Biology subjects

Padoa-Schioppa, C.

Publications and source records attributed to Padoa-Schioppa, C..

16 recordsLinked to original sources

bioRxiv2026

Inferred Structure of a Neuronal Circuit for Economic Decisions

Previous work suggests that different groups of neurons in orbitofrontal cortex (OFC) constitute the building blocks of a circuit in which economic decisions are formed. Here we used network inference analysis (Ising model) to shed light on the internal organization of this circuit. We examined populations of neurons recorded simultaneously, and inferred the functional couplings. We then computed a reduced, effective network (EN) where each node corresponded to an encoded variable. The EN had a recognizable structure, with enhanced couplings between input and output neurons supporting the same decision, and enhanced couplings between neurons encoding value variables with the same sign. This structure was highly reproducible across individuals and hemispheres. Importantly, it depended on the internal state of the animal and the behavioral conditions. The EN reproducibility decreased with the distance between cells but it increased with the number of cell pairs, suggesting that OFC operates as a single distributed assembly.

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bioRxiv2026

The Laminar Organization of a Decision Circuit in Orbitofrontal Cortex is Agnostic to the Variable Encoding Scheme

Economic choices are believed to depend on the orbitofrontal cortex (OFC). Work in primates and rodents indicates that neurons in OFC participate in computing and comparing subjective values, suggesting that different groups of cells constitute the building blocks of a decision circuit. In a recent study (Livi et al., 2025), we examined the laminar organization of this circuit in mice. We found that different decision variables were differentially represented in layer 2/3 (L2/3) and layer 5 (L5). Furthermore, the temporal dynamics of decision signals indicated a combination of feed-forward and feed-back across layers, and pointed to L5 as the locus for winner-take-all value comparison. Importantly, these results were obtained under the constraint that each neuron encoded a single variable. Here, we tested whether our results on laminar organization depended on the categorical framework. We applied LASSO regression to identify a minimal set of variables explaining each neurons activity. Even with approximately half of all neurons representing two or more variables, the layer specificity of decision variables was preserved. In addition, Granger Causality Analysis and activity profiles reached similar conclusions as for analyses conducted under the single-variable constraint. We conclude that the decision circuit in OFC exhibits a laminar architecture, independently of whether the representation of decision variables in this area is categorical or mixed.

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bioRxiv2025

Neuronal Activity in Orbitofrontal Cortex during Trinary Choices under Risk

Economic choice entails computing and comparing the subjective values of different goods. Orbitofrontal cortex (OFC) is thought to contribute to both operations. However, previous work focused almost exclusively on binary choices, raising the question of whether current notions hold for multinary choices. Here we recorded from rhesus monkeys making trinary choices. Offers varied on three dimensions - juice flavor, quantity, and probability. In these experiments, quantity and probability varied continuously within a preset range. Animal choices were generally risk seeking and satisfied independence of irrelevant alternatives (IIA) - a fundamental assumption in standard economic theory. Different neurons encoded the values of individual offers, the choice outcome, and the chosen value - i.e., the same variables previously identified under binary choices. In addition, other cell groups encoded the chosen probability and the chosen hemifield. Notably, the activity of offer value cells reflected the risk attitude and fluctuated from session to session in ways that matched fluctuations observed behaviorally. In other words, the activity of these neurons reflected the subjective nature of value. Importantly, the representation of decision variables in OFC was invariant to changes in menu size - a property that effectively implies IIA. SIGNIFICANCEOrbitofrontal cortex (OFC) is necessary for the computation and the comparison of subjective values underlying economic choices. However, most previous studies examined choices between two options, and it remains unclear whether current notions apply to multinary choices. Barretto-Garcia and colleagues recorded from the OFC of monkeys choosing between three juice flavors offered in variable quantities and probabilities. Animals choices were consistent with the independence of irrelevant alternatives (IIA) - a condition necessary for rational behavior. Different neurons in OFC encoded the values of individual offers, the choice outcome, and the chosen value. The activity of value-encoding cells reflected the animals risk attitude. Importantly, the representation of decision variables was invariant to changes in menu size - a property that effectively implies IIA.

