Multilevel Explanation Research Articles

Scientific Practice in Modeling Diseases: Stances from Cancer Research and Neuropsychiatry.

In the last few decades, philosophy of science has increasingly focused on multilevel models and causal mechanistic explanations to account for complex biological phenomena. On the one hand, biological and biomedical works make extensive use of mechanistic concepts; on the other hand, philosophers have analyzed an increasing range of examples taken from different domains in the life sciences to test-support or criticize-the adequacy of mechanistic accounts. The article highlights some challenges in the elaboration of mechanistic explanations with a focus on cancer research and neuropsychiatry. It jointly considers fields, which are usually dealt with separately, and keeps a close eye on scientific practice. The article has a twofold aim. First, it shows that identification of the explananda is a key issue when looking at dynamic processes and their implications in medical research and clinical practice. Second, it discusses the relevance of organizational accounts of mechanisms, and questions whether thorough self-sustaining mechanistic explanations can actually be provided when addressing cancer and psychiatric diseases. While acknowledging the merits of the wide ongoing debate on mechanistic models, the article challenges the mechanistic approach to explanation by discussing, in particular, explanatory and conceptual terms in the light of stances from medical cases.

Developmental Psychopathology Approach in Addiction Diagnosis in Adolescence

In order to provide multilevel potential explanations for the co-occurrence of addiction disorders and their developmental complex influence, developmental psychopathology has been considered to be an integrative perspective in re-search and in clinical treatment. This paper examined developmental psycho-pathology approach in addiction diagnosis and treatment. There is an historical and informative perspective that discusses two issues. The former is connected with the antecedents of addiction diagnosis. The latter parts of the article refer to the principles of developmental psychopathology and studies carried out in this field. In conclusion, the value of this perspective in diagnostic deci-sion-making processes in adolescents is also discussed.

Pragmatism, Religion and Ethics: A Review Essay. H. Deuser et al, The Varieties of Transcendence: Pragmatism and the Theory of Religion, New York: Fordham University Press, 2016; N. Brunsveld, The Many Faces of Religious Truth: Hilary Putnam’s Pragmatic Pluralism on Religion, Leuven: Peeters, 2017; D.B. Heney, Toward a Pragmatist Metaethics, London: Routledge, 2016

In the last decades, pragmatism is consolidating its influence on social sciences, both in terms of epistemology and ontology. A series of recent philosophical publications deal with a rather classical pragmatist topic — the relationship between morality, religion, and truth — in quite a new shape. First, they deal with the conception of a pragmatist epistemology based on situated morality and truth aptness of moral judgments. Second, they propose a large reflection on the relationship between theology and pluralism in terms of truth regimes. Finally, they try to overcome the pitfalls of the Jamesian phenomenological conception of religion, through both the semiotic lens of Charles S. Peirce and the rediscovery of the Josiah Royce’s works. This paper uses the stimuli of the three books listed above to introduce the reader to a socio-philosophical perspective rather not considered in the European debate, despite its importance for the development of American sociology (symbolic interactionism, the School of Chicago, R.K. Merton, among the others) and for a variety of European scholars. A second objective is to understand how the problems pragmatist philosophers encounter in analysing the religious phenomena could help understanding the need for a multifactorial and multilevel explanation of religion and ethics. Finally, in the discussion, the author critically enlightens the need to avoid collapsing morality into religion — as sometimes pragmatists do — and extends and reframes Hans Joas’ appropriation of Mead and Durkheim in his pragmatist approach to religion and morality.

Multi-level Explanations in Neuroscience I: From Genes to Subjective Experiences

Multi-level Explanations in Neuroscience I: From Genes to Subjective Experiences

Multi-level Explanations in Neuroscience II: EEG Spectral Fingerprints and Tensor Decompositions for Understanding Brain Activity --- Initial Results

Multi-level Explanations in Neuroscience II: EEG Spectral Fingerprints and Tensor Decompositions for Understanding Brain Activity --- Initial Results

Enhanced AMPA Receptor Trafficking Mediates the Anorexigenic Effect of Endogenous Glucagon Like Peptide-1 in the Paraventricular Hypothalamus

