Relation between reactions to pain and the hierarchical rank of animals

Intraspecies experience of domination or subordination in mice is an important factor predetermining their specific behaviour in response to painful stimuli, The significance is emphasized of ethological investigations for studying behavioural reactivity to pain and correct differentiation of responses of "defence-subordination" and "aggression-offence" types. The specificity of diazepam effect on the character of behaviour in response to pain was analysed in animals of different hierarchic rank.     

Attachment in integrative neuroscientific perspective

Attachment theory is a very influential general concept of human social and emotional development, which emphasizes the role of early mother-infant interactions for infant's adaptive behavioural and stress copying strategies, personality organization and mental health. Individuals with disrupted development of secure attachment to mother/primary caregiver are at higher risk of developing mental disorders. This theory consists of the complex developmental psycho-neurobiological model of attachment and emerges from principles of psychoanalysis, evolutionary biology, cognitive-developmental psychology, ethology, physiology and control systems theory. The progress of modern neuroscience enables interpretation of neurobiological aspects of the theory as multi-level neural interactions and functional development of important neural structures, effects of neuromediattors, hormones and essential neurobiological processes including emotional, cognitive, social interactions and the special key role of mentalizing. It has multiple neurobiological, neuroendocrine, neurophysiological, ethological, genetic, developmental, psychological, psychotherapeutic and neuropsychiatric consequences and is a prototype of complex neuroscientific concept as interpretation of modern integrated neuroscience.     

Implications of absence of measurement invariance for detecting sex limitation and genotype by environment interaction.

Using univariate sum scores in genetic studies of twin data is common practice. This practice precludes an investigation of the measurement model relating the individual items to an underlying factor. Absence of measurement invariance across a grouping variable such as gender or environmental exposure refers to group differences with respect to the measurement model. It is shown that a decomposition of a sum score into genetic and environmental variance components leads to path coefficients of the additive genetic factor that are biased differentially across groups if individual items are non-invariant. The arising group differences in path coefficients are identical to what is known as "scalar sex limitation" when gender is the grouping variable, or as "gene by environment interaction" when environmental exposure is the grouping variable. In both cases the interpretation would be in terms of a group-specific effect size of the genetic factor. This interpretation may be incorrect if individual items are non-invariant.     

Olfaction and olfactory-mediated behaviour in psychiatric disease models

Rats and mice are the most widely used species for modelling psychiatric disease. Assessment of these rodent models typically involves the analysis of aberrant behaviour with behavioural interactions often being manipulated to generate the model. Rodents rely heavily on their excellent sense of smell and almost all their social interactions have a strong olfactory component. Therefore, experimental paradigms that exploit these olfactory-mediated behaviours are among the most robust available and are highly prevalent in psychiatric disease research. These include tests of aggression and maternal instinct, foraging, olfactory memory and habituation and the establishment of social hierarchies. An appreciation of the way that rodents regulate these behaviours in an ethological context can assist experimenters to generate better data from their models and to avoid common pitfalls. We describe some of the more commonly used behavioural paradigms from a rodent olfactory perspective and discuss their application in existing models of psychiatric disease. We introduce the four olfactory subsystems that integrate to mediate the behavioural responses and the types of sensory cue that promote them and discuss their control and practical implementation to improve experimental outcomes. In addition, because smell is critical for normal behaviour in rodents and yet olfactory dysfunction is often associated with neuropsychiatric disease, we introduce some tests for olfactory function that can be applied to rodent models of psychiatric disorders as part of behavioural analysis.     

Behavioural Profiles in Captive-Bred Cynomolgus Macaques: Towards Monkey Models of Mental Disorders?

Background

To date, experimental and preclinical studies on neuropsychiatric conditions have almost exclusively been performed in experimentally-induced animal models and have only rarely relied upon an ethological approach where animals have been observed in more naturalistic settings. The laboratory species of choice has been the rodent while the potential of more closely-related non-human primates have remained largely underexplored.

