Social group during housing and testing modulates the effect of ethanol on zebrafish (Danio rerio) behavior.

Zebrafish (Danio rerio) are a popular model organism in behavioral pharmacology research due to many genetic and neurological similarities with humans. As a social species, the presence (or absence) of conspecifics during housing and testing is likely to affect behavior, but these effects have not yet been well characterized. The goal of the current study was to better understand how social variables influence depth preference in zebrafish. Subjects were housed individually, in pairs, or in groups of four, then tested in a novel tank either individually or with their tankmates. Prior to testing, fish were exposed to 0.0%, 0.5%, or 1.0% ethanol. Behavior was recorded using a combination of manual coding methods and ANYMaze (™) video-tracking. Our results demonstrated more exploration by fish tested with their tankmates, and less exploration by fish tested in isolation. Additionally, the effects of ethanol on diving behavior were modulated by social groups during both housing and testing. We conclude that social variables likely contribute to the variability of behavior often observed in pharmacological research with zebrafish, and that additional effort should be directed to both standardization and further characterization of these variables.

Contribution of the hippocampus to performance on the traveling salesperson problem in rats.

The Traveling Salesman Problem (TSP) is an optimization problem in which the subject attempts to find the shortest possible route that passes through a set of fixed locations exactly once. The TSP is used in cognitive and behavioral research to study problem solving and spatial navigation. While the TSP has been studied in some depth from this perspective, the biological mechanisms underlying the behavior have not yet been explored. The hippocampus is a structure in the brain that is known to be involved in tasks that require spatial memory. Because the TSP requires spatial problem solving, we designed the current study to determine whether the hippocampus is required to find efficient solutions to the TSP, and if so, what role the hippocampus serves. Rats were pretrained on the TSP, which involved learning to retrieve bait from targets in a variety of spatial configurations. Matched for performance, rats were then divided into two groups, receiving either a hippocampal lesion or a control sham surgery. After recovering from surgery, the rats were tested on eight new configurations. A variety of behavioral measures were recorded, including distance travelled, number of revisits, memory span, and latency. The results showed that the sham group outperformed the lesion group on most of these measures. Based on the behavioral data and histological tissue analysis of each group, we determined that the hippocampus is involved in successful performance in the TSP, particularly regarding memory for which targets have already been visited.

The Traveling Salesman Problem (TSP): A Spatial Navigation Task for Rats.

The Traveling Salesman Problem (TSP) is a behavioral test used to measure the efficiency of spatial navigation. It is an optimization problem, in which a number of baited targets are placed in an arena, and as the subject travels between the targets, the route is recorded and compared to chance and optimal routes. The TSP is appealing for the study of learning, memory, and executive function in nonhuman animals because the memory requirements can easily be modified with minor adjustments to task parameters. In the standard version of the task, rats are initially pre-trained to forage for bait in the arena. Once the animals consistently retrieve the bait, they are tested with a set of novel target configurations, and their behavior is recorded. The videos are then scored to produce several measures of performance.

Some factors affecting performance of rats in the traveling salesman problem.

The traveling salesman problem (TSP) is used to measure the efficiency of spatial route selection. Among researchers in cognitive psychology and neuroscience, it has been utilized to examine the mechanisms of decision making, planning, and spatial navigation. While both human and non-human animals produce good solutions to the TSP, the solution strategies engaged by non-human species are not well understood. We conducted two experiments on the TSP using Long-Evans laboratory rats as subjects. The first experiment examined the role of arena walls in route selection. Rats tend to display thigmotaxis in testing conditions comparable to the TSP, which could produce results similar to a convex hull type strategy suggested for humans. The second experiment examined the role of turn angle between targets along the optimal route, to determine whether rats exhibit a preferential turning bias. Our results indicated that both thigmotaxis and preferential turn angles do affect performance in the TSP, but neither is sufficient as a predictor of route choice in this task.

Experiments on learning in zebrafish (Danio rerio): a promising model of neurocognitive function.

The past decade has seen rapid proliferation of behavioral research with zebrafish, and an emergence of interest in their potential as a model of neurocognitive function. Already, zebrafish have been proposed as a model of autism, Alzheimer's, drug abuse, schizophrenia, and other disorders involving cognitive dysfunction. Zebrafish have the sophisticated sensory and motor systems necessary for complex learning experiments, and their power as a genetic and developmental model has already been established. Currently, however, learning procedures remain unrefined, and behavioral variability presents a major problem for researchers. Before zebrafish can be effectively used to study the neurological bases of learning, a set of robust and replicable techniques must be characterized and standardized. The purpose of this review is to provide an overview and critique of learning procedures that have been used with zebrafish and their results. We hope that such an analysis will prove useful in this early stage of research to guide future learning experiments and thereby improve the efficiency and validity of research with this promising new animal model.