Glucagon Like Peptide 1 (GLP-1) positive neurons in the hindbrain Nucleus Tractus Solitarius (NTS) send robust projections to the paraventricular nucleus of the hypothalamus (PVN), which is involved in the regulation of food intake. However, it is unclear whether this pathway is sufficient and necessary to control feeding behavior, or how the GLP-1 neurons affect synaptic function to modulate food intake. Here, we found that specific stimulation of GLP-1 afferent fibers within the PVN is sufficient to suppress food intake independent of glutamate release. GLP-1 receptor (GLP-1R) activation augments excitatory synaptic strength in PVN corticotropin-releasing hormone (CRH) neurons. Moreover, a protein kinase A (PKA) dependent signaling cascade is initiated by GLP-1R activation, which results in the phosphorylation of serine S845 of GluA1 AMPA receptors and subsequently promotes GluA1 trafficking to the plasma membrane. Finally, we show that postnatal depletion of GLP-1R in the PVN increases food intake and causes obesity. This study provides a comprehensive multi-level (circuit-, synaptic-, and molecular-) explanation of how food intake behavior and body weight are regulated by endogenous central GLP-1.

Enhanced AMPA Receptor Trafficking Mediates the Anorexigenic Effect of Endogenous Glucagon-like Peptide-1 in the Paraventricular Hypothalamus

Glucagon-like Peptide 1 (GLP-1)-expressing neurons in the hindbrain send robust projections to the paraventricular nucleus of the hypothalamus (PVN), which is involved in the regulation of food intake. Here, we describe that stimulation of GLP-1 afferent fibers within the PVN is sufficient to suppress food intake independent of glutamate release. We also show that GLP-1 receptor (GLP-1R) activation augments excitatory synaptic strength in PVN corticotropin-releasing hormone (CRH) neurons, with GLP-1R activation promoting a protein kinase A (PKA)-dependent signaling cascade leading to phosphorylation of serine S845 on GluA1 AMPA receptors and their trafficking to the plasma membrane. Finally, we show that postnatal depletion of GLP-1R in the PVN increases food intake and causes obesity. This study provides a comprehensive multi-level (circuit, synaptic, and molecular) explanation of how food intake behavior and body weight are regulated by endogenous central GLP-1. VIDEO ABSTRACT.

Sculpting Computational-Level Models.

In this commentary, I advocate for strict relations between Marr's levels of analysis. Under a strict relationship, each level is exactly implemented by the subordinate level. This yields two benefits. First, it brings consistency for multilevel explanations. Second, similar to how a sculptor chisels away superfluous marble, a modeler can chisel a computational-level model by applying constraints. By sculpting the model, one restricts the (potentially infinitely large) set of possible algorithmic- and implementational-level theories.

Toward a complex system understanding of bipolar disorder: A chaotic model of abnormal circadian activity rhythms in euthymic bipolar disorder.

In the absence of a comprehensive neural model to explain the underlying mechanisms of disturbed circadian function in bipolar disorder, mathematical modeling is a helpful tool. Here, circadian activity as a response to exogenous daily cycles is proposed to be the product of interactions between neuronal networks in cortical (cognitive processing) and subcortical (pacemaker) areas of the brain. To investigate the dynamical aspects of the link between disturbed circadian activity rhythms and abnormalities of neurotransmitter functioning in frontal areas of the brain, we developed a novel mathematical model of a chaotic system which represents fluctuations in circadian activity in bipolar disorder as changes in the model's parameters. A novel map-based chaotic system was developed to capture disturbances in circadian activity across the two extreme mood states of bipolar disorder. The model uses chaos theory to characterize interplay between neurotransmitter functions and rhythm generation; it aims to illuminate key activity phenomenology in bipolar disorder, including prolonged sleep intervals, decreased total activity and attenuated amplitude of the diurnal activity rhythm. To test our new cortical-circadian mathematical model of bipolar disorder, we utilized previously collected locomotor activity data recorded from normal subjects and bipolar patients by wrist-worn actigraphs. All control parameters in the proposed model have an important role in replicating the different aspects of circadian activity rhythm generation in the brain. The model can successfully replicate deviations in sleep/wake time intervals corresponding to manic and depressive episodes of bipolar disorder, in which one of the excitatory or inhibitory pathways is abnormally dominant. Although neuroimaging research has strongly implicated a reciprocal interaction between cortical and subcortical regions as pathogenic in bipolar disorder, this is the first model to mathematically represent this multilevel explanation of the phenomena of bipolar disorder.

