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Perceptual decision-making involves multiple cognitive processes, including accumulation of sensory evidence, planning, and executing a motor action. How these processes are intertwined is unclear; some models assume that decision-related processes precede motor execution, whereas others propose that movements reflecting on-going decision processes occur before commitment to a choice. Here we combine and apply two complementary methods to study the relationship between decision processes and the movements leading up to a choice. The first is a free response pulse-based evidence accumulation task, in which stimuli continue until choice is reported and the second is a motion-based drift diffusion model (mDDM), in which movement variables from video pose estimation constrain decision parameters on a trial-by-trial basis. We find the mDDM provides a better model fit to rats' decisions in the free response accumulation task than traditional DDM models. Interestingly, on each trial we observed a period of time, prior to choice, that was characterized by head immobility. The length of this period was positively correlated with the rats' decision bounds and stimuli presented during this period had the greatest impact on choice. Together these results support a model in which internal decision dynamics are reflected in movements and demonstrate that inclusion of movement parameters improves the performance of diffusion-to-bound decision models.

Evidence accumulation, an essential component of perception and decision making, is frequently studied with psychophysical tasks involving noisy or ambiguous stimuli. In these tasks, participants typically receive verbal or written instructions that describe the strategy that should be used to guide decisions. Although convenient and effective, explicit instructions can influence learning and decision making strategies and can limit comparisons with animal models, in which behaviors are reinforced through feedback. Here, we developed an online video game and nonverbal training pipeline, inspired by pulse-based tasks for rodents, as an alternative to traditional psychophysical tasks used to study evidence accumulation. Using this game, we collected behavioral data from hundreds of participants trained with an explicit description of the decision rule or with experiential feedback. Participants trained with feedback alone learned the game rules rapidly and used strategies and displayed biases similar to those who received explicit instructions. Finally, by leveraging data across hundreds of participants, we show that perceptual judgments were well described by an accumulation process in which noise scaled nonlinearly with evidence, consistent with previous animal studies but inconsistent with diffusion models widely used to describe perceptual decisions in humans. These results challenge the conventional description of the accumulation process and suggest that online games provide a valuable platform to examine perceptual decision making and learning in humans. In addition, the feedback-based training pipeline developed for this game may be useful for evaluating perceptual decision making in human populations with difficulty following verbal instructions. NEW & NOTEWORTHY Perceptual uncertainty sets critical constraints on our ability to accumulate evidence and make decisions; however, its sources remain unclear. We developed a video game, and feedback-based training pipeline, to study uncertainty during decision making. Leveraging choices from hundreds of subjects, we demonstrate that human choices are inconsistent with popular diffusion models of human decision making and instead are best fit by models in which perceptual uncertainty scales nonlinearly with the strength of sensory evidence.

In patch foraging tasks, animals must decide whether to remain with a depleting resource or to leave it in search of a potentially better source of reward. In such tasks, animals consistently follow the general predictions of optimal foraging theory (the marginal value theorem; MVT): to leave a patch when the reward rate in the current patch depletes to the average reward rate across patches. Prior studies implicate an important role for the anterior cingulate cortex (ACC) in foraging decisions based on MVT: within single trials, ACC activity increases immediately preceding foraging decisions, and across trials, these dynamics are modulated as the value of staying in the patch depletes to the average reward rate. Here, we test whether these activity patterns reflect dynamic encoding of decision-variables and whether these signals are directly involved in decision-making. We developed a leaky accumulator model based on the MVT that generates estimates of decision variables within and across trials, and tested model predictions against ACC activity recorded from male rats performing a patch foraging task. Model predicted changes in MVT decision variables closely matched rat ACC activity. Next, we pharmacologically inactivated ACC in male rats to test the contribution of these signals to decision-making. ACC inactivation had a profound effect on rats' foraging decisions and response times (RTs) yet rats still followed the MVT decision rule. These findings indicate that the ACC encodes foraging-related variables for reasons unrelated to patch-leaving decisions. SIGNIFICANCE STATEMENT The ability to make adaptive patch-foraging decisions, to remain with a depleting resource or search for better alternatives, is critical to animal well-being. Previous studies have found that anterior cingulate cortex (ACC) activity is modulated at different points in the foraging decision process, raising questions about whether the ACC guides ongoing decisions or serves a more general purpose of regulating cognitive control. To investigate the function of the ACC in foraging, the present study developed a dynamic model of behavior and neural activity, and tested model predictions using recordings and inactivation of ACC. Findings revealed that ACC continuously signals decision variables but that these signals are more likely used to monitor and regulate ongoing processes than to guide foraging decisions., (Copyright © 2022 the authors.)

