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Descriptive accounts of the nature of explanation in neuroscience and the global goals of such explanation have recently proliferated in the philosophy of neuroscience and with them new understandings of the experimental practices of neuroscientists have emerged. In this paper, I consider two models of such practices; one that takes them to be reductive; another that takes them to be integrative. I investigate those areas of the neuroscience of learning and memory from which the examples used to substantiate these models (...) are culled, and argue that the multiplicity of experimental protocols used in these research areas presents specific challenges for both models. In my view, these challenges have been overlooked largely because philosophers have hitherto failed to pay sufficient attention to fundamental features of experimental practice. I demonstrate that when we do pay attention to such features, evidence for reduction and integrative unity in neuroscience is simply not borne out. I end by suggesting some new directions for the philosophy of neuroscience that pertain to taking a closer look at the nature of neuroscientific experiments. (shrink)

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In this volume, leading philosophers of psychiatry examine psychiatric classification systems, including the Diagnostic and Statistical Manual of Mental Disorders, asking whether current systems are sufficient for effective diagnosis, treatment, and research. Doing so, they take up the question of whether mental disorders are natural kinds, grounded in something in the outside world. Psychiatric categories based on natural kinds should group phenomena in such a way that they are subject to the same type of causal explanations and respond similarly to (...) the same type of causal interventions. When these categories do not evince such groupings, there is reason to revise existing classifications. The contributors all question current psychiatric classifications systems and the assumptions on which they are based. They differ, however, as to why and to what extent the categories are inadequate and how to address the problem. Topics discussed include taxometric methods for identifying natural kinds, the error and bias inherent in DSM categories, and the complexities involved in classifying such specific mental disorders as "oppositional defiance disorder" and pathological gambling. -/- Contributors George Graham, Nick Haslam, Allan Horwitz, Harold Kincaid, Dominic Murphy, Jeffrey Poland, Nancy Nyquist Potter, Don Ross, Dan Stein, Jacqueline Sullivan, Serife Tekin, Peter Zachar. (shrink)

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The past decade has witnessed a growing awareness of conceptual and methodological hurdles within psychology and neuroscience that must be addressed for taxonomic and explanatory progress in understanding psychological functions to be possible. In this paper, I evaluate several recent knowledge-building initiatives aimed at overcoming these obstacles. I argue that while each initiative offers important insights about how to facilitate taxonomic and explanatory progress in psychology and neuroscience, only a “coordinated pluralism” that incorporates positive aspects of each initiative will have (...) the potential for success. (shrink)

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The Morris water maze has been put forward in the philosophy of neuroscience as an example of an experimental arrangement that may be used to delineate the cognitive faculty of spatial memory (e.g., Craver and Darden, Theory and method in the neurosciences, University of Pittsburgh Press, Pittsburgh, 2001; Craver, Explaining the brain: Mechanisms and the mosaic unity of neuroscience, Oxford University Press, Oxford, 2007). However, in the experimental and review literature on the water maze throughout the history of its use, (...) we encounter numerous responses to the question of “what” phenomenon it circumscribes ranging from cognitive functions (e.g., “spatial learning”, “spatial navigation”), to representational changes (e.g., “cognitive map formation”) to terms that appear to refer exclusively to observable changes in behavior (e.g., “water maze performance”). To date philosophical analyses of the water maze have not been directed at sorting out what phenomenon the device delineates nor the sources of the different answers to the question of what. I undertake both of these tasks in this paper. I begin with an analysis of Morris’s first published research study using the water maze and demonstrate that he emerged from it with an experimental learning paradigm that at best circumscribed a discrete set of observable changes in behavior. However, it delineated neither a discrete set of representational changes nor a discrete cognitive function. I cite this in combination with a reductionist-oriented research agenda in cellular and molecular neurobiology dating back to the 1980s as two sources of the lack of consistency across the history of the experimental and review literature as to what is under study in the water maze. (shrink)

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In this chapter I investigate the kinds of changes that psychiatric kinds undergo when they become explanatory targets of areas of sciences that are not “mature” and are in the early stages of discovering mechanisms. The two areas of science that are the targets of my analysis are cognitive neuroscience and cognitive neurobiology.