A comparison of human performance in figural and navigational versions of the traveling salesman problem.

Performance on a typical pen-and-paper (figural) version of the Traveling Salesman Problem was compared to performance on a room-sized navigational version of the same task. Nine configurations were designed to examine the use of the nearest-neighbor (NN), cluster approach, and convex-hull strategies. Performance decreased with an increasing number of nodes internal to the hull, and improved when the NN strategy produced the optimal path. There was no overall difference in performance between figural and navigational task modalities. However, there was an interaction between modality and configuration, with evidence that participants relied more heavily on the NN strategy in the figural condition. Our results suggest that participants employed similar, but not identical, strategies when solving figural and navigational versions of the problem. Surprisingly, there was no evidence that participants favored global strategies in the figural version and local strategies in the navigational version.

Stimuli affecting zebrafish (Danio rerio) behavior in the light/dark preference test.

Ethanol has been suggested to have an anxiolytic effect on zebrafish, primarily based on its disruption of the novel tank diving response and of some social behaviors. The light/dark preference test offers a complementary measure of anxiety-like behavior in fish, and the purpose of the current study was to determine the effects of acute ethanol exposure on behavior in the light/dark task. In Experiment 1, the stimuli used to induce light/dark preference in zebrafish were varied in order to determine how best to measure the behavior. Subjects exhibited phototaxis (preference for light) when illumination was manipulated, but scototaxis (preference for dark) when wall and substrate color were manipulated. There was a clear interaction between locomotor activity and color preference, with animals preferentially freezing in darker locations. Because of ambiguity in interpreting behavior in the open/covered version of the test, the black/white version was used in Experiment 2. In Experiment 2, zebrafish were exposed to ethanol (0.25%, 0.5%, or 1.0%) or water for 30 minutes, and then placed in a black/white preference tank containing either ethanol (same doses) or water for a 30-minute test. Ethanol exposure increased locomotor activity and reduced freezing. Additionally, there was a significant interaction between ethanol treatment and locomotor activity on side preference. Low doses of ethanol increased white avoidance in normally swimming fish, while high doses did not.

Long-term training effects on masticatory muscles.

Neuromuscular adaptations during skill acquisition have been extensively investigated for skeletal muscles. Motor rehabilitation is the main target for application of motor training. Such measures are also relevant for the musculature of the jaw, but few data are available for motor adaptation of the masticatory system. The objective of this study was to evaluate and compare long-term training effects of different motor tasks on masseter and temporal muscles. In 20 healthy subjects, the electromyographic response to unilateral and bilateral maximum voluntary tooth clenching, balancing the mandible on a hydrostatic system under force-feedback-controlled conditions, and unilateral chewing was investigated in an initial session and then in two follow-up sessions separated by 2 and 10 weeks from baseline. Motor tasks were repeated three times for chewing, nine times for maximum biting (MB) and 24 times for the coordination tasks (CT). The sequences of the various motor tasks were applied once in the first session and twice in the second and third sessions. No effects of training were observed for MB tasks except for MB in intercuspation, for which significant yet transient avoidance behaviour occurred in the second session. No significant effects were found for chewing tests. For the CT, however, a robust significant long-term training effect was detected which reduced the electric muscle activity in session 2 by approximately 20% and in session 3 by approximately 40% compared with the initial measurements. The study showed that the masticatory muscles are remarkably prone to motor adaptation if demanding CT must be accomplished.

The effect of various jaw motor tasks on body sway.

Alterations of body sway caused by isometric contractions of the jaw muscles have been reported previously. The objective of this study was to test if motor tasks of the masticatory system with different control demands affect body posture differently during quiet stance. Position and sway displacements of the center of foot pressure (COP) were measured for 20 healthy subjects who either kept the mandible at rest or performed unilateral and bilateral maximum voluntary teeth clenching, feedback-controlled biting tasks at submaximum bite forces, or unilateral chewing. Two weeks later the measurements were repeated. Compared with quiet stance, the COP results revealed significant changes during the feedback-controlled biting tasks. Robust sway reduction and anterior displacement of the COP were observed under these conditions. Body oscillations were not significantly affected by maximum bites or by unilateral chewing. For most of the variables investigated there were no significant differences between unilateral and bilateral biting. Robust sway reduction during feedback-controlled biting tasks in healthy subjects involved a stiffening phenomenon that was attributed to the common physiological repertoire of posture control, and might optimize the stability of posture under these conditions.