Cognitive and physical effort are typically regarded as costly, but demands for effort also seemingly boost the appeal of prospects under certain conditions. One contextual factor that might influence choices for or against effort is the mix of different types of demand a decision maker encounters in a given environment. In two foraging experiments, participants encountered prospective rewards that required equally long intervals of cognitive effort, physical effort, or unfilled delay. Monetary offers varied per trial, and the two experiments differed in whether the type of effort or delay cost was the same on every trial, or varied across trials. When each participant faced only one type of cost, cognitive effort persistently produced the highest acceptance rate compared to trials with an equivalent period of either physical effort or unfilled delay. We theorized that if cognitive effort were intrinsically rewarding, we would observe the same pattern of preferences when participants foraged for varying cost types in addition to rewards. Contrary to this prediction, in the second experiment, an initially higher acceptance rate for cognitive effort trials disappeared over time amid an overall decline in acceptance rates as participants gained experience with all three conditions. Our results indicate that cognitive demands may reduce the discounting effect of delays, but not because decision makers assign intrinsic value to cognitive effort. Rather, the results suggest that a cognitive effort requirement might influence contextual factors such as subjective delay duration estimates, which can be recalibrated if multiple forms of demand are interleaved., (© 2021. The Psychonomic Society, Inc.)

The ability to control a behavioral task or stimulate neural activity based on animal behavior in real-time is an important tool for experimental neuroscientists. Ideally, such tools are noninvasive, low-latency, and provide interfaces to trigger external hardware based on posture. Recent advances in pose estimation with deep learning allows researchers to train deep neural networks to accurately quantify a wide variety of animal behaviors. Here, we provide a new DeepLabCut-Live! package that achieves low-latency real-time pose estimation (within 15 ms, >100 FPS), with an additional forward-prediction module that achieves zero-latency feedback, and a dynamic-cropping mode that allows for higher inference speeds. We also provide three options for using this tool with ease: (1) a stand-alone GUI (called DLC-Live! GUI), and integration into (2) Bonsai, and (3) AutoPilot. Lastly, we benchmarked performance on a wide range of systems so that experimentalists can easily decide what hardware is required for their needs., Competing Interests: GK, JS, AM, MM No competing interests declared, GL Gonçalo Lopes is director at NeuroGEARS Ltd., (© 2020, Kane et al.)

Animals, including humans, consistently exhibit myopia in two different contexts: foraging, in which they harvest locally beyond what is predicted by optimal foraging theory, and intertemporal choice, in which they exhibit a preference for immediate vs. delayed rewards beyond what is predicted by rational (exponential) discounting. Despite the similarity in behavior between these two contexts, previous efforts to reconcile these observations in terms of a consistent pattern of time preferences have failed. Here, via extensive behavioral testing and quantitative modeling, we show that rats exhibit similar time preferences in both contexts: they prefer immediate vs. delayed rewards and they are sensitive to opportunity costs of delays to future decisions. Further, a quasi-hyperbolic discounting model, a form of hyperbolic discounting with separate components for short- and long-term rewards, explains individual rats' time preferences across both contexts, providing evidence for a common mechanism for myopic behavior in foraging and intertemporal choice., Competing Interests: GK, AB, AS, RW, ND, JC No competing interests declared, (© 2019, Kane et al.)

