Geographic and temporal trends in pediatric and young adult brain tumors in Kentucky, 1995-2019.

INTRODUCTION: Pediatric and young adult brain tumors (PYBT) account for a large share of cancer-related morbidity and mortality among children in the United States, but their etiology is not well understood. Previous research suggests the Appalachian region of Kentucky has high rates of PYBT. This study explored PYBT incidence over 25 years in Kentucky to identify geographic and temporal trends and generate hypotheses for future research. METHODS: The Kentucky Cancer Registry contributed data on all PYBT diagnosed among those aged 0-29 during years 1995-2019. Age- and sex-adjusted spatio-temporal scan statistics-one for each type of PYBT, and one for all types-comprised the primary analysis. These results were mapped along with environmental and occupational data. RESULTS: Findings indicated that north-central Kentucky and the Appalachian region experienced higher rates of some PYBT. High rates of astrocytomas were clustered in a north-south strip of central Kentucky toward the end of the study period, while high rates of other specified types of intracranial and intraspinal neoplasms were significantly clustered in eastern Kentucky. The area where these clusters overlapped, in north-central Kentucky, had significantly higher rates of PYBT generally. DISCUSSION: This study demonstrates north-central Kentucky and the Appalachian region experienced higher PYBT risk than the rest of the state. These regions are home to some of Kentucky's signature industries, which should be examined in further research. Future population-based and individual-level studies of genetic factors are needed to explore how the occupations of parents, as well as prenatal and childhood exposures to pesticides and air pollutants, impact PYBT incidence.

Creating and Studying the Behavior of Artificial Organisms Animated by an Evolutionary Theory of Behavior Dynamics.

The evolutionary theory of behavior dynamics (ETBD) is a complexity theory, which means that it is stated in the form of simple low-level rules, the repeated operation of which generates high-level outcomes that can be compared to data. The low-level rules of the theory implement Darwinian processes of selection, reproduction, and mutation. This tutorial is an introduction to the ETBD for a general audience, and illustrates how the theory is used to animate artificial organisms that can behave continuously in any experimental environment. Extensive research has shown that the theory generates behavior in artificial organisms that is indistinguishable in qualitative and quantitative detail from the behavior of live organisms in a wide variety of experimental environments. An overview and summary of this supporting evidence is provided. The theory may be understood to be computationally equivalent to the biological nervous system, which means that the algorithmic operation of the theory and the material operation of the nervous system give the same answers. The applied relevance of the theory is also discussed, including the creation of artificial organisms with various forms of psychopathology that can be used to study clinical problems and their treatment. Finally, possible future directions are discussed, such as the extension of the theory to behavior in a two-dimensional grid world.

Emotional scene processing in biotypes of psychosis.

Social-emotional deficits in psychosis may be indexed by deviations in emotional scene processing, but event-related potential (ERP) studies indicate such deviations may not map cleanly to diagnostic categories. Neurobiologically defined psychosis subgroups offer an alternative that may better capture neurophysiological correlates of social-emotional deficits. The current study investigates emotional scene-elicited ERPs in Biotypes of psychosis in a large (N = 622), well-characterized sample. Electroencephalography was recorded in healthy persons (N = 129), Biotype-1 (N = 195), Biotype-2 (N = 131), and Biotype-3 (N = 167) psychosis cases. ERPs were measured from posterior and centroparietal scalp locations. Neural responses to emotional scenes were compared between healthy and psychosis groups. Multivariate group discrimination analyses resulted in two composite variates that differentiated groups. The first variate displayed large differences between low-cognition (Biotype-1, Biotype-2) and intact-cognition groups (Biotype-3, healthy persons). The second indicated a small-to-moderate distinction of Biotypes-2 and -3 from Biotype-1 and healthy persons. Two multivariate correlations were identified indicating associations between 1) self-reported emotional experience and generalized cognition and 2) socio-occupational functioning and late-stage emotional processing. Psychosis Biotypes displayed emotional processing deficits not apparent in DSM psychosis subgroups. Future translational research may benefit from exploring emotional scene processing in such neurobiologically-defined psychosis groups.

