bluuebunny/crossref_metadata_2025 huggingface dataset:
Localized near–infrared spectroscopy and functional optical imaging of brain activity
Authors: Tamura Mamoru , Hoshi Yoko , Okada Fumihiko
Published: October 2002

Changes in cerebral blood flow (CBF) and cerebral metabolic rates (CMRO2) have been used as indices for changes in neuronal activity. Near–infrared spectroscopy (NIRS) can also measure cerebral haemodynamics and metabolic changes, enabling the possible use of multichannel recording of NIRS for functional optical imaging of human brain activity. Spatio–temporal variations of brain regions were demonstrated during various mental tasks. Non–synchronous behaviour of cerebral haemodynamics during the neuronsl activation was observed. Gender– and handedness–dependent lateralization of the function between right and left hemispheres was demonstrated by simultaneous measurement using two NIR instruments during the mirror–drawing task. A lack of interhemispheric integration was observed with schizophrenic patients. These observations suggest an application for NIRS in psychiatric disease management, as an addition to clinical monitoring at the bedside.

A time–resolved 64–channel optical imaging system was constructed. This consisted of three picosecond laser diodes and 64 channels of TAC and CFD systems. Image reconstruction for phantom model systems was performed. Time–resolved quantitative optical imaging will become real in the very near future.
Imaging brain structure and function, infection and gene expression in the body using light
Authors: Benaron David A. , Contag Pamela R. , Contag Christopher H.
Published: October 2002

Light can be used to probe the function and structure of human tissues. We have been exploring two distinct methods: (i) externally emitting light into tissue and measuring the transmitted light to characterize a region through which the light has passed, and (ii) internally generating light within tissue and using the radiated light as a quantitative homing beacon. The emitted–light approach falls within the domain of spectroscopy, and has allowed for imaging of intracranial haemorrhage in newborns and of brain function in adults. The generated–light approach is conceptually parallel to positron emission tomography (PET) or nuclear medicine scanning, and has allowed for real–time, non–invasive monitoring and imaging of infection and gene expressionin vivousing low–light cameras and ordinary lenses. In this paper, we discuss recent results and speculate on the applications of such techniques.
The epidemiology of BSE in cattle herds in Great Britain. II. Model construction and analysis of transmission dynamics
Authors: Ferguson N. M. , Donnelly C. A. , Woolhouse M. E. J. , Anderson R. M.
Published: October 2002

Mathematical models that describe the key processes determining the pattern of the bovine spongiform encephalopathy (BSE) epidemic in British cattle are derived that allow for infection from feed as well as maternal and direct horizontal transmission. Heterogeneous susceptibility classes are also incorporated into the analysis. Maximum likelihood methods are used to estimate parameters and to obtain confidence intervals from available experimental and epidemiological data. A comprehensive sensitivity analysis of all model parameters and distributional assumptions is presented. Additional validation is provided by fitting the model to independent data collected in Northern Ireland. Model estimates and predictions based on BSE case data for Great Britain and Northern Ireland, together with their implications, are reviewed, and future research priorities discussed.
Density–dependent selection on horn phenotype in Soay sheep
Authors: Clutton-brock T. H. , Wilson K. , Stevenson I. R.
Published: October 2002

In the naturally regulated population of Soay sheepOvis ariesL.) on Hirta (St Kilda), 12 % of males and 24% of females have scurred horns. This trait reduces the competitive ability of males in the mating season but is associated with higher overwinter survival rates in both sexes (Moorcroftet al. 1996). In this paper, we show that scurred females also show higher conception rates and weaning rates than non–scurred ones, and that these differences are associated with heavier maternal body weight as well as higher birth weights of offspring. Selection pressures favouring scurredness in females vary with population density and are generally more pronounced among younger animals than adults. We discuss these results with reference to recent suggestions that temporal fluctuation in selection pressures may help to maintain genetic diversity within populations. We suggest that selection against scurredness operating through male mating success is opposed by selection favouring this trait, operating through the breeding success of females and the survival of both sexes.
Growth and metabolism in the Antarctic brachiopodLiothyrella uva
Authors: Peck Lloyd S. , Brockington Simon , Brey Thomas
Published: October 2002

Summer and winter growth rates were assessed separately for a population of the Antarctic brachiopodLiothyrella uvabetween early January 1992 and December 1993. Annual shell growth rates (1.6–2.3 mm yr−1for a 5 mm individual; 0.96–1.44 mm−1for a 20 mm specimen) were two to six times slower than those reported for temperate species. Growth in specimens less than 20 mm in length was faster in 1992 than in 1993, although differences between years over the whole size range were not significant. Surprisingly, growth was much faster in winter periods than during the summers. A 5 mm long individual grew five times faster in winter than in summer, and for a 20 mm long specimen the difference was 13 times. This runs contrary to current ideas on the effects of seasonality on the biology of polar marine invertebrates, but may be an effect of maximizing the efficiency of resource utilization. Comparisons with previous work showed shell growth to be decoupled from periods of tissue mass increase, and also from the main period of phytoplankton productivity. Oxygen consumption of 75 of the specimens used in the growth study was measured to test the hypothesis that basal metabolic rates should be inversely correlated with growth rates. Unexpectedly, an analysis of residuals produced no significant relationship, positive or negative, between growth rate and basal metabolism (F= 1.37,p=0.25,n= 75).
Agroecological zones and the assessment of crop production potential
Authors: Sivakumar M. V. K. , Valentin C.
Published: October 2002

