Dopamine Alters the Effect of Brain Stimulation on Decision-Making.

Noninvasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS), show promise in treating a range of psychiatric and neurologic conditions. However, optimization of such applications requires a better understanding of how tDCS alters cognition and behavior. Existing evidence implicates dopamine in tDCS alterations of brain activity and plasticity; however, there is as yet no causal evidence for a role of dopamine in tDCS effects on cognition and behavior. Here, in a preregistered, double-blinded study, we examined how pharmacologically manipulating dopamine altered the effect of tDCS on the speed-accuracy trade-off, which taps ubiquitous strategic operations. Cathodal tDCS was delivered over the left prefrontal cortex and the superior medial frontal cortex before participants (N = 62, 24 males, 38 females) completed a dot-motion task, making judgments on the direction of a field of moving dots under instructions to emphasize speed, accuracy, or both. We leveraged computational modeling to uncover how our interventions altered latent decisional processes driving the speed-accuracy trade-off. We show that dopamine in combination with tDCS (but not tDCS alone nor dopamine alone) not only impaired decision accuracy but also impaired discriminability, which suggests that these manipulations altered the encoding or representation of discriminative evidence. This is, to the best of our knowledge, the first direct evidence implicating dopamine in the way tDCS affects cognition and behavior.SIGNIFICANCE STATEMENT tDCS can improve cognitive and behavioral impairments in clinical conditions; however, a better understanding of its mechanisms is required to optimize future clinical applications. Here, using a pharmacological approach to manipulate brain dopamine levels in healthy adults, we demonstrate a role for dopamine in the effects of tDCS in the speed-accuracy trade-off, a strategic cognitive process ubiquitous in many contexts. In doing so, we provide direct evidence implicating dopamine in the way tDCS affects cognition and behavior.

Individual Differences in Decision Strategy Relate to Neurochemical Excitability and Cortical Thickness.

The speed-accuracy trade-off (SAT), whereby faster decisions increase the likelihood of an error, reflects a cognitive strategy humans must engage in during the performance of almost all daily tasks. To date, computational modeling has implicated the latent decision variable of response caution (thresholds), the amount of evidence required for a decision to be made, in the SAT. Previous imaging has associated frontal regions, notably the left prefrontal cortex and the presupplementary motor area (pre-SMA), with the setting of such caution levels. In addition, causal brain stimulation studies, using transcranial direct current stimulation (tDCS), have indicated that while both of these regions are involved in the SAT, their role appears to be dissociable. tDCS efficacy to impact decision-making processes has previously been linked with neurochemical concentrations and cortical thickness of stimulated regions. However, to date, it is unknown whether these neurophysiological measures predict individual differences in the SAT, and brain stimulation effects on the SAT. Using ultra-high field (7T) imaging, here we report that instruction-based adjustments in caution are associated with both neurochemical excitability (the balance between GABA+ and glutamate) and cortical thickness across a range of frontal regions in both sexes. In addition, cortical thickness, but not neurochemical concentrations, was associated with the efficacy of left prefrontal and superior medial frontal cortex (SMFC) stimulation to modulate performance. Overall, our findings elucidate key neurophysiological predictors, frontal neural excitation, of individual differences in latent psychological processes and the efficacy of stimulation to modulate these.SIGNIFICANCE STATEMENT The speed-accuracy trade-off (SAT), faster decisions increase the likelihood of an error, reflects a cognitive strategy humans must engage in during most daily tasks. The SAT is often investigated by explicitly instructing participants to prioritize speed or accuracy when responding to stimuli. Using ultra-high field (7T) magnetic resonance imaging (MRI), we found that individual differences in the extent to which participants adjust their decision strategies with instruction related to neurochemical excitability (ratio of GABA+ to glutamate) and cortical thickness in the frontal cortex. Moreover, brain stimulation to the left prefrontal cortex and the superior medial frontal cortex (SMFC) modulated performance, with the efficacy specifically related to cortical thickness. This work sheds new light on the neurophysiological basis of decision strategies and brain stimulation.

Modality independent or modality specific? Common computations underlie confidence judgements in visual and auditory decisions.

