A. David Redish

• University of Minnesota

Psychosis spectrum illnesses are characterized by impaired goal-directed behavior and significant neurophysiological heterogeneity. To investigate the neurocomputational underpinnings of this heterogeneity, 75 participants with Early Psychosis (EP) and 68 controls completed a dynamic decision-making task. Consistent with prior studies, EP exhibited...

Fundamentally, we talk of both the symbolic and the subsymbolic processes as computation — components have mutual information with the world, that information is combined with other information, transformed, and reintegrated into new structures. The questions become: What information is there? How is it stored? How is it transformed? How is it used...

Worrying about perceived threats is a hallmark of multiple psychological disorders including anxiety. This concern about future events is particularly important when an individual is faced with an approach-avoidance conflict. Potential goals to approach are known to be represented in the dorsal hippocampus during theta cycles. Similarly, important...

Because imagination activates the same neural circuits used in understanding the present, one can access that imagination even in non‐linguistic animals through decoding techniques applied to large neural ensembles. This personal retrospective traces the history of the initial discovery that hippocampal theta sequences sweep forward to goals during...

Contingency management (CM) is notably successful as a substance use disorder treatment and is most effective when targeting monosubstance use. Evidence suggests the effects of CM exceed predictions based on the value of the incentives delivered for monosubstance abstinence. In this systematic review, we examine common variations of CM intervention...

Nucleus accumbens dopamine signaling is an important neural substrate for decision-making. Dominant theories generally discretize and homogenize decision-making, when it is in fact a continuous process, with evaluation and re-evaluation components that extend beyond simple outcome prediction into consideration of past and future value. Extensive wo...

Current theories of decision making suggest that the neural circuits in mammalian brains (including humans) computationally combine representations of the past (memory), present (perception), and future (agentic goals) to take actions that achieve the needs of the agent. How information is represented within those neural circuits changes what compu...

Contingency management is incredibly successful as substance use disorder treatment and is most effective when targeting mono-drug use. In fact, there is evidence. the effects of contingency management exceed predictions based on the value of the incentives delivered for mono-drug abstinence. In this systematic review, we examine common variations...

The orbitofrontal cortex (OFC) is functionally heterogeneous across its medial-to-lateral axis, though the nature of this heterogeneity is unclear. The present study leveraged high-density neural recording across the medial-to-lateral span of the OFC using a neuroeconomic task in rats to clarify how functional heterogeneity within the OFC participa...

Across systems, higher-order interactions between components govern emergent dynamics. Here we tested whether contextual threat memory retrieval in mice relies on higher-order interactions between dorsal CA1 hippocampal neurons requiring learning-induced dendritic spine plasticity. We compared population-level Ca2⁺ transients as wild-type mice (wit...

Humans presented with the same problem in the same environment commonly adopt wildly different strategies for attention and learning. Indeed, psychiatric conditions are defined by qualitative differences in behavior. However, most tasks measure an individual's deviation from a single expected strategy rather than the utilization of distinct strateg...

Current theories suggest that adaptive decision-making necessitates the interaction between multiple decision-making systems. The computational definitions of different models of decision-making suggest interactions with task demands and complexity. We review these computational theories and derive experimental predictions that will shed light on t...

Decision-making relies on dynamic interplay between multiple neural circuits and decision-making systems integrating past experiences, current goals, and environmental demands. Past studies of rodent decision-making have largely occurred in simple environments and on isolated brain areas. This leaves unclear the impact of environmental complexity o...

Worrying about perceived threats is a hallmark of multiple psychological disorders including anxiety. This concern about future events is particularly important when an individual is faced with an approach-avoidance conflict. Potential goals to approach are known to be represented in the dorsal hippocampus during theta sweeps. Similarly, important...

Background and Hypothesis Cognitive control deficits are prominent in individuals with psychotic psychopathology. Studies providing evidence for deficits in proactive control generally examine average performance and not variation across trials for individuals—potentially obscuring detection of essential contributors to cognitive control. Here, we...

The balance between excitation and inhibition is critical to brain functioning, and dysregulation of this balance is a hallmark of numerous psychiatric conditions. Measuring this excitation-inhibition (E:I) balance in vivo has remained difficult, but theoretical models have proposed that characteristics of local field potentials (LFP) may provide a...

Dysfunction in learning and motivational systems are thought to contribute to addictive behaviours. Previous models have suggested that dopaminergic roles in learning and motivation could produce addictive behaviours through pharmacological manipulations that provide excess dopaminergic signalling towards these learning and motivational systems. Re...