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This paper offers a critique of an account of explanatory integration that claims that explanations of cognitive capacities by functional analyses and mechanistic explanations can be seamlessly integrated. It is shown that achieving such explanatory integration requires that the terms designating cognitive capacities in the two forms of explanation are stable but that experimental practice in the mind-brain sciences currently is not directed at achieving such stability. A positive proposal for changing experimental practice so as to promote such stability is (...) put forward and its implications for explanatory integration are briefly considered. (shrink)

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Optogenetic techniques are described as “revolutionary” for the unprecedented causal control they allow neuroscientists to exert over neural activity in awake behaving animals. In this paper, I demonstrate by means of a case study that optogenetic techniques will only illuminate causal links between the brain and behavior to the extent that their error characteristics are known and, further, that determining these error characteristics requires comparison of optogenetic techniques with techniques having well known error characteristics and consideration of the broader neural (...) and behavioral context in which the targets of optogenetic interventions are situated. (shrink)

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Scientists represent their world, grouping and organizing phenomena into classes by means of concepts. Philosophers of science have historically been interested in the nature of these concepts, the criteria that inform their application and the nature of the kinds that the concepts individuate. They also have sought to understand whether and how different systems of classification are related and more recently, how investigative practices shape conceptual development and change. Our aim in this paper is to provide a critical overview of (...) some of the key developments in this philosophical literature and identify some interesting issues it raises about the prospects of the so-called “special sciences”, including psychiatry, psychology, and the mind-brain sciences more generally, to discover natural kinds. (shrink)

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In this article, I explain why stabilizing constructs is important to the success of the Research Domain Criteria Project and identify one measure for facilitating such stability.

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In 2007, ten world-renowned neuroscientists proposed “A Decade of the Mind Initiative.” The contention was that, despite the successes of the Decade of the Brain, “a fundamental understanding of how the brain gives rise to the mind [was] still lacking” (2007, 1321). The primary aims of the decade of the mind were “to build on the progress of the recent Decade of the Brain (1990-99)” by focusing on “four broad but intertwined areas” of research, including: healing and protecting, understanding, enriching, (...) and modeling the mind. These four aims were to be the result of “transdisciplinary and multiagency” research spanning “across disparate fields, such as cognitive science, medicine, neuroscience, psychology, mathematics, engineering, and computer science.” The proposal for a decade of the mind prompted many questions (See Spitzer 2008). In this chapter, I address three of them: (1) How do proponents of this new decade conceive of the mind? (2) Why should a decade be devoted to understanding it? (3) What should this decade look like? (shrink)

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Do neurobiologists aim to discover natural kinds? I address this question in this chapter via a critical analysis of classification practices operative across the 43-year history of research on long-term potentiation. I suggest that this 43-year history supports the idea that the structure of scientific practice surrounding LTP research has remained an obstacle to the discovery of natural kinds as philosophers of science have traditionally conceived them.

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What role does the concept of representation play in the contexts of experimentation and explanation in cognitive neurobiology? In this article, a distinction is drawn between minimal and substantive roles for representation. It is argued by appeal to a case study that representation currently plays a role in cognitive neurobiology somewhere in between minimal and substantive and that this is problematic given the ultimate explanatory goals of cognitive neurobiological research. It is suggested that what is needed is for representation to (...) instead play a more substantive role. (shrink)

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Neuroscience is a laboratory-based science that spans multiple levels of analysis from molecular genetics to behavior. At every level of analysis experiments are designed in order to answer empirical questions about phenomena of interest. Understanding the nature and structure of experimentation in neuroscience is fundamental for assessing the quality of the evidence produced by such experiments and the kinds of claims that are warranted by the data. This article provides a general conceptual framework for thinking about evidence and experimentation in (...) neuroscience with a particular focus on two research areas: cognitive neuroscience and cognitive neurobiology. (shrink)

