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.

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.

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.

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.

Functional Heterogeneity within Rat Orbitofrontal Cortex in Reward Learning and Decision Making.

Rat orbitofrontal cortex (OFC) is located in the dorsal bank of the rhinal sulcus, and is divided into the medial orbital area, ventral orbital area, ventrolateral orbital area, lateral orbital area, dorsolateral orbital area, and agranular insular areas. Over the past 20 years, there has been a marked increase in the number of publications focused on the functions of rat OFC. While collectively this extensive body of work has provided great insight into the functions of OFC, leading to theoretical and computational models of its functions, one issue that has emerged relates to what is defined as OFC because targeting of this region can be quite variable between studies of appetitive behavior, even within the same species. Also apparent is that there is an oversampling and undersampling of certain subregions of rat OFC for study, and this will be demonstrated here. The intent of the Viewpoint is to summarize studies in rat OFC, given the diversity of what groups refer to as "OFC," and to integrate these with the findings of recent anatomical studies. The primary aim is to help discern functions in reward learning and decision-making, clearing the course for future empirical work.

Basolateral amygdala supports the maintenance of value and effortful choice of a preferred option.

The basolateral amygdala (BLA) is known to be involved in appetitive behavior, yet its role in cost-benefit choice of qualitatively different rewards (more/less preferred), beyond magnitude differences (larger/smaller), is poorly understood. We assessed the effects of BLA inactivations on effortful choice behavior. Rats were implanted with cannulae in BLA and trained to stable lever pressing for sucrose pellets on a progressive ratio schedule. Rats were then introduced to a choice: chow was concurrently available while they could work for the preferred sucrose pellets. Rats were infused with either vehicle control (aCSF) or baclofen/muscimol prior to test. BLA inactivations produced a significant decrease in lever presses for sucrose pellets compared to vehicle, and chow consumption was unaffected. Inactivation had no effect on sucrose pellet preference when both options were freely available. Critically, when lab chow was not concurrently available, BLA inactivations had no effect on the number of lever presses for sucrose pellets, indicating that primary motivation in the absence of choice remains intact with BLA offline. After a test under specific satiety for sucrose pellets, BLA inactivation rendered animals less sensitive to devaluation relative to control. The effects of BLA inactivations in our task are not mediated by decreased appetite, an inability to perform the task, a change in food preference, or decrements in primary motivation. Taken together, BLA supports the specific value and effortful choice of a preferred option.

Anterior cingulate cortex supports effort allocation towards a qualitatively preferred option.

The anterior cingulate cortex (ACC) is known to be involved in effortful choice, yet its role in cost-benefit evaluation of qualitatively different rewards (more/less preferred), beyond magnitude differences (larger/smaller), is poorly understood. Selecting between qualitatively different options is a decision type commonly faced by humans. Here, we assessed the role of ACC on a task that has primarily been used to probe striatal function in motivation. Rats were trained to stable performance on a progressive ratio schedule for sucrose pellets and were then given sham surgeries (control) or excitotoxic NMDA lesions of ACC. Subsequently, a choice was introduced: chow was concurrently available while animals could work for the preferred sucrose pellets. ACC lesions produced a significant decrease in lever presses for sucrose pellets compared to control, whereas chow consumption was unaffected. Lesions had no effect on sucrose pellet preference when both options were freely available. When laboratory chow was not concurrently available, ACC-lesioned rats exhibited similar lever pressing as controls. During a test under specific satiety for sucrose pellets, ACC-lesioned rats also showed intact devaluation effects. The effects of ACC lesions in our task are not mediated by decreased appetite, a change in food preference, a failure to update value or a learning deficit. Taken together, we found that ACC lesions decreased effort for a qualitatively preferred option. These results are discussed with reference to effects of striatal manipulations and our recent report of a role for basolateral amygdala in effortful choice.

Rigid patterns of effortful choice behavior after acute stress in rats.

Physical effort is a common cost of acquiring rewards, and decreased effort is a feature of many neuropsychiatric disorders. Stress affects performance on several tests of cognition and decision making in both humans and nonhumans. Only a few recent reports show impairing effects of stress in operant tasks involving effort and cognitive flexibility. Brain regions affected by stress, such as the medial prefrontal cortex and amygdala, are also implicated in mediating effortful choices. Here, we assessed effort-based decision making after an acute stress procedure known to induce persistent impairment in shuttle escape and elevated plasma corticosterone. In these animals, we also probed levels of polysialyted neural cell adhesion molecule (PSA-NCAM), a marker of structural plasticity, in medial frontal cortex and amygdala. We found that animals that consistently worked for high magnitude rewards continued to do so, even after acute shock stress. We also found that PSA-NCAM was increased in both regions after effortful choice experience but not after shock stress alone. These findings are discussed with reference to the existing broad literature on cognitive effects of stress and in the context of how acute stress may bias effortful decisions to a rigid pattern of responding.