Cognitive control deficits are consistently identified in individuals with schizophrenia and other psychotic psychopathologies. In this analysis, we delineated proactive and reactive control deficits in psychotic psychopathology via hierarchical Drift Diffusion Modeling (hDDM). People with psychosis (PwP; N=123), their first-degree relatives (N=79)...

Spatial navigation is a complex cognitive process that involves neural computations in distributed regions of the brain. Little is known about how cortical regions are coordinated when animals navigate novel spatial environments or how that coordination changes as environments become familiar. We recorded mesoscale calcium (Ca²⁺) dynamics across la...

Current theories suggest that adaptive decision-making necessitates the interaction between multiple decision-making systems. The computational definitions of different models of decision-making suggest interactions with task demands and complexity. We review these computational theories and derive experimental predictions that will shed light on t...

The Cambridge Handbook of Computational Cognitive Sciences is a comprehensive reference for this rapidly developing and highly interdisciplinary field. Written with both newcomers and experts in mind, it provides an accessible introduction of paradigms, methodologies, approaches, and models, with ample detail and illustrated by examples. It should...

Spatial navigation is a complex cognitive process that involves neural computations in distributed regions of the brain. Little is known about how cortical regions are coordinated when animals navigate novel spatial environments or how that coordination changes as environments become familiar. We recorded mesoscale calcium dynamics across large swa...

Dysfunction in learning and motivational systems are thought to contribute to addictive behaviors. Previous models have suggested that dopaminergic roles in learning and motivation could produce addictive behaviors through pharmacological manipulations that provide excess dopaminergic signaling towards these learning and motivational systems. Redis...

The world is overabundant with feature-rich information obscuring the latent causes of experience. How do people approximate the complexities of the external world with simplified internal representations that generalize to novel examples or situations? Theories suggest that internal representations could be determined by decision boundaries that d...

In recent years, the field of neuroscience has gone through rapid experimental advances and a significant increase in the use of quantitative and computational methods. This growth has created a need for clearer analyses of the theory and modeling approaches used in the field. This issue is particularly complex in neuroscience because the field stu...

Rats demonstrate a preference for smaller, immediate rewards over larger, delayed ones, a phenomenon known as delay-discounting (DD). Behavior arises from the interaction of multiple decision-making systems, and the medial prefrontal cortex (mPFC) has been identified as a central component in the mediation between these decision systems. To investi...

The nucleus accumbens shell (NAcSh) is critically important for reward valuations, yet it remains unclear how valuation information is integrated in this region to drive behaviour during reinforcement learning. Using an optogenetic spatial self-stimulation task in mice, here we show that contingent activation of different excitatory inputs to the N...

Decision-making involves multiple cognitive processes requiring different aspects of information about the situation at hand. The rodent medial prefrontal cortex (mPFC) has been hypothesized to be central to these abilities. Functional studies have sought to link specific processes to specific anatomical subregions, but past studies of mPFC have yi...

The purchase and sale of assets such as housing will increasingly be affected by forces related to a changing climate. This article considers decisions over assets as a neurobiological process in which an associative memory with pattern completion informs choices. We develop these neuroeconomic explanations and analyze their implications for climat...

Sunk cost sensitivity describes escalating decision commitment with increased spent resources. On neuroeconomic foraging tasks, mice, rats, and humans show similar escalations from sunk costs while quitting an ongoing countdown to reward. In a new analysis taken across computationally parallel foraging tasks across species and laboratories, we find...

The “new science of morality” that will change how we see each other, how we build our communities, and how we live our lives. In Changing How We Choose, David Redish makes a bold claim: Science has “cracked” the problem of morality. Redish argues that moral questions have a scientific basis and that morality is best viewed as a technology—a set of...

Decision-making involves multiple cognitive processes requiring different aspects of information about the situation at hand. The rodent medial prefrontal cortex (mPFC) has been hypothesized to be central to these abilities. Functional studies have sought to link specific processes to specific anatomical subregions, but past studies of mPFC have yi...

Etiopathogenic models for psychosis spectrum illnesses are converging on a number of key processes, such as the influence of specific genes on the synthesis of proteins important in synaptic functioning, alterations in how neurons respond to synaptic inputs and engage in synaptic pruning, and microcircuit dysfunction that leads to more global corti...

Purpose of Review Despite decades of research, knowledge of the mechanisms maintaining anorexia nervosa (AN) remains incomplete and clearly effective treatments elusive. Novel theoretical frameworks are needed to advance mechanistic and treatment research for this disorder. Here, we argue the utility of engaging a novel lens that differs from exist...