Methods

The present study, therefore, aimed at investigating the possible existence of spontaneous atypical/abnormal behaviours displayed by 40 cynomolgus macaques in captive conditions using an unbiased ethological scan-sampling analysis followed by multifactorial correspondence analysis and a hierarchical clustering.

Results

The study identified five distinct profiles (groups A to E) that significantly differed on several behaviours, body postures, body orientations, gaze directions and locations in the cage environment. We suggest that animals from the low n groups (D and E) present depressive-like and anxious-like symptoms, reminiscent of depressive and generalized anxiety disorders. Inter-individual differences were highlighted through unbiased ethological observations of spontaneous behaviours and associated parameters, although these were not associated with differences in plasma or cerebrospinal fluid levels of either stress-related hormones or monoamines, i.e. in accordance with the human situation.

Conclusions

No interventional behavioural testing was required to discriminate between 3 typical and 2 atypical ethologically-defined behavioural profiles, reminiscent of certain depressive-like and anxiety-like symptoms. The use of unbiased behavioural observations might, thus, allow the identification of animal models of human mental/behavioural disorders and their most appropriate control groups.     

On some generative orders of behaviour

The sociobiological fashion has for a long time discouraged the development of theories of the immediate causation of behaviour. It is only recently that new approaches are being developed to improve on the classical ethological theory originated by Lorenz and Tinbergen. One new departure is behavioural field theory (BFT) which brings back the concept of energy in behaviour, without being susceptible to the drawbacks of the energy or fuel concept of classical theory. In this paper the new theory is explained in some detail and it is shown to be illuminating, predictive and testable in examples of play-like and territorial behaviour.     

An evaluation of what the mouse knockout experiments are telling us about mammalian behaviour

The early gene knockout studies with a neurobiological focus were directed at fairly obvious target genes and added very little to our knowledge of behavioural neuroscience. On the contrary, since the behavioural consequences were often predictable, this helped confirm that the technology was working. However, a substantial number of knockouts of genes expressed in the brain have been without obvious behavioural consequences, supporting the concept of genetic canalisation and redundancy. Others have produced a behavioural deficit for which there is no obvious explanation. Many cells of different tissue types have a capacity for memory, and in the brain, cells of the hippocampus are important for spatial learning and memory. Deleting genes that are expressed in the happpocampus has received considerable attention in this behavioural context. Although the initial studies experienced problems of interpretation, considerable advances have since been made. Knockout mice are now subject to tests of different forms of learning, multicellular hippocampal recordings, and restricted gene deletion specific to cells of component regions. This multi-level approach is proving more informative. Nevertheless, there is still a need to recognise that behavioural expression is several steps removed from gene expression, and that the relationship between genes and behaviour can be reciprocal.     

The importance of the prediction model in the validation of alternative tests

An overview is presented of the validation process adopted by the European Centre for the Validation of Alternative Methods, with particular emphasis on the central role of the prediction model (PM). The development of an adequate PM is considered to be just as important as the development of an adequate test system, since the validity of an alternative test can only be established when both components (the test system and the PM) have successfully undergone validation. It is argued, however, that alternative tests and their associated PMs do not necessarily need to undergo validation at the same time, and that retrospective validation may be appropriate when a test system is found to be reliable, but the case for its relevance remains to be demonstrated. For an alternative test to be considered "scientifically valid", it is necessary for three conditions to be fulfilled, referred to here as the criteria for scientific relevance, predictive relevance, and reliability. A minimal set of criteria for the acceptance of any PM is defined, but it should be noted that required levels of predictive ability need to be established on a case-by-case basis, taking into account the inherent variability of the alternative and in vivo test data. Finally, in view of the growing shift in emphasis from the use of stand-alone alternative tests to alternative testing strategies, the importance of making the PM an integral part of the testing strategy is discussed.     