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bioRxiv2025

A Neural Circuit Framework for Economic Choice: From Building Blocks of Valuation to Compositionality in Multitasking

Value-guided decisions are a cornerstone of cognition, yet the underlying circuit-level mechanisms remain elusive. We used reinforcement learning to train recurrent neural network models endowed with Dales law on a battery of economic choice tasks, which revealed a two-stage computational framework. First, value estimation occurs at input level where learned weights store subjective preferences and approximate the nonlinear multiplication of reward magnitude and probability to yield expected values. This feedforward mechanism enables generalization to novel choice options. Second, option values are compared within the recurrent network, where specific connectivity patterns mediate robust winner-take-all decisions, with both excitatory and inhibitory neurons exhibiting value and choice selectivity. By training a single network on multiple tasks, we show compositional representations combining a shared computational schema with specialized neural modules. Reproducing key neurophysiological findings from the primate orbitofrontal cortex, our model unifies value computation, comparison, and generalization into a coherent framework with testable predictions. IN BRIEFBattista et al. use biologically plausible RNNs to uncover circuit mechanisms of economic choice. They propose a two-stage framework where feedforward inputs compute offer values and recurrent inhibition drives comparison. This architecture explains how the brain generalizes preferences and multitasks using compositional neural codes, offering a unified theory of decisionmaking. HIGHLIGHTSO_LIBiologically plausible RNN reveals a two-stage economic choice framework C_LIO_LIInput weights store preferences and multiply features to compute offer value C_LIO_LICompetitive recurrent inhibition mediates winner-take-all comparison C_LIO_LIMultitasking relies on compositional shared and specialized neural modules C_LI

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bioRxiv2025

Laminar Architecture of a Decision Circuit in Orbitofrontal Cortex

During economic choice, different neurons in orbitofrontal cortex (OFC) encode individual offer values, the binary choice outcome, and the chosen value. Previous work suggests that these cell groups form a decision circuit, but the anatomical organization of this circuit is poorly understood. Using calcium imaging, we recorded from layer 2/3 (L2/3) and layer 5 (L5) of mice choosing between juice flavors. Decision variables were differentially represented across layers: juice-specific offer values and their spatial configuration were predominant in L2/3, while spatial offer values, chosen side, and chosen value were predominant in L5. Within each layer, functional cell groups were organized in clusters. The temporal dynamics of neural signals in the two layers indicated a combination of feed-forward and feed-back processes, and pointed to L5 as the locus for winner-take-all value comparison. These results reveal that economic decisions rely on a complex architecture distributed across layers of OFC.

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bioRxiv2024

The Representation of Decision Variables in Orbitofrontal Cortex is Longitudinally Stable

The computation and comparison of subjective values underlying economic choices rely on the orbitofrontal cortex (OFC). In this area, distinct groups of neurons encode the value of individual options, the binary choice outcome, and the chosen value. These variables capture both the input and the output of the choice process, suggesting that the cell groups found in OFC constitute the building blocks of a decision circuit. Here we show that this neural circuit is longitudinally stable. Using two-photon calcium imaging, we recorded from mice choosing between different juice flavors. Recordings of individual cells continued for up to 20 weeks. For each cell and each pair of sessions, we compared the activity profiles using cosine similarity, and we assessed whether the cell encoded the same variable in both sessions. These analyses revealed a high degree of stability and a modest representational drift. A quantitative estimate indicated this drift would not randomize the circuit within the animals lifetime.

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bioRxiv2021

Orbitofrontal cortex contributes to the comparison of values underlying economic choices

Economic choices between goods entail the computation and comparison of subjective values. Previous studies examined neuronal activity in the orbitofrontal cortex (OFC) of monkeys choosing between different types of juices. Three groups of neurons were identified: offer value cells encoding the value of individual offers, chosen juice cells encoding the identity of the chosen juice, and chosen value cells encoding the value of the chosen offer. The encoded variables capture both the input (offer value) and the output (chosen juice, chosen value) of the decision process, suggesting that values are compared within OFC. Recent work demonstrates that choices are causally linked to the activity of offer value cells. Conversely, the hypothesis that OFC contributes to value comparison has not been confirmed. Here we show that weak electrical stimulation of OFC specifically disrupts value comparison without altering offer values. This result implies that neuronal populations in OFC participate in the decision process. SignificanceEconomic choices encompass two mental stages: values are assigned to the available offers, and a decision is made by comparing values. Previous work showed that choices are causally related to offer values encoded in the orbitofrontal cortex (OFC). Conversely, the neural underpinnings of value comparison remain poorly understood. Here we show that weak electrical stimulation of OFC selectively disrupts the decision process without affecting offer values. Hence, neurons in OFC contribute to value comparison.

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bioRxiv2021

Neuronal origins of biases in economic choices under sequential offers

Economic choices are characterized by a variety of biases. Understanding their origins is a long-term goal for neuroeconomics, but progress on this front has been limited. Here we examined choice biases observed when two goods are offered sequentially. In the experiments, rhesus monkeys chose between different juices offered simultaneously or in sequence. Choices under sequential offers were less accurate (higher variability). They were also biased in favor of the second offer (order bias) and in favor of the preferred juice (preference bias). Analysis of neuronal activity recorded in orbitofrontal cortex revealed that these phenomena emerged at different computational stages. The lower choice accuracy reflected weaker offer value signals (valuation stage), the order bias emerged during value comparison (decision stage), and the preference bias emerged late in the trial (post-comparison). Our approach, leveraging recent notions on the neural mechanisms of economic decisions, may shed light on other aspects of choice behavior.