Basolateral amygdala lesions facilitate reward choices after negative feedback in rats.

The orbitofrontal cortex (OFC) and basolateral amygdala (BLA) constitute part of a neural circuit important for adaptive, goal-directed learning. One task measuring flexibility of response to changes in reward is discrimination reversal learning. Damage to OFC produces well documented impairments on various forms of reversal learning in rodents, monkeys, and humans. Recent reports show that BLA, though highly interconnected with OFC, may be differentially involved in reversal learning. In the present experiment, we compared the effects of bilateral, ibotenic acid lesions of OFC or BLA (or SHAM) on visual discrimination and reversal learning. Specifically, we used pairwise visual discrimination methods, as is commonly administered in non-human primate studies, and analyzed how animals use positive and negative trial-by-trial feedback, domains not previously explored in a rat study. As expected, OFC lesions displayed significantly slower reversal learning than SHAM and BLA rats across sessions. Rats with BLA lesions, conversely, showed facilitated reversal learning relative to SHAM and OFC groups. Furthermore, a trial-by-trial analysis of the errors committed showed the BLA group benefited more from incorrectly performed trials (or negative feedback) on future choices than either SHAM or OFC rats. This provides evidence that BLA and OFC are involved in updating responses to changes in reward contingency and that the roles are distinct. Our results are discussed in relation to a competitive framework model for OFC and BLA in reward processing.

Zim17/Tim15 links mitochondrial iron-sulfur cluster biosynthesis to nuclear genome stability.

Genomic instability is related to a wide-range of human diseases. Here, we show that mitochondrial iron-sulfur cluster biosynthesis is important for the maintenance of nuclear genome stability in Saccharomyces cerevisiae. Cells lacking the mitochondrial chaperone Zim17 (Tim15/Hep1), a component of the iron-sulfur biosynthesis machinery, have limited respiration activity, mimic the metabolic response to iron starvation and suffer a dramatic increase in nuclear genome recombination. Increased oxidative damage or deficient DNA repair do not account for the observed genomic hyperrecombination. Impaired cell-cycle progression and genetic interactions of ZIM17 with components of the RFC-like complex involved in mitotic checkpoints indicate that replicative stress causes hyperrecombination in zim17Δ mutants. Furthermore, nuclear accumulation of pre-ribosomal particles in zim17Δ mutants reinforces the importance of iron-sulfur clusters in normal ribosome biosynthesis. We propose that compromised ribosome biosynthesis and cell-cycle progression are interconnected, together contributing to replicative stress and nuclear genome instability in zim17Δ mutants.

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.

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.

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.

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.

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.

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).

[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.

Functional interaction of medial mediodorsal thalamic nucleus but not nucleus accumbens with amygdala and orbital prefrontal cortex is essential for adaptive response selection after reinforcer devaluation.

In nonhuman primates, reward-based decision making may be assessed through choices of objects overlying two different foods, one of which has been devalued by selective satiation. The most adaptive object choices yield the food of higher value. A large body of data identifies the amygdala and orbital prefrontal cortex (PFo) as neural mediators of adaptive responses to reinforcer devaluation. More recent work in nonhuman primates reveals the critical role of the medial, magnocellular portion of the mediodorsal nucleus of the thalamus (MDm) as well. Because both the nucleus accumbens (NA) and the MDm are anatomically related to the amygdala and PFo, and because both regions are implicated in reward processing, we tested whether either region necessarily interacts with the amygdala and PFo to mediate reinforcer devaluation effects. We used a crossed-disconnection design in which monkeys received amygdala and PFo lesions in one hemisphere combined with either NA or MDm lesions in the contralateral hemisphere. Monkeys that sustained NA disconnection, like controls, showed robust shifts in object choices in response to reinforcer devaluation. In contrast, monkeys that sustained MDm disconnection failed to adjust their object choices. Thus, MDm, but not NA, works together with the amygdala and PFo to support reward-based decision making.