A special role for anterior cingulate cortex, but not orbitofrontal cortex or basolateral amygdala, in choices involving information.

Subjects are often willing to pay a cost for information. In a procedure that promotes paradoxical choices, animals choose between a richer option followed by a cue that is rewarded 50% of the time (No Info) vs. a leaner option followed by one of two cues that signal certain outcomes: one always rewarded (100%) and the other never rewarded, 0% (Info). Since decisions involve comparing the subjective value of options after integrating all their features, preference for information may rely on cortico-amygdalar circuitry. To test this, male and female rats were prepared with bilateral inhibitory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in the anterior cingulate cortex, orbitofrontal cortex, basolateral amygdala, or null virus (control). We inhibited these regions after stable preference was acquired. We found that inhibition of the anterior cingulate cortex destabilized choice preference in female rats without affecting latency to choose or response rate to cues. A logistic regression fit revealed that previous choice predicted current choice in all conditions, however previously rewarded Info trials strongly predicted preference in all conditions except in female rats following anterior cingulate cortex inhibition. The results reveal a causal, sex-dependent role for the anterior cingulate cortex in decisions involving information.

Emotion Regulation Strategies in Educational, Work and Sport Contexts: An Approach in Five Countries.

One of the greatest challenges in the domain of emotional regulation is comprehending the functionality of strategies and their utilization in various social contexts. In this sense, this study analyzes differences in the use and efficacy of regulation strategies, particularly of interpersonal strategies like altruism, social support, negotiation, mediation, regulation, and rituals, in samples of workers (N = 687) and students (N = 959) from Brazil, Chile, Cuba, Spain, and Uruguay, and athletes (N =144) from Spain. Participants answered questions pertaining to measures of affect or emotional regulation (MARS and ERQ self-regulation scales and EROS heteroregulation), as well as questions of a wellbeing scale (PHI) and questions related to emotional creativity (ECI), humor styles (HSQ), and adjustment to stress. Athletes reported less emotional discharge, use of humor, and affection, and greater confrontation and use of rituals than students and workers. A congruent relationship was found between the use of functional strategies (like direct coping, distraction, reevaluation, and active physiological regulation) and adjustment to stress, well-being, and creativity. Seeking social support, negotiation, and, to an extent, altruism, confirmed their predicted adaptive character. Mediation and delegation did not confirm their predicted adaptive character. Rumination, social comparison, rituals, confrontation, and suppression were maladaptive for workers and students, but the first four strategies were functional for athletes, who display a higher self-control and a more team-oriented and competitive emotional culture. Finally, the results show that adaptive regulation strategies mediate the relationship between well-being and adjustment to stress.

A special role for anterior cingulate cortex, but not orbitofrontal cortex or basolateral amygdala, in choices involving information.

Subjects often are willing to pay a cost for information. In a procedure that promotes paradoxical choices, animals choose between a richer option followed by a cue that is rewarded 50% of the time (No-info) vs a leaner option followed by one of two cues that signal certain outcomes: one always rewarded (100%), and the other never rewarded, 0% (Info). Since decisions involve comparing the subjective value of options after integrating all their features, preference for information may rely on cortico-amygdalar circuitry. To test this, male and female rats were prepared with bilateral inhibitory DREADDs in the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), basolateral amygdala (BLA), or null virus (control). We inhibited these regions after stable preference was acquired. We found that inhibition of ACC destabilized choice preference in female rats without affecting latency to choose or response rate to cues. A logistic regression fit revealed that the previous choice strongly predicted preference in control animals, but not in female rats following ACC inhibition. The results reveal a causal, sex-dependent role for ACC in decisions involving information.

Theta oscillations in anterior cingulate cortex and orbitofrontal cortex differentially modulate accuracy and speed in flexible reward learning.

Flexible reward learning relies on frontal cortex, with substantial evidence indicating that anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC) subregions play important roles. Recent studies in both rat and macaque suggest theta oscillations (5-10 Hz) may be a spectral signature that coordinates this learning. However, network-level interactions between ACC and OFC in flexible learning remain unclear. We investigated the learning of stimulus-reward associations using a combination of simultaneous in vivo electrophysiology in dorsal ACC and ventral OFC, partnered with bilateral inhibitory DREADDs in ACC. In freely behaving male and female rats and using a within-subject design, we examined accuracy and speed of response across distinct and precisely defined trial epochs during initial visual discrimination learning and subsequent reversal of stimulus-reward contingencies. Following ACC inhibition, there was a propensity for random responding in early reversal learning, with correct vs. incorrect trials distinguished only from OFC, not ACC, theta power differences in the reversal phase. ACC inhibition also hastened incorrect choices during reversal. This same pattern of change in accuracy and speed was not observed in viral control animals. Thus, characteristics of impaired reversal learning following ACC inhibition are poor deliberation and weak theta signaling of accuracy in this region. The present results also point to OFC theta oscillations as a prominent feature of reversal learning, unperturbed by ACC inhibition.