The rapidly growing world population puts considerable pressure on the scarce natural resources, and there is an urgent need to develop more efficient and sustainable agricultural production systems to feed the growing population. This should be based on an initial assessment of the physical and biological potential of natural resources, which can vary greatly. The agroecological zonation (AEZ) approach presents a useful preliminary evaluation of this potential, and ensures that representation is maintained at an appropriate biogeographic scale for regional sustainable development planning. The principal AEZs of the world, as described by the Technical Advisory Committee of the Consultative Group on International Agricultural Research, are presented along with their extent and characteristics. Net primary productivity of terrestrial vegetation can be assessed from weather data, and it varies from 1 t dry matter ha
−1
yr
−1
in high latitude zones and dry regions to 29 t ha
−1
yr
−1
in tropical wet regions, depending on the climatic conditions. To assess the crop production potential, length of the growing period zones, a concept introduced by the UN Food and Agriculture Organization, is very useful as it describes an area within which rainfall and temperature conditions are suitable for crop growth for a given number of days in the year. These data, combined with the information on soils and known requirements of different food crops, can be used to assess the potential crop productivity. Some perspectives on AEZs and crop production potential are presented by describing the manner in which production potential can be integrated with present constraints. Efforts to intensify production should place emphasis on methods appropriate to the socio-economic conditions in a given AEZ, and on promotion of conservation-effective and sustainable production systems to meet the food, fodder and fuel needs for the future.
Potential and attainable food production and food security in different regions
Authors: De Vries F.W. T. Penning , Rabbinge R. , Groot J. J. R.
Published: October 2002

Growing prosperity in the South is accompanied by human diets that will claim more natural resources per capita. This reality, combined with growing populations, may raise the global demand for food crops two– to four–fold within two generations. Considering the large volume of natural resources and potential crop yields, it seems that this demand can be met smoothly. However, this is a fallacy for the following reasons. (i) Geographic regions differ widely in their potential food security: policy choices for agricultural use of natural resources are limited in Asia. For example, to ensure national self–sufficiency and food security, most of the suitable land (China) and nearly all of the surface water (India) are needed. Degradation restricts options further. (ii) The attainable level of agricultural production depends also on socio–economic conditions. Extensive poverty keeps the attainable food production too low to achieve food security, even when the yield gap is wide, as in Africa. (iii) Bio–energy, non–food crops and nature ‘compete’ with food crops for natural resources.

Global and regional food security are attainable, but only with major efforts. Strategies to achieve alternative aims will be discussed.
Meeting water requirements of an expanding world population
Authors: Falkenmark Malin
Published: October 2002

Water availability in the root zone (‘green water’) is a critical component of plant production, but is often deficient in many Third World regions. When deficient, runoff water (‘blue water’) can be added. Focusing on ten physiographic regions in Africa and Asia, characterized by mainly or partly dry climates and rapid population growth, this study analyses whether in a 30–years' perspective enough blue water could be provided to allow food self–sufficiency. It is assumed that for food self–sufficiency some 900 cubic metres of water per person per year has to be provided. In judging the realism it is assumed that a maximum 25 per cent increase in water mobilization rate would be manageable in a 30–year period. The study suggests that by 2025, water scarcity will make regions populated by some 55 % of the world's population dependent on food imports. For water–wasting regions in Central Asia, water saving might, however, free the water needed. The paper closes by proposing some urgent measures.
Degradation and resilience of soils
Authors: Lal R.
Published: October 2002

Debate on global soil degradation, its extent and agronomic impact, can only be resolved through understanding of the processes and factors leading to establishment of the cause–effect relationships for major soils, ecoregions, and land uses. Systematic evaluation through long–term experimentation is needed for establishing quantitative criteria of (i) soil quality in relation to specific functions; (ii) soil degradation in relation to critical limits of key soil properties and processes; and (iii) soil resilience in relation to the ease of restoration through judicious management and discriminate use of essential input. Quantitative assessment of soil degradation can be obtained by evaluating its impact on productivity for different land uses and management systems. Interdisciplinary research is needed to quantify soil degradation effects on decrease in productivity, reduction in biomass, and decline in environment quality throught pollution and eutrophication of natural waters and emission of radiatively–active gases from terrestrial ecosystems to the atmosphere. Data from long–term field experiments in principal ecoregions are specifically needed to (i) establish relationships between soil quality versus soil degradation and soil quality versus soil resilience; (ii) identify indicators of soil quality and soil resilience; and (iii) establish critical limits of important properties for soil degradation and soil resilience. There is a need to develop and standardize techniques for measuring soil resilience.
Closing remarks
Authors: Daykin C. D.
Published: October 2002

