterization of the developing human brain has revealed molecules that are differentially expressed in the developing primate and or human association cortices (Johnson et al., 2009). The wealth of genes identified by this and similar studies will likely guide many future explorations of molecules mediating cortical development. Importantly, differential gene expression was prevalent even within the developing PFC.

Summary And Conclusions

In summary, research conducted over the past four decades has established the ERP as one of the main tools available to cognitive neuroscientists. The advantages of ERPs include their exquisite temporal resolution, relatively low cost and portability, and their high level of sensitivity to - and specificity for - aspects of cognitive processing. These qualities have allowed ERPs to be applied to the investigation of a number of theoretical issues that are relevant to cognitive psychology and cognitive neuroscience. Recently, several other neuroimaging techniques have flanked ERPs as tools for investigating the function of the human brain. However, rather than replacing ERPs as a method of choice, it appears that a combination of different approaches (including not only imaging methods but also neuropsychological and neurophysiological data) may provide a more complete description of the mind-brain system than the use of one technique alone.

Equivalent dipole approaches Dipole Source Modeling

In recent years, substantial progress has been made to extend the original dipole fitting approach implemented using simplified spherical head models to more realistic geometry head model constructed from single subject's MRI images, in particular using boundary element methods (BEM) or finite element methods (FEM). Not surprisingly, simulation and experimental studies have shown that a more accurate localization can be achieved by using realistic head models (e.g., Fuchs, Wagner, & Kastner, 2001). In a recent study (Cuffin, Schomer, Ives, & Blume, 2001), the best average localization that could be achieved with spherical head model was 10 mm. In addition to improved localization capability, co-registration with MRI images can be used to visualize the dipole location coordinates relative to brain anatomy, facilitating comparisons with other functional imaging modalities. Studies combining electrophysiological and hemodynamic measures have further extended dipole source localization...

Oxidations and reductions of alcohols aldehydes and ketones

Human brain enzyme is composed of at least five isozymes, pI 5.3, 6.0, 6.3, 7.0 and 7.9. They all act on p -nitrobenzaldehyde and indole-3-acetaldehyde, but are distinguished by their relative activities towards menadione, daunorubicin, p -hydroxyphenylacetaldehyde and p -hydroxymandelaldehyde as potential substrates. All require NADPH one that can also utilize NADH appears to be succinic semialdehyde reductase (E.C. 1.2.1.16 E.C. 1.2.1.24). The pI 7.9 enzyme is strongly inhibited by quercetin and quercitrin B569 . Human brain aflatoxin B1 aldehyde reductase is identical with succinic semialdehyde reductase, which also reduces phenanthrene-9,10-quinone, phenylglyoxal and p -nitrobenzaldehyde K273 . Four or possibly 5 isozymes of aldehyde reductase in human brain reduce indole-3-acetaldehyde and p -nitrobenzaldehyde, with pI 5.3 (this isozyme appears to be E.C. 1.1.1.2), 6.0, 6.3, and the fourth fraction shows two values at 7.0 (minor) and 7.9. They require NADPH, although one isozyme...

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...

Historical Developments

The soul or mind squeezed the pineal gland this way and that, nudging the animal fluids in the human brain into the pores or valves, 'and according as they enter or even only as they tend to enter more or less into this or that nerve, they have the power of changing the form of the muscle into which the nerve is inserted, and by this means making the limbs move.' (Jaynes, 1973, p. 172, paraphrasing and quoting from Descartes, 1824, p. 347)

Collaborative Organization

Tremendous diversity has occurred in receptors in mammals. There are hundreds of serotonin receptor clones, and the human brain has at least 20 separate neuronal transcripts of 5-HT receptors (Moroz et al., 2006). Serotonin is specifically bound to at least 16 specific receptor proteins in the human brain which regulate ion channels, c-AMP levels and kinase activity in neurons. The 5-HT receptors are found in every cell of the body. Why so many, and why such a large distribution It can be speculated that the difficulty in making and obtaining tryptophan in animals results in low serotonin availability. The function of a receptor is to alert a cell that a chemical is present in the environment, without removing or altering the chemical. Thus, if a chemical is in short supply, the appearance of receptor molecules permits its actions The idea that serotonin functions as a trophic factor in vertebrate brains requires a new concept for how serotonin can be most efficiently distributed from...