Dissociable contributions of basolateral amygdala and ventrolateral orbitofrontal cortex to flexible learning under uncertainty.

Reversal learning measures the ability to form flexible associations between choice outcomes with stimuli and actions that precede them. This type of learning is thought to rely on several cortical and subcortical areas, including highly interconnected orbitofrontal cortex (OFC) and basolateral amygdala (BLA), and is often impaired in various neuropsychiatric and substance use disorders. However, unique contributions of these regions to stimulus- and action-based reversal learning have not been systematically compared using a chemogenetic approach and particularly before and after the first reversal that introduces new uncertainty. Here, we examined the roles of ventrolateral OFC (vlOFC) and BLA during reversal learning. Male and female rats were prepared with inhibitory DREADDs targeting projection neurons in these regions and tested on a series of deterministic and probabilistic reversals during which they learned about stimulus identity or side (left or right) associated with different reward probabilities. Using a counterbalanced within-subject design, we inhibited these regions prior to reversal sessions. We assessed initial and pre-post reversal changes in performance to measure learning and adjustments to reversals, respectively. We found that inhibition of vlOFC, but not BLA, eliminated adjustments to stimulus-based reversals. Inhibition of BLA, but not vlOFC, selectively impaired action-based probabilistic reversal learning, leaving deterministic reversal learning intact. vlOFC exhibited a sex-dependent role in early adjustment to action-based reversals, but not in overall learning. These results reveal dissociable roles for BLA and vlOFC in flexible learning and highlight a more crucial role for BLA in learning meaningful changes in the reward environment.

Mechanisms of adjustments to different types of uncertainty in the reward environment across mice and monkeys.

Despite being unpredictable and uncertain, reward environments often exhibit certain regularities, and animals navigating these environments try to detect and utilize such regularities to adapt their behavior. However, successful learning requires that animals also adjust to uncertainty associated with those regularities. Here, we analyzed choice data from two comparable dynamic foraging tasks in mice and monkeys to investigate mechanisms underlying adjustments to different types of uncertainty. In these tasks, animals selected between two choice options that delivered reward probabilistically, while baseline reward probabilities changed after a variable number (block) of trials without any cues to the animals. To measure adjustments in behavior, we applied multiple metrics based on information theory that quantify consistency in behavior, and fit choice data using reinforcement learning models. We found that in both species, learning and choice were affected by uncertainty about reward outcomes (in terms of determining the better option) and by expectation about when the environment may change. However, these effects were mediated through different mechanisms. First, more uncertainty about the better option resulted in slower learning and forgetting in mice, whereas it had no significant effect in monkeys. Second, expectation of block switches accompanied slower learning, faster forgetting, and increased stochasticity in choice in mice, whereas it only reduced learning rates in monkeys. Overall, while demonstrating the usefulness of metrics based on information theory in examining adaptive behavior, our study provides evidence for multiple types of adjustments in learning and choice behavior according to uncertainty in the reward environment.

A hardware system for real-time decoding of in vivo calcium imaging data.

Epifluorescence miniature microscopes ('miniscopes') are widely used for in vivo calcium imaging of neural population activity. Imaging data are typically collected during a behavioral task and stored for later offline analysis, but emerging techniques for online imaging can support novel closed-loop experiments in which neural population activity is decoded in real time to trigger neurostimulation or sensory feedback. To achieve short feedback latencies, online imaging systems must be optimally designed to maximize computational speed and efficiency while minimizing errors in population decoding. Here we introduce DeCalciOn, an open-source device for real-time imaging and population decoding of in vivo calcium signals that is hardware compatible with all miniscopes that use the UCLA Data Acquisition (DAQ) interface. DeCalciOn performs online motion stabilization, neural enhancement, calcium trace extraction, and decoding of up to 1024 traces per frame at latencies of <50 ms after fluorescence photons arrive at the miniscope image sensor. We show that DeCalciOn can accurately decode the position of rats (n = 12) running on a linear track from calcium fluorescence in the hippocampal CA1 layer, and can categorically classify behaviors performed by rats (n = 2) during an instrumental task from calcium fluorescence in orbitofrontal cortex. DeCalciOn achieves high decoding accuracy at short latencies using innovations such as field-programmable gate array hardware for real-time image processing and contour-free methods to efficiently extract calcium traces from sensor images. In summary, our system offers an affordable plug-and-play solution for real-time calcium imaging experiments in behaving animals.