Background: In humans, accumulated adverse experiences during childhood increase the risk of anxiety disorders and attention-deficit/hyperactivity disorder. In rodents, the ventral hippocampus (vHIP) is associated with anxiety regulation, and lesions in this region alter both anxiety-like behavior and activity levels. Neuronal oscillations in the vHIP of the theta frequency range (4-12 Hz) have been implicated in anxious states and derive in part from the activity of inhibitory interneurons in the hippocampus, some of which are enwrapped with perineuronal nets (PNNs), extracellular matrix structures known to regulate plasticity. We sought to investigate the associations among early life stress-induced anxiety and hyperactivity with vHIP neuronal oscillations, inhibitory interneurons, and PNNs in mice., Methods: We used repeated maternal separation with early weaning (MSEW) to model accumulated early life adversity in mouse offspring and studied the underlying cellular and electrophysiological changes in the vHIP that are associated with excessive anxiety and hyperactivity., Results: We found increased anxiety-like behavior and activity levels in MSEW adult males, along with increased theta power and enhanced theta-gamma coupling in the vHIP. MSEW mice showed reduced intensity of parvalbumin as well as increased PNN intensity around parvalbumin-positive interneurons in the vHIP. We further observed that MSEW increased orthodenticle homeobox protein 2, a transcription factor promoting PNN development, in the choroid plexus, where it is produced, as well as in parvalbumin-positive interneurons, where it is sequestered., Conclusions: These findings raise the possibility of causal links among parvalbumin-positive interneurons, PNNs, orthodenticle homeobox protein 2, and MSEW-induced anxiety and hyperactivity., (Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

The medial prefrontal cortex (mPFC) is important for cognitive flexibility, the ability to switch between two task-relevant dimensions. Changes in neuronal oscillations and alterations in the coupling across frequency ranges have been correlated with attention and cognitive flexibility. Here we show that astrocytes in the mPFC of adult male Sprague Dawley rats, participate in cognitive flexibility through the astrocyte-specific Ca2+ binding protein S100β, which improves cognitive flexibility and increases phase amplitude coupling between theta and gamma oscillations. We further show that reduction of astrocyte number in the mPFC impairs cognitive flexibility and diminishes delta, alpha and gamma power. Conversely, chemogenetic activation of astrocytic intracellular Ca2+ signaling in the mPFC enhances cognitive flexibility, while inactivation of endogenous S100β among chemogenetically activated astrocytes in the mPFC prevents this improvement. Collectively, our work suggests that astrocytes make important contributions to cognitive flexibility and that they do so by releasing a Ca2+ binding protein which in turn enhances coordinated neuronal oscillations.

High levels of locus coeruleus (LC) tonic activity are associated with distraction and poor performance within a task. Adaptive gain theory (AGT; Aston-Jones & Cohen, 2005) suggests that this may reflect an adaptive function of the LC, encouraging search for more remunerative opportunities in times of low utility. Here, we examine whether stimulating LC tonic activity using designer receptors (DREADDs) promotes searching for better opportunities in a patch-foraging task as the value of a patch diminishes. The task required rats to decide repeatedly whether to exploit an immediate but depleting reward within a patch or to incur the cost of a time delay to travel to a new, fuller patch. Similar to behavior associated with high LC tonic activity in other tasks, we found that stimulating LC tonic activity impaired task performance, resulting in reduced task participation and increased response times and omission rates. However, this was accompanied by a more specific, predicted effect: a significant tendency to leave patches earlier, which was best explained by an increase in decision noise rather than a systematic bias to leave earlier (i.e., at higher values). This effect is consistent with the hypothesis that high LC tonic activity favors disengagement from current behavior, and the pursuit of alternatives, by augmenting processing noise. These results provide direct causal evidence for the relationship between LC tonic activity and flexible task switching proposed by AGT.