Closing remarks to Human genetics– uncertainties and the financial implications ahead. A Discussion held at the Royal Society on 25 and 26 September 1996, and organized and edited by R. M. Anderson.
Knowledge in perception and illusion
Authors: Gregory Richard L.
Published: October 2002

Following Hermann von Helmholtz, who described visual perceptions as unconscious inferences from sensory data and knowledge derived from the past, perceptions are regarded as similar to predictive hypotheses of science, but are psychologically projected into external space and accepted as our most immediate reality. There are increasing discrepancies between perceptions and conceptions with science's advances, which makes it hard to define ‘illusion’. Visual illusions can provide evidence of object knowledge and working rules for vision, but only when the phenomena are explained and classified. A tentative classification is presented, in terms of appearances and kinds of causes. The large contribution of knowledge from the past for vision raises the issue: how do we recognize the present, without confusion from the past. This danger is generally avoided as the present is signalled by real–time sensory inputs— perhaps flagged by
qualia
of consciousness.
Generative models for discovering sparse distributed representations
Authors: Hinton Geoffrey E. , Ghahramani Zoubin
Published: October 2002

We describe a hierarchical, generative model that can be viewed as a nonlinear generalization of factor analysis and can be implemented in a neural network. The model uses bottom–up, top–down and lateral connections to perform Bayesian perceptual inference correctly. Once perceptual inference has been performed the connection strengths can be updated using a very simple learning rule that only requires locally available information. We demonstrate that the network learns to extract sparse, distributed, hierarchical representations.
Neurocomputational bases of object and face recognition
Authors: Biederman Irving , Kalocsais Peter
Published: October 2002

A number of behavioural phenomena distinguish the recognition of faces and objects, even when members of a set of objects are highly similar. Because faces have the same parts in approximately the same relations, individuation of faces typically requires specification of the metric variation in a holistic and integral representation of the facial surface. The direct mapping of a hypercolumn–like pattern of activation onto a representation layer that preserves relative spatial filter values in a two–dimensional (2D) coordinate space, as proposed by C. von der Malsburg and his associates, may account for many of the phenomena associated with face recognition. An additional refinement, in which each column of filters (termed a ‘jet’) is centered on a particular facial feature (or fiducial point), allows selectivity of the input into the holistic representation to avoid incorporation of occluding or nearby surfaces. The initial hypercolumn representation also characterizes the first stage of object perception, but the image variation for objects at a given location in a 2D coordinate space may be too great to yield sufficient predictability directly from the output of spatial kernels. Consequently, objects can be represented by a structural description specifying qualitative (typically, non–accidental) characterizations of an object's parts, the attributes of the parts, and the relations among the parts, largely based on orientation and depth discontinuities (as shown by Hummel and Biederman). A series of experiments on the name priming or physical matching of complementary images (in the Fourier domain) of objects and faces documents that whereas face recognition is strongly dependent on the original spatial filter values, evidence from object recognition indicates strong invariance to these values, even when distinguishing among objects that are as similar as faces.
Brain mechanisms associated with top-down processes in perception
Authors: Frith Chris , Dolan Raymond J.
Published: October 2002

Perception arises through an interaction between sensory input and prior knowledge. We propose that at least two brain areas are required for such an interaction: the ‘site’ where analysis of afferent signals occurs and the ‘source’ which applies the relevant prior knowledge. In the human brain, functional imaging studies have demonstrated that selective attention modifies activity in early visual processing areas specific to the attended feature. Early processing areas are also modified when prior knowledge permits a percept to emerge from an otherwise meaningless stimulus. Sources of this modification have been identified in parietal cortex and in prefrontal cortex. Modification of early processing areas also occurs on the basis of prior knowledge about the predicted sensory effects of the subject's own actions. Activity associated with mental imagery resembles that associated with response preparation (for motor imagery) and selective attention (for sensory imagery) suggesting that mental imagery reflects the effects of prior knowledge on sensory processing areas in the absence of sensory input. Damage to sensory processing areas can lead to a form of sensory hallucination which seems to arise from the interaction of prior knowledge with random sensory activity. In contrast, hallucinations associated with schizophrenia may arise from a failure of prior knowledge about motor intentions to modify activity in relevant sensory areas. When functioning normally, this mechanism permits us to distinguish our own actions from those of independent agents in the outside world. Failure to make this distinction correctly may account for the strong association between hallucinations and paranoid delusions in schizophrenia; the patient not only hears voices, but attributes (usually hostile) intentions to these voices.
Why intracellular parasitism need not be a degrading experience forMycobacterium
Authors: Russell David G. , Sturgill-Koszycki Sheila , Vanheyningen Tambryn , Collins Helen , Schaible Ulrich E.
Published: October 2002

