The rat frontal orienting field dynamically encodes value for economic decisions under risk.

Frontal and parietal cortex are implicated in economic decision-making, but their causal roles are untested. Here we silenced the frontal orienting field (FOF) and posterior parietal cortex (PPC) while rats chose between a cued lottery and a small stable surebet. PPC inactivations produced minimal short-lived effects. FOF inactivations reliably reduced lottery choices. A mixed-agent model of choice indicated that silencing the FOF caused a change in the curvature of the rats' utility function (U = Vρ). Consistent with this finding, single-neuron and population analyses of neural activity confirmed that the FOF encodes the lottery value on each trial. A dynamical model, which accounts for electrophysiological and silencing results, suggests that the FOF represents the current lottery value to compare against the remembered surebet value. These results demonstrate that the FOF is a critical node in the neural circuit for the dynamic representation of action values for choice under risk.

Recommendations for empowering early career researchers to improve research culture and practice.

Early career researchers (ECRs) are important stakeholders leading efforts to catalyze systemic change in research culture and practice. Here, we summarize the outputs from a virtual unconventional conference (unconference), which brought together 54 invited experts from 20 countries with extensive experience in ECR initiatives designed to improve the culture and practice of science. Together, we drafted 2 sets of recommendations for (1) ECRs directly involved in initiatives or activities to change research culture and practice; and (2) stakeholders who wish to support ECRs in these efforts. Importantly, these points apply to ECRs working to promote change on a systemic level, not only those improving aspects of their own work. In both sets of recommendations, we underline the importance of incentivizing and providing time and resources for systems-level science improvement activities, including ECRs in organizational decision-making processes, and working to dismantle structural barriers to participation for marginalized groups. We further highlight obstacles that ECRs face when working to promote reform, as well as proposed solutions and examples of current best practices. The abstract and recommendations for stakeholders are available in Dutch, German, Greek (abstract only), Italian, Japanese, Polish, Portuguese, Spanish, and Serbian.

The Importance of Accounting for Movement When Relating Neuronal Activity to Sensory and Cognitive Processes.

A surprising finding of recent studies in mouse is the dominance of widespread movement-related activity throughout the brain, including in early sensory areas. In awake subjects, failing to account for movement risks misattributing movement-related activity to other (e.g., sensory or cognitive) processes. In this article, we (1) review task designs for separating task-related and movement-related activity, (2) review three "case studies" in which not considering movement would have resulted in critically different interpretations of neuronal function, and (3) discuss functional couplings that may prevent us from ever fully isolating sensory, motor, and cognitive-related activity. Our main thesis is that neural signals related to movement are ubiquitous, and therefore ought to be considered first and foremost when attempting to correlate neuronal activity with task-related processes.

Quantifying the contribution of individual variation in timing to delay-discounting.

Delay-discounting studies in neuroscience, psychology, and economics have been mostly focused on concepts of self-control, reward evaluation, and discounting. Another important relationship to consider is the link between intertemporal choice and time perception. We presented 50 college students with timing tasks on the range of seconds to minutes and intertemporal-choice tasks on both the time-scale of seconds and of days. We hypothesized that individual differences in time perception would influence decisions about short experienced delays but not long delays. While we found some evidence that individual differences in internal clock speed account for some unexplained variance between choices across time-horizons, overall our findings suggest a nominal contribution of the altered sense of time in intertemporal choice.

Collicular circuits for flexible sensorimotor routing.

Context-based sensorimotor routing is a hallmark of executive control. Pharmacological inactivations in rats have implicated the midbrain superior colliculus (SC) in this process. But what specific role is this, and what circuit mechanisms support it? Here we report a subset of rat SC neurons that instantiate a specific link between the representations of context and motor choice. Moreover, these neurons encode animals' choice far earlier than other neurons in the SC or in the frontal cortex, suggesting that their neural dynamics lead choice computation. Optogenetic inactivations revealed that SC activity during context encoding is necessary for choice behavior, even while that choice behavior is robust to inactivations during choice formation. Searches for SC circuit models matching our experimental results identified key circuit predictions while revealing some a priori expected features as unnecessary. Our results reveal circuit mechanisms within the SC that implement response inhibition and context-based vector inversion during executive control.