A test of the evolutionary theory's account of punishment superimposed on single-alternative schedules.

A test of the evolutionary theory was conducted by replicating Bradshaw et al.'s (1977, 1978, 1979) experiments in which human participants worked on single-alternative variable-interval (VI) schedules of reinforcement under three punishment conditions: no punishment, superimposed VI punishment, and superimposed variable-ratio (VR) punishment. Artificial organisms (AOs) animated by the theory worked in the same environments. Four principal findings were reported for the human participants: (1) their behavior was well described by an hyperbola in all conditions, (2) the asymptote of the hyperbola under VI punishment was equal to the asymptote in the absence of punishment, but the asymptote under VR punishment was lower than the asymptote in the absence of punishment, (3) the parameter in the denominator of the hyperbola was larger under both VI and VR punishment than in the absence of punishment, and (4) response suppression under punishment was greater at lower than at higher reinforcement frequencies. These four outcomes were also observed in the behavior of the AOs working in the same environments, thereby confirming the theory's first-order predictions about the effects of punishment on single-alternative responding.

Evolutionary theory prediction: Response rate as a joint function of reinforcement rate and reinforcer magnitude.

Artificial organisms (AOs) animated by an evolutionary theory of behavior dynamics (ETBD) worked on concurrent interval schedules with a standard reinforcer magnitude on 1 alternative and a range of reinforcer magnitudes on the other. The reinforcer magnitudes on the second alternative were hedonically scaled using the generalized matching law. The AOs then worked on single interval schedules that arranged various combinations of the scaled reinforcer magnitudes and a range of nominal schedule values. This produced bivariate response rate data to which 5 candidate equations were fitted. One equation was found to provide the best description of the bivariate data in terms of percentage of variance accounted for, information criterion value, and residual profile. This equation consisted of 2 factors, 1 entailing the scaled magnitude, 1 entailing the obtained reinforcement rate, and both expressed in the form of exponentiated hyperbolas. The theory's prediction of the bivariate equation, along with additional predictions of the theory, were tested on data from an experiment in which rats pressed levers for various concentrations of sucrose pellets. The bivariate equation predicted by the theory was confirmed, as were all the additional predictions of the theory that could be tested on this data set.

Methodological improvements to a Procedure for Rapidly Establishing Steady-State Behavior.

We performed three experiments to improve the quality and retention of data obtained from a Procedure for Rapidly Establishing Steady-State Behavior (PRESS-B; Klapes et al., 2020). In Experiment 1, 120 participants worked on nine concurrent random-interval random-interval (conc RI RI) schedules and were assigned to four conditions of varying changeover delay (COD) length. The 0.5-s COD condition group exhibited the fewest instances of exclusive reinforcer acquisition. Importantly, this group did not differ in generalized matching law (GML) fit quality from the other groups. In Experiment 2, 60 participants worked on nine conc RI RI schedules with a wider range of scheduled reinforcement rate ratios than was used in Experiment 1. Participants showed dramatic reductions in exclusive reinforcer acquisition. Experiment 3 entailed a replication of Experiment 2 wherein blackout periods were implemented between the schedule presentations and each schedule remained in operation until at least one reinforcer was acquired on each alternative. GML fit quality was slightly more consistent in Experiment 3 than in the previous experiments. Thus, these results suggest that future PRESS-B studies should implement a shorter COD, a wider and richer scheduled reinforcement rate ratio range, and brief blackouts between schedule presentations for optimal data quality and retention.

Empirical Matching, Matching Theory, and an Evolutionary Theory of Behavior Dynamics in Clinical Application.