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Ian Hacking instigated a revolution in 20th century philosophy of science by putting experiments (“interventions”) at the top of a philosophical agenda that historically had focused nearly exclusively on representations (“theories”). In this paper, I focus on a set of conceptual tools Hacking (1992) put forward to understand how laboratory sciences become stable and to explain what such stability meant for the prospects of unity of science and kind discovery in experimental science. I first use Hacking’s tools to understand sources (...) of instability and disunity in rodent behavioral neuroscience. I then use them to understand recent grass-roots collaborative open science initiatives aimed at establishing stability in this research area and tease out some implications for unity of science and kind creation and discovery in cognitive neuroscience. -/- . (shrink)

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Many neurodegenerative and neuropsychiatric diseases and other brain disorders are accompanied by impairments in high-level cognitive functions including memory, attention, motivation, and decision-making. Despite several decades of extensive research, neuroscience is little closer to discovering new treatments. Key impediments include the absence of validated and robust cognitive assessment tools for facilitating translation from animal models to humans. In this review, we describe a state-of-the-art platform poised to overcome these impediments and improve the success of translational research, the Mouse Translational Research (...) Accelerator Platform (MouseTRAP), which is centered on the touchscreen cognitive testing system for rodents. It integrates touchscreen-based tests of high-level cognitive assessment with state-of-the art neurotechnology to record and manipulate molecular and circuit level activity in vivo in animal models during human-relevant cognitive performance. The platform also is integrated with two Open Science platforms designed to facilitate knowledge and data-sharing practices within the rodent touchscreen community, touchscreencognition and mousebytes. Touchscreencognition includes the Wall, showcasing touchscreen news and publications, the Forum, for community discussion, and Training, which includes courses, videos, SOPs, and symposia. To get started, interested researchers simply create user accounts. We describe the origins of the touchscreen testing system, the novel lines of research it has facilitated, and its increasingly widespread use in translational research, which is attributable in part to knowledge-sharing efforts over the past decade. We then identify the unique features of MouseTRAP that stand to potentially revolutionize translational research, and describe new initiatives to partner with similar platforms such as McGill’s M3 platform. (shrink)

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Clinical psychology is characterized by persistent disagreement about fundamental aspects of the discipline ranging from what mental disorders are to what constitutes effective treatment. Attempts to address the problem of epistemic disagreement have been frequently based on establishing the correct answer by fiat without identifying and addressing the sources of the disagreement. We argue that this strategy has not worked very well and the result is frequently ongoing and intractable disagreement, with each side in an argument convinced they are correct. (...) In this paper, we outline an epistemic disagreement procedural model intended to assist researchers and clinicians in the field of clinical psychology to identify, explore, and develop inquiry strategies that capitalize on situations where competing knowledge claims are made. The result is a flexible conceptual framework committed to a defensible epistemic pluralism, fallibilism, and contextualism, across the various research tasks constituting the field of clinical psychology. (shrink)

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In this chapter, I argue that scientific practice in the neurosciences of cognition is not conducive to the discovery of natural kinds of cognitive capacities. The “neurosciences of cognition” include cognitive neuroscience and cognitive neurobiology, two research areas that aim to understand how the brain gives rise to cognition and behavior. Some philosophers of neuroscience have claimed that explanatory progress in these research areas ultimately will result in the discovery of the underlying mechanisms of cognitive capacities. Once such mechanistic understanding (...) is achieved, cognitive capacities purportedly will be relegated into natural kind categories that correspond to real divisions in the causal structure of the world. I provide reasons here, however, in support of the claim that the neurosciences of cognition currently are not on a trajectory for discovering natural kinds. As I explain, this has to do with how mechanistic explanations of cognitive capacities are developed. Mechanistic explanations and the kinds they explain are abstract representational byproducts of the conceptual, experimental and integrative practices of neuroscientists. If these practices are not coordinated towards developing mechanistic explanations that mirror the causal structure of the world, then natural kinds of cognitive capacities will not be discovered. I provide reasons to think that such coordination is currently lacking in the neurosciences of cognition and indicate where changes in these practices appropriate to the natural kinds ideal would be required if achieving this ideal is indeed the goal. However, I suggest that an evaluation of current practices in these research areas is suggestive that discovering natural kinds of cognitive capacities is not the goal. (shrink)