Adaptive walks on behavioural landscapes and the evolution of optimal behaviour by natural selection

Summary One of the main challenges to the adaptationist programme in general and to the use of optimality models in behavioural and evolutionary ecology in particular is that natural selection need not optimise fitness. This challenge is addressed by considering the evolution of optimal patch choice by natural selection. The behavioural model is based on a state variable approach in which a strategy consists of a sequence denoting the patch to be visited as a function of the organism's state and time. The optimal strategy maximises expected terminal reproduction. The fitnesses of alternative strategies are computed by iteration of the associated equations for fitness; this characterises the adaptive behavioural landscape. There may be enormous numbers of strategies that have near optimal fitnesses. A population model is used to connect frequencies of behavioural types from one generation to the next. Theories on adaptive walks on fitness landscapes are considered in the context of behaviour. The main result is that within the context of optimality arguments at selective equilibrium, sub-optimal behaviours can persist. General implications for research in behavioural ecology, including tests of behavioural theories, are discussed.     

Restructuring Illness Meaning Through the Clinical Encounter: A Process of Disruption and Coherence

This study explores restructuring of illness meaning among ten Turkish-born women, assessed as somatizing, encountering caregivers imposing a psychological language for understanding distress. Participants were referred from local health care services in Western Stockholm, Sweden. Data were collected between 1997 and 2001 from 37 interviews with ten women. Data were analyzed using a qualitative method with a grounded theory approach to construct an understanding of meaning making from an emic perspective. Participants' restructuring included loss of earlier meanings given to illness, shifts in expressions and healing strategies, and a push toward giving illness and suffering a psychological or psychiatric meaning. Restructuring had in many ways been a disruptive and complicated experience. In their everyday context participants were engaged in bridging gaps between different perspectives of looking upon their illness. They had poor support from their social context in creating coherence between frames of meaning. On the basis of the results the author suggests that Antonovsky's concept of sense of coherence (SOC) may have relevance to the process of restructuring illness meaning, and that constructing coherence between experience, expression, past, and new meanings given to illness may be significant for patients' recovery. For clinical care, results indicate that restructuring should be done so as not to impose too alien a reordering of the disruptive experiences of illness. With regard to further research, results indicate the importance of gaining insight into how individuals and social and cultural groups make sense of their interaction with caregivers and local health care services.     

Strategy for genotoxicity testing: hazard identification and risk assessment in relation to in vitro testing

This report summarizes the proceedings of the September 9-10, 2005 meeting of the Expert Working Group on Hazard Identification and Risk Assessment in Relation to In Vitro Testing, part of an initiative on genetic toxicology. The objective of the Working Group was to develop recommendations for interpretation of results from tests commonly included in regulatory genetic toxicology test batteries, and to propose an appropriate strategy for follow-up testing when positive in vitro results were obtained in these assays. The Group noted the high frequency of positive in vitro findings in the genotoxicity test batteries with agents found not to be carcinogenic and thought not to pose a carcinogenic health hazard to humans. The Group agreed that a set of consensus principles for appropriate interpretation and follow-up testing when initial in vitro tests are positive was needed. Current differences in emphasis and policy among different regulatory agencies were recognized as a basis of this need. Using a consensus process among a balanced group of recognized international authorities from industry, government, and academia, it was agreed that a strategy based on these principles should include guidance on: (1) interpretation of initial results in the "core" test battery; (2) criteria for determining when follow-up testing is needed; (3) criteria for selecting appropriate follow-up tests; (4) definition of when the evidence is sufficient to define the mode of action and the relevance to human exposure; and (5) definition of approaches to evaluate the degree of health risk under conditions of exposure of the species of concern (generally the human). A framework for addressing these issues was discussed, and a general "decision tree" was developed that included criteria for assessing the need for further testing, selecting appropriate follow-up tests, and determining a sufficient weight of evidence to attribute a level of risk and stop testing. The discussion included case studies based on actual test results that illustrated common situations encountered, and consensus opinions were developed based on group analysis of these cases. The Working Group defined circumstances in which the pattern and magnitude of positive results was such that there was very low or no concern (e.g., non-reproducible or marginal responses), and no further testing would be needed. This included a discussion of the importance of the use of historical control data. The criteria for determining when follow-up testing is needed included factors, such as evidence of reproducibility, level of cytotoxicity at which an increased DNA damage or mutation frequency is observed, relationship of results to the historical control range of values, and total weight of evidence across assays. When the initial battery is negative, further testing might be required based on information from the published literature, structure activity considerations, or the potential for significant human metabolites not generated in the test systems. Additional testing might also be needed retrospectively when increase in tumors or evidence of pre-neoplastic change is seen. When follow-up testing is needed, it should be based on knowledge about the mode of action, based on reports in the literature or learned from the nature of the responses observed in the initial tests. The initial findings, and available information about the biochemical and pharmacological nature of the agent, are generally sufficient to conclude that the responses observed are consistent with certain molecular mechanisms and inconsistent with others. Follow-up tests should be sensitive to the types of genetic damage known to be capable of inducing the response observed initially. It was recognized that genotoxic events might arise from processes other than direct reactivity with DNA, that these mechanisms may have a non-linear, or threshold, dose-response relationship, and that in such cases it may be possible to determine an exposure level below which there is negligible concern about an effect due to human exposures. When a test result is clearly positive, consideration of relevance to human health includes whether other assays for the same endpoint support the results observed, whether the mode or mechanism of action is relevant to the human, and - most importantly - whether the effect observed is likely to occur in vivo at concentrations expected as a result of human exposure. Although general principles were agreed upon, time did not permit the development of recommendations for the selection of specific tests beyond those commonly employed in initial test batteries.     