Timing, neural timescales, and temporal cognition.

This special issue provides a representative snapshot of cutting-edge behavioral neuroscience research on sense of time, cognitive and behavioral functioning, and neural processes. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Foraging with the frontal cortex: A cross-species evaluation of reward-guided behavior.

Efficient foraging is essential to survival and depends on frontal cortex in mammals. Because of its role in psychiatric disorders, frontal cortex and its contributions to reward procurement have been studied extensively in both rodents and non-human primates. How frontal cortex of these animal models compares is a source of intense debate. Here we argue that translating findings from rodents to non-human primates requires an appreciation of both the niche in which each animal forages as well as the similarities in frontal cortex anatomy and function. Consequently, we highlight similarities and differences in behavior and anatomy, before focusing on points of convergence in how parts of frontal cortex contribute to distinct aspects of foraging in rats and macaques, more specifically. In doing so, our aim is to emphasize where translation of frontal cortex function between species is clearer, where there is divergence, and where future work should focus. We finish by highlighting aspects of foraging for which have received less attention but we believe are critical to uncovering how frontal cortex promotes survival in each species.

[Association between diet of the vegan population and self-perception of periodontal state in Metropolitan Lima]. / Asociación entre la dieta de la población vegana y la autopercepción del estado periodontal en Lima Metropolitana.

INTRODUCTION: Objective: to determine the association between vegan diet and self-perceived periodontal status in a vegan population of Metropolitan Lima, Peru. Materials and methods: a total of 240 people (120 vegans and 120 non-vegans) were surveyed in this study during the months of August to December 2020 in a virtual way. To evaluate self-perception of periodontal status and oral hygiene habits, the self-report of periodontal disease was used, which is validated with a Cronbach's alpha of 0.77. In addition, other variables such as age, sex, socioeconomic level, educational level, and tobacco consumption were registered. A Poisson regression with robust variance estimator was used both for the association of variables, and prevalence ratios were reported in a crude and adjusted model. The confidence level was 95 % and the significance level was p < 0.05. Results and conclusions: a statistically significant association was found between the appearance of reddish and/or swollen gums (PR = 0.67; 95 % CI: 0.25-0.54) and poor perception of the state of the gums (PR = 0.43; 95 % CI: 0.33-0.56) with the vegan diet. Finally, for the gum bleeding dimension during brushing, no statistically significant differences were observed between vegans and non-vegans.

INTRODUCCIÓN: Objetivo: determinar la asociación entre la dieta vegana y la autopercepción del estado periodontal en una población vegana de Lima Metropolitana, Perú. Materiales y métodos: un total de 240 personas (120 veganas y 120 no veganas) fueron encuestadas en este estudio durante los meses de agosto a diciembre del año 2020 de manera virtual. Para evaluar la autopercepción del estado periodontal y los hábitos de higiene oral se utilizó el autorreporte de enfermedad periodontal, que se encuentra validado con una alfa de Cronbach de 0,77. Además se registraron otras variables como la edad, el sexo, el nivel socioeconómico, el grado de estudio y el consumo de tabaco. Se utilizó la regresión de Poisson con estimador robusto de la varianza para la asociación de las variables y se reportaron razones de prevalencia en un modelo crudo y ajustado. El nivel de confianza fue del 95 % y el de significancia fue de p < 0,05. Resultados y conclusiones: se encontró asociación estadísticamente significativa entre la apariencia de encías rojizas y/o hinchadas (RP = 0,67; IC 95 %: 0,25-0,54) y la mala percepción del estado de las encías (RP = 0,43; IC 95 %: 0,33-0,56) con la dieta vegana. Por último, para la dimensión del sangrado de encías durante el cepillado no se observaron diferencias estadísticamente significativas entre las personas veganas y las no veganas.

Translational opportunities in animal and human models to study alcohol use disorder.