Obesity is a major public health problem affecting overall physical and emotional well-being. Despite compelling data suggesting an association between obesity and cognitive dysfunction, this phenomenon has received relatively little attention. Neuroimaging studies in obese humans report reduced size of brain regions involved in cognition, but few studies have investigated the cellular processes underlying cognitive decline in obesity or the influence of obesity on cognition in the absence of obesity-related illnesses. Here, a rat model of diet-induced obesity was used to explore changes in brain regions important for cognition. Obese rats showed deficits on cognitive tasks requiring the prefrontal and perirhinal cortex. Cognitive deficits were accompanied by decreased dendritic spine density and synaptic marker expression in both brain regions. Microglial morphology was also changed in the prefrontal cortex. Detrimental changes in the prefrontal cortex and perirhinal cortex occurred before metabolic syndrome or diabetes, suggesting that these brain regions may be particularly vulnerable to early stage obesity.

Thousands of neurons are born each day in the dentate gyrus (DG), but many of these cells die before reaching maturity. Both death and survival of adult-born neurons are regulated by neuronal activity in the DG. The immediate-early gene (IEG) zif268 appears to be an important mediator of these effects, as its expression can be induced by neural activity and knockout of zif268 impairs survival of adult-born neurons (Richardson et al., 1992; Veyrac et al., 2013). Despite the apparent importance of zif268 for adult neurogenesis, its behavior-induced expression has not been fully characterized in adult-born neurons. Here we characterize behavior-evoked expression of zif268 in mature and newborn dentate granule cells (DGCs). We first quantified zif268 expression in doublecortin-positive (DCX+) immature neurons and in the general granule cell population after brief exposure to a novel environment (NE). In the general granule cell population, zif268 expression peaked 1 h after NE exposure and returned to baseline by 8 h post-exposure. However, in the DCX+ cells, zif268 expression was suppressed relative to home cage for at least 8 h post-exposure. We next asked whether suppression of zif268 in DCX+ immature cells occurs in other behavioral paradigms that recruit the hippocampus. Exposure to Morris water maze (MWM) training, an enriched environment, or a NE caused approximately equal suppression of zif268 expression in DCX+ cells and approximately equal activation of zif268 expression among the general granule cell population. The same behavioral procedures activated zif268 expression in 6-week-old BrdU-labeled adult-born neurons, indicating that zif268 suppression is specific to immature neurons. Finally, we asked whether zif268 suppression varied as a function of age within the DCX+ population, which ranges in age from 0 to approximately 4 weeks. NE exposure had no significant effect on zif268 expression in 2- or 4-week-old BrdU-labeled neurons, but it significantly suppressed zif268 expression in 3-week-old neurons. In summary, behavioral experience transiently activated expression of zif268 in mature granule cells but caused a more long-lasting suppression of zif268 expression in immature, adult-born granule cells. We hypothesize that zif268 suppression inhibits memory-related synaptic plasticity in immature neurons or mediates learning-induced apoptosis of immature adult-born neurons.

Anxiety disorders are highly prevalent but little is known about their underlying mechanisms. Gap junctions exist in brain regions important for anxiety regulation, such as the ventral hippocampus (vHIP) and mPFC, but their functions in these areas have not been investigated. Using pharmacological blockade of neuronal gap junctions combined with electrophysiological recordings, we found that gap junctions play a role in theta rhythm in the vHIP and mPFC of adult mice. Bilateral infusion of neuronal gap junction blockers into the vHIP decreased anxiety-like behavior on the elevated plus maze and open field. Similar anxiolytic effects were observed with unilateral infusion of these drugs into the vHIP combined with contralateral infusion into the mPFC. No change in anxious behavior was observed with gap junction blockade in the unilateral vHIP alone or in the bilateral dorsal HIP. Since physical exercise is known to reduce anxiety, we examined the effects of long-term running on the expression of the neuronal gap junction protein connexin-36 among inhibitory interneurons and found a reduction in the vHIP. Despite this change, we observed no alteration in theta frequency or power in long-term runners. Collectively, these findings suggest that neuronal gap junctions in the vHIP-mPFC pathway are important for theta rhythm and anxiety regulation under sedentary conditions but that additional mechanisms are likely involved in running-induced reduction in anxiety., (Copyright © 2014 the authors 0270-6474/14/3415679-10$15.00/0.)