Spatial aspects of SZ etiology andor pathophysiology

Mouse Brain Stereotaxic Coordinates

Unlike the studies with postmortem brains, in which the results might be affected by long-term medication in the subjects and other confounding factors (Halim et al., 2008 Hashimoto et al., 2007 Li et al., 2004), human brain imaging techniques including fMRI (functional magnetic resonance imaging), PET (positron emission tomography), SPECT (single-photon emission computed tomography), DTI (diffusion tensor imaging), and MRS (magnetic resonance spectroscopy) are able to assess brain functions from first episode-, drug naive-patients (Davidson and Heinrichs, 2003 McGuire et al., 2008 Pantelis et al., 2003 Sun et al., 2008 Thompson et al., 2001 Vidal et al., 2006 Wright et al., 2000). It has been repeatedly reported that hypofrontality occurs in SZ individuals as evidenced through PET scanning (Andreasen et al., 1992) this was reinforced by the meta-analysis of 41 functional neuroimaging studies (Minzenberg et al., 2009), which suggested that patients with SZ show altered activity with...

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.

Conclusion

Time in one individual patient, or between populations. Knowledge of the deformation of the label atlas would allow nonrigid multimodal registration of images of different patients and provide a common reference frame for population studies. Deriving realistic statistical models for the shape of the human brain is, therefore, a major challenge for further research.

Douglas S Portman

As a well-characterized, genetically tractable animal, the nematode Caenorhabditis elegans is an ideal model to explore the connections between genes and the sexual regulation of the nervous system and behavior. The two sexes of C. elegans, males and hermaphrodites, have precisely defined differences in neuroanatomy superimposed onto a core nervous system of exactly 294 neurons, hermaphrodites

Introduction

The key diagnostic test for RP is the electroretinogram (ERG), which measures rod and cone function. The ERG detects changes in rod function early in the disease process, often before patients are mentally aware of visual dysfunction. Because of the remarkable adaptive abilities of the human brain, as much as 90 of rod cells can be lost before a patient is aware of visual changes. Thus, by the time most patients seek medical attention, the disease is in advanced stages. The slow, progressive degeneration of rod photoreceptors inevitably leads to the loss of cone photoreceptors, which are responsible for high acuity, bright light vision. Cone photoreceptors are concentrated in the center of the retina in the ''fovea.'' The reason for the sequential degeneration is not fully understood, but it appears that cone survival is dependent upon the survival of rod photoreceptors.

Physical Context

Another structural scanning technique is diffusion tensor imaging. This technique allows one to identify white-matter tracts (such as corpus callosum) in the human brain and changes in these structures as a function of some variable, such as age or training. Although not a technique to image brain function, tractography, most often performed using diffusion tensor imaging (DTI) in MRI, is a technique that allows the investigator to map the white matter tracts that connect regions of the brain and hence determine the physical connectivity network underlying brain activity (Peled, Gudb-jartsson, Westin, Kikinis, & Jolesz, 1998). MR images can

Summary

The unique ability of MR imaging to reveal not only gross structural organization of the human brain but also macroscopic changes in intra- and extracellular water (diffusion-weighted MR imaging) enables us to see the in vivo human brain as never before. In this chapter, the process and sequence of brain myelination have been reviewed, as has the correlate appearance on MR images. In tandem with the structural changes that occur with myelination are functional changes of the human central nervous system. Over the past five years, and certainly over the next five years, cognitive neuro-scientists and their neuroradiological counterparts have had and will have incredible opportunities to see brain function with the relatively new field of functional MR imaging. While fMRI of the pediatric brain remains in its infancy (see Casey, Thomas, and McCandliss, chapter 10), it is anticipated that the field of developmental fMRI will emerge and offer the opportunity to marry anatomic structure...