The mechanisms that enable humans to evaluate their confidence across a range of different decisions remain poorly understood. To bridge this gap in understanding, we used computational modelling to investigate the processes that underlie confidence judgements for perceptual decisions and the extent to which these computations are the same in the visual and auditory modalities. Participants completed two versions of a categorisation task with visual or auditory stimuli and made confidence judgements about their category decisions. In each modality, we varied both evidence strength, (i.e., the strength of the evidence for a particular category) and sensory uncertainty (i.e., the intensity of the sensory signal). We evaluated several classes of computational models which formalise the mapping of evidence strength and sensory uncertainty to confidence in different ways: 1) unscaled evidence strength models, 2) scaled evidence strength models, and 3) Bayesian models. Our model comparison results showed that across tasks and modalities, participants take evidence strength and sensory uncertainty into account in a way that is consistent with the scaled evidence strength class. Notably, the Bayesian class provided a relatively poor account of the data across modalities, particularly in the more complex categorisation task. Our findings suggest that a common process is used for evaluating confidence in perceptual decisions across domains, but that the parameter settings governing the process are tuned differently in each modality. Overall, our results highlight the impact of sensory uncertainty on confidence and the unity of metacognitive processing across sensory modalities.

The impact of cognitive resource constraints on goal prioritization.

Many decisions we face daily entail deliberation about how to coordinate resources shared between multiple, competing goals. When time permits, people appear to approach these goal prioritization problems by analytically considering all goal-relevant information to arrive at a prioritization decision. However, it is not yet clear if this normative strategy extends to situations characterized by resource constraints such as when deliberation time is scarce or cognitive load is high. We evaluated the questions of how limited deliberation time and cognitive load affect goal prioritization decisions across a series of experiments using a gamified experimental task, which required participants to make a series of interdependent goal prioritization decisions. We fit several candidate models to experimental data to identify decision strategy adaptations at the individual subject-level. Results indicated that participants tended to opt for a simple heuristic strategy when cognitive resources were constrained rather than making a general tradeoff between speed and accuracy (e.g., the type of tradeoff that would be predicted by evidence accumulation models). The most common heuristic strategy involved disproportionately weighing information about goal deadlines compared to other goal-relevant information such as the goal's difficulty and the goal's subjective value.

Using mixture modeling to examine differences in perceptual decision-making as a function of the time and method of participant recruitment.

We examine whether perceptual decision-making differs as a function of the time in the academic term and whether the participant is an undergraduate participating for course credit, a paid in-person participant, or a paid online participant recruited via Amazon Mechanical Turk. We use a mixture modeling approach within an evidence accumulation framework that separates stimulus-driven responses from contaminant responses, allowing us to distinguish between performance when a participant is engaged in the task and the consistency in this task focus. We first report a survey showing cognitive psychologists expect performance and response caution to be lower among undergraduate participants recruited at the end of the academic term compared to those recruited near the start, and highest among paid in-person participants. The findings from two experiments using common paradigms revealed very little evidence of time-of-semester effects among course credit participants on accuracy, response time, efficiency of information processing (when engaged in the task), caution, and non-decision time, or consistency in task focus. However, paid in-person participants did tend to be more accurate than the other two groups. Groups showed similar effects of speed/accuracy emphasis on response caution and of discrimination difficulty on information processing efficiency, but the effect of speed/accuracy emphasis on information processing efficiency was less consistent among groups. We conclude that online crowdsourcing platforms can provide quality perceptual decision-making data, but recommend that mixture modeling be used to adequately account for data generated by processes other than the psychological phenomena under investigation.

Information Processing Under Reward Versus Under Punishment.

Much is known about the effects of reward and punishment on behavior, yet little research has considered how these incentives influence the information-processing dynamics that underlie decision making. We fitted the linear ballistic accumulator to data from a perceptual-judgment task to examine the impacts of reward- and punishment-based incentives on three distinct components of information processing: the quality of the information processed, the quantity of that information, and the decision threshold. The threat of punishment lowered the average quality and quantity of information processed, compared with the prospect of reward or no performance incentive at all. The threat of punishment also induced less cautious decision making by lowering people's decision thresholds relative to the prospect of reward. These findings suggest that information-processing dynamics are determined not only by objective properties of the decision environment but also by the higher order goals of the system.