We propose a new conceptual framework (computational validity) for translation across species and populations based on the computational similarity between the information processing underlying parallel tasks. Translating between species depends not on the superficial similarity of the tasks presented, but rather on the computational similarity of...

People cannot access the latent causes giving rise to experience. How then do they approximate the high-dimensional feature space of the external world with lower-dimensional internal models that generalize to novel examples or contexts? Here, we developed and tested a theoretical framework that internally identifies states by feature regularity (i...

Despite decades of research, anorexia nervosa (AN) remains poorly understood and clearly effective treatments continue to be elusive. Thus, novel theoretical frameworks are needed to advance mechanistic and treatment research for this disorder. Progress in research on AN may have been slowed by systematic biases historically affecting psychiatric r...

In a recent bioRxiv preprint, Ott et al. argue that sensitivities to sunk costs that have been reported in two serial foraging tasks (the Restaurant Row task in mice and rats, and the Web-Surf task in humans) may be due to simple consequences of the way that subjects perform these tasks and not due to an actual sensitivity to sunk costs. However, s...

The dorsolateral striatum (DLS) is involved in learning and executing procedural actions. Cell ensembles in the DLS, but not the dorsomedial striatum (DMS), exhibit a burst of firing at the start of a well-learned action sequence ("task-bracketing"). However, it is currently unclear what information is contained in these bursts. Some theories sugge...

Many foraging experiments have found that subjects are suboptimal in foraging tasks, waiting out delays longer than they should given the reward structure of the environment. Additionally, theories of decision-making suggest that actions arise from interactions between multiple decision-making systems and that these systems should depend on the ava...

Decisions made by mammals and birds are often temporally extended. They require planning and sampling of decision-relevant information. Our understanding of such decision-making remains in its infancy compared with simpler, forced-choice paradigms. However, recent advances in algorithms supporting planning and information search provide a lens thro...

The hippocampus and medial prefrontal cortex (mPFC) interact during a myriad of cognitive processes including decision‐making and long‐term memory consolidation. Exactly how the mPFC and hippocampus interact during goal‐directed decision‐making remains to be fully elucidated. During periods of rest, bursts of high‐frequency oscillations, termed sha...

Poor context integration, the process of incorporating both previous and current information in decision making, is a cognitive symptom of schizophrenia. The maintenance of the contextual information has been shown to be sensitive to changes in excitation-inhibition (EI) balance. Many regions of the brain are sensitive to EI imbalances, however, so...

Multimodal approaches combining cognitive behavioral therapies (CBT) with non-invasive brain stimulation (NIBS) hold promise for improving the treatment of neuropsychiatric disorders. As this is a relatively new approach, it is a critical time to identify guiding principles and methodological considerations to enhance research rigor. In the current...

A central question in aging and Alzheimer's disease (AD) is when and how neural substrates underlying decision-making are altered. Here we show that while APP mice, a commonly used mouse model of AD, were able to learn Restaurant Row, a complex neuroeconomic decision-making task, they were significantly impaired in procedural, habit-forming, aspect...

In the WebSurf task, humans forage for videos paying costs in terms of wait times on a time-limited task. A variant of the task in which demands during the wait time were manipulated revealed the role of attention in susceptibility to sunk costs. Consistent with parallel tasks in rodents, previous studies have found that humans (undergraduates meas...

Adapting to the changing environment is a key component of optimal decision-making. Internal-models that accurately represent and selectively update from behaviorally relevant/salient stimuli may facilitate adaptive behaviors. Anterior cingulate cortex (ACC) and dopaminergic systems may produce these adaptive internal-models through selective updat...

Mammalian decision-making is mediated by the interaction of multiple, neurally and computationally separable decision systems. Having multiple systems requires a mechanism to manage conflict and converge onto the selection of singular actions. A long history of evidence has pointed to the prefrontal cortex as a central component in processing the i...

A frequent assumption in value-based decision-making tasks is that agents make decisions based on the feature dimension that reward probabilities vary on. However, in complex, multidimensional environments, stimuli can vary on multiple dimensions at once, meaning that the feature deserving the most credit for outcomes is not always obvious. As a re...

Deliberation is thought to involve the internal simulation of the outcomes of candidate actions, the valuation of those outcomes, and the selection of the actions with the highest expected value. While it is known that deliberation involves prefrontal cortical areas, specifically the dorsomedial prefrontal cortex (dmPFC), as well as the hippocampus...

OBJECTIVES/GOALS: Decision-making impairments in addiction can arise from dysfunction in distinct neural circuits. Such processes can be dissociated by measuring complex, computationally distinct behaviors within an economic framework. We aim to characterize computational changes conserved across models of addiction. METHODS/STUDY POPULATION: We us...