Neuropathology

In parallel with our work on characterizing cognitive and behavioral changes in aging dogs, a third strategy in developing the canine as a model system of human brain aging involves identifying pathological brain changes related to age-associated cognitive-behavioral dysfunction in the dog. Specifically, we have examined beta-amyloid deposition, neuron loss, oxidative damage, and structural anatomy in the aging canine brain. These studies reveal that brain aging in dogs begins as early as middle age, varies across brain regions, and correlates with cognitive and behavioral impairments dogs develop some of the pathological hallmarks found in Alzheimer's disease. This final section will summarize current knowledge on neuropathological and neuroanatomical markers of brain aging in the canine.

Efrain C Azmitia

It has always been an enigma how serotonin, a monoamine neurotransmitter, can have such diverse and important functions in the human brain. The question is further complicated when it is recognized that serotonin exists in all the organs of the body (e.g., the skin, gut, lung, kidney, liver, and testis) and in nearly every living organism on Earth (e.g., fungi, plants, and animals) (Azmitia, 1999). Serotonin is phylogentically ancient, and evolved prior to the appearance of neurons. Whatever function serotonin has in the brain, it should be consistent with its evolutionary history. However, little attention has been given to the biological emergence of serotonin. Most neuroscience studies focus on serotonin in mediating particular behaviors (e.g., feeding, sex, sleep, and learning) or its

Monkey Studies

In parallel to the MRI aging studies of the human brain, there have been similar monkey-based reports of global volumetric changes with age, with decreases in gray matter, compensatory increases in CSF, but stability in white matter volume (Andersen et al., 1999). Age-related changes in the monkey brain were analyzed in another MRI-based study and linked cognitive deficits to white matter loss (Lai et al., 1995 reviewed in Peters et al., 1996 Wisco et al., 2001). A more recent study on the effects of aging in squirrel monkeys also showed cognitive deficits with age, but with an increase in white matter content in the anterior half of the brain (Lyons et al., 2004). However, it is important to note that the other studies cited above used rhesus monkeys and examined a wider range of older animals. Evaluations of subcortical structures have also been published, such as the report on the decrease in overall volume with age in the male rhesus monkey striatum (Matochik et al., 2000). This...

Amyloid Angiopathy

The deposition of amyloid in the wall of cerebral blood vessels is a well-documented change found in physiological and pathological (AD) aging of the human brain. Amyloid fibrils are deposited extracellularly and are derived from soluble circulating proteins that have undergone partial proteolysis and polymerization resulting in insoluble aggregates. Different components take part in the final composition of amyloid deposits and include, in addition to the straight, nonbranching protein fibrils (diameter 7-10 nm), a serum glycoprotein (P-component) showing a structural homology with c-reactive protein (an acute phase reactant) and sulphated proteoglycans. Since amyloid fibrils have an affinity for Congo red stain, show a green birefringence in polarized light and a -plated sheet pattern at X-ray diffraction analysis, they have been reliably identified and precisely localized in selected areas of the brain tissue. The favorite sites of amyloid deposition are the outer surface of the...

Age Pigments

Since lipofuscin forms during adult life and increases with age, it has been suggested that it represents the morphological outcome of ''wear and tear'' cellular function. Lipofuscin is a by-product of lipid peroxidation and originates from secondary lysosomes that transform into lipopigment granules. In neurons, the membranes undergo a continuous turnover with the involvement of lysosomal degradation of proteins and lipids. The interaction between the products of the peroxidation of polyunsaturated fatty acids and other biological molecules leads to the formation of these pigments, which are difficult to digest, and accumulate as residual bodies within the cytoplasm. Any type of biological molecule may become a constituent of lipofuscin, and this finds a well-grounded support in the documented ultrastructural heterogeneity of neuronal pigments reported in the aging human brain (Boellaard and Schlote, 1986). Autofluorescence is the most consistent property of lipofuscin. Under...