Behavioural ecology's ethological roots

Since Krebs and Davies's (1978) landmark publication, it is acknowledged that behavioural ecology owes much to the ethological tradition in the study of animal behaviour. Although this assumption seems to be right-many of the first behavioural ecologists were trained in departments where ethology developed and matured-it still to be properly assessed. In this paper, I undertake to identify the approaches used by ethologists that contributed to behavioural ecology's constitution as a field of inquiry. It is my contention that the current practices in behavioural biology owe ethology something much subtler than the simple transposition of Tinbergen's Four Problems for heuristic purposes. Demonstrating what ethology inherited from the long naturalist tradition shows the tensions that strained the field and that later led to the loss of both its unity and its specificity. It also allows for a precise delineating of what behavioural ecology picked up from the ethological practice, and it helps to cast some light on the introduction of economical thinking in behavioural sciences.     

Development and Validation of the Chinese Version of the Multicultural Quality of Life Index (MQLI-Ch)

This study documents the validation study of the Multicultural Quality of Life Index, Chinese version (MQLI-Ch). This self-rated instrument is composed of ten items that correspond to multiple dimensions of the concept of quality of life. Each item is rated on a scale from 1 to 10, according to the subject’s culture-informed understanding of the concept. The MQLI-Ch was tested on 144 Chinese subjects (124 psychiatric patients and 20 professionals). It was found to be quite efficient (about 3 min to be completed) and easy to use. A Cronbach’s α of 0.94 demonstrated its internal consistency. The factor analysis of the ten items yielded one single factor, which accounted for 65.19% of the variance. The test–retest reliability correlation coefficient was 0.80. Its discriminant validity was documented by a highly significant difference (P < 0.001) between the mean scores of the two samples with presumed differences in quality of life. Thus, the MQLI-Ch showed high feasibility, internal structure, reliability and discriminant validity.     

Towards a theory of meaning in biology: a proposal for an operative definition.

Information is a concept developed inside the context of computational and computer sciences. Entropy is a concept developed inside physics context. The best concept in biology is that of "meaning" which is quite impossible to be measured as stated by some examples which are reported. A suggestion to develop a discussion in order to obtain an integration of these concepts inside the general problems of evolutionary biology is here reported to the attention of researchers.     