Enhancing the functionality of a microscale bioreactor system as an industrial process development tool for mammalian perfusion culture.

Without a scale-down model for perfusion, high resource demand makes cell line screening or process development challenging, therefore, potentially successful cell lines or perfusion processes are unrealized and their ability untapped. We present here the refunctioning of a high-capacity microscale system that is typically used in fed-batch process development to allow perfusion operation utilizing in situ gravity settling and automated sampling. In this low resource setting, which involved routine perturbations in mixing, pH and dissolved oxygen concentrations, the specific productivity and the maximum cell concentration were higher than 3.0 × 106 mg/cell/day and 7 × 10 7 cells/ml, respectively, across replicate microscale perfusion runs conducted at one vessel volume exchange per day. A comparative analysis was conducted at bench scale with vessels operated in perfusion mode utilizing a cell retention device. Neither specific productivity nor product quality indicated by product aggregation (6%) was significantly different across scales 19 days after inoculation, thus demonstrating this setup to be a suitable and reliable platform for evaluating the performance of cell lines and the effect of process parameters, relevant to perfusion mode of culturing.

Diffusing the bilingual lexicon: Task-based and lexical components of language switch costs.

Bilingual speakers show a response time (RT) cost when switching between languages. These costs could reflect the organization of language in a shared bilingual lexicon (Grainger, Midgley, & Holcomb, 2010) or a domain general cognitive processing cost (Green & Abutalebi, 2013). To test these accounts, we analysed RT distributions of bilingual (Spanish-English) performance on generalized lexical decision (GLD) tasks using Ratcliff (1978) diffusion model. Experiment 1 revealed that language switches decrease the rate of evidence accumulation (drift rate) and slow the cognitive processes that occur prior to decision-making (non-decision time). Experiment 2 showed that the anticipation of language switches did not change these effects. The results suggest that language switch costs originate from a combination of at least two loci: lexical access and a task-specific decision process.

The separable effects of feature precision and item load in visual short-term memory.

Visual short-term memory (VSTM) has been described as being limited by the number of discrete visual objects, the aggregate quantity of information across multiple visual objects, or some combination of the two. Many recent studies examining these capacity limitations have shown that increasing the number of items in VSTM increases the frequency and magnitude of errors in a participant's recall of the stimulus. This increase in response dispersion has been interpreted as a loss of precision in an item's representation as the number of items in memory increases, possibly due to a change in the tuning of the underlying representation. However, increased response dispersion can also be caused by a reduction in the total memory strength available for decision making as a consequence of a reduction in the total amount of a fixed resource representing a stimulus. We investigated the effects of load on the precision of memory representations in a fine orientation discrimination task. Accuracy was well captured by extending a simple sample-size model of VSTM, using a tuning function to account for the effect of orientation precision on performance. The best model of the data was one in which the item strength decreased progressively with memory load at all stimulus exposure durations but in which tuning bandwidth was invariant. Our results imply that memory strength and feature precision are experimentally dissociable attributes of VSTM.

A heuristic approach to handling missing data in biologics manufacturing databases.

The biologics sector has amassed a wealth of data in the past three decades, in line with the bioprocess development and manufacturing guidelines, and analysis of these data with precision is expected to reveal behavioural patterns in cell populations that can be used for making predictions on how future culture processes might behave. The historical bioprocessing data likely comprise experiments conducted using different cell lines, to produce different products and may be years apart; the situation causing inter-batch variability and missing data points to human- and instrument-associated technical oversights. These unavoidable complications necessitate the introduction of a pre-processing step prior to data mining. This study investigated the efficiency of mean imputation and multivariate regression for filling in the missing information in historical bio-manufacturing datasets, and evaluated their performance by symbolic regression models and Bayesian non-parametric models in subsequent data processing. Mean substitution was shown to be a simple and efficient imputation method for relatively smooth, non-dynamical datasets, and regression imputation was effective whilst maintaining the existing standard deviation and shape of the distribution in dynamical datasets with less than 30% missing data. The nature of the missing information, whether Missing Completely At Random, Missing At Random or Missing Not At Random, emerged as the key feature for selecting the imputation method.

