A dissociation between symbolic number knowledge and analogue magnitude information.

Semantic understanding of numbers and related concepts can be dissociated from rote knowledge of arithmetic facts. However, distinctions among different kinds of semantic representations related to numbers have not been fully explored. Working with numbers and arithmetic requires representing semantic information that is both analogue (e.g., the approximate magnitude of a number) and symbolic (e.g., what / means). In this article, the authors describe a patient (MC) who exhibits a dissociation between tasks that require symbolic number knowledge (e.g., knowledge of arithmetic symbols including numbers, knowledge of concepts related to numbers such as rounding) and tasks that require an analogue magnitude representation (e.g., comparing size or frequency). MC is impaired on a variety of tasks that require symbolic number knowledge, but her ability to represent and process analogue magnitude information is intact. Her deficit in symbolic number knowledge extends to a variety of concepts related to numbers (e.g., decimal points, Roman numerals, what a quartet is) but not to any other semantic categories that we have tested. These findings suggest that symbolic number knowledge is a functionally independent component of the number processing system, that it is category specific, and that it is anatomically and functionally distinct from magnitude representations.

Genetic-environment analysis of sensitivity and acute tolerance to ethanol in mice.

The purpose of this study was to characterize initial sensitivity (IS), acute functional tolerance (AFT), and rate of tolerance development to ethanol in lines of mice selected for aggression mice as well as to investigate the impact of isolate housing on these phenotypes. The results showed that for IS, there were no differences among treatment groups. For acute tolerance and rate of tolerance development, a Line x Sex x Housing interaction was present, with the response to housing being more pronounced in the low aggressive line than the high aggressive line, and the females being more affected than the males. Correlational analysis showed low to moderate associations between rate of tolerance development and IS, as well as between rate of tolerance and AFT. Housing condition significantly influenced female expression of ethanol phenotypes as compared to males. The line of the subject also influenced the magnitude of expression of these phenotypes. These findings suggest that environmental and genetic influences interact to influence acute tolerance and rate of tolerance development.

A review of "noncontingent" reinforcement as treatment for the aberrant behavior of individuals with developmental disabilities.

The term noncontingent reinforcement (NCR) refers to the delivery of an aberrant behavior's known reinforcer on a response-independent basis. The typical result is a decrease in responding from baseline (i.e., reinforcement) levels. NCR has become one of the most reported function-based treatments for aberrant behavior in the recent literature. The purpose of this review is to briefly discuss the history of the procedure and summarize the findings from the treatment research literature. The review is organized into the following sections: (a) basic research on NCR, (b) NCR as a control procedure, (c) NCR as a function-based treatment, (d) considerations in the programming of NCR schedules, (e) behavior-change mechanisms underlying NCR effects, and (t) directions for future research.

Quantitative-trait loci analysis of cocaine-related behaviours and neurochemistry.

We recently conducted a dose-response study of the effects of cocaine on several activity measures in the panel of BxD/Ty recombinant inbred mice. Animals were tested in an automated activity chamber over 2 days with i.p. saline on day 1 and i.p. cocaine on day 2, at one of four doses, 5, 15, 30 or 45 mg kg(-1). The monitor recorded total distance traveled, nosepokes in a holeboard, repeated movements and time spent by an individual in proximity to the centre of the apparatus. Dose-response curves for locomotor activation, i.e. the difference between cocaine and saline scores, showed that for all strains tested, scores increased 5-30 mg kg(-1). With few exceptions, locomotor activity at 45 mg kg(-1) was not significantly higher than that at 30 mg kg(-1). Repeated movement scores showed patterns similar to locomotor activity and nosepokes tended to be progressively inhibited by increasing doses of cocaine. Recombinant inbred strain mean distributions for all behaviours and at all doses exhibited continuous, rather than discrete variation, thus providing evidence of multiple-gene effects on cocaine-related behaviours. Quantitative trait loci (QTL) analysis pointed to several chromosomal locations associated with variations in cocaine-related behaviours and some are either identical or close to QTL reported by others. In separate groups of animals, densities of dopamine D1, and D2 receptors and dopamine uptake transporters were measured in the medial prefrontal cortex, caudate-putamen, nucleus accumbens and ventral midbrain. In all areas, all measures showed distributions consistent with polygenic influence and were associated with QTL. Of particular interest was our finding of a large segment on chromosome 15, which is related to dopamine receptor densities and cocaine-related behaviours.