The success of mycobacteria as pathogens hinges on their ability to infect and persist within the macrophages of their host. However, activation of host macrophages by cytokines from a productive cellular immune response can stimulate the cells to kill their resident pathogens. This suggests that the interaction between host cell and microbe is in delicate balance, which can be tipped in favour of either organism. Biochemical analysis of mycobacterial vacuoles has shown them to be integral to the host cell's recycling endosomal system. As such they show limited acidification and hydrolytic activity despite possession of known lysosomal constituents such as cathepsins D, B and L, and LAMP 1. Even in established infections, they remain dynamic compartments accessible to several plasmalemma–derived constituents. Once the macrophage has been activated by IFN–γ and TNF–α the vacuoles coalesce and acidify. This marks a distinct alteration in vacuole physiology and leads to stasis and death of the mycobacteria. Mycobacteria have developed several strategies to avoid this outcome. Most notably, live bacilli induce sustained release of IL–6 from infected macrophages. IL–6 blocks the ability of both polyclonal primary T cells and T–cell hybridomas to respond to appropriate stimuli. Such an activity could render the centers of infection foci, such as granulomas, anergic and thus avoid release of macrophage–activating cytokines. This paper discusses both the mechanisms by which mycobacteria try to ensure their success as intracellular pathogens and the relevance of these strategies to the overall understanding of mycobacterial diseases.
Th2–mediated host protective immunity to intestinal nematode infections
Authors: Grencis R. K.
Published: October 2002

Despite many years of study, relatively little is known about the effector mechanisms that operate against intestine–dwelling nematodes. Most of the current understanding comes from studies of laboratory model systems in rodents. It is clear that when an intestinal helminth infection takes place the immune system generates a strong Th2–mediated response, which regulates a variety of responses characteristic of helminth infections such as eosinophilia, intestinal mastocytosis and elevated IgE production. The ability to modulate the host's immune responsein vivowith cytokine–specific monoclonal antibodies and recombinant cytokines, together with the use of animals with disruption of key genes involved in the immune response, have provided powerful tools with which to dissect the potential effector mechanisms operating. In the absence of a T–cell compartment the host is unable to expel the parasite. If a Th1–dominated response is generated, protective immunity is almost universally compromised. Thus, it would appear that some aspect of Th2–mediated response controls effector mechanisms. Although it is clear that for some infections the mast cell appears to be involved in protection, probably through the generation of a non–specific inflammatory response, how these cells become activated remains unclear. Data from infections in transgenic animals suggest that activation is not through the high–affinity receptor for IgE. Such studies also call into doubt the importance of conventional interactions between effector leucocytes and antibody. There is little evidence to support a protective role for eosinophilia in any system. New data also imply that , although interleukin 4 (IL–4) is generally important (and can exert effects independent of an adaptive immune response), it is not always sufficient to mediate protection; other Th2 cytokines (e.g. IL–13) may warrant closer investigation. It is apparent that a number of potential Th2–controlled effector mechanisms (some of which may be particularly important at mucosal surfaces) remain to be explored. Overall, it is likely that worm expulsion is the result of a combination of multiple mechanisms, some of which are more critical to some species of parasite than to others.
Spatial orientation and the representation of space with parietal lobe lesions
Authors: Karnath Hans–Otto
Published: October 2002

Damage to the human parietal cortex leads to disturbances of spatial perception and of motor behaviour. Within the parietal lobe, lesions of the superior and of the inferior lobule induce quite different, characteristic deficits. Patients with inferior (predominantly right) parietal–lobe lesions fail to explore the contralesional part of space by eye or limb movements (spatial neglect). In contrast, superior parietal lobe lesions lead to specific impairments of goal–directed movements (optic ataxia). The observations reported in this paper support the view of dissociated functions represented in the inferior and the superior lobule of the human parietal cortex. They suggest that a spatial reference frame for exploratory behaviour is disturbed in patients with neglect. Data from these patients’ visual search argue that their failure to explore the contralesional side is due to a disturbed input transformation leading to a deviation of egocentric space representation to the ipsilesional side. Data further show that this deviation follows a rotation around the earth–vertical body axis to the ipsilesional side rather than a translation towards that side. The results are in clear contrast to explanations that assume a lateral gradient ranging from a minimum of exploration in the extreme contralesional to a maximum in the extreme ipsilesional hemispace. Moreover, the failure to orient towards and to explore the contralesional part of space appears to be distinct from those deficits observed once an object of interest has been located and releases reaching. Although patients with neglect exhibit a severe bias of exploratory movements, their hand trajectories to targets in peripersonal space may follow a straight path. This result suggests that (i) exploratory and (ii) goal–directed behaviour in space do not share the same neural control mechanisms. Neural representation of space in the inferior parietal lobule seems to serve as a matrix for spatial exploration and for orienting in space but not for visuomotor processes involved in reaching for objects. Disturbances of such processes rather appear to be prominent in patients with more superior parietal lobe lesions and optic ataxia.
Dissociation of exteroceptive and idiothetic orientation cues⋮ effect on hippocampal place cells and place navigation
Authors: Bures J. , Fenton A. A. , Kaminsky Yu. , Rossier J. , Sacchetti B. , Zinyuk L.
Published: October 2002