MEDICAL MANAGEMENT OF DILATED CARDIOMYOPATHY IN LIVINGSTONE FRUIT BATS ( PTEROPUS LIVINGSTONII).

Eleven cases of dilated cardiomyopathy have been diagnosed and treated in captive Livingstone fruit bats ( Pteropus livingstonii) in the United Kingdom over the past 7 yr. All but one case received treatment with a diuretic plus an angiotensin-converting enzyme inhibitor (ACEI), and, or pimobendan. One case is still under treatment with pimobendan alone, following diagnosis before onset of clinical signs. Diuretic treatment consisted of furosemide at a dose rate of 0.5-5 mg/kg, one to three times daily, and, or spironolactone at a dose rate of 1-4 mg/kg, once or twice daily. When used, the ACEI imidapril was given at a dose rate of 0.24-0.38 mg/kg q 24 hr, and pimobendan at a dose rate of 0.2-0.5 mg/kg bid. This report is intended to provide anyone seeking to medically manage heart failure in Pteropus species, particularly P. livingstonii, with a review of drugs and doses that have been used.

The attention-weighted sample-size model of visual short-term memory: Attention capture predicts resource allocation and memory load.

We investigated the capacity of visual short-term memory (VSTM) in a phase discrimination task that required judgments about the configural relations between pairs of black and white features. Sewell et al. (2014) previously showed that VSTM capacity in an orientation discrimination task was well described by a sample-size model, which views VSTM as a resource comprised of a finite number of noisy stimulus samples. The model predicts the invariance of [Formula: see text] , the sum of squared sensitivities across items, for displays of different sizes. For phase discrimination, the set-size effect significantly exceeded that predicted by the sample-size model for both simultaneously and sequentially presented stimuli. Instead, the set-size effect and the serial position curves with sequential presentation were predicted by an attention-weighted version of the sample-size model, which assumes that one of the items in the display captures attention and receives a disproportionate share of resources. The choice probabilities and response time distributions from the task were well described by a diffusion decision model in which the drift rates embodied the assumptions of the attention-weighted sample-size model.

A revised diffusion model for conflict tasks.

The recently developed diffusion model for conflict tasks (DMC) Ulrich et al. (Cognitive Psychology, 78, 148-174, 2015) provides a good account of data from all standard conflict tasks (e.g., Stroop, Simon, and flanker tasks) within a common evidence accumulation framework. A central feature of DMC's processing dynamics is that there is an initial phase of rapid accumulation of distractor evidence that is then selectively withdrawn from the decision mechanism as processing continues. We argue that this assumption is potentially troubling because it could be viewed as implying qualitative changes in the representation of distractor information over the time course of processing. These changes suggest more than simple inhibition or suppression of distractor information, as they involve evidence produced by distractor processing "changing sign" over time. In this article, we (a) develop a revised DMC (RDMC) whose dynamics operate strictly within the limits of inhibition/suppression (i.e., evidence strength can change monotonically, but cannot change sign); (b) demonstrate that RDMC can predict the full range of delta plots observed in the literature (i.e., both positive-going and negative-going); and (c) show that the model provides excellent fits to Simon and flanker data used to benchmark the original DMC at both the individual and group level. Our model provides a novel account of processing differences across Simon and flanker tasks. Specifically, that they differ in how distractor information is processed on congruent trials, rather than incongruent trials: congruent trials in the Simon task show relatively slow attention shifting away from distractor information (i.e., location) while complete and rapid attention shifting occurs in the flanker task. Our new model highlights the importance of considering dynamic interactions between top-down goals and bottom-up stimulus effects in conflict processing.

Modelling the impact of single vs. dual presentation on visual discrimination across resolutions.