Dendritic Changes

And the limbic system in the human brain. The first step in the age-related alterations of dendrites is the loss of spines followed by changes in shape and size of basilar dendrites and then of the branches of the apical shaft (Scheibel et al., 1975). Dendrites are receptor membranes of the neurons, and their spines amplify this function and have been reported to isolate increases of synaptic calcium transport utilized for information storage (Koch et al., 1992). As a consequence, the age-related loss of dendrites and dendritic spines isolates neurons and leads to disturbances in cell-to-cell communication. Because of its dynamic condition, the old CNS is capable of a significant compensating response to the age-related loss of neurons and dendritic retraction by increasing the dendritic growth to fill the neuropil space left by the dendritic trees of dead neurons. In parahippocampal pyramidal cells of cognitively normal individuals the continual growth of dendrites occurs well into...

Znf127fnz127

The DNA methylation imprint that distinguishes the inactive maternal from the functional paternal ZNF127 allele was first recognized by Driscoll et al. (1992) and has been proposed as a pilot diagnostic test. This differential methylation imprint is probably more pronounced in a human brain, as it is in the developing mouse brain (Barr et al., 1995), and the gene is also highly expressed in the testes of both species.

Conclusions

The past 20 years have witnessed unprecedented progress in our ability to study human brain function noninva-sively. The high temporal resolution of electromagnetic measurements (EEG MEG) continues to offer a unique window into the dynamics of brain function. In particular, EEG MEG measures are exquisitely sensitive to spontaneous and induced changes of the functional brain state allowing investigation of brain mechanisms associated with covert internal states, which may not necessarily be accessible to introspection or behavioral observation.

Protein Function

E46L is a cytoplasmic protein, which forms homotrimeric complexes via a tip-to-tip contact with the concave sides of the molecules facing each other (Marz et al. 2004). Immunostaining of mouse and human brain sections with an antibody against rat ataxin-10 revealed a predominantly cytoplasmic and perinuclear localization. Knockdown of SCA10 in primary cerebellar and cortical neurons in culture by small interfering RNAs (siRNAs) caused increased apoptosis (Marz et al. 2004). It is of note that cerebellar neurons were significantly more sensitive to reduced level of ataxin-10. It would be interesting to see (1) if ataxin-10 in SCA10 patients is reduced,

Topdown Methods

Cognitive models make assumptions about the types of functions that mediate a cognitive task. In many cases these models do not have any relationship to the functional neuroanatomy of the brain. For example, a well-known cognitive model of reading (Coltheart et al. 2001) includes, among others, modules for visual analysis and for grapheme-phoneme conversion, although no attempt was made to link activity in these modules to fMI or PET data, or even to link them to specific brain regions based on lesion studies. Recently, however, such efforts have been made by imposing additional assumptions relating each cognitive function to specified brain regions. An early attempt at combining a cognitive model with fMRI data can be found in the work of Just et al. (1999), who used a computational (production) model of sentence comprehension called 4CAPS to explain how fMRI activation levels varied as a function of sentence complexity in three brain areas (Broca, Wernicke and dorsolateral...

Before Intervention

As a function of development and learning, we now turn to an illustration of how we can push the methodology a step further and investigate changes in the human brain in response to pharmacologic probes. A number of recent studies with both humans and animals have shown the detection of neurotransmitter activity using pharmacologic MRI (phMRI) and demonstrated how results from this technique are correlated with PET, mi-crodialysis, and behavioral data (e.g., Chen et al., 1997). These studies have focused largely on animal work, but more recent work illustrates the utility of the method with humans (Braus et al., 1997 Chen et al., 1997 Kleinschmidt et al., 1997 Sell et al.,1997 Vaidya et al. 1998). Ultimately, pharmacologic MRI studies may be sensitive probes in elucidating brain regions involved in developmental disorders. These studies may prove extremely useful in addressing questions relevant to why some individuals are nonresponders to medications and why some medications are less...