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bioRxiv2021

Economic Choices under Simultaneous or Sequential Offers Rely on the Same Neural Circuit

A series of studies in which monkeys chose between two juices offered in variable amounts identified in the orbitofrontal cortex (OFC) different groups of neurons encoding the value of individual options (offer value), the binary choice outcome (chosen juice) and the chosen value. These variables capture both the input and the output of the choice process, suggesting that the cell groups identified in OFC constitute the building blocks of a decision circuit. Several lines of evidence support this hypothesis. However, in previous experiments offers were presented simultaneously, raising the question of whether current notions generalize to when goods are presented or are examined in sequence. Recently, Ballesta and Padoa-Schioppa (2019) examined OFC activity under sequential offers. An analysis of neuronal responses across time windows revealed that a small number of cell groups encoded specific sequences of variables. These sequences appeared analogous to the variables identified under simultaneous offers, but the correspondence remained tentative. Thus in the present study we examined the relation between cell groups found under sequential versus simultaneous offers. We recorded from the OFC while monkeys chose between different juices. Trials with simultaneous and sequential offers were randomly interleaved in each session. We classified cells in each choice modality and we examined the relation between the two classifications. We found a strong correspondence - in other words, the cell groups measured under simultaneous offers and under sequential offers were one and the same. This result indicates that economic choices under simultaneous or sequential offers rely on the same neural circuit. Significance StatementResearch in the past 20 years has shed light on the neuronal underpinnings of economic choices. A large number of results indicates that decisions between goods are formed in a neural circuit within the orbitofrontal cortex (OFC). In most previous studies, subjects chose between two goods offered simultaneously. Yet, in daily situations, goods available for choice are often presented or examined in sequence. Here we recorded neuronal activity in the primate OFC alternating trials under simultaneous and under sequential offers. Our analyses demonstrate that the same neural circuit supports choices in the two modalities. Hence current notions on the neuronal mechanisms underlying economic decisions generalize to choices under sequential offers.

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bioRxiv2021

Neuronal Activity in Dorsal Anterior Cingulate Cortex during EconomicChoices under Variable Action Costs

The role of the dorsal anterior cingulate cortex (ACCd) in decision making has often been discussed but remains somewhat unclear. On the one hand, numerous studies implicated this area in decisions driven by effort or action cost. On the other hand, work on economic choices between goods (under fixed action costs) found that neurons in ACCd encoded only post-decision variables. To advance our understanding of the role played by this area in decision making, we trained monkeys to choose between different goods (juice types) offered in variable amounts and with different action costs. Importantly, the task design dissociated computation of the action cost from planning of any particular action. Neurons in ACCd encoded the chosen value and the binary choice outcome in several reference frames (chosen juice, chosen cost, chosen action). Thus, this area provided a rich representation of post-decision variables. In contrast, neurons in ACCd did not represent pre-decision variables such as individual offer values in any reference frame. Hence, ongoing decisions are unlikely guided by ACCd. Conversely, neuronal activity in this area might inform subsequent choices.

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bioRxiv2020

Values Encoded in Orbitofrontal Cortex Are Causally Related to Economic Choices

It has long been hypothesized that economic choices rely on the assignment and comparison of subjective values. Indeed, when agents make decisions, neurons in orbitofrontal cortex encode the values of offered and chosen goods. Moreover, neuronal activity in this area suggests the formation of a decision. However, it is unclear whether these neural processes are causally related to choices. More generally, the evidence linking economic choices to value signals in the brain remains correlational. We address this fundamental issue using electrical stimulation in rhesus monkeys. We show that suitable currents bias choices by increasing the value of individual offers. Furthermore, high-current stimulation disrupts both the computation and the comparison of subjective values. These results demonstrate that values encoded in orbitofrontal cortex are causal to economic choices.

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bioRxiv2019

Neural Mechanisms of Economic Choices in Mice

Economic choices entail computing and comparing subjective values. Evidence from primates indicates that this behavior relies on the orbitofrontal cortex. Conversely, previous work in rodents provided conflicting results. Here we present a mouse model of economic choice behavior, and we show that the lateral orbital (LO) area is intimately related to the decision process. In the experiments, mice chose between different juices offered in variable amounts. Choice patterns closely resembled those measured in primates. Optogenetic inactivation of LO dramatically disrupted choices by inducing erratic changes of relative value and by increasing choice variability. Neuronal recordings revealed that different groups of cells encoded the values of individual options, the binary choice outcome and the chosen value. These groups match those previously identified in primates, except that the neuronal representation in mice is spatial (in monkeys it is good-based). Our results lay the foundations for a circuit-level analysis of economic decisions.

