Rationality in discovery: a study of logic, cognition, computation and neuropharmacology

Part I Introduction The specific problem adressed in this thesis is: what is the rational use of theory and experiment in the process of scientific discovery, in theory and in the practice of drug research for Parkinson’s disease? The thesis aims to answer the following specific questions: what is: 1) the structure of a theory?; 2) the process of scientific reasoning?; 3) the route between theory and experiment? In the first part I further discuss issues about rationality in science as introduction to part II, and I present an overview of my case-study of neuropharmacology, for which I interviewed researchers from the Groningen Pharmacy Department, as an introduction to part III. Part II Discovery In this part I discuss three theoretical models of scientific discovery according to studies in the fields of Logic, Cognition, and Computation. In those fields the structure of a theory is respectively explicated as: a set of sentences; a set of associated memory chunks; and as a computer program that can generate the observed data. Rationality in discovery is characterized by: finding axioms that imply observation sentences; heuristic search for a hypothesis, as part of problem solving, by applying memory chunks and production rules that represent skill; and finding the shortest program that generates the data, respectively. I further argue that reasoning in discovery includes logical fallacies, which are neccesary to introduce new hypotheses. I also argue that, while human subjects often make errors in hypothesis evaluation tasks from a logical perspective, these evaluations are rational given a probabilistic interpretation. Part III Neuropharmacology In this last part I discusses my case-study and a model of discovery in a practice of drug research for Parkinson’s disease. I discuss the dopamine theory of Parkinson’s disease and model its structure as a qualitative differential equation. Then I discuss the use and reasons for particular experiments to both test a drug and explore the function of the brain. I describe different kinds of problems in drug research leading to a discovery. Based on that description I distinguish three kinds of reasoning tasks in discovery, inference to: the best explanation, the best prediction and the best intervention. I further demonstrate how a part of reasoning in neuropharmacology can be computationally modeled as qualitative reasoning, and aided by a computer supported discovery system

[1]  R. Giere Cognitive Models of Science , 1992 .

[2]  Rolf Kötter,et al.  Striatal mechanisms in Parkinson's disease: new insights from computer modeling , 1998, Artif. Intell. Medicine.

[3]  David Marr,et al.  VISION A Computational Investigation into the Human Representation and Processing of Visual Information , 2009 .

[4]  Ming Li,et al.  An Introduction to Kolmogorov Complexity and Its Applications , 2019, Texts in Computer Science.

[5]  Benjamin Kuipers,et al.  Automatic Abduction of Qualitative Models , 1992, AAAI.

[6]  Marc Weeber Literature-based discovery in biomedicine , 2001 .

[7]  P. Thagard,et al.  Computational Philosophy of Science , 1988 .

[8]  A.P.M. van den Bosch,et al.  Abductieve inferentie als primaire cognitie , 1996 .

[9]  F. Bloom Principles of Neural Science, 3rd ed , 1993 .

[10]  J. Kamps,et al.  A logical approach to computational theory building - with applications to sociology , 2000, ILLC dissertation series.

[11]  L. Laudan Progress and Its Problems , 1977 .

[12]  Benjamin Kuipers,et al.  Causal Reasoning in Medicine: Analysis of a Protocol , 1984 .

[13]  Joel L. Davis,et al.  Adaptive Critics and the Basal Ganglia , 1995 .

[14]  Herbert A. Simon,et al.  Causality and Model Abstraction , 1994, Artif. Intell..

[15]  Allen Newell,et al.  Human Problem Solving. , 1973 .

[16]  Ming Li,et al.  Kolmogorov Complexity and its Applications , 1991, Handbook of Theoretical Computer Science, Volume A: Algorithms and Complexity.

[17]  John H. Holland,et al.  Induction: Processes of Inference, Learning, and Discovery , 1987, IEEE Expert.

[18]  W. Bechtel Philosophy of Science : An Overview for Cognitive Science , 1988 .

[19]  J. Fodor The Language of Thought , 1980 .

[20]  Peter D. Karp,et al.  Representing, analyzing, and synthesizing biochemical pathways , 1994, IEEE Expert.

[21]  Floortje Rikken Adverse drug reactions in a different context: a scientometric approach towards adverse drug reactions as a trigger for the development of new drugs , 1998 .

[22]  Oosterling Henk,et al.  Van Agora tot Markt. Acta van de 18e Nederlands-Vlaamse Filosofiedag , 1996 .

[23]  A. Parent,et al.  The current model of basal ganglia organization under scrutiny , 1998, Movement disorders : official journal of the Movement Disorder Society.

[24]  Lawrence Hunter,et al.  Artificial Intelligence and Molecular Biology , 1992, AI Mag..

[25]  P. Langley,et al.  Computational Models of Scientific Discovery and Theory Formation , 1990 .

[26]  I. Lakatos Falsification and the Methodology of Scientific Research Programmes , 1976 .

[27]  N. Chater,et al.  RATIONAL EXPLANATION OF THE SELECTION TASK , 1996 .

[28]  Anne-Ruth Mackor,et al.  Cognitive Patterns in science and common sense , 1995 .

[29]  M. Kendall,et al.  The Logic of Scientific Discovery. , 1959 .