Animal and human laboratory paradigms offer invaluable approaches to study the complex etiologies and mechanisms of alcohol use disorder (AUD). We contend that human laboratory models provide a "bridge" between preclinical and clinical studies of AUD by allowing for well-controlled experimental manipulations in humans with AUD. As such, examining the consilience between experimental models in animals and humans in the laboratory provides unique opportunities to refine the translational utility of such models. The overall goal of the present review is to provide a systematic description and contrast of commonly used animal paradigms for the study of AUD, as well as their human laboratory analogs if applicable. While there is a wide breadth of animal species in AUD research, the paradigms discussed in this review rely predominately on rodent research. The overarching goal of this effort is to provide critical analysis of these animal models and to link them to human laboratory models of AUD. By systematically contrasting preclinical and controlled human laboratory models, we seek to identify opportunities to enhance their translational value through forward and reverse translation. We provide future directions to reconcile differences between animal and human work and to improve translational research for AUD.

Unique features of stimulus-based probabilistic reversal learning.

Reversal learning paradigms are widely used assays of behavioral flexibility with their probabilistic versions being more amenable to studying integration of reward outcomes over time. Prior research suggests differences between initial and reversal learning, including higher learning rates, a greater need for inhibitory control, and more perseveration after reversals. However, it is not well-understood what aspects of stimulus-based reversal learning are unique to reversals, and whether and how observed differences depend on reward probability. Here, we used a visual probabilistic discrimination and reversal learning paradigm where male and female rats selected between a pair of stimuli associated with different reward probabilities. We compared accuracy, rewards collected, omissions, latencies, win-stay/lose-shift strategies, and indices of perseveration across two different reward probability schedules. We found that discrimination and reversal learning are behaviorally more unique than similar: Fit of choice behavior using reinforcement learning models revealed a lower sensitivity to the difference in subjective reward values (greater exploration) and higher learning rates for the reversal phase. We also found latencies to choose the better option were greater in females than males, but only for the reversal phase. Further, animals employed more win-stay strategies during early discrimination and increased perseveration during early reversal learning. Interestingly, a consistent reward probability group difference emerged with a richer environment associated with longer reward collection latencies than a leaner environment. Future studies should systematically compare the neural correlates of fine-grained behavioral measures to reveal possible dissociations in how the circuitry is recruited in each phase. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The orbitofrontal cortex in temporal cognition.

One of the most important factors in decision-making is estimating the value of available options. Subregions of the prefrontal cortex, including the orbitofrontal cortex (OFC), have been deemed essential for this process. Value computations require a complex integration across numerous dimensions, including, reward magnitude, effort, internal state, and time. The importance of the temporal dimension is well illustrated by temporal discounting tasks, in which subjects select between smaller-sooner versus larger-later rewards. The specific role of OFC in telling time and integrating temporal information into decision-making remains unclear. Based on the current literature, in this review we reevaluate current theories of OFC function, accounting for the influence of time. Incorporating temporal information into value estimation and decision-making requires distinct, yet interrelated, forms of temporal information including the ability to tell time, represent time, create temporal expectations, and the ability to use this information for optimal decision-making in a wide range of tasks, including temporal discounting and wagering. We use the term "temporal cognition" to refer to the integrated use of these different aspects of temporal information. We suggest that the OFC may be a critical site for the integration of reward magnitude and delay, and thus important for temporal cognition. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Chemogenetic Modulation and Single-Photon Calcium Imaging in Anterior Cingulate Cortex Reveal a Mechanism for Effort-Based Decisions.

The ACC is implicated in effort exertion and choices based on effort cost, but it is still unclear how it mediates this cost-benefit evaluation. Here, male rats were trained to exert effort for a high-value reward (sucrose pellets) in a progressive ratio lever-pressing task. Trained rats were then tested in two conditions: a no-choice condition where lever-pressing for sucrose was the only available food option, and a choice condition where a low-value reward (lab chow) was freely available as an alternative to pressing for sucrose. Disruption of ACC, via either chemogenetic inhibition or excitation, reduced lever-pressing in the choice, but not in the no-choice, condition. We next looked for value coding cells in ACC during effortful behavior and reward consumption phases during choice and no-choice conditions. For this, we used in vivo miniaturized fluorescence microscopy to reliably track responses of the same cells and compare how ACC neurons respond during the same effortful behavior where there was a choice versus when there was no-choice. We found that lever-press and sucrose-evoked responses were significantly weaker during choice compared with no-choice sessions, which may have rendered them more susceptible to chemogenetic disruption. Together, findings from our interference experiments and neural recordings suggest that a mechanism by which ACC mediates effortful decisions is in the discrimination of the utility of available options. ACC regulates these choices by providing a stable population code for the relative value of different options.SIGNIFICANCE STATEMENT The ACC is implicated in effort-based decision-making. Here, we used chemogenetics and in vivo calcium imaging to explore its mechanism. Rats were trained to lever press for a high-value reward and tested in two conditions: a no-choice condition where lever-pressing for the high-value reward was the only option, and a choice condition where a low-value reward was also available. Inhibition or excitation of ACC reduced effort toward the high-value option, but only in the choice condition. Neural responses in ACC were weaker in the choice compared with the no-choice condition. A mechanism by which ACC regulates effortful decisions is in providing a stable population code for the discrimination of the utility of available options.