Contribution of sex and genetics to neuroendocrine adaptation to stress in mice.

Male and female C57BL/6 (B6) and DBA/2 (D2) mice were subjected to either acute or 5 days of repeated restraint in ventilated, 50 ml centrifuge tubes. Control animals were not disturbed. The acute restraint animals were killed immediately following 15, 30 or 60 min of restraint and blood collected for corticosterone (CORT) analysis. The results of the acute restraint procedure revealed a strain difference in time to peak CORT in plasma with D2 animals showing an earlier peak. The males of both strains evinced similar maximum response and similar to B6 females; however, the D2 females showed a 2-fold greater CORT response than did the B6 females. Repeated restraint consisted of 5 days of 12 h in the tubes. At the end of 5 days, the animals were weighted and adrenalectomized in preparation for determination of brain corticosteroid receptors. Upon sacrifice, brains, thymus, adrenals and blood were harvested, the last for corticosteroid binding globulin (CBG). Five days of repeated restraint produced body weight loss in both strains, with B6s less affected than D2s. Repeated restraint reduced the mass of the adrenals in the B6s only. Restraint also reduced the mass of the thymus in both strains and sexes, but to a greater extent in the B6s. Plasma CBG densities were also sensitive to restraint, but only in females, showing a restraint-related decrease. Repeated restraint had no effect on hippocampal glucocorticoid or mineralocorticoid receptors; however for the latter, we observed significant strain and sex effects with D2 having higher Bmax than B6 and females having higher Bmax than males. In the pituitary, glucocorticoid receptors (GR) were reduced by repeated restraint in males, but increased in females, especially in the B6. These findings lend preliminary evidence for involvement of sex and genetics as sources of individual differences in bioadaptation to stress.

Ethanol modulates cocaine-induced behavioral change in inbred mice.

We recently conducted a study of the behavioral effects of combined cocaine and ethanol in genetically defined mice. Male and female C57BL/6 (B6) and DBA/2 (D2) were tested in an automated activity monitor on 2 consecutive days. On day 1, all animals received an IP injection of sterile saline and were placed into the activity monitor for 30 min. Behaviors measured were total distance traveled, stereotypy, nosepokes, and wall-seeking. On day 2, all animals were tested again for 15 min following injection of one of the following: saline, 10% v/v ethanol at 2.0 g kg(-1) or 2.0 g kg(-1) ethanol plus 5, 15, or 30 mg kg(-1) cocaine. Cocaine alone at the same doses was injected into separate groups of animals. For the B6 strain, the overall effect of ethanol was to reduce cocaine-induced locomotor stimulation; no consistent effect of ethanol on cocaine-induced locomotion was observed in D2 mice. Cocaine-induced inhibition of nosepokes in both strains and sexes was partially reversed by ethanol. Ethanol also partially reversed cocaine-elevated stereotypy in both strains and both sexes. In B6 mice, cocaine-increased wall seeking tended to be reversed by coadministration of ethanol, whereas no consistent pattern was observed in the D2s. Results from this study suggest that the several measures affected by cocaine (locomotor activity, stereotypy, exploration, thigmotaxis) were, in turn, differentially affected by concurrent treatment with ethanol. Furthermore, our results point to genetic-based differences in ethanol's effects on cocaine-related behaviors. We address the implications for combined ethanol and cocaine use in humans.

Evidence for movement preprogramming and on line control in differentially impaired patients with Parkinson's disease.