This article provides an overview of highlights from 60 years of basic research on choice that are relevant to the assessment and treatment of clinical problems. The quantitative relations developed in this research provide useful information about a variety of clinical problems including aggressive, antisocial, and delinquent behavior, attention-deficit/hyperactivity disorder (ADHD), bipolar disorder, chronic pain syndrome, intellectual disabilities, pedophilia, and self-injurious behavior. A recent development in this field is an evolutionary theory of behavior dynamics that is used to animate artificial organisms (AOs). The behavior of AOs animated by the theory has been shown to conform to the quantitative relations that have been developed in the choice literature over the years, which means that the theory generates these relations as emergent outcomes, and therefore provides a theoretical basis for them. The theory has also been used to create AOs that exhibit specific psychopathological behavior, the assessment and treatment of which has been studied virtually. This modeling of psychopathological behavior has contributed to our understanding of the nature and treatment of the problems in humans.

Modeling Subtypes of Automatically Reinforced Self-Injurious Behavior with the Evolutionary Theory of Behavior Dynamics.

The subtypes of automatically reinforced self-injurious behavior (ASIB) delineated by Hagopian and colleagues (Hagopian et al., 2015; 2017) demonstrated how functional-analysis (FA) outcomes may predict the efficacy of various treatments. However, the mechanisms underlying the different patterns of responding obtained during FAs and corresponding differences in treatment efficacy have remained unclear. A central cause of this lack of clarity is that some proposed mechanisms, such as differences in the reinforcing efficacy of the products of ASIB, are difficult to manipulate. One solution may be to model subtypes of ASIB using mathematical models of behavior in which all aspects of the behavior can be controlled. In the current study, we used the evolutionary theory of behavior dynamics (ETBD; McDowell, 2019) to model the subtypes of ASIB, evaluate predictions of treatment efficacy, and replicate recent research aiming to test explanations for subtype differences. Implications for future research related to ASIB are discussed.

All Behavior is choice: Revisiting an evolutionary theory's account of behavior on single schedules.

The axiomatic principle that all behavior is choice was incorporated into a revised implementation of an evolutionary theory's account of behavior on single schedules. According to this implementation, target responding occurs in the context of background responding and reinforcement. In Phase 1 of the research, the target responding of artificial organisms (AOs) animated by the revised theory was found to be well described by an exponentiated hyperbola, the parameters of which varied as a function of the background reinforcement rate. In Phase 2, the effect of reinforcer magnitude on the target behavior of the AOs was studied. As in Phase 1, the AOs' behavior was well described by an exponentiated hyperbola, the parameters of which varied with both the target reinforcer magnitude and the background reinforcement rate. Evidence from experiments with live organisms was found to be consistent with the Phase-1 predictions of the revised theory. The Phase-2 predictions have not been tested. The revised implementation of the theory can be used to study the effects of superimposing punishment on single-schedule responding, and it may lead to the discovery of a function that relates response rate to both the rate and magnitude of reinforcement on single schedules.

A discriminated rapid-acquisition laboratory procedure for human continuous choice.

Previous continuous choice laboratory procedures for human participants are either prohibitively time-intensive or result in inadequate fits of the generalized matching law (GML). We developed a rapid-acquisition laboratory procedure (Procedure for Rapidly Establishing Steady-State Behavior, or PRESS-B) for studying human continuous choice that reduces participant burden and produces data that is well-described by the GML. To test the procedure, 27 human participants were exposed to 9 independent concurrent random-interval random-interval reinforcement schedules over the course of a single, 37-min session. Fits of the GML to the participants' data accounted for large proportions of variance (median R2 : 0.94), with parameter estimates that were similar to those previously found in human continuous choice studies [median a: 0.67; median log(b): -0.02]. In summary, PRESS-B generates human continuous choice behavior in the laboratory that conforms to the GML with limited experimental duration.

PlantSimLab - a modeling and simulation web tool for plant biologists.