Dorsomedial prefrontal cortex (dmPFC) and hippocampus (HPC) are thought to play complementary roles in a spatial working memory and decision-making network, where spatial information from HPC informs representations in dmPFC, and contextual information from dmPFC biases how HPC recalls that information. We recorded simultaneously from neural ensemb...

Background The causal biology underlying schizophrenia is not well understood, but it is likely to involve a malfunction in how neurons adjust synaptic connections in response to patterns of activity in networks. We examined statistical dependencies between neural signals at the cell, local circuit, and distributed network levels in the prefrontal...

In recent years, the field of neuroscience has gone through rapid experimental advances and extensive use of quantitative and computational methods. This accelerating growth has created a need for methodological analysis of the role of theory and the modeling approaches currently used in this field. Toward that end, we start from the general view t...

Reported sex differences in decision-making and learning can be inconsistent across studies. One interpretation is that these sex differences are not driven by differences in ability, but by differences in strategy, which interact with task design. Here, we examined the strategies adopted by female and male mice as they learned the value of stimuli...

Whether fear or anxiety is expressed is thought to depend on an animal’s proximity to threat. In general, fear is elicited when threat is proximal, while anxiety is a response to threat that is distal and uncertain. This threat gradient model suggests that fear and anxiety involve non-overlapping neural circuitry, yet few behavioral paradigms exist...

Humans have a remarkable capacity to mentally project themselves far ahead in time. This ability, which entails the mental simulation of events, is thought to be fundamental to deliberative decision making, as it allows us to search through and evaluate possible choices. Many decisions that humans make are foraging decisions, in which one must deci...

A fundamental feature of addiction is continued use despite high-cost losses. One possible driver of this feature is a dissociation between reward pursuit and reward valuation. To test for this dissociation, we employed a foraging paradigm with real-time delays and video rewards. Subjects made stay/skip choices on risky and non-risky offers; risky...

Current theories of deliberative decision making suggest that deliberative decisions arise from imagined simulations that require interactions between the prefrontal cortex and hippocampus. In rodent navigation experiments, hippocampal theta sequences advance from the location of the rat ahead to the subsequent goal. To examine the role of the medi...

An engineer's viewpoint on psychiatry asks: What are the failure modes that underlie psychiatric dysfunction? And: How can we modify the system? Psychiatry has made great strides in understanding and treating disorders using biology; however, failure modes and modification access points can also exist extrinsically in environmental interactions. Th...

[This corrects the article DOI: 10.3389/fnint.2018.00030.].

The decision to apply to a PhD-granting graduate program is both exciting and daunting. Understanding what graduate programs look for in an applicant will increase the chance of successful admission into a PhD program. It is also helpful for an applicant to understand what graduate training will look like once they matriculate into a PhD program to...

Addiction is considered to be a neurobiological disorder of learning and memory because addiction is capable of producing lasting changes in the brain. Recovering addicts chronically struggle with making poor decisions that ultimately lead to relapse, suggesting a view of addiction also as a neurobiological disorder of decision-making information p...

Current theories suggest that decision-making arises from multiple, competing action-selection systems. Rodent studies dissociate deliberation and procedural behavior, and find a transition from procedural to deliberative behavior with experience. However, it remains unknown how this transition from deliberative to procedural control evolves within...

The impact of time wasted The amount of time already spent on a task influences human choice about whether to continue. This dedicated time, known as the “sunk cost,” reduces the likelihood of giving up the pursuit of a reward, even when there is no indication of likely success. Sweis et al. show that this sensitivity to time invested occurs simila...

In the version of this article initially published, author Charan Ranganath's last name was misspelled Rangananth in the author list. Also, A. David Redish (redish@umn.edu) has been added as a corresponding author. The error has been corrected, and the corresponding author added, in the HTML and PDF versions of the article.

Neuroeconomic theories propose changes in decision making drive relapse in recovering drug addicts, resulting in continued drug use despite stated wishes not to. Such conflict is thought to arise from multiple valuation systems dependent on separable neural components, yet many neurobiology of addiction studies employ only simple tests of value. He...

Regret can be defined as the subjective experience of recognizing that one has made a mistake and that a better alternative could have been selected. The experience of regret is thought to carry negative utility. This typically takes two distinct forms: augmenting immediate postregret valuations to make up for losses, and augmenting long-term chang...

Interactions between subjective flavor preferences and longitudinal economic decision processes. Flavors were ranked from least preferred to most preferred based on total pellet earnings in each restaurant at the end of each session. (A) Pellets earned in each restaurant show early development of flavor preferences that persist throughout the entir...