Visual categorisation relies on our ability to extract useful diagnostic information from complex stimuli. To do this, we can utilise both the "high-level" and "low-level" information in a stimulus; however, the extent to which changes in these properties impact the decision-making process is less clear. We manipulated participants' access to high-level category features via gradated reductions to image resolution while exploring the impact of access to additional category features through a dual-stimulus presentation when compared with single stimulus presentation. Results showed that while increasing image resolution consistently resulted in better choice performance, no benefit was found for dual presentation over single presentation, despite responses for dual presentation being slower compared with single presentation. Applying the diffusion decision model revealed increases in drift rate as a function of resolution, but no change in drift rate for single versus dual presentation. The increase in response time for dual presentation was instead accounted for by an increase in response caution for dual presentations. These findings suggest that while increasing access to high-level features (via increased resolution) can improve participants' categorisation performance, increasing access to both high- and low-level features (via an additional stimulus) does not.

Investigating mechanisms of the attentional repulsion effect: A diffusion model analysis.

This article investigates the decisional and attentional drivers of the attentional repulsion effect (ARE) using the diffusion decision model (DDM). The ARE is a phenomenon in which a subjective expansion of space is experienced outside the focus of attention. It is thought to occur due to changes in the functioning of visual cell receptive fields. The DDM is a model of the decision-making process that assumes responses are selected by sequentially sampling an encoded representation of a stimulus until sufficient evidence has been accumulated favoring one response alternative over the other. The model decomposes observed choice and response times into different latent variables corresponding to the rate of evidence accumulation, response caution, response bias, and the time course of stimulus encoding and response execution. In this article, we interpret changes in the rate of evidence accumulation as primarily reflecting perceptual-driven changes in stimulus representation. We interpret changes in response bias as primarily reflecting decision-level changes. We utilize the DDM's ability to estimate these variables independently to explore how they are each affected by cueing manipulations to clarify whether the ARE emerges due to attentional or decisional drivers, or some combination of the two. The results of this study could shed light on the mechanisms underlying the ARE, and has implications in our understanding of spatial attention.

Are there jumps in evidence accumulation, and what, if anything, do they reflect psychologically? An analysis of Lévy Flights models of decision-making.

According to existing theories of simple decision-making, decisions are initiated by continuously sampling and accumulating perceptual evidence until a threshold value has been reached. Many models, such as the diffusion decision model, assume a noisy accumulation process, described mathematically as a stochastic Wiener process with Gaussian distributed noise. Recently, an alternative account of decision-making has been proposed in the Lévy Flights (LF) model, in which accumulation noise is characterized by a heavy-tailed power-law distribution, controlled by a parameter, [Formula: see text]. The LF model produces sudden large "jumps" in evidence accumulation that are not produced by the standard Wiener diffusion model, which some have argued provide better fits to data. It remains unclear, however, whether jumps in evidence accumulation have any real psychological meaning. Here, we investigate the conjecture by Voss et al. (Psychonomic Bulletin & Review, 26(3), 813-832, 2019) that jumps might reflect sudden shifts in the source of evidence people rely on to make decisions. We reason that if jumps are psychologically real, we should observe systematic reductions in jumps as people become more practiced with a task (i.e., as people converge on a stable decision strategy with experience). We fitted five versions of the LF model to behavioral data from a study by Evans and Brown (Psychonomic Bulletin & Review, 24(2), 597-606, 2017), using a five-layer deep inference neural network for parameter estimation. The analysis revealed systematic reductions in jumps as a function of practice, such that the LF model more closely approximated the standard Wiener model over time. This trend could not be attributed to other sources of parameter variability, speaking against the possibility of trade-offs with other model parameters. Our analysis suggests that jumps in the LF model might be capturing strategy instability exhibited by relatively inexperienced observers early on in task performance. We conclude that further investigation of a potential psychological interpretation of jumps in evidence accumulation is warranted.

Uncovering the cognitive mechanisms underlying the gaze cueing effect.