BACKGROUND: At the molecular level, nonlinear networks of heterogeneous molecules control many biological processes, so that systems biology provides a valuable approach in this field, building on the integration of experimental biology with mathematical modeling. One of the biggest challenges to making this integration a reality is that many life scientists do not possess the mathematical expertise needed to build and manipulate mathematical models well enough to use them as tools for hypothesis generation. Available modeling software packages often assume some modeling expertise. There is a need for software tools that are easy to use and intuitive for experimentalists. RESULTS: This paper introduces PlantSimLab, a web-based application developed to allow plant biologists to construct dynamic mathematical models of molecular networks, interrogate them in a manner similar to what is done in the laboratory, and use them as a tool for biological hypothesis generation. It is designed to be used by experimentalists, without direct assistance from mathematical modelers. CONCLUSIONS: Mathematical modeling techniques are a useful tool for analyzing complex biological systems, and there is a need for accessible, efficient analysis tools within the biological community. PlantSimLab enables users to build, validate, and use intuitive qualitative dynamic computer models, with a graphical user interface that does not require mathematical modeling expertise. It makes analysis of complex models accessible to a larger community, as it is platform-independent and does not require extensive mathematical expertise.

An implementation of punishment in the evolutionary theory of behavior dynamics.

An implementation of punishment in the evolutionary theory of behavior dynamics is proposed, and is applied to responding on concurrent schedules of reinforcement with superimposed punishment. In this implementation, punishment causes behaviors to mutate, and to do so with a higher probability in a lean reinforcement context than in a rich one. Computational experiments were conducted in an attempt to replicate three findings from experiments with live organisms. These are (1) when punishment is superimposed on one component of a concurrent schedule, response rate decreases in the punished component and increases in the unpunished component, (2) when punishment is superimposed on both components at equal scheduled rates, preference increases over its no-punishment baseline, and (3) when punishment is superimposed on both components at rates that are proportional to the scheduled rates of reinforcement, preference remains unchanged from the baseline preference. Artificial organisms animated by the theory, and working on concurrent schedules with superimposed punishment, reproduced all of these findings. Given this outcome, it may be possible to discover a steady-state mathematical description of punished choice in live organisms by studying the punished choice behavior of artificial organisms animated by the evolutionary theory.

The WIG (weighted individual and group) shrinkage estimator.

Regularization, or shrinkage estimation, refers to a class of statistical methods that constrain the variability of parameter estimates when fitting models to data. These constraints move parameters toward a group mean or toward a fixed point (e.g., 0). Regularization has gained popularity across many fields for its ability to increase predictive power over classical techniques. However, articles published in JEAB and other behavioral journals have yet to adopt these methods. This paper reviews some common regularization schemes and speculates as to why articles published in JEAB do not use them. In response, we propose our own shrinkage estimator that avoids some of the possible objections associated with the reviewed regularization methods. Our estimator works by mixing weighted individual and group (WIG) data rather than by constraining parameters. We test this method on a problem of model selection. Specifically, we conduct a simulation study on the selection of matching-law-based punishment models, comparing WIG with ordinary least squares (OLS) regression, and find that, on average, WIG outperforms OLS in this context.

On the current status of the evolutionary theory of behavior dynamics.

The evolutionary theory of behavior dynamics is a complexity theory that instantiates the Darwinian principles of selection, reproduction, and mutation in a genetic algorithm. The algorithm is used to animate artificial organisms that behave continuously in time and can be placed in any experimental environment. The present paper is an update on the status of the theory. It includes a summary of the evidence supporting the theory, a list of the theory's untested predictions, and a discussion of how the algorithmic operations of the theory may correspond to material reality. Based on the evidence reviewed here, the evolutionary theory appears to be a strong candidate for a comprehensive theory of adaptive behavior.

An evolutionary theory of behavior dynamics applied to concurrent ratio schedules.

An evolutionary theory of adaptive behavior dynamics was tested by studying the behavior of artificial organisms (AOs) animated by the theory, working on concurrent ratio schedules with unequal and equal ratios in the components. The evolutionary theory implements Darwinian rules of selection, reproduction, and mutation in the form of a genetic algorithm that causes a population of potential behaviors to evolve under the selection pressure of consequences from the environment. On concurrent ratio schedules with unequal ratios in the components, the AOs tended to respond exclusively on the component with the smaller ratio, provided that ratio was not too large and the difference between the ratios was not too small. On concurrent ratio schedules with equal ratios in the components, the AOs tended to respond exclusively on one component, provided the equal ratios were not too large. In addition, the AOs' preference on the latter schedules adjusted rapidly when the equal ratios were changed between conditions, but their steady-state preference was a continuous function of the value of the equal ratios. Most of these outcomes are consistent with the results of experiments with live organisms, and consequently support the evolutionary theory.