Navigation by means of cognitive maps appears to require the hippocampus; hippocampal place cells (PCs) appear to store spatial memories because their discharge is confined to cell–specific places called firing fields (FFs). Experiments with rats manipulated idiothetic and landmark–related information to understand the relationship between PC activity and spatial cognition. Rotating a circular arena in the light caused a discrepancy between these cues. This discrepancy caused most FFs to disappear in both the arena and room reference frames. However, FFs persisted in the rotating arena frame when the discrepancy was reduced by darkness or by a card in the arena. The discrepancy was increased by ’field clamping’the rat in a room–defined FF location by rotations that countered its locomotion. Most FFs dissipated and reappeared an hour or more after the clamp. Place–avoidance experiments showed that navigation uses independent idiothetic and exteroceptive memories. Rats learned to avoid the unmarked footshock region within a circular arena. When acquired on the stable arena in the light, the location of the punishment was learned by using both room and idiothetic cues; extinction in the dark transferred to the following session in the light. If, however, extinction occurred during rotation, only the arena–frame avoidance was extinguished in darkness; the room–defined location was avoided when the lights were turned back on. Idiothetic memory of room–defined avoidance was not formed during rotation in light; regardless of rotation, there was no avoidance when the lights were turned off, but room–frame avoidance reappeared when the lights were turned back on. The place–preference task rewarded visits to an allocentric target location with a randomly dispersed pellet. The resulting behaviour alternated between random pellet searching and target–directed navigation, making it possible to examine PC correlates of these two classes of spatial behaviour. The independence of idiothetic and exteroceptive spatial memories and the disruption of PC firing during rotation suggest that PCs may not be necessary for spatial cognition; this idea can be tested by recordings during the place–avoidance and preference tasks.
Amygdala and bed nucleus of the stria terminalis: differential roles in fear and anxiety measured with the acoustic startle reflex
Authors:   The American Association for Research into Nervous and Mental Diseases, Davis Michael , Walker David L. , Lee Younglim
Published: October 2002

Neural stimuli associated with traumatic events can readily become conditioned so as to reinstate the memory of the original trauma. These conditioned fear responses can last a lifetime and may be especially resistant to extinction. A large amount of data from many different laboratories indicate that the amygdala plays a crucial role in conditioned fear. The amygdala receives information from all sensory modalities and projects to a variety of hypothalamic and brainstem target areas known to be critically involved in specific signs that are used to define fear and anxiety. Electrical stimulation of the amygdala elicits a pattern of behaviours that mimic natural or conditioned states of fear. Lesions of the amygdala block innate or conditioned fear and local infusion of drugs into the amygdala have anxiolytic effects in several behavioural tests. Excitatory amino acid receptors in the amygdala are critical for the acquisition, expression and extinction of conditioned fear.
The cognitive neuroscience of memory: perspectives from neuroimaging research
Authors:   The American Association for Research into Nervous and Mental Diseases, Schacter Daniel L.
Published: October 2002

Cognitive neuroscience approaches to memory attempt to elucidate the brain processes and systems that are involved in different forms of memory and learning. This paper examines recent research from brain-damaged patients and neuroimaging studies that bears on the distinction between explicit and implicit forms of memory. Explicit memory refers to conscious recollection of previous experiences, whereas implicit memory refers to the non-conscious effects of past experiences on subsequent performance and behaviour. Converging evidence suggests that an implicit form of memory known as priming is associated with changes in posterior cortical regions that are involved in perceptual processing; some of the same regions may contribute to explicit memory. The hippocampal formation and prefrontal cortex also play important roles in explicit memory. Evidence is presented from recent PET scanning studies that suggests that frontal regions are associated with intentional strategic efforts to retrieve recent experiences, whereas the hippocampal formation is associated with some aspect of the actual recollection of an event.
The ecological study of memory
Authors:   The American Association for Research into Nervous and Mental Diseases, Neisser Ulric
Published: October 2002

The study of memory has long been dominated by the structural tradition, and especially by the experimental analysis of mechanisms of information processing. That dominance may soon be brought to an end by the progress of neuroscience, which offers more direct ways of studying the mechanisms in question. At that point functional issues may move to centre stage. Those issues include the act of remembering and its social functions, the skills and presuppositions of the rememberer, the interaction of those skills and presuppositions with the particular material being remembered, and the determinants of accuracy and confabulation in recall.
Animal models of memory impairment
Authors:   The American Association for Research into Nervous and Mental Diseases, Gallagher Michela
Published: October 2002