The gaze cueing effect is the tendency for people to respond faster to targets appearing at locations gazed at by others, compared with locations gazed away from by others. The effect is robust, widely studied, and is an influential finding within social cognition. Formal evidence accumulation models provide the dominant theoretical account of the cognitive processes underlying speeded decision-making, but they have rarely been applied to social cognition research. In this study, using a combination of individual-level and hierarchical computational modelling techniques, we applied evidence accumulation models to gaze cueing data (three data sets total, N = 171, 139,001 trials) for the first time to assess the relative capacity that an attentional orienting mechanism and information processing mechanisms have for explaining the gaze cueing effect. We found that most participants were best described by the attentional orienting mechanism, such that response times were slower at gazed away from locations because they had to reorient to the target before they could process the cue. However, we found evidence for individual differences, whereby the models suggested that some gaze cueing effects were driven by a short allocation of information processing resources to the gazed at location, allowing for a brief period where orienting and processing could occur in parallel. There was exceptionally little evidence to suggest any sustained reallocation of information processing resources neither at the group nor individual level. We discuss how this individual variability might represent credible individual differences in the cognitive mechanisms that subserve behaviourally observed gaze cueing effects.

Predicting perceptual decision biases from early brain activity.

Perceptual decision making is believed to be driven by the accumulation of sensory evidence following stimulus encoding. More controversially, some studies report that neural activity preceding the stimulus also affects the decision process. We used a multivariate pattern classification approach for the analysis of the human electroencephalogram (EEG) to decode choice outcomes in a perceptual decision task from spatially and temporally distributed patterns of brain signals. When stimuli provided discriminative information, choice outcomes were predicted by neural activity following stimulus encoding; when stimuli provided no discriminative information, choice outcomes were predicted by neural activity preceding the stimulus. Moreover, in the absence of discriminative information, the recent choice history primed the choices on subsequent trials. A diffusion model fitted to the choice probabilities and response time distributions showed that the starting point of the evidence accumulation process was shifted toward the previous choice, consistent with the hypothesis that choice priming biases the accumulation process toward a decision boundary. This bias is reflected in prestimulus brain activity, which, in turn, becomes predictive of future decisions. Our results provide a model of how non-stimulus-driven decision making in humans could be accomplished on a neural level.

Sustainability, Collective Self-Regulation, and Human-Nature Interdependence.

Like any organism, humanity constructs its niche and adapts to the rest of nature by modifying available materials around them. In the era that some have dubbed the "Anthropocene," human niche construction has gone so far as to threaten the planetary climate system. The central question of sustainability is how humanity can collectively self-regulate niche construction, that is, humanity's relationship with the rest of nature. In this article, we argue that to resolve the collective self-regulation problem for sustainability, sufficiently accurate and relevant aspects of causal knowledge about the functioning of complex social-ecological systems need to be cognized, communicated, and collectively shared. More specifically, causal knowledge about human-nature interdependence-how humans interact with each other and the rest of nature-is critical for coordinating cognitive agents' thoughts, feelings, and actions for the greater good without falling into the trap of free riding. Here, we will develop a theoretical framework to consider the role of causal knowledge about human-nature interdependence in collective self-regulation for sustainability, review the relevant empirical research primarily focusing on climate change, and take stock of what is currently known and what we need to investigate in the future.

The causal role of the prefrontal and superior medial frontal cortices in the incidental manipulation of decision strategies.

A key strategic decision one must make in virtually every task context concerns the speed accuracy trade-off (SAT). Experimentally, this ubiquitous phenomenon, whereby response speed and task accuracy are inversely related, is typically studied by explicitly instructing participants to adjust their strategy: by either focusing on speed, or on accuracy. Computational modelling has been applied to deconvolve the latent decision processes involved in the SAT, with considerable evidence suggesting that response caution (the amount of evidence needed for a decision to be reached) is a key variable in the setting of SAT strategy. Neuroimaging has implicated the prefrontal cortex, the pre-supplementary motor area (preSMA), and the striatum in the setting of response caution. In addition, brain stimulation has provided causal evidence for the involvement of the left prefrontal cortex and superior medial frontal cortex (SMFC, which includes the preSMA) in adjustments of response caution following explicit instructions, although stimulation of the two regions has dissociable effects. Here, in a double-blind and preregistered study we investigated the role of these two regions using an incidental manipulation of SAT strategy - via stimulus signal variability - which has previously been shown to influence decision confidence. We again found tDCS applied to both regions modulated response caution, and there was a dissociation: stimulating prefrontal cortex increased, and stimulating SMFC decreased, response caution. These findings provide further support for key, but dissociable, roles of these brain regions in decision strategies whether they are implemented explicitly or incidentally.