Toward a contemporary quantitative model of punishment.

A direct-suppression, or subtractive, model of punishment has been supported as the qualitatively and quantitatively superior matching law-based punishment model (Critchfield, Paletz, MacAleese, & Newland, 2003; de Villiers, 1980; Farley, 1980). However, this conclusion was made without testing the model against its predecessors, including the original (Herrnstein, 1961) and generalized (Baum, 1974) matching laws, which have different numbers of parameters. To rectify this issue, we reanalyzed a set of data collected by Critchfield et al. (2003) using information theoretic model selection criteria. We found that the most advanced version of the direct-suppression model (Critchfield et al., 2003) does not convincingly outperform the generalized matching law, an account that does not include punishment rates in its prediction of behavior allocation. We hypothesize that this failure to outperform the generalized matching law is due to significant theoretical shortcomings in model development. To address these shortcomings, we present a list of requirements that all punishment models should satisfy. The requirements include formal statements of flexibility, efficiency, and adherence to theory. We compare all past punishment models to the items on this list through algebraic arguments and model selection criteria. None of the models presented in the literature thus far meets all of the requirements.

Genome-wide association studies of smooth pursuit and antisaccade eye movements in psychotic disorders: findings from the B-SNIP study.

Eye movement deviations, particularly deficits of initial sensorimotor processing and sustained pursuit maintenance, and antisaccade inhibition errors, are established intermediate phenotypes for psychotic disorders. We here studied eye movement measures of 849 participants from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study (schizophrenia N=230, schizoaffective disorder N=155, psychotic bipolar disorder N=206 and healthy controls N=258) as quantitative phenotypes in relation to genetic data, while controlling for genetically derived ancestry measures, age and sex. A mixed-modeling genome-wide association studies approach was used including ~4.4 million genotypes (PsychChip and 1000 Genomes imputation). Across participants, sensorimotor processing at pursuit initiation was significantly associated with a single nucleotide polymorphism in IPO8 (12p11.21, P=8 × 10-11), whereas suggestive associations with sustained pursuit maintenance were identified with SNPs in SH3GL2 (9p22.2, P=3 × 10-8). In participants of predominantly African ancestry, sensorimotor processing was also significantly associated with SNPs in PCDH12 (5q31.3, P=1.6 × 10-10), and suggestive associations were observed with NRSN1 (6p22.3, P=5.4 × 10-8) and LMO7 (13q22.2, P=7.3x10-8), whereas antisaccade error rate was significantly associated with a non-coding region at chromosome 7 (P=6.5 × 10-9). Exploratory pathway analyses revealed associations with nervous system development and function for 40 top genes with sensorimotor processing and pursuit maintenance (P=4.9 × 10-2-9.8 × 10-4). Our findings suggest novel patterns of genetic variation relevant for brain systems subserving eye movement control known to be impaired in psychotic disorders. They include genes involved in nuclear trafficking and gene silencing (IPO8), fast axonal guidance and synaptic specificity (PCDH12), transduction of nerve signals (NRSN1), retinal degeneration (LMO7), synaptic glutamate release (SH3GL2), and broader nervous system development and function.

Falsification of matching theory and confirmation of an evolutionary theory of behavior dynamics in a critical experiment.

Two competing predictions of matching theory and an evolutionary theory of behavior dynamics, and one additional prediction of the evolutionary theory, were tested in a critical experiment in which human participants worked on concurrent schedules for money (Dallery et al., 2005). The three predictions concerned the descriptive adequacy of matching theory equations, and of equations describing emergent equilibria of the evolutionary theory. Tests of the predictions falsified matching theory and supported the evolutionary theory.