Memory impairment in the elderly resembles a mild temporal lobe dysfunction. Alterations in the hippocampal formation are also a probable basis for cognitive deficits in some animal models of ageing. For example, aged rats are impaired in hippocampal-dependent tests of spatial memory. Recent studies have revealed considerable structural integrity in the aged hippocampus, even in aged rats with the most impaired spatial memory. In contrast, atrophy/loss of cholinergic neurons in the basal forebrain and deficiency in cholinergic transduction in hippocampus correlate with the severity of spatial memory impairment in aged rats. This evidence supports the longstanding view that age-related loss of memory has a cholinergic basis. In this context, it is somewhat surprising that the use of a selective cholinergic immunotoxin in young rats to further test this hypothesis has revealed normal spatial memory after removing septo-hippocampal cholinergic neurons. Young rats with immunotoxic lesions, however, have other behavioural impairments in tests of attentional processing. These lines of research have implications for understanding the neurobiological basis of memory deficits in ageing and for selecting an optimal behavioural setting in which to examine therapies aimed at restoring neurobiological function.
Emotional memory and psychopathology
Authors:   The American Association for Research into Nervous and Mental Diseases, Ledoux Joseph E. , Muller Jeff
Published: October 2002

A leading model for studying how the brain forms memories about unpleasant experiences is fear conditioning. A cumulative body of work has identified major components of the neural system mediating this form of learning. The pathways involve transmission of sensory information from processing areas in the thalamus and cortex to the amygdala. The amygdala's lateral nucleus receives and integrates the sensory inputs from the thalamic and cortical areas, and the central nucleus provides the interface with motor systems controlling specific fear responses in various modalities (behavioural, autonomic, endocrine). Internal connections within the amygdala allow the lateral and central nuclei to communicate. Recent studies have begun to identify some sites of plasticity in the circuitry and the cellular mechanisms involved in fear conditioning. Through studies of fear conditioning, our understanding of emotional memory is being taken to the level of cells and synapses in the brain. Advances in understanding emotional memory hold out the possibility that emotional disorders may be better defined and treatment improved.
Source monitoring and memory distortion
Authors:   The American Association for Research into Nervous and Mental Diseases, Johnson Marcia K.
Published: October 2002

Memory distortion reflects failures to identify the sources of mental experience (reality monitoring failures or source misattributions). For example, people sometimes confuse what they inferred or imagined and what actually happened, what they saw and what was suggested to them, one person's actions and another's, what they heard and what they previously knew, and fiction and fact. Source confusions arise because activated information is incomplete or ambiguous and the evaluative processes responsible for attributing information to sources are imperfect. Both accurate and inaccurate source attributions result from heuristic processes and more reflectively complex processes that evaluate a mental experience for various qualities such as amount and type of perceptual, contextual, affective, semantic and cognitive detail, that retrieve additional supporting or disconfirming evidence, and that evaluate plausibility and consistency given general knowledge, schemes, biases and goals. Experimental and clinical evidence regarding cognitive mechanisms and underlying brain structures of source monitoring are discussed.
Transient global amnesia and functional retrograde amnesia: contrasting examples of episodic memory loss
Authors:   The American Association for Research into Nervous and Mental Diseases, Kritchevsky Mark , Zouzounis Joyce , Squire Larry R.
Published: October 2002

We studied 11 patients with transient global amnesia (TGA) and 10 patients with functional retrograde amnesia (FRA). Patients with TGA had a uniform clinical picture: a severe, relatively isolated amnesic syndrome that started suddenly, persisted for 4−12 h, and then gradually improved to essentially normal over the next 12−24 h. During the episode, the patients had severe anterograde amnesia for verbal and non-verbal material and retrograde amnesia that typically covered at least two decades. Thirty hours to 42 days after the episode, the patients had recovered completely and performed normally on tests of anterograde and retrograde amnesia. By contrast, patients with FRA had a sudden onset of memory problems that were characterized by severe retrograde amnesia without associated anterograde amnesia and with a clinical presentation that otherwise varied considerably. The episodes persisted from several weeks to more than two years, and some of the patients had not recovered at the time of our last contact with them. The uniform clinical picture of TGA and the variable clinical picture of FRA presumably reflect their respective neurologic (‘organic’) and psychogenic (‘non-organic’) aetiologies.
The origins of human ageing
Authors: Kirkwood T. B. L.
Published: October 2002