A community-led initiative for training in reproducible research.

Open and reproducible research practices increase the reusability and impact of scientific research. The reproducibility of research results is influenced by many factors, most of which can be addressed by improved education and training. Here we describe how workshops developed by the Reproducibility for Everyone (R4E) initiative can be customized to provide researchers at all career stages and across most disciplines with education and training in reproducible research practices. The R4E initiative, which is led by volunteers, has reached more than 3000 researchers worldwide to date, and all workshop materials, including accompanying resources, are available under a CC-BY 4.0 license at https://www.repro4everyone.org/.

Time preferences are reliable across time-horizons and verbal versus experiential tasks.

Individual differences in delay-discounting correlate with important real world outcomes, for example education, income, drug use, and criminality. As such, delay-discounting has been extensively studied by economists, psychologists and neuroscientists to reveal its behavioral and biological mechanisms in both human and non-human animal models. However, two major methodological differences hinder comparing results across species. Human studies present long time-horizon options verbally, whereas animal studies employ experiential cues and short delays. To bridge these divides, we developed a novel language-free experiential task inspired by animal decision-making studies. We found that the ranks of subjects' time-preferences were reliable across both verbal/experiential and second/day differences. Yet, discount factors scaled dramatically across the tasks, indicating a strong effect of temporal context. Taken together, this indicates that individuals have a stable, but context-dependent, time-preference that can be reliably assessed using different methods, providing a foundation to bridge studies of time-preferences across species. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).

More than Just a "Motor": Recent Surprises from the Frontal Cortex.

Motor and premotor cortices are crucial for the control of movements. However, we still know little about how these areas contribute to higher-order motor control, such as deciding which movements to make and when to make them. Here we focus on rodent studies and review recent findings, which suggest that-in addition to motor control-neurons in motor cortices play a role in sensory integration, behavioral strategizing, working memory, and decision-making. We suggest that these seemingly disparate functions may subserve an evolutionarily conserved role in sensorimotor cognition and that further study of rodent motor cortices could make a major contribution to our understanding of the evolution and function of the mammalian frontal cortex.

Decision-making behaviors: weighing ethology, complexity, and sensorimotor compatibility.

Rodent decision-making research aims to uncover the neural circuitry underlying the ability to evaluate alternatives and select appropriate actions. Designing behavioral paradigms that provide a solid foundation to ask questions about decision-making computations and mechanisms is a difficult and often underestimated challenge. Here, we propose three dimensions on which we can consider rodent decision-making tasks: ethological validity, task complexity, and stimulus-response compatibility. We review recent research through this lens, and provide practical guidance for researchers in the decision-making field.

Rat Prefrontal Cortex Inactivations during Decision Making Are Explained by Bistable Attractor Dynamics.

Two-node attractor networks are flexible models for neural activity during decision making. Depending on the network configuration, these networks can model distinct aspects of decisions including evidence integration, evidence categorization, and decision memory. Here, we use attractor networks to model recent causal perturbations of the frontal orienting fields (FOF) in rat cortex during a perceptual decision-making task (Erlich, Brunton, Duan, Hanks, & Brody, 2015 ). We focus on a striking feature of the perturbation results. Pharmacological silencing of the FOF resulted in a stimulus-independent bias. We fit several models to test whether integration, categorization, or decision memory could account for this bias and found that only the memory configuration successfully accounts for it. This memory model naturally accounts for optogenetic perturbations of FOF in the same task and correctly predicts a memory-duration-dependent deficit caused by silencing FOF in a different task. Our results provide mechanistic support for a "postcategorization" memory role of the FOF in upcoming choices.

Sources of noise during accumulation of evidence in unrestrained and voluntarily head-restrained rats.