Performativity, Identity and Economic Naturalism: A Comment on John Davis" „Economics, Neuroeconomics, and the Problem of Identity"

Abstract This paper is an extensive comment on John Davis’ paper “Economics, Neuroeconomics, and the Problem of Identity“ published in this very journal (Vol. 136, No. 1). So far, the methodological assessments of neuroeconomics by economists vacillate between the Scylla of neuro-reductionism and the Charybdis of Friedman’s instrumentalism. Following Davis’ approach to identity economics, I argue that there is a third way shown by methodological approaches to the neurosciences which are non-reductionist and highlight complex multi-level explanations, including external interactions, such as in distributed cognition theories. I suggest that newly emerging areas of study – such as social neuroscience – can be traced back to G.H Mead’s theory of the individual, with important implications for economics. JEL Codes: B41, D87

Development of Mechanistic Reasoning and Multilevel Explanations of Ecology in Third Grade Using Agent‐Based Models

AbstractIn this paper, we present a third‐grade ecology learning environment that integrates two forms of modeling––embodied modeling and agent‐based modeling (ABMs)––through the generation of mathematical representations that are common to both forms of modeling. The term “agent” in the context of ABMs indicates individual computational objects or actors that obey simple rules assigned or controlled by the user. It is the interactions between these agents that give rise to emergent, aggregate‐level behaviors in complex systems. While several researchers have argued for the effectiveness of ABMs for learning about complex systems, the design of classroom activity systems using ABMs, especially for elementary students, has received relatively less attention. In this paper, we report on a 2‐week long proof‐of‐concept study conducted in a third‐grade classroom of 15 students in which students began with an embodied modeling activity of foraging behavior, followed with the generation of mathematical inscriptions based on their embodied actions, and finally, conducted further inquiry of interdependence in an ecosystem using two separate ABMs. Furthermore, we show that the lens of mechanistic reasoning can be productively used to identify the process of students’ conceptual development of interdependence in an ecosystem as they engage in the modeling activities.

A Multi-Level Explanation of Mass Support for the Judiciary

ABSTRACTPredispositions about regime type affect individuals' support for the judiciary on both the individual and the group level. I also show that the level of judicial independence affects public support for the judiciary in countries with dependent judiciaries, but the effect of judicial independence is conditioned by the predisposition that people have toward regime type. I show that judicial independence affects both (1) diffuse support and (2) specific political support for the judiciary. In particular, judicial independence has a positive effect on the diffuse support of liberal democrats. Meanwhile, delegative democratic specific political support is significantly higher than the specific political support of liberal democrats and authoritarians. Taken together, findings suggest that liberal democrats and delegative democrats support majoritarian governance in such a manner that judiciaries may promote certain decisions to these important constituents in the courts interactions with the executive and legislature.

Organizational Behavior: A Brief Overview and Safety Orientation

Organizational Behavior (OB) is a discipline of social science that seeks explanations for human behavior in organizations. OB draws on core disciplines such as psychology, sociology, anthropology, economics, communication, and law to create and investigate multilevel explanations of why people engage in particular behaviors, and which behaviors under which circumstances lead to better outcomes in organizations. Created using an applied or pragmatic lens and tested with a wide range of both quantitative and qualitative methodologies, most OB theories and research have direct implications for managers and for other organizational participants. Not surprisingly, one focal area of OB research concerns safety in organizations, and a growing body of safety-oriented literature in OB is based on data collected during simulation training across a variety of organizations such as hospitals, airlines, nuclear power plants, and other high reliability organizations.

Social Capital or Ethnic Enclave Location? A Multilevel Explanation of Immigrant Business Growth

The rapid increase in migration into host countries and the growth of immigrant‐owned business enterprises has revitalized research on ethnic business. Does micro (individual)‐level social capital, or meso (group)‐level location within the ethnic enclave lead to immigrant business growth? Or do you need both? We analyze quantitative data collected from 110 Chinese restaurants in Australia, a major host country. At the micro level we find that coethnic (same ethnic group) networks are critical to the growth of an immigrant entrepreneur's business, particularly in the early years. But non‐coethnic (different ethnic group) social capital only has a positive impact on business growth for immigrant businesses outside the ethnic enclave. Our findings are relevant, not only to host‐country policymakers, but also for future immigrant business owners and ethnic community leaders trying to better understand how to promote healthy communities and sustainable economic growth. © 2015 Wiley Periodicals, Inc.