Investigated were those aspects of motor planning and execution underlying movem ent dysfunction in patients with Parkinson's disease (PD). Specifically examined was the effect of disease severity on these processes. An experiment is reported that dissociates preprogramm ing processes from on-line programming processes in a simple motor task that varies in movement complexity. Dependent m easures included reaction time, movement time, as well as kinematic measures of peak velocity, peak acceleration, peak deceleration, and their respective time values, plus inter-trial variability and EMG activation. While PD patients as a whole were able to pre-program movem ents, inter-trial variability for these measures was increased for more severely affected PD patients. Nonetheless, evidence for on-line programm ing occurred for all PD patients in later intervals of more complex movements. Further, EMG impulses correspond with acceleration trace deviations. The data as a whole support the hypothesis that disrupted basal ganglia function influences the consistency of cortical activation and the selection of motor program com ponents.

Neonatal endotoxin exposure alters the development of social behavior and the hypothalamic-pituitary-adrenal axis in selectively bred mice.

Developmental differences in the biobehavioral consequences of immune activation in early life were investigated in two lines of mice selectively bred for high and low levels of inter-male aggressive behavior. At age 5 or 6 days, male mice were administered saline or 0.05 mg/kg gram-negative bacterial endotoxin (Escherichia coli, LPS, ip). There was a transient endotoxin-induced reduction in the growth rate of the neonates in the high-aggressive line. At age 45-50 days, the animals' behaviors were assessed in a dyadic task. Hypothalami and sera were harvested 20 min later. Rates of socially reactive behaviors to conspecific contact (i.e., kick, startle) were increased in the endotoxin-treated groups from both lines. For the high-aggressive line only, endotoxin treatment increased behavioral immobility, decreased attack frequency, and decreased levels of hypothalamic corticotrophin-releasing factor (CRF). The effects of endotoxin exposure in early life on socially reactive behaviors in later life were associated with endotoxin-induced individual differences in CRF levels in the high-aggressive line but not the low-aggressive line. The findings demonstrate long-term social developmental consequences of immune activation during the neonatal period.

Conceptual effects on representational momentum.

Four experiments addressed the question of whether prior knowledge of an object's typical movement in the real world affects the representation of motion. Representational momentum (RM) is the tendency for the short-term memory representation of an object to undergo a transformation corresponding to the object's trajectory. Using the standard RM paradigm, the RM elicited by objects with different typical motions was compared. Results indicate that conceptual knowledge about an object's typical motion affects the magnitude of RM and, as such, the representation of motion.

Tactile agnosia. Underlying impairment and implications for normal tactile object recognition.

In a series of experimental investigations of a subject with a unilateral impairment of tactile object recognition without impaired tactile sensation, several issues were addressed. First, is tactile agnosia secondary to a general impairment of spatial cognition? On tests of spatial ability, including those directed at the same spatial integration process assumed to be taxed by tactile object recognition, the subject performed well, implying a more specific impairment of high level, modality specific tactile perception. Secondly, within the realm of high level tactile perception, is there a distinction between the ability to derive shape ('what') and spatial ('where') information? Our testing showed an impairment confined to shape perception. Thirdly, what aspects of shape perception are impaired in tactile agnosia? Our results indicate that despite accurate encoding of metric length and normal manual exploration strategies, the ability tactually to perceive objects with the impaired hand, deteriorated as the complexity of shape increased. In addition, asymmetrical performance was not found for other body surfaces (e.g. her feet). Our results suggest that tactile shape perception can be disrupted independent of general spatial ability, tactile spatial ability, manual shape exploration, or even the precise perception of metric length in the tactile modality.

The psychological reality of the body schema: a test with normal participants.

Neuropsychological dissociations suggest the existence of a body schema, a representation of the spatial relations among body parts, not used for other spatial stimuli. Four experiments verify the psychological reality of the body schema in normal participants. In Experiments 1 and 2, proprioceptive information concerning one's own body position influences visual perception of others' body positions. Contrary to expectations, facilitation is observed rather than interference in the dual-performance task. Experiment 3 eliminates the possibility that the effect is due to a particular mnemonic strategy. In Experiment 4, this effect is shown to be specific to the perception of bodies, as opposed to other complex 3-dimensional forms.

The nature of tactile agnosia: a case study.