Controlling for the effects of VTE on reinforcement rate. Reinforcement rate (inter-earn-interval) is plotted across days, comparing observed date (black) versus 4 different computer models that simulated what the expected reinforcement rate would be if high-VTE trials were adjusted. High- versus low-VTE trials were determined by a median split of...

Supplemental analyses and discussion. Additional analyses and discussion are available in the supplemental text, including analyses and discussion on (1) early conditioned place behaviors; (2) the development of default responses in the reward-rich components of training; (3) how demand elasticity changed across the longitudinal design; (4) evidenc...

Decision outcomes as function of offer costs across stages of training. Choice probability to enter versus skip in the offer zone (A-D) or earn versus quit in the wait zone (E-H) relative to all offers (normalized to all session trials) as a function of cost during 1–5 s training (A,E), 1–15 s training (B,F), early 1–30 s training (C,G, first 5 d),...

Economic characterization of wait zone strategy across stages of training. (A-D) Histogram of wait zone events as a function of time spent waiting and as a function of offer cost. Diagonal unity line (time spent waiting = offer cost) represents earned trials, while the remaining data points represent quit decisions. Horizontal and vertical dashed l...

Visualization of offer-length distributions between skip and quit events. (A) Histogram of offer length distributions comparing trials that ended as skips versus quits from data pooled across animals from days 60–70. (B) Samples were randomly selected from the skip distribution to match the number of samples from the quit distribution. Skip resampl...

Controlling for flavor preferences in regret-like sequence effects. To control for potential differences in restaurant sequences due to the identity of flavor preferences in Restaurant 2 following quits versus skips in Restaurant 1, we sorted scenarios such that the Restaurant 2 was always either the least or most preferred flavor. (A) Probability...

Development of deliberative decisions as a function of VO across training. (A-B) Offer zone reaction time (A) and VTE behavior (B) as a function of VO (VO = WZ–O) over days of learning in the 1–30 s offer block (red epoch). Blue line represents 0 value trials (where offer = WZ). Pink line represents onset of food intake and reinforcement rate renor...

Signal detection theory approach to characterize the development of deliberative value-based discriminability and biases. (A) Offer zone decision distributions as a function of VO (VO = WZ–O) split by enter versus skip decisions. As a function of a sliding R.O.C. criterion, R.O.C. curves (B) can be generated by plotting calculated hit rate and fals...

Example behavior on Restaurant Row. In this excerpt, a top-down view of the maze is presented. The mouse’s position is tracked automatically at center-of-mass (orange dot). The 4 corners of the maze represent the 4 restaurants, each fixed in location with unique visual patterns on the walls (chocolate vertical stripes, banana checker, grape triangl...

Significance Synaptic remodeling in the infralimbic-to-accumbens shell (IL–NAcSh) circuit is linked to addiction relapse susceptibility; however, how these changes interact with decision-making computations remains unclear. We develop a neurophysiological assay to measure the strength of a specific circuit at the ensemble level. We then use that as...

During decision making, hippocampal activity encodes information sometimes about present and sometimes about potential future plans. The mechanisms underlying this transition remain unknown. Building on the evidence that gamma oscillations at different frequencies (low gamma [LG], 30-55 Hz; high gamma [HG], 60-90 Hz; and epsilon, 100-140 Hz) reflec...

p>The hippocampus serves a critical function in memory, navigation, and cognition. Nature Neuroscience asked John Lisman to lead a group of researchers in a dialog on shared and distinct viewpoints on the hippocampus.</p

This article provides an illustrative treatment of psychiatric morbidity that offers an alternative to the standard nosological model in psychiatry. It considers what would happen if we treated diagnostic categories not as causes of signs and symptoms, but as diagnostic consequences of psychopathology and pathophysiology. This reformulation (of the...

Psychiatrists and neuroscientists discuss the potential of computational approaches to address problems in psychiatry including diagnosis, treatment, and integration with neurobiology. Modern psychiatry is at a crossroads, as it attempts to balance neurological analysis with psychological assessment. Computational neuroscience offers a new lens thr...

Psychiatrists and neuroscientists discuss the potential of computational approaches to address problems in psychiatry including diagnosis, treatment, and integration with neurobiology. Modern psychiatry is at a crossroads, as it attempts to balance neurological analysis with psychological assessment. Computational neuroscience offers a new lens thr...

Psychiatrists and neuroscientists discuss the potential of computational approaches to address problems in psychiatry including diagnosis, treatment, and integration with neurobiology. Modern psychiatry is at a crossroads, as it attempts to balance neurological analysis with psychological assessment. Computational neuroscience offers a new lens thr...