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bioRxiv2019

Mechanisms of Economic Decisions under Sequential Offers

Binary choices between goods are thought to take place in orbitofrontal cortex (OFC). However, current notions emerged mostly from studies where two offers were presented simultaneously, and other work suggested that choices under sequential offers rely on fundamentally different mechanisms. Here we recorded from the OFC of macaques choosing between two juices offered sequentially. Analyzing neuronal responses across time windows, we discovered different groups of neurons that closely resemble those identified under simultaneous offers, suggesting that decisions in the two modalities are formed in the same neural circuit. Building on this result, we examined four hypotheses on the decision mechanisms. OFC neurons encoded goods and values in a juice-based representation (labeled lines). Contrary to previous assessments, decisions did not involve mutual inhibition between pools of offer value cells. Instead, decisions involved mechanisms of circuit inhibition, whereby each offer value indirectly inhibits neurons encoding the opposite choice outcome. These results reconcile disparate findings and provide a unitary account for the neuronal mechanisms underlying economic decisions.

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bioRxiv2018

Categorical encoding of decision variables in orbitofrontal cortex

A fundamental and recurrent question in systems neuroscience is that of assessing what variables are encoded by a given population of neurons. Such assessments are often challenging because neurons in one brain area may encode multiple variables, and because neuronal representations might be categorical (different neurons encoding different variables) or mixed (individual neurons encoding a combination of variables). These issues are particularly pertinent to the representation of decision variables in the orbitofrontal cortex (OFC) - an area implicated in economic choices. Here we present a new algorithm to assess whether a neuronal representation is categorical or mixed, and to identify the encoded variables if the representation is indeed categorical. The algorithm is based on two clustering procedures, one variable-independent and the other variable-based. The two partitions are then compared through adjusted mutual information. The present algorithm overcomes limitations of previous approaches and is widely applicable. We tested the algorithm on synthetic data and then used it to examine neuronal data recorded in the primate OFC during economic decisions. Confirming previous assessments, we found the neuronal representation in OFC to be categorical in nature. We also found that neurons in this area encode the value of individual offers, the binary choice outcome and the chosen value. In other words, during economic choice, neurons in the primate OFC encode decision variables in a categorical way.\n\nAuthor SummaryMental functions such as sensory perception or decision making ultimately rely on the activity of neuronal populations in different brain regions. Much research in neuroscience is devoted to understanding how different groups of neurons support specific brain functions by representing behaviorally relevant variables. In this respect, one important question is whether individual neurons represent single variables, or linear combination of variables. Here we developed a new algorithm to assess this general issue. We then used the algorithm to examine neurons in the orbitofrontal cortex (OFC) recorded while non-human primates performed economic decisions. We found that different neurons represent different variables (categorical encoding). Specifically, neurons in the OFC encoded the value of individual offers, the binary choice outcome, and the chosen value. The present results support the hypothesis that economic decisions are formed within the OFC.

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bioRxiv2018

Neuronal Adaptation to the Value Range in Macaque Orbitofrontal Cortex

Economic choice involves computing and comparing the subjective values of different options. The magnitude of these values can vary immensely in different situations. To compensate for this variability, decision-making neural circuits adapt to the current behavioral context. In orbitofrontal cortex (OFC), neurons encode the subjective value of offered and chosen goods in a quasi-linear way. Previous work found that the gain of the encoding is lower when the value range is wider. However, previous studies did not disambiguate between neurons adapting to the value range or to the maximum value. Furthermore, they did not examine changes in baseline activity. Here we investigated how neurons in the macaque OFC adapt to changes in the value distribution. We found that neurons adapt to both the maximum and the minimum value, but only partially. Concurrently, the baseline response is higher when the minimum value is larger. Using a simulated decision circuit, we showed that higher baseline activity increases choice variability, and thus lowers the expected payoff in high value contexts.

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bioRxiv2017

Neuronal adaptation and optimal coding in economic decisions

During economic decisions, neurons in orbitofrontal cortex (OFC) encode the values of offered goods. Importantly, their responses adapt to the range of values available in any given context. Prima facie, range adaptation seems to provide an efficient representation. However, uncorrected adaptation in the encoding of offer values would induce arbitrary choice biases. Thus a fundamental and open question is whether range adaptation is behaviorally advantageous. Here we present a theory of optimal coding for economic decisions. In a nutshell, the representation of offer values is optimal if it ensures maximal expected payoff. In this framework, we examine the activity of offer value cells in non-human primates. We show that their firing rates are quasi-linear functions of the offered values, even when optimal tuning functions would be highly non-linear. Most importantly, we demonstrate that for linear tuning functions range adaptation maximizes the expected payoff, even if the effects of adaptation are corrected to avoid choice biases. Thus value coding in OFC is functionally rigid (linear tuning) but parametrically plastic (range adaptation with optimal gain). Importantly, the benefit of range adaptation outweighs the cost of functional rigidity. While generally suboptimal, linear tuning may facilitate transitive choices.

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