Decision-making behavior is often characterized by substantial variability, but its source remains unclear. We developed a visual accumulation of evidence task designed to quantify sources of noise and to be performed during voluntary head restraint, enabling cellular resolution imaging in future studies. Rats accumulated discrete numbers of flashes presented to the left and right visual hemifields and indicated the side that had the greater number of flashes. Using a signal-detection theory-based model, we found that the standard deviation in their internal estimate of flash number scaled linearly with the number of flashes. This indicates a major source of noise that, surprisingly, is not consistent with the widely used 'drift-diffusion modeling' (DDM) approach but is instead closely related to proposed models of numerical cognition and counting. We speculate that this form of noise could be important in accumulation of evidence tasks generally.

Cortical and Subcortical Contributions to Short-Term Memory for Orienting Movements.

Neural activity in frontal cortical areas has been causally linked to short-term memory (STM), but whether this activity is necessary for forming, maintaining, or reading out STM remains unclear. In rats performing a memory-guided orienting task, the frontal orienting fields in cortex (FOF) are considered critical for STM maintenance, and during each trial display a monotonically increasing neural encoding for STM. Here, we transiently inactivated either the FOF or the superior colliculus and found that the resulting impairments in memory-guided orienting performance followed a monotonically decreasing time course, surprisingly opposite to the neural encoding. A dynamical attractor model in which STM relies equally on cortical and subcortical regions reconciled the encoding and inactivation data. We confirmed key predictions of the model, including a time-dependent relationship between trial difficulty and perturbability, and substantial, supralinear, impairment following simultaneous inactivation of the FOF and superior colliculus during memory maintenance.

Requirement of Prefrontal and Midbrain Regions for Rapid Executive Control of Behavior in the Rat.

To study rapid sensorimotor remapping, we developed a method to train rats in a behavior in which subjects are cued, on each trial, to apply a sensorimotor association to orient either toward a visual target ("Pro") or away from it, toward its reverse ("Anti"). Multiple behavioral asymmetries suggested that Anti behavior is cognitively demanding while Pro is easier to learn and perform. This is consistent with a prominent hypothesis in the primate literature that Anti requires prefrontal cortex (PFC), whereas Pro could be mediated by midbrain superior colliculus (SC). Pharmacological inactivation of rat medial PFC supported its expected role in Anti. Remarkably, bilateral SC inactivation substantially impaired Anti while leaving Pro essentially intact. Moreover, SC inactivation eliminated the performance cost of switching from Anti to Pro tasks. Our results establish a rodent model of single-trial sensorimotor remapping and suggest a critical role for SC in the cognitively demanding Anti task.

Distinct effects of prefrontal and parietal cortex inactivations on an accumulation of evidence task in the rat.

Numerous brain regions have been shown to have neural correlates of gradually accumulating evidence for decision-making, but the causal roles of these regions in decisions driven by accumulation of evidence have yet to be determined. Here, in rats performing an auditory evidence accumulation task, we inactivated the frontal orienting fields (FOF) and posterior parietal cortex (PPC), two rat cortical regions that have neural correlates of accumulating evidence and that have been proposed as central to decision-making. We used a detailed model of the decision process to analyze the effect of inactivations. Inactivation of the FOF induced substantial performance impairments that were quantitatively best described as an impairment in the output pathway of an evidence accumulator with a long integration time constant (>240 ms). In contrast, we found a minimal role for PPC in decisions guided by accumulating auditory evidence, even while finding a strong role for PPC in internally-guided decisions.

Distinct relationships of parietal and prefrontal cortices to evidence accumulation.

Gradual accumulation of evidence is thought to be fundamental for decision-making, and its neural correlates have been found in several brain regions. Here we develop a generalizable method to measure tuning curves that specify the relationship between neural responses and mentally accumulated evidence, and apply it to distinguish the encoding of decision variables in posterior parietal cortex and prefrontal cortex (frontal orienting fields, FOF). We recorded the firing rates of neurons in posterior parietal cortex and FOF from rats performing a perceptual decision-making task. Classical analyses uncovered correlates of accumulating evidence, similar to previous observations in primates and also similar across the two regions. However, tuning curve assays revealed that while the posterior parietal cortex encodes a graded value of the accumulating evidence, the FOF has a more categorical encoding that indicates, throughout the trial, the decision provisionally favoured by the evidence accumulated so far. Contrary to current views, this suggests that premotor activity in the frontal cortex does not have a role in the accumulation process, but instead has a more categorical function, such as transforming accumulated evidence into a discrete choice. To probe causally the role of FOF activity, we optogenetically silenced it during different time points of the trial. Consistent with a role in committing to a categorical choice at the end of the evidence accumulation process, but not consistent with a role during the accumulation itself, a behavioural effect was observed only when FOF silencing occurred at the end of the perceptual stimulus. Our results place important constraints on the circuit logic of brain regions involved in decision-making.