The origins of human ageing are to be found in the origins and evolution of senescence as a general feature in the life histories of higher animals. Ageing is an intriguing problem in evolutionary biology because a trait that limits the duration of life, including the fertile period, has a negative impact on Darwinian fitness. Current theory suggests that senescence occurs because the force of natural selection declines with age and because longevity is only acquired at some metabolic cost. In effect, organisms may trade late survival for enhanced reproductive investments in earlier life. The comparative study of ageing supports the general evolutionary theory and reveals that human senescence, while broadly similar to senescence in other mammalian species, has distinct features, such as menopause, that may derive from the interplay of biological and social evolution.
Kinship resources for the elderly
Authors: Wachter Kennethl W.
Published: October 2002

As population ageing strains social insurance systems, cohorts whose own fertility was low will be reaching elderly status, leaving close biological kin in short supply. However, there is a countervailing trend, inasmuch as burgeoning divorce, remarriage and family blending have expanded the numbers and varieties of step–kin and other non–standard kinship ties. Methods of computer microsimulation in conjunction with richer sample surveys can help us to foresee the contours of kin numbers and kinship relations in the future. Prime areas include the likely frequency of kin–deprived elderly, the overlap with economic deprivation and the interaction between kin frequency and intensity of contact. Step–ties may be weaker but nonetheless critical in raising the probability of at least one compatible member with whom one can choose to maintain contact and rely on. Kinship networks extended through half– and step–links, by stretching across racial and economic lines, may promote social cohesion.
Health expectancy and the problem of substitute morbidity
Authors: Van De Water Harry P. A.
Published: October 2002

During the past century, the developed world has not only witnessed a dramatic increase in life expectancy (ageing), but also a concomitant rise in chronic disease and disability. Consequently, the tension between ‘living longer’ on the one hand and health–related ‘quality of life’ on the other has become an increasingly important health policy problem. The paper deals with two consequences of this so–called epidemiological transition in population health. The first one concerns the question of how— given the impressive changes, population health can be measured in an adequate and policy relevant present–day fashion. The second one is the so–called phenomenon of ‘substitute morbidity and mortality’: more and more acute fatal diseases are replaced by non–fatal delayed degenerative diseases like dementia and arthritis. How the phenomenon of substitute morbidity and mortality affects the development of population health is illustrated with the epidemiological transitions, worldwide shifts in the main causes of death, assumptions used in models, adverse consequences of medical technologies and some results from intervention trials. Substitute morbidity and mortality may thwart our disease–specific expectations of interventions and asks for a shift to a ‘total population health’ perspective when judging potential health gains of interventions. Better understanding of the dynamics that underly the changes in population health is necessary. Implications for data collections are more emphasis on morbidity data and their relation with mortality, more longitudinal studies, stricter requirements for intervention trials and more use of modelling as a tool. A final recommendation is the promotion of integrative measures of population health. For the latter several results are presented suggesting that, although the amount of morbidity and disability is growing with an increasing life expectancy, this is mild unhealthiness in particular. This finding supports the ‘dynamic equilibrium’ theory. In absolute numbers, however, the burden of disease will continue to increase with further ageing of the population.
Memory, language, and ageing
Authors: Burke Deborah M. , Mackay D. G.
Published: October 2002

This overview provides both theoretical and empirical reasons for emphasizing practice and familiar skills as a practical strategy for enhancing cognitive functioning in old age. Our review of empirical research on age–related changes in memory and language reveals a consistent pattern of spared and impaired abilities in normal old age. Relatively preserved in old age is memory performance involving highly practised skills and familiar information, including factual, semantic and autobiographical information. Relatively impaired in old age is memory performance that requires the formation of new connections, for example, recall of recent autobiographical experiences, new facts or the source of newly acquired facts. This pattern of impaired new learning versus preserved old learning cuts across distinctions between semantic memory, episodic memory, explicit memory and perhaps also implicit memory. However, familiar verbal information is not completely preserved when accessed on the output side rather than the input side: aspects of language production, namely word finding and spelling, exhibit significant age–related declines. This emerging pattern of preserved and impaired abilities presents a fundamental challenge for theories of cognitive ageing, which must explain why some aspects of language and memory are more vulnerable to effects of ageing than others. Information–universal theories, involving mechanisms such as general slowing that are independent of the type or structure of the information being processed, require additional mechanisms to account for this pattern of cognitive aging. Information–specific theories, where the type or structure of the postulated memory units can influence the effects of cognitive ageing, are able to account for this emerging pattern, but in some cases require further development to account for comprehensive cognitive changes such as general slowing.
Axonal processes and neural plasticity. III. Competition for dendrites
Authors: Elliott T. , Howarth C. I. , Shadbolt N. R.
Published: October 2002