Developing Multilingual Capacity: A Challenge for the Multinational Enterprise

In this article, we examine how the multinational enterprise (MNE) develops the ability to function as a multilingual entity in order to facilitate communication, knowledge transfer, and absorptive capacity. While we acknowledge the role played by the adoption of a common corporate language, we argue that this response alone is insufficient to cope with the diverse foreign language demands that accompany global expansion. MNEs need what we conceptualize as language operative capacity (LOC): language resources that have been assembled and deployed in a context-relevant and timely manner throughout the MNE’s global network. Language resources are mainly derived from human and social capital, and their interaction, to form what is termed language capital. Managerial motivation and a preparedness to act are necessary to ensure that language capital is converted into LOC. Our theoretical explanation of LOC derivation is multilevel, incorporating two interacting processes: individuals develop, maintain, and contribute their own foreign language resources, but the MNE also plays a key role. It can influence individual behavior and, at the organizational level, provide its own language resources through the provision of computerized translation software and the like. The interaction between these two processes is seen to be critical in the formation and use of LOC. This multilevel explanation contributes to the growing body of literature that considers how human capital resources in general can be converted for productive purposes.

Multi-Level Selection and the Explanatory Value of Mathematical Decompositions

Do multi-level selection explanations of the evolution of social traits deepen the understanding provided by single-level explanations? Central to multi-level explanations is a mathematical theorem, the multi-level Price decomposition. I build a framework through which to understand the explanatory role of such non-empirical decompositions in scientific practice. Applying this general framework to the present case places two tasks on the agenda. The first task is to distinguish the various ways by which one might suppress within-collective variation in fitness, or indeed between-collective variation in fitness. I distinguish five such ways: increasing retaliatory capacity; homogenising assortment; collapsing either fitness structure or character distribution to a mean value; and boosting fitness uniformly within collectives. I then evaluate the biological interest of each of these hypothetical interventions. The second task is to discover whether one of the right-hand terms of the Price decomposition measures the effect of any of these interventions. On this basis I argue that the multi-level Price decomposition has explanatory value primarily when the sharing-out of collective resources is 'subtractable'. Thus its value is more circumscribed than its champions Sober and Wilson (1998) suppose.

How does psychotherapy work? A case study in multilevel explanation.

Multilevel explanations abound in psychiatry. However, formulating useful such explanations is difficult or (some argue) impossible. I point to several ways in which Lane et al. successfully use multilevel explanations to advance understanding of psychotherapeutic effectiveness. I argue that the usefulness of an explanation depends largely on one's purpose, and conclude that this point has been inadequately recognised in psychiatry.

Addressing students’ difficulties with Faraday’s law: A guided problem solving approach

In traditional teaching, the fundamental concepts of electromagnetic induction are usually quickly analyzed, spending most of the time solving problems in a more or less rote manner. However, physics education research has shown that the fundamental concepts of the electromagnetic induction theory are barely understood by students. This article proposes an interactive teaching sequence introducing the topic of electromagnetic induction. The sequence has been designed based on contributions from physics education research. Particular attention is paid to the relationship between experimental findings (macroscopic level) and theoretical interpretation (microscopic level). An example of the activities that have been designed will also be presented, describing the implementation context and the corresponding findings. Since implementing the sequence, a considerable number of students have a more satisfactory grasp of the electromagnetic induction explicative model. However, difficulties are manifested in aspects that require a multilevel explanation, referring to deep structures where the system description is better defined.

Bridging psychiatry and neurology through social neuroscience.