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Efforts by governments, firms, and patients to deliver pioneering drugs for critical health needs face a challenge of diminishing efficiency in developing those medicines. While multi-sectoral collaborations involving firms, researchers, patients, and policymakers are widely recognized as crucial for countering this decline, existing incentives to engage in drug development predominantly target drug manufacturers and thereby do little to stimulate collaborative innovation. In this mini review, we consider the unexplored potential within pharmaceutical regulations to create novel incentives to encourage a diverse (...) set of actors from the public and private spheres to engage in the kind of collaborative knowledge exchange requisite for fostering enhanced innovation in early drug development. (shrink)

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Crime is a serious social problem, but its causes are not exclusively social. There is growing consensus that explaining and preventing it requires interdisciplinary research efforts. Indeed, the landscape of contemporary criminology includes a variety of theoretical models that incorporate psychological, biological and sociological factors. These multi-disciplinary approaches, however, have yet to radically advance scientific understandings of crime and shed light on how to manage it. In this paper, using conceptual tools on offer in the philosophy of science in combination (...) with theoretical work represented in this special volume of Psychology, Crime and Law, I provide some perspective on why explanatory progress in criminology has remained elusive and evaluate some positive proposals for attaining it. -/- . (shrink)

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In the last decade alone, a growing body of preliminary evidence suggests that classic psychedelics (CPs) can rapidly and durably ameliorate symptoms and cognitive deficits associated with depression. However, the mechanisms by which CPs work in the brain are not well understood. Rodent translational research, in which experimental findings from rodents are translated to humans, is fundamental in achieving this goal. This chapter focuses on a representative subset of human and rodent studies investigating CPs for depression, including the various lines (...) of research that have been initiated to understand how they work. Our aim is to show that in addition to epistemic challenges that scientists face in translating findings from rodents to humans, there is also mismatch between experimental approaches used to investigate CPs in humans and rodents. We thus show current experimental practices are not conducive to mechanistic discovery. We end with a set of positive proposals to expedite the drive to translate CPs into effective treatments for depression. -/- Keywords: classic psychedelics, psychiatry, clinical trials, collaboration, extrapolation, major depressive disorder, open science, philosophy of science, rodent models, scientific practice, translation, validity . (shrink)

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This article investigates several consequences of a recent trend in philosophy of mind to shift the relata of realization from mental state–physical state to function‐mechanism. It is shown, by applying both frameworks to the neuroscientific case study of memory consolidation, that, although this shift can be used to avoid the immediate antireductionist consequences of the traditional argument from multiple realizability, what is gained is a far more modest form of reductionism than recent philosophical accounts have intimated and neuroscientists themselves have (...) claimed. (shrink)

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Do neurobiologists aim to discover natural kinds? I address this question in this chapter via a critical analysis of classification practices operative across the 43-year history of research on long-term potentiation (LTP). I argue that this 43-year history supports the idea that the structure of scientific practice surrounding LTP research has remained an obstacle to the discovery of natural kinds.

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One might be inclined to assume, given the mouse donning its cover, that the behavior of interest in Nicole Nelson's book Model Behavior (2018) is that of organisms like mice that are widely used as “stand-ins” for investigating the causes of human behavior. Instead, Nelson's ethnographic study focuses on the strategies adopted by a community of rodent behavioral researchers to identify and respond to epistemic challenges they face in using mice as models to understand the causes of disordered human behaviors (...) associated with mental illness. Although Nelson never explicitly describes the knowledge production activities in which her behavioral geneticist research subjects engage as “exemplary”, the question of whether or not these activities constitute “model behavior(s)”—generalizable norms for engaging in scientific research—is one of the many thought-provoking questions raised by her book. As a philosopher of science interested in this question, I take it up here. (shrink)

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The use of neuroscientific evidence in criminal trials has been steadily increasing. Despite progress made in recent decades in understanding the mechanisms of psychological and behavioral functioning, neuroscience is still in an early stage of development and its potential for influencing legal decision-making is highly contentious. Scholars disagree about whether or how neuroscientific evidence might impact prescriptions of criminal culpability, particularly in instances in which evidence of an accused’s history of mental illness or brain abnormality is offered to support a (...) plea of not criminally responsible. In the context of these debates, philosophers and legal scholars have identified numerous problems with admitting neuroscientific evidence in legal contexts. To date, however, less has been said about the challenges of evaluating the evidence upon which integrative mechanistic explanations that bring together evidence from different areas of neuroscience are based. As we explain, current criteria for evaluating such evidence to determine its admissibility in legal contexts are inadequate. Appealing to literature in the philosophy of scientific experimentation and theoretical work in the social, cognitive and behavioral sciences, we lay the groundwork for reforming these criteria and identify some of the implications of modifying them. (shrink)