[30]  B. Westerink,et al.  Striatal dopamine–glutamate interactions reflected in substantia nigra reticulata firing , 1998, Neuroreport.

[31]  Benjamin Kuipers,et al.  Qualitative reasoning: Modeling and simulation with incomplete knowledge , 1994, Autom..

[32]  Alexander P. M. van den Bosch Inference to the Best Manipulation - a case study of qualitative reasoning in neuropharmacy. Special Issue on Scientific Discovery and Creativity: Case Studies and Computational Approaches. Guest Editors: J. Meheus and T. Nickles , 1999 .

[33]  M. Alexander,et al.  Principles of Neural Science , 1981 .

[34]  Anthony G. Cohn,et al.  Qualitative Reasoning , 1987, Advanced Topics in Artificial Intelligence.

[35]  John R. Anderson Cognitive Psychology and Its Implications , 1980 .

[36]  John R. Anderson,et al.  Rules of the Mind , 1993 .

[37]  F. H. Eemeren,et al.  Argumentation, Communication, and Fallacies: A Pragma-dialectical Perspective , 1992 .

[38]  Hidde de Jong,et al.  Comparative Analysis of STructurally Different Dynamical Systems , 1997, IJCAI.

[39]  Ming Li,et al.  Inductive Reasoning and Kolmogorov Complexity , 1992, J. Comput. Syst. Sci..

[40]  Kenneth D. Forbus Qualitative Process Theory , 1984, Artif. Intell..

[41]  J. Brotchie,et al.  Modeling the functional organization of the basal ganglia. A parallel distributed processing approach , 1991, Movement disorders : official journal of the Movement Disorder Society.

[42]  R. Giere Explaining Science: A Cognitive Approach , 1991 .

[43]  C. Lebiere,et al.  The Atomic Components of Thought , 1998 .

[44]  T. Kuhn,et al.  The Structure of Scientific Revolutions. , 1964 .

[45]  P. Thagard,et al.  How Scientists Explain Disease , 1999 .

[46]  M. Delong,et al.  Pathophysiology of parkinsonian motor abnormalities. , 1993, Advances in neurology.

[47]  A.P.M. van den Bosch,et al.  Learning Abductive Search by Analogy in ACT-R , 1996 .

[48]  H. Simon,et al.  The sciences of the artificial (3rd ed.) , 1996 .

[49]  Rein Vos,et al.  Drugs Looking for Diseases: Innovative Drug Research and the Development of the Beta Blockers and the Calcium Antagonists , 1990 .

[50]  M. Delong,et al.  Primate models of movement disorders of basal ganglia origin , 1990, Trends in Neurosciences.

[51]  P. Flach Conjectures: an inquiry concerning the logic of induction , 1995 .

[52]  Arie Rip,et al.  The Computer Revolution in Science: Steps Towards the Realization of Computer-Supported Discovery Environments , 1997, Artif. Intell..

[53]  Ray J. Solomonoff,et al.  A Formal Theory of Inductive Inference. Part II , 1964, Inf. Control..

[54]  H. Mclennan,et al.  Synaptic Transmission , 2003 .

[55]  Ronald N. Giere,et al.  Cognitive Models in the Philosophy of Science , 1986, PSA: Proceedings of the Biennial Meeting of the Philosophy of Science Association.

[56]  Atocha Aliseda-Llera,et al.  Seeking explanations: abduction in logic, philosophy of science and artificial intelligence , 1998 .

[57]  I. Hacking,et al.  Representing and Intervening. , 1986 .

[58]  Paul Thagard,et al.  Coherence as Constraint Satisfaction , 2019, Cogn. Sci..

[59]  Wilma Dianne Johanna Verhagen-Kamerbeek Noradrenergic and dopaminergic therapy in Parkinson's disease , 1994 .

[60]  Theo A.F. Kuipers,et al.  Design research programs and the logic of their development , 1992 .

[61]  Neil R. Smalheiser,et al.  Artificial Intelligence An interactive system for finding complementary literatures : a stimulus to scientific discovery , 1995 .

[62]  B. Kuipers,et al.  Critical Decisions under Uncertainty: Representation and Structure , 1990, Cogn. Sci..

[63]  John R. Anderson ACT: A simple theory of complex cognition. , 1996 .

[64]  Peter D. Karp,et al.  Representations of Metabolic Knowledge , 1993, ISMB.

[65]  Petra Hendriks,et al.  Breinmakers & Breinbrekers: inleiding cognitiewetenschap , 1997 .

[66]  Theo A.F. Kuipers,et al.  Abduction aiming at empirical progress or eventruth approximationleading to a challenge for computational modelling , 1999 .

[67]  P. Jenner,et al.  The rationale for the use of dopamine agonists in Parkinson's disease , 1995, Neurology.

[68]  A. Goldman Epistemology and Cognition , 1986 .

[69]  M. Ebert,et al.  The Biochemical Basis of Neuropharmacology, 7th ed , 1998 .

[70]  Kenneth F. Schaffner,et al.  Logic of Discovery and Diagnosis in Medicine , 2023 .

[71]  K. Popper,et al.  The Logic of Scientific Discovery , 1960 .

[72]  Philip Kitcher,et al.  Theory Structure and Theory Change in Contemporary Molecular Biology , 1989, The British Journal for the Philosophy of Science.