Sex-dependent effects of chronic intermittent voluntary alcohol consumption on attentional, not motivational, measures during probabilistic learning and reversal.

BACKGROUND: Forced alcohol (ethanol, EtOH) exposure has been shown to cause significant impairments on reversal learning, a widely-used assay of cognitive flexibility, specifically on fully-predictive, deterministic versions of this task. However, previous studies have not adequately considered voluntary EtOH consumption and sex effects on probabilistic reversal learning. The present study aimed to fill this gap in the literature. METHODS: Male and female Long-Evans rats underwent either 10 weeks of voluntary intermittent 20% EtOH access or water only (H2O) access. Rats were then pretrained to initiate trials and learn stimulus-reward associations via touchscreen response, and subsequently required to select between two visual stimuli, rewarded with probability 0.70 or 0.30. In the final phase, reinforcement contingencies were reversed. RESULTS: We found significant sex differences on several EtOH-drinking variables, with females reaching a higher maximum EtOH consumption, exhibiting more high-drinking days, and escalating their EtOH at a quicker rate compared to males. During early abstinence, EtOH drinkers (and particularly EtOH-drinking females) made more initiation omissions and were slower to initiate trials than H2O drinking controls, especially during pretraining. A similar pattern in trial initiations was also observed in discrimination, but not in reversal learning. EtOH drinking rats were unaffected in their reward collection and stimulus response times, indicating intact motivation and motor responding. Although there were sex differences in discrimination and reversal phases, performance improved over time. We also observed sex-independent drinking group differences in win-stay and lose-shift strategies specific to the reversal phase. CONCLUSIONS: Females exhibit increased vulnerability to EtOH effects in early learning: there were sex-dependent EtOH effects on attentional measures during pretraining and discrimination phases. We also found sex-independent EtOH effects on exploration strategies during reversal. Future studies should aim to uncover the neural mechanisms for changes in attention and exploration in both acute and prolonged EtOH withdrawal.

Rodent Models of Adaptive Value Learning and Decision-Making.

Real-world decisions are rarely as straightforward as choosing between clearly "good" vs. "bad" options. More often, options must be evaluated carefully because they differ in relative value. For example, we typically learn about (and make decisions between) options in comparison, where one outcome may be more costly or risky than the other. Several neuropsychiatric conditions are characterized by atypical evaluation of effort and risk costs, including major depression, schizophrenia, autism, obsessive-compulsive disorder, and substance use disorders. Aberrant value learning and decision-making have long been considered a cognitive-behavioral endophenotype of these disorders and can be modeled in rodents. This chapter presents two general methodological domains that the experimenter can manipulate in animal decision-making tasks: risk and effort. Here, we present detailed methods of rodent tasks frequently employed within these domains: probabilistic reversal learning (PRL) and effort choice. These tasks recruit regions within rodent frontal cortex, the amygdala, and the striatum, and performance is heavily modulated by dopamine, making these assays highly valid measures in the study of behavioral and substance addictions, in particular.

Adaptive learning under expected and unexpected uncertainty.

The outcome of a decision is often uncertain, and outcomes can vary over repeated decisions. Whether decision outcomes should substantially affect behaviour and learning depends on whether they are representative of a typically experienced range of outcomes or signal a change in the reward environment. Successful learning and decision-making therefore require the ability to estimate expected uncertainty (related to the variability of outcomes) and unexpected uncertainty (related to the variability of the environment). Understanding the bases and effects of these two types of uncertainty and the interactions between them - at the computational and the neural level - is crucial for understanding adaptive learning. Here, we examine computational models and experimental findings to distil computational principles and neural mechanisms for adaptive learning under uncertainty.