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Biomedical science has been remarkably successful in explaining illness by categorizing diseases and then by identifying localizable lesions such as a virus and neoplasm in the body that cause those diseases. Not surprisingly, researchers have aspired to apply this powerful paradigm to addiction. So, for example, in a review of the neuroscience of addiction literature, Hyman and Malenka (2001, p. 695) acknowledge a general consensus among addiction researchers that “[a]ddiction can appropriately be considered as a chronic medical illness.” Like other (...) diseases, “Once addiction has taken hold, it tends to follow a chronic course.” (Koob and La Moal 2006, p. ?). Working from this perspective, much effort has gone into characterizing the symptomology of addiction and the brain changes that underlie them. Evidence for involvement of dopamine transmission changes in the ventral tegmental area (VTA) and nucleus accumbens (NAc) have received the greatest attention. Kauer and Malenka (2007, p. 844) put it well: “drugs of abuse can co-opt synaptic plasticity mechanisms in brain circuits involved in reinforcement and reward processing”. Our goal in this chapter to provide an explicit description of the assumptions of medical models, the different forms they may take, and the challenges they face in providing explanations with solid evidence of addiction. <br>. (shrink)

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This chapter has two aims. The first aim is to compare and contrast three different conceptual-explanatory models for thinking about mental illness with an eye towards identifying the assumptions upon which each model is based, and exploring the model’s advantages and limitations in clinical contexts. Major Depressive Disorder is used as an example to illustrate these points. The second aim is to address the question of what conceptual-theoretical framework for thinking about mental illness is most likely to facilitate the discovery (...) of causes and treatments of mental illness in research contexts. To this end, the National Institute of Mental Health’s Research Domain Criteria (RDoC) Project is briefly considered. (shrink)

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In the quest to discover the neural bases of cognition, rigorous behavioral tools are equally as important as sophisticated tools for neural intervention. This paper evaluates several episodes in the development of a novel behavioral tool for rodent cognitive testing, the rodent touchscreen operant chamber. Using conceptual tools on offer in the philosophical literature on exploratory experimentation and control, I illuminate how optimization of this behavioral tool and an understanding of the causal knowledge it may be used to generate historically (...) has involved dynamic interplay between community-driven exploratory practices operating in parallel with causal hypothesis-driven research. (shrink)

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To develop rehabilitative treatment programs for persons who have committed crimes, correctional psychologists build theoretical structures that weld theoretical ideas about the causes of criminal behavior, theoretical perspectives about appropriate targets for correctional intervention and normative assumptions about crime and the aims of correctional intervention. To differentiate the tri-partite theoretical structure with which correctional program designers' work, Ward and Durrant (2021) introduce the metatheoretical concept of “practice frameworks”. In this paper, I describe and evaluate this concept, situating my analysis within (...) the broader contexts of philosophical work on scientific theories and models and metatheoretical work on the structure of explanatory and intervention theories in correctional psychology. (shrink)

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This study aimed to understand the preserved elements of self-identity in persons with moderate to severe dementia attributable to Alzheimer’s disease. A semi-structured interview was developed to explore the narrative self among residents with dementia in a residential care facility and residents without dementia in an independent living setting. The interviews were transcribed verbatim from audio recordings and analyzed for common themes, while being sensitive to possible differences between the groups. The participants with dementia showed evidence of self-reference even though (...) losses in explicit memory were evident. The most noticeable difference between the two groups was time frame reference. Nonetheless, all participants showed understanding of their role in relationships and exhibited concrete preferences. Our findings suggest that memory loss and other cognitive deficits associated with moderate to severe dementia do not necessarily lead to a loss of “self.”. (shrink)

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This paper is a response to a commentary by Walter Glannon (2016, Frontiers in Human Neuroscience) on my paper "Stabilizing Constructs Across Research Fields as a Way to Foster the Integrative Approach of the Research Domain Criteria Project".