A chronic tactile agnosic with a small, MRI-documented left inferior parietal infarction underwent detailed somesthetic testing to assess (1) the acquisition of sensory data, (2) the manipulation of somatosensory percept and its association with previous knowledge, and (3) recognition occurring at a deeper taxonomic level. Results suggest that tactile agnosia can arise from faulty high-level perceptual processes, but that the ability to associate tactually defined objects and object parts with episodic memory can be preserved. Consistent with anatomic and physiologic studies in nonhuman primates, inferior parietal cortex (including Brodmann area 40, possibly area 39) appears to serve as a high-level somatosensory region.

Perceptual dependence for shape and texture during haptic processing.

Perceptual dependence--the existence of perceptual interactions between the component dimensions of the same stimulus--was investigated for shape and texture during haptic processing. The haptic system combines tactual and kinesthetic information. Previous research has demonstrated that haptic exploration influences the extent to which object properties are integrated. Conditions designed to promote and impede the integration of shape and texture were compared. Perceptual independence was assessed by the use of a speeded-classification paradigm and quantitative tests developed by Ashby and Maddox. Results indicate that shape and texture are perceptually dependent for both conditions. Hand-movement analysis show simultaneous exploration for both dimensions. The tendency to process dimensions dependently is discussed in terms of a limited-capacity model of haptic-information processing.

Pharmacogenetics of cocaine: I. Locomotor activity and self-selection.

We investigated the effects of cocaine on multiple activity measures and cocaine self-selection in C57BL/6Ibg and DBA/2Ibg mice. Male mice were tested in an automated activity monitor at three doses of cocaine, 5, 15 and 30 mg kg-1. Activity measures included locomotion, rearings, stereotyped movements and wall-seeking. Testing was conducted on 2 days with saline injection, i.p. on day one and cocaine i.p. injected on day two. We also tested other mice of both strains for cocaine ingestion in a two-choice test, pairing tap water with 40 mg% cocaine HCl in tap water. Two separate groups of mice received 15 or 30 mg kg-1 of cocaine i.p., killed at 5 min and brain cocaine levels were determined by HPLC. Cocaine produced dose-related increases in locomotion in both strains, with a delay in initial activation noticed at 30 mg kg-1 in C57s but not in DBAs. In DBAs, cocaine suppressed rearings and increased stereotyped movements while having no consistent effect on either behaviour in C57s. At all doses, cocaine produced moderate increases in proximity to the wall in DBAs and 30 mg kg-1 produced pronounced wall-seeking in C57s. At 15 and 30 mg kg-1 DBAs tended to have higher levels of cocaine in whole brain than did C57s. Finally, C57s consumed significantly more cocaine than did the DBAs.

Constraints on haptic integration of spatially shared object dimensions.

A study of the haptic integration of texture, shape, and hardness of nonplanar solid objects is reported. In experiment 1 the relative discriminability of the objects along each dimension was assessed. While levels of texture and shape were equally discriminable, hardness discriminations proved considerably more difficult. The extent of dimensional integration in a speeded classification task when both dimensions could be extracted from the same local patch was investigated in experiments 2 and 3. In experiment 2 subjects were initially encouraged to attend to a nontargeted dimension covarying with a targeted one. The nontargeted dimension was subsequently held constant (withdrawn). In experiment 3 dimensional variation was introduced which was uncorrelated with the targeted property during the course of categorization and hence discouraged subjects from attending to the nontargeted property. The results of these two studies converged in showing evidence of bidirectional dimensional integration between texture and shape and unidirectional integration when hardness was the targeted dimension. The failure to integrate hardness into categorization based on texture or shape was attributed to the difficulty of hardness discriminations. Integration effects in experiment 3 were not consistently smaller than those in experiment 2, which suggests a strong involuntary component to dimensional integration. The results of an analysis of the accompanying hand movements are interpreted in terms of constraints on dimensional integration. Implications for visual, cross-modal, and two-handed codimensional processing are also discussed.

Haptic integration of planar size with hardness, texture, and planar contour.