Behavioral measures of anxiety in zebrafish (Danio rerio).

While zebrafish may be a useful behavioral model of human anxiety, it is not obvious which behaviors are accurate measures of anxiety in zebrafish. Beginning with the premise that the most fundamental indicator of fear is avoidance, the goal of the current study was to determine which behaviors are systematically observed in the presence of an avoided stimulus. In a dark/bright preference task, adult zebrafish preferred a black chamber and avoided a white chamber. Then, subjects were confined to each chamber, and their behaviors recorded. A principal component analysis was used to determine which behaviors clustered with the tendency to avoid white. Additionally, the behaviors of High-avoidant and Low-avoidant animals were compared using analysis of variance. Results indicate that confinement to white systematically elicited freezing in animals with a strong dark preference, but not in animals with little preference. Turn rate (erratic movement) was weakly related to avoidance, while thigmotaxis and locomotor activity were poor predictors. Freezing is therefore suggested to be a viable measure of white-induced anxiety, while interpretation of the other behaviors is more ambiguous and will require further investigation.

Within-subjects experiments on blocking and facilitation in honeybees (Apis mellifera).

It has long been suspected in the vertebrate literature, but demonstrated only recently in work with honeybees (Apis mellifera), that the different treatments of nontarget stimuli in conventional between-groups blocking experiments may give the appearance of blocking independently of experience with the target stimulus. The same difficulty does not arise in within-subjects experiments, and in a series of such experiments with odors and colors free-flying honeybees gave no evidence of blocking; separate reinforced presentations of one element of a reinforced compound failed to reduce responding to the second. There was, however, clear evidence of facilitation; separate nonreinforced presentations of one element of a reinforced compound increased responding to the second. The implications of the results for further work on compound conditioning in honeybees and other animals are considered.

IT support for clinical pathways--lessons learned.

Clinical pathways are an effective instrument to decrease undesired practice variability and improve clinician performance. IT-applications embedded into clinical routine work can help to increase pathway compliance. Successfully implementing such applications requires both a responsive IT infrastructure and a participatory and iterative design process aimed at achieving user acceptance and usability. Experiences from the implementation and iterative improvement of an online surgical pathway at Marburg University Medical Centre have shown that pathway conformance actually could be improved by the use of IT. An analysis of the iterative design process has shown that future pathway projects can benefit from the lessons learned during this project. Based on these lessons recommendations for developing well adapted interaction mechanisms are presented, aimed at improving process alignment. Our goal is to build up a library of tested reusable components to reduce the number of iterations for pathway implementation.

Improving pathway compliance and clinician performance by using information technology.

To deliver patient-specific advice at the time and place of a consultation is an important contribution to improving clinician performance. Using computer-based decision support on the basis of clinical pathways is a promising strategy to achieve this goal. Thereby integration of IT applications into the clinical workflow is a core precondition for success. User acceptance and usability play a critical role: additional effort has to be balanced with enough benefit for the users and interaction design and evaluation should be handled as an intertwined, continuous process. Experiences from routine use of an online surgical pathway at Marburg University Medical Center show that it is possible to successfully address this issue by seamlessly integrating patient-specific pathway recommendations with documentation tasks which have to be done anyway, by substantially reusing entered data to accelerate routine tasks (e.g. by automatically generating orders and reports), and by continuously and systematically monitoring pathway conformance and documentation quality.

IT support for clinical pathways--lessons learned.

Clinical pathways are an effective instrument to decrease undesired practice variability and improve clinician performance. IT applications embedded into clinical routine work can help to increase pathway compliance. Successfully implementing such applications requires both a responsive IT infrastructure and a participatory and iterative design process aimed at achieving user acceptance and usability. Experiences from the implementation and iterative improvement of an online surgical pathway at Marburg University Medical Centre have shown that pathway conformance actually could be improved by the use of IT. An analysis of the iterative design process has shown that future pathway projects can benefit from the lessons learned during this project. Based on these lessons a method for developing well adapted interaction mechanisms is presented, which is aimed at improving process alignment. Our goal is to build up a library of tested reusable components to reduce the number of iterations for pathway implementation.

Blocking and pseudoblocking: new control experiments with honeybees.