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Muhammad Ali Khalidi contends that because cognitive science casts a wider net than neuroscience in searching for the causes of cognition, it is in the superior position to discover “real” cognitive kinds. I argue that while Khalidi identifies appropriate norms for individuating cognitive kinds, these norms ground his characterization of taxonomic practices in cognitive science, rather than the other way around. If we instead treat Khalidi's norms not as descriptively accurate characterizations of taxonomic practices in cognitive science, but as a (...) set of best practices for kinding cognition, is cognitive science in and neuroscience definitively out of the cognitive kinding game? (shrink)

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Anorexia Nervosa (AN) is widely considered to be a bodily disorder accompanied by unrealistic perceptions about one’s own body. Some researchers thus have wondered whether deficits in interoception, a conscious or non-conscious sense of one’s own body, could be a primary cause of AN. In this paper, we make the case that rather than interoception being a primary cause, deficits in interoception may occur as by-products of emotions that arise upstream in the pathogenesis of AN and interact with feelings of (...) a loss of self-control. We consider interoception, emotion, and self-control as a dynamical triad involved in the explanation of AN, with emotions as the central aspect of their interactions. We begin with a critical analysis of recent empirical literature on AN and differentiate three types of interoceptive processes. We then consider the role of self-control in AN. We go on to evaluate recent empirical and philosophical work on the role of emotions in AN and assess their importance in both interoception and self-control dynamics. We develop a testable integrative model that we believe best captures how self-control, emotional and interoceptive processes causally interact in the pathogenesis of AN. In this model, AN behaviors are not caused by interoceptive abnormalities, but rather interact with changes in emotional regulation and feelings of loss of self-control, subsequently leading to interoceptive deficits downstream. To capture a later stage in the pathogenesis of AN, we show how AN behaviors are maintained as a result of feedback among components in the model. We briefly explain future plans to further complement the model using a semi-structured interview to probe patient perspectives in AN. To develop a more valid understanding of AN, this model will have to be integrated into pluralistic approaches that include patient perspectives. (shrink)

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Titles and abstracts for the Pitt-London Workshop in the Philosophy of Biology and Neuroscience: September 2001.

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This volume brings together a number of perspectives on the nature of realization explanation and experimentation in the ‘special’ and biological sciences as well as the related issues of psychoneural reduction and cognitive extension. The first two papers in the volume may be regarded as offering direct responses to the questions: (1) What model of realization is appropriate for understanding the metaphysics of science? and (2) What kind of philosophical work is such a model ultimately supposed to do?

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This volume is a collection of original essays focusing on a wide range of topics in the History and Philosophy of Science. It is a festschrift for Peter Machamer, which includes contributions from scholars who, at one time or another, were his students. The essays bring together analyses of issues and debates spanning from early modern science and philosophy through the 21st century. Machamer’s influence is reflected in the volume’s broad range of topics. These include: underdetermination, scientific practice, scientific models, (...) mechanistic explanation in contemporary and historical science, values in science, the relationship between philosophy and psychology, experimentation, supervenience and reductionism. (shrink)

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The vestibulo-ocular reflex (VOR) adaptation is an ideal model for investigating how the neurosteroid 17 beta-estradiol (E2) contributes to the modification of behavior by regulating synaptic activities. We hypothesized that E2 impacts VOR adaptation by affecting cerebellar synaptic plasticity at the parallel fiber–Purkinje cell (PF) synapse. To verify this hypothesis, we investigated the acute effect of blocking E2 synthesis on gain increases and decreases in adaptation of the VOR in male rats using an oral dose (2.5 mg/kg) of the aromatase (...) inhibitor letrozole. We also assessed the effect of letrozole on synaptic plasticity at the PF synapse in vitro, using cerebellar slices from male rats. We found that letrozole acutely impaired both gain increases and decreases adaptation of the VOR without altering basal ocular-motor performance. Moreover, letrozole prevented long-term potentiation at the PF synapse (PF-LTP) without affecting long-term depression (PF-LTD). Thus, in male rats neurosteroid E2 has a relevant impact on VOR adaptation and affects exclusively PF-LTP. These findings suggest that E2 might regulate changes in VOR adaptation by acting locally on cerebellar and extra-cerebellar synaptic plasticity sites. (shrink)