Social neuroscience launched a novel multilevel (neural, hormonal, molecular and genetic) explanation of social cognition in psychiatry. In particular, the use of different levels of scientific inquiry assessing a) behavioral social cognition sensitivity to psychiatric impairment, b) neural networks engaged in social behaviors, c) the genetic underpinning of social phenomena, and d) the influence of the social environment on biological processes, have been outstandingly addressed by Cacioppo et al's paper 1. Neuroscientific progress suggests that the separation between psychiatry and neurology is counterproductive. Classical neurological conditions present a range of social cognition impairments that are often underrecognized and frequently undertreated. Social neuroscience has made important progress in elucidating the neurobiology of the social brain, but has not focused sufficiently on neurological disorders. Here we consider the implications of social neuroscience research for a specific neuropsychiatric condition, the behavioral variant of frontotemporal dementia (bvFTD). Moreover, we highlight the importance of social neuroscience for the cross-talk among psychiatry and neurology. BvFTD is a neurodegenerative disease whose initial symptoms are often confused with several psychiatric conditions. It is characterized by early decline in social interpersonal behavior, personality changes, and progressive deterioration in social functioning 2. Conventional neuropsychological assessment as well as clinical routine neuroimaging have been not been very useful for early diagnosis 2. The social neuroscience approach has raised new opportunities for research and translational applications in bvFTD. First, social cognition assessment in bvFTD has allowed the detection of early and subtle behavioral impairments, appearing even before imaging signatures of brain atrophy, or a clear decline in formal cognitive status 3. In particular, social cognition tasks that resemble everyday behavior seem to be a far more adequate assessment for this purpose 4. Social cognition assessment may soon become part of the clinical screening for bvFTD. Second, it has been proposed that models of social cognition associated with a degeneration of the fronto-insulo-temporal (social context network model) or fronto-insular (salience network) regions may explain the myriad of bvFTD social cognition impairments 2. For instance, Von Economo neurons are large spindle-shaped cells, abundant in the insular and anterior cingulate cortex. Among primates, these neurons have evolved only in hominids, and seem to be particularly vulnerable in neuropsychiatric conditions resulting in social cognition impairments. In bvFTD, a specific loss of these neurons within fronto-temporo-insular atrophy, at early stages, has been associated clinically with changes in empathy, social awareness, and other social cognition domains 5. Third, an important genetic component of bvFTD has been related with social cognition impairment. There are three main genes for bvFTD: MAPT, GRN, and C9ORF72. Patients with C9ORF72 mutations exhibit widespread frontotemporal atrophy, associated with psychiatric presentations as well as with social neglect 6. In a similar way, animal models and clinical studies of GRN have shown early social and emotional changes, without gross impairment in overall health 6. Fourth, the potential role of the social world, and its interaction with brain changes in bvFTD, deserves consideration. For instance, feeling lonely is associated with increased risk for dementia 7 and with a wish to hasten death in FTD 8. An inter-level social neuroscience approach combining the study of social behavior, neural networks, genetic influences, and the interactions between social behaviors and social cognition would help to provide a more in-depth understanding of bvFTD, as well as of the overlaps of this disorder with the symptomatology and social cognition impairments of several psychiatric conditions 9. A new form of cross-talk between psychiatry and neurology may thus be developed in the social neuroscience arena, spearheaded by work on bvFTD as perhaps the clearest example of the bridges between the two disciplines. Stimulating this cross-talk between neurological and psychiatric research seems to be one of the most promising roles for social neuroscience. Several neurological conditions with mental health manifestations (e.g., neurodegenerative conditions, prosopagnosia, tuberous sclerosis, and Angelman, Heller, Prader-Willi, Williams, Turner and Klinefelter syndromes) present impaired social functioning 10. Here, we have highlighted the multilevel social neuroscience approach to bvFTD, but the understanding of several other neurological conditions could benefit from this approach. Many social cognition domains (social emotions, decision making, theory of mind, empathy, moral cognition, and social norms) may be impacted differentially in various psychiatric and neurological conditions, and the differences in such parameters could be built into technologies for diagnosis and measurement of treatment efficacy. Psychiatrists and neurologists within this novel social neuroscience approach may be able to contribute a powerful multidisciplinary and transdisciplinary approach 11, that would be both clinically and theoretically relevant to major advances in contemporary neuropsychiatry.

The third wave of biological psychiatry

In this article I will argue that we are witnessing at this moment the third wave of biological psychiatry. This framework conceptualizes mental disorders as brain disorders of a special kind that requires a multilevel approach ranging from genes to psychosocial mechanisms. In contrast to earlier biological psychiatry approaches, the mental plays a more prominent role in the third wave. This will become apparent by discussing the recent controversy evolving around the recently published DSM-5 and the competing transdiagnostic Research Domain Criteria approach of the National Institute of Mental Health that is build on concepts of cognitive neuroscience. A look at current conceptualizations in biological psychiatry as well as at some discussions in current philosophy of mind on situated cognition, reveals that the thesis, that mental brain disorders are brain disorders has to be qualified with respect to how mental states are constituted and with respect to multilevel explanations of which factors contribute to stable patterns of psychopathological signs and symptoms.