Prompted by doubts about the adequacy of the various control procedures long used in research on blocking, we repeated some earlier experiments with honeybees that had given the appearance of forward, concurrent, and backward blocking. The new experiments differed from the earlier experiments only in that the target stimulus was omitted during the training and was encountered for the first time in the test. In the new experiments, just as in the earlier experiments, the blocking groups responded less to the target stimulus than did the control groups. The results show that the effects of the different treatments of nontarget stimuli commonly compared in blocking experiments may generalize to the target stimulus and thus affect responding to that stimulus independently of experience with it. Implications for research on blocking in honeybees and other animals are considered.

Improving pathway compliance and clinician performance by using information technology.

To deliver patient-specific advice at the time and place of a consultation, to improve clinician performance and compliance by using computer-based decision support, and to integrate such IT solutions with the clinical workflow are important strategies for the implementation of clinical pathways. User acceptance plays a critical role: additional effort has to be balanced with enough benefit for the users. Experiences from routine use of an online surgical pathway at Marburg University Medical Center show that it is possible to successfully address this issue by seamlessly integrating patient-specific pat documentation tasks which have to be done anyway and by substantially reusing entered data to accelerate routine tasks (e.g. by automatically generating orders and reports).

Differential activity patterns in the masseter muscle under simulated clenching and grinding forces.

The aim of this study was to investigate (i) whether the masseter muscle shows differential activation under experimental conditions which simulate force generation during clenching and grinding activities; and (ii) whether there are (a) preferentially active muscle regions or (b) force directions which show enhanced muscle activation. To answer these questions, the electromyographic (EMG) activity of the right masseter muscle was recorded with five intramuscular electrodes placed in two deep muscle areas and in three surface regions. Intraoral force transfer and force measurement were achieved by a central bearing pin device equipped with three strain gauges (SG). The activity distribution in the muscle was recorded in four different mandibular positions (central, left, right, anterior). In each position, maximum voluntary contraction (MVC) was exerted in vertical, posterior, anterior, medial and lateral directions. The investigated muscle regions showed different amount of EMG activity. The relative intensity of the activation, with respect to other regions, changed depending on the task. In other words, the muscle regions demonstrated heterogeneous changes of the EMG pattern for the various motor tasks. The resultant force vectors demonstrated similar amounts in all horizontal bite directions. Protrusive force directions revealed the highest relative activation of the masseter muscle. The posterior deep muscle region seemed to be the most active compartment during the different motor tasks. The results indicate a heterogeneous activation of the masseter muscle under test conditions simulating force generation during clenching and grinding. Protrusively directed bite forces were accompanied by the highest activation in the muscle, with the posterior deep region as the most active area.

Backward blocking in honeybees.

Three experiments with foraging honeybees were designed to study the effect of experience with A on responding to B after AB+ training. In the first experiment, responding to B was the same whether the AB+ training was preceded or followed by A+ training. In the second experiment, responding to B after AB+ training was less in animals that also had A+ training than in control animals that were equally often reinforced in the absence of A; whether the A+ training preceded, was concurrent with, or followed the AB+ training made no difference. In the third experiment, responding to B after AB+ training was less when the AB+ training was followed by A+C- training than when it was followed by C+/A- training. These results, like those of some recent vertebrate experiments, take us beyond the traditional explanation of blocking in terms of impaired conditioning of B on AB+ trials and support the suggestion that the mechanism, still poorly understood, may nevertheless be a relatively simple one.

[Selection of a hospital information system--experiences and critical aspects]. / Auswahl eines Krankenhausinformationssystems--Erfahrungen und Kernkriterien.

Due to typical problems (heterogeneity, lack of clinical functionality, Y2K problems) the board of directors of the university hospital of Marburg decided in 1997 to replace major components of the existing system by commercially available software. The products available on the market were analyzed, and, under participation of different user groups, a comprehensive functional specification was generated. This was the basis for a Europe-wide vendor selection process. In this context, several key aspects were identified, which are critically important for realizing a HIS that fulfills the specified functional requirements. Among these key aspects are the integration of heterogeneous system components, the support of cross-departmental workflow, and flexibility as well as adaptability to specific clinical requirements. As a result, we found that with today's commercially available products and standards there is no single solution that fully meets all requirements. However, some "generalist" vendors are offering integrated systems with acceptable clinical functionality. Tools are emerging which enable the clinical user to generate forms for data input and data flow. Still, a hospital information system will consist of separate components that have to be integrated, but the role of integrated, component-based approaches is becoming more important.