The role of the lateral amygdala in the retrieval and maintenance of fear-memories formed by repeated probabilistic reinforcement.

The lateral nucleus of the amygdala (LA) is a key element in the neural circuit subserving Pavlovian fear-conditioning, an animal model of fear and anxiety. Most studies have focused on the role of the LA in fear acquisition and extinction, i.e., how neural plasticity results from changing contingencies between a neutral conditioned stimulus (CS) (e.g., a tone) and an aversive unconditioned stimulus (US) (e.g., a shock). However, outside of the lab, fear-memories are often the result of repeated and unpredictable experiences. Examples include domestic violence, child abuse or combat. To better understand the role of the LA in the expression of fear resulting from repeated and uncertain reinforcement, rats experienced a 30% partial reinforcement (PR) fear-conditioning schedule four days a week for four weeks. Rats reached asymptotic levels of conditioned-fear expression after the first week. We then manipulated LA activity with drug (or vehicle) (VEH) infusions once a week, for the next three weeks, before the training session. LA infusions of muscimol (MUSC), a GABA-A agonist that inhibits neural activity, reduced CS evoked fear-behavior to pre-conditioning levels. LA infusions of pentagastrin (PENT), a cholecystokinin-2 (CCK) agonist that increases neural excitability, resulted in CS-evoked fear-behavior that continued past the offset of the CS. This suggests that neural activity in the LA is required for the retrieval of fear memories that stem from repeated and uncertain reinforcement, and that CCK signaling in the LA plays a role in the recovery from fear after the removal of the fear-evoking stimulus.

A cortical substrate for memory-guided orienting in the rat.

Anatomical, stimulation, and lesion data have suggested a homology between the rat frontal orienting fields (FOF) (centered at +2 AP, ±1.3 ML mm from Bregma) and primate frontal cortices such as the frontal or supplementary eye fields. We investigated the functional role of the FOF using rats trained to perform a memory-guided orienting task, in which there was a delay period between the end of a sensory stimulus instructing orienting direction and the time of the allowed motor response. Unilateral inactivation of the FOF resulted in impaired contralateral responses. Extracellular recordings of single units revealed that 37% of FOF neurons had delay period firing rates that predicted the direction of the rats' later orienting motion. Our data provide the first electrophysiological and pharmacological evidence supporting the existence in the rat, as in the primate, of a frontal cortical area involved in the preparation and/or planning of orienting responses.

Minimal impairment in a rat model of duration discrimination following excitotoxic lesions of primary auditory and prefrontal cortices.

We present a behavioral paradigm for the study of duration perception in the rat, and report the result of neurotoxic lesions that have the goal of identifying sites that mediate duration perception. Using a two-alternative forced-choice paradigm, rats were either trained to discriminate durations of pure tones (range = [200,500] ms; boundary = 316 ms; Weber fraction after training = 0.24 ± 0.04), or were trained to discriminate frequencies of pure tones (range = [8,16] kHz; boundary = 11.3 kHz; Weber = 0.16 ± 0.11); the latter task is a control for non-timing-specific aspects of the former. Both groups discriminate the same class of sensory stimuli, use the same motions to indicate decisions, have identical trial structures, and are trained to psychophysical threshold; the tasks are thus matched in a number of sensorimotor and cognitive demands. We made neurotoxic lesions of candidate timing-perception areas in the cerebral cortex of both groups. Following extensive bilateral lesions of the auditory cortex, the performance of the frequency discrimination group was significantly more impaired than that of the duration discrimination group. We also found that extensive bilateral lesions of the medial prefrontal cortex resulted in little to no impairment of both groups. The behavioral framework presented here provides an audition-based approach to study the neural mechanisms of time estimation and memory for durations.