Three studies investigate the role of size information in haptic classification of custom-made planar objects when size covaries with hardness, texture, or planar contour. The haptic exploratory procedure (Lederman & Klatzky, 1987) associated with size extraction is also sufficient for encoding shape, which should promote their integration. Experiment 1 showed substantial facilitation of classification by redundant size and shape cues, indicating the coprocessing of size and shape. Experiments 2 and 3 used a withdrawal paradigm: Classification trials began with two redundant properties, and one was then held constant (withdrawn). Experiment 2 showed that when size and shape were redundant, withdrawal of either impaired responses, whereas when size was redundant with texture or hardness, only size withdrawal had an effect. Experiment 3 demonstrated that this size weighting was not restricted to a single procedure for exploration. Size appears to be highly weighted in haptic classification and potentially integrated with other properties having compatible methods of extraction.

Cryptosporidiosis in the West of Scotland.

During the two years 1986 and 1987 83 cases of cryptosporidiosis were identified by the finding of oocysts in the faecal samples submitted to a single microbiology laboratory. There were 58 children and 25 adults. Cryptosporidiosis was the commonest cause of gastrointestinal infection identified in children and the third commonest overall. Spring and autumn peaks were identified. The main symptoms were diarrhoea (median 10 days), vomiting (median seven days), abdominal pain (median seven days) and fever (median three days). A variety of other less common symptoms were noted including reactive arthritis. Three cases occurred during late pregnancy and the puerperium. Contact tracing supported both person-to-person transmission and an animal origin for cases within the group. Cryptosporidiosis is shown to be an important cause of traveller's diarrhoea. The incubation period was from two to 11 days.

Shedding of oocysts of Cryptosporidium in immunocompetent patients.

Forty nine patients (19 adults and 30 children) with oocysts of Cryptosporidium in their faeces had repeated stool specimens taken until oocysts could no longer be identified. They were found in the stools up to 35 days after the onset of symptoms in one patient, but most had stopped shedding them by 20 days. In 25 of the 49 patients in whom symptoms could be compared with the shedding of oocysts, 19 (76%) had symptoms corresponding to the shedding period while symptoms persisted in four (16%) after shedding had stopped.

The viral etiology of cancer: a realistic approach.

The etiology of cancer resembles that of many other diseases in that multiple factors may be required. Because of this, the role or viruses in the etiology of human cancers is especially difficult to assess. When animal tumor systems were used as models, the roles of various predisposing characteristics in virus oncogenesis were elucidated. Extrapolation of these findings to the human diseases suggests the importance of genetics, age, hormones, immune competence, and stress in determining susceptibility to tumor development in individuals infected with an oncogenic virus. The importance of cofactors in induction of those human tumors most strongly associated with virus infection, including Burkitt's lymphoma, nasopharyngeal carcinoma, cerviccal carcinoma, acute myelogenous leukemia, and breast cancer, is reviewed. Understanding of the role of these cofactors in virus carcinogenesis may lead to disease prevention through elimination of one or more of the cofactors.

Induction of murine p30 by superinfecting herpesviruses.

The interaction of endogenous type C viruses with superinfecting herpes simplex virus type 2 (HSV-2) was investigated in two murine cell lines. Replication of HSV-2 was suboptimal in random-bred Swiss/3T3A cells and, in initial experiments, infection with a low virus-to-cell ratio resulted in carrier cultures with enhanced murine leukemia virus (MuLV) p30 expression. Immunofluorescence tests with Swiss/3T3A cells productively infected with HSV-2 also showed HSV-associated cytoplasmic antigens and enhanced MuLV p30 expression when compared with uninfected controls. Inactivation of HSV-2 with UV light did not abolish this reaction, although the number of cells expressing p30 was reduced. HSV-2 replicated more efficiently in a line of NIH Swiss cells (N c1 A c1 10). These cells are not readily inducible for type C expression by conventional methods; however, untreated and UV-inactivated HSV-2 induced both HSV-2-associated antigens and MuLV p30 in these cells. Although the Birch strain of human cytomegalovirus induced MuLV p30, neither mouse cytomegalovirus nor vesicular stomatitis virus induced MuLV p30 in either cell line.