In previous work we have developed a computational framework for topographic map formation and plasticity based on axonal process sprouting and retraction, in which sprouting and retraction are governed by competition for neurotrophic support. Here we show that such an approach can account for certain aspects of the dendritic morphology of cortical maps. In particular, we model the development of ocular dominance columns in the primary visual cortex and show that cortical cells near to column boundaries prefer to elaborate dendritic fields which avoid crossing the boundaries. This emerges as different functional inputs are spatially separated. We predict that afferent segregation occurs before or simultaneously with, but not after, the emergence of dendritic bias. We predict that animals reared with complete but asynchronous stimulation of the optic nerves do not develop a dendritic bias. We suggest that the emergence of a dendritic bias might provide a partial account for the critical period for a response to monocular deprivation. In particular, we predict that animals reared with asynchronous optic nerve stimulation might exhibit an extended critical period. Our results also indicate that the number of synapses supported by cortical cells depends on the intra–ocular image correlations used in our simulations. This suggests that inter–ocular image correlations, and thus strabismic rearing of kittens, may also affect the innervation density.
The Drosophila heterochromatic gene encoding poly(ADP-ribose) polymerase (PARP) is required to modulate chromatin structure during development
Authors: Tulin Alexei , Stewart Dianne , Spradling Allan C.
Published: October 2002

Poly(ADP-ribose) polymerase (PARP) is a major NAD-dependent modifying enzyme that mediates important steps in DNA repair, transcription, and apoptosis, but its role during development is poorly understood. We found that a single Drosophila Parp gene spans more than 150 kb of transposon-rich centromeric heterochromatin and produces several differentially spliced transcripts, including a novel isoform, PARP-e, predicted to encode a protein lacking enzymatic activity. An insertion mutation near the upstream promoter for Parp-e disrupts all Parp expression. Heterochromatic but not euchromatic sequences become hypersensitive to micrococcal nuclease, nucleoli fail to form, and transcript levels of the copia retrotransposon are elevated more than 50-fold; the variegated expression of certain transgenes is dominantly enhanced. Larval lethality can be rescued and PARP activity restored by expressing a cDNA encoding PARP-e. We propose that PARP-e autoregulates Parptranscription by influencing the chromatin structure of its heterochromatic environment. Our results indicate that Parpplays a fundamental role organizing the structure of Drosophilachromatin.
Molecular mechanisms governing Pcdh-γ gene expression: Evidence for a multiple promoter and cis-alternative splicing model
Authors: Wang Xiaozhong , Su Hong , Bradley Allan
Published: October 2002

The genomic architecture of protocadherin (Pcdh) gene clusters is remarkably similar to that of the immunoglobulin and T cell receptor gene clusters, and can potentially provide significant molecular diversity. Pcdh genes are abundantly expressed in the central nervous system. These molecules are primary candidates for establishing specific neuronal connectivity. Despite the extensive analyses of the genomic structure of both human and mouse Pcdhgene clusters, the definitive molecular mechanisms that controlPcdh gene expression are still unknown. Four theories have been proposed, including (1) DNA recombination followed bycis-splicing, (2) single promoter and cis-alternative splicing, (3) multiple promoters and cis-alternative splicing, and (4) multiple promoters and trans-splicing. Using a combination of molecular and genetic analyses, we evaluated the four models at the Pcdh-γ locus. Our analysis provides evidence that the transcription of individual Pcdh-γ genes is under the control of a distinct but related promoter upstream of eachPcdh-γ variable exon, and posttranscriptional processing of each Pcdh-γ transcript is predominantly mediated throughcis-alternative splicing.
The ankyrin repeat protein Diversin recruits Casein kinase Iε to the β-catenin degradation complex and acts in both canonical Wnt and Wnt/JNK signaling
Authors: Schwarz-Romond Thomas , Asbrand Christian , Bakkers Jeroen , Kühl Michael , Schaeffer Hans-Joerg , Huelsken Jörg , Behrens Jürgen , Hammerschmidt Matthias , Birchmeier Walter
Published: October 2002

Wnt signals control decisive steps in development and can induce the formation of tumors. Canonical Wnt signals control the formation of the embryonic axis, and are mediated by stabilization and interaction of β-catenin with Lef/Tcf transcription factors. An alternative branch of the Wnt pathway uses JNK to establish planar cell polarity inDrosophila and gastrulation movements in vertebrates. We describe here the vertebrate protein Diversin that interacts with two components of the canonical Wnt pathway, Casein kinase Iε (CKIε) and Axin/Conductin. Diversin recruits CKIε to the β-catenin degradation complex that consists of Axin/Conductin and GSK3β and allows efficient phosphorylation of β-catenin, thereby inhibiting β-catenin/Tcf signals. Morpholino-based gene ablation in zebrafish shows that Diversin is crucial for axis formation, which depends on β-catenin signaling. Diversin is also involved in JNK activation and gastrulation movements in zebrafish. Diversin is distantly related to Diego of Drosophila, which functions only in the pathway that controls planar cell polarity. Our data show that Diversin is an essential component of the Wnt-signaling pathway and acts as a molecular switch, which suppresses Wnt signals mediated by the canonical β-catenin pathway and stimulates signaling via JNK.