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A role of perirhinal cortex (PrC) in recognition memory for objects has been well established. Contributions of parahippocampal cortex (PhC) to this function, while documented, remain less well understood. Here, we used fMRI to examine whether the organization of item-based recognition memory signals across these two structures is shaped by object category, independent of any difference in representing episodic context. Guided by research suggesting that PhC plays a critical role in processing landmarks, we focused on three categories of objects that (...) differ from each other in their landmark suitability as confirmed with behavioral ratings (buildings > trees > aircraft). Participants made item-based recognition-memory decisions for novel and previously studied objects from these categories, which were matched in accuracy. Multi-voxel pattern classification revealed category-specific item-recognition memory signals along the long axis of PrC and PhC, with no sharp functional boundaries between these structures. Memory signals for buildings were observed in the mid to posterior extent of PhC, signals for trees in anterior to posterior segments of PhC, and signals for aircraft in mid to posterior aspects of PrC and the anterior extent of PhC. Notably, item-based memory signals for the category with highest landmark suitability ratings were observed only in those posterior segments of PhC that also allowed for classification of landmark suitability of objects when memory status was held constant. These findings provide new evidence in support of the notion that item-based memory signals for objects are not limited to PrC, and that the organization of these signals along the longitudinal axis that crosses PrC and PhC can be captured with reference to landmark suitability. (shrink)

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Neurosteroid 17 beta-estradiol (E2) is a steroid synthesized de novo in the nervous system that might influence neuronal activity and behavior. Nevertheless, the impact of E2 on the functioning of those neural systems in which it is slightly synthesized is less questioned. The vestibulo-ocular reflex (VOR) adaptation, may provide an ideal arena for investigating this issue. Indeed, E2 modulates cerebellar parallel fiber-Purkinje cell synaptic plasticity that underlies encoding of VOR adaptation. Moreover, aromatase expression in the cerebellum of adult rodents is (...) maintained at very low levels and localized to Purkinje cells. The significance of age-related maintenance of low levels of aromatase expression in the cerebellum on behavior, however, has yet to be explored. Our aim in this study was to determine whether E2 synthesis exerts an effective and persistent modulation of VOR adaptation in adult male rats. To answer this question, we investigated the acute effect of blocking E2 synthesis on gain increases and decreases in VOR adaptation using an oral dose (2.5 mg/kg) of the aromatase inhibitor Letrozole in peri-pubertal and post-pubertal male rats. We found that Letrozole acutely impaired gain increases and decreases in VOR adaptation without altering basal ocular-motor performance and that these effects were similar in peri-pubertal and post-pubertal rats. Thus, in adult male rats neurosteroid E2 effectively modulates VOR adaptation in both of the periods studied. These findings imply that the adult cerebellum uses E2 synthesis for modulating motor memory formation and suggest that low and extremely localized E2 production may play a role in adaptive phenomena. (shrink)

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Proceedings of the Pittsburgh Workshop in History and Philosophy of Biology, Center for Philosophy of Science, University of Pittsburgh, March 23-24 2001 Session 5: Development, Neuroscience and Evolutionary Psychology.

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This chapter explores some of the ways that mechanisms are invoked in neuroscience and looks at a selection of the philosophical problems that arise when trying to understand mechanistic explanations. It introduces a series of historical case studies that illustrate how neuroscientists have depended on mechanistic metaphors in their efforts to understand the mind and brain, and how their mechanistic explanations have developed over time. The chapter highlights what contemporary philosophers have identified as the fundamental features of mechanisms and mechanistic (...) explanation. It considers some of the methodological issues that arise in neuroscience including how to integrate psychological with neural models, how to generalize findings in model organisms like the sea slug Aplysia to human learning and memory, and whether to favor top-down or bottom-up methods. Constructing multi-level mechanistic explanations involves intensive collaboration across different branches of science, and involves many challenges, both pragmatic and methodological. (shrink)

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