Acknowledgements

Large-scale properties of neural networks. Human Brain Mapp. 2, 225-233 Arbib MA (Ed.) (2003) The Handbook of Brain Theory and Neural Networks. MIT Rev. Neurosci. 18, 193-222 Desimone R, Ungerleider LG (1989). Neural mechanisms of visual processing in monkeys. In Goodglass H & Damasio AR (Eds.), Handbook of Neuropsychology 267-300. Elsevier, Amsterdam Dominey PF, Arbib MA (1992) A cortico-subcortical model for generation of spatially accurate sequential saccades. Cereb. Cortex 2, 153-175 Frackowiak RSJ, Friston KJ, Frith CD, Dolan RJ, Price CJ, Zeki S, Ashburner J, Penny W (Eds.) (2004) Human Brain Function. Elsevier, Academic Press, San Diego, CA Human Brain Mapp. 2, 56-78 Friston KJ, Frith CD, Liddle PF, Frackowiak RSJ (1991) Investigating a network model of word generation with positron emission tomography. Proc. R. Soc. Lond. B 244, 101-106 Friston KJ, Harrison L, Penny W (2003) Dynamic causal modelling. Neuroimage 19, 1273-1302 Harrison RV, Harel N, Hamrahi H, Panesar J, Mori N,...

Perspectives

Li, J., Yen, C., Liaw, D., Podsypanina, K., Bose, S., Wang, S. I., Puc, J., Miliaresis, C., Rodgers, L., McCombie, R., Bigner, S. H., Giovanella, B. C., Ittmann, M., Tycko, B., Hibshoosh, H., Wigler, M. H., and Parsons, R. (1997). PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275, 1943-1947.

Concluding Remarks

First, it is now clear that functional imaging can detect multiple areas of the human brain associated with time measurement tasks, and while the variation among different experiments is high, some areas activate consistently in association with timing tasks having specific characteristics and are thus strong candidates for further exploration. Second, we have argued that much of the variation between the experiments may be due to the diversity of timing tasks used these tasks may even be drawing on quite separate systems. We can draw an analogy here with functional localization within the visual cortex. When an obvious, but inappropriate stimulus (such as a natural scene) is used, one gets the impression that the visual areas of the brain are horribly difficult to distinguish functionally. When a more appropriate stimulus is used (moving bars of light or drifting fields of dots), the organization becomes apparent. Thus, when appropriate timing tasks...

Rcocooh 0 Rcho

The presence of the enzyme in human brain has been a matter of controversy. For instance in one study only a few P.M. brains showed any activity, and these were considered to show activity only because the enzyme had been carried there by blood as a result of trauma A3753 . This was clearly erroneous, since the brain needs to synthesize these neurotransmitters. In P.M. parkinsonian brain dopa decarboxylase activity is reduced about 10-fold in those areas that normally show high activity, especially caudate nucleus, putamen, substantia nigra and putamen. Only a small decrease has been found in other brain regions, and an increase has been detected in cerebellar cortex A381 . In aromatic l-amino acid decarboxylase deficiency, a rare autosomal recessive, a catecholamine deficiency is observed, with associated symptoms K380 .

Bruce F Pennington

That the genes expressed uniquely in the central nervous system are less polymorphic than other genes. (In this context, being less polymorphic means having fewer alternate forms, or alleles, where an allele of a gene is a variant DNA sequence of that gene.) In fact, given the relatively recent evolution of some human behaviors, we have good reasons for supposing they are more polymorphic. Because much of human evolution has involved brain evolution, we should expect the genes expressed in the brain to be more polymorphic than those expressed in evolutionarily older organs. Therefore, we expect individual differences in the alleles of the genes that influence human brain development. Consistent with this theoretical prediction, behavioral geneticists have documented moderate her-itability (about 0.50) for most human cognitive and personality traits (Plomin and McClearn, 1993).

Rat lungworm

Especially dangerous to humans because it ruptures vessels in the brain. The presence of juveniles in the blood vessels, meninges, or tissue of the human brain can result in symptoms such as headache, fever, paralysis, neurological disorders, and even coma and death. The appearance of worms is often associated with eosinophilia, and is the primary cause of eosinophilic meningoenciphalitis, a disease that occurs when humans eat infected, raw snails.

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