Evolutionary stability: States and strategies

Different aspects and modifications of the definition of an evolutionarily stable (ES) strategy that have been considered in the literature can be incorporated in a unifying concept which regards the population context. This concept of evolutionary stability will generally characterize population states in both pure- and mixed-strategist models. In particular, it includes ES strategies, represented as a phenotype unique in an ES population. For an important class of mixed-strategist models, no strict ESS can exist. This will be the case whenever the success of an individual strategy is considered to follow as an average from the successes of its behavioural components. Instead, ESS results may be obtained from what will be called a “degenerate” form of the model, which is simply an ESS model on the level of elementary actions. Then, however, the correct interpretation of an ESS is not an individual phenotype but rather a population mixture of elementary actions. If an ES state exists in a mixed-strategist model it may be determined by an equilibrium condition; if there is an ES strategy, a different approach—mainly maximum considerations—is needed for finding it. An equilibrium condition does not hold for the components of an ES strategy straightforwardly; but it can be derived in terms of an auxiliary ESS model that considers first-order effects of the components. Several examples illustrate the significance of these results. Particularly, two models on “Games between Relatives” are reconsidered in order to display both their formal interrelation and the different meaning of their results in the context of mixed-strategist models.     

Beyond the sentence given

A central and influential idea among researchers of language is that our language faculty is organized according to Fregean compositionality, which states that the meaning of an utterance is a function of the meaning of its parts and of the syntactic rules by which these parts are combined. Since the domain of syntactic rules is the sentence, the implication of this idea is that language interpretation takes place in a two-step fashion. First, the meaning of a sentence is computed. In a second step, the sentence meaning is integrated with information from prior discourse, world knowledge, information about the speaker and semantic information from extra-linguistic domains such as co-speech gestures or the visual world. Here, we present results from recordings of event-related brain potentials that are inconsistent with this classical two-step model of language interpretation. Our data support a one-step model in which knowledge about the context and the world, concomitant information from other modalities, and the speaker are brought to bear immediately, by the same fast-acting brain system that combines the meanings of individual words into a message-level representation. Underlying the one-step model is the immediacy assumption, according to which all available information will immediately be used to co-determine the interpretation of the speaker's message. Functional magnetic resonance imaging data that we collected indicate that Broca's area plays an important role in semantic unification. Language comprehension involves the rapid incorporation of information in a 'single unification space', coming from a broader range of cognitive domains than presupposed in the standard two-step model of interpretation.     

Stereochemical terminology and its discontents

Scrutiny of the purported misuse of some current stereochemical terms shows that obsolescence and faulty syntax may be less of a problem than previously assumed. Furthermore, changes in stereochemical terminology over time are not always due to obsolescence or to novel developments in chemical technology; for example, technical developments played no role whatsoever in the semantic transmutations over time of the terms "diastereomer" and "pseudoasymmetry." Finally, definitions of many stereochemical terms acquire meaning only within a given context and therefore cannot always be easily formulated. A prime example is the definition of "chirality," the concept at the heart of stereochemistry and, not coincidentally, the name of the journal in which this essay appears in print.     

Improvisation and authority in illness meaning

Using the example of psychosomatic diagnosis, I argue that the clinical context has unique epistemological constraints that limit the certainty of diagnosis and so make meaning indeterminate for sufferer and healer. As a result, forms of clinical truth are borrowed from the therapeutic context to create and authorize meanings for ambiguous or ill-defined conditions and inchoate suffering. Diagnostic interpretation is concerned with classification and legitimation through the production of authoritative truth. In contrast, therapeutic interpretation is fundamentally concerned with the pragmatic problem of how to continue and hence, with the improvisation of meaning. These different ends give rise to tensions and contradictions in psychosomatic theory and practice. While authority is necessary to provide a structure on which variations of meaning can be improvised, authoritative meanings may also restrict the possibilities for invention by clinician and patient. The goal of patient and physician is to create enough certainty to diminish the threat of the inchoate while preserving enough ambiguity to allow for fresh improvisation. Accounts of illness meaning must recognize the interdependence of normative rigidity and metaphoric invention.A RUMBLING: truth itself has appeared among humankind in the very thick of their flurrying metaphors.