Charles D. Kopec

Center-port fixation is a common prerequisite for many freely-moving rodent tasks in neuroscience and psychology. However, typical protocols for shaping this behavior are non-standardized and inefficient. Moreover, motor errors in fixation termed ‘violations’ often account for a significant fraction of experimental trials, leading to notable data loss during experiments. In light of this, we developed FixGrower, a standardized protocol for center-port fixation training. FixGrower (1) requires a longer initial fixation requirement, (2) increases the required fixation duration at session boundaries customized to each animals’ performance, and (3) delays the introduction of violation penalties until the end of training. We demonstrate FixGrower decreases training time by 61%, yields low violation rates, and generalizes across rodent species and task difficulty. Moreover, the success of this curriculum is well supported by theories of operant conditioning and reinforcement learning. Our findings establish FixGrower as an efficient and broadly applicable curriculum for training fixation behavior in rodents, thereby accelerating training of many tasks in the field.

A common approach in the study of cognition is to train subjects to perform a task that requires a particular cognitive process to solve. Analysis of the subjects' response behavior while they perform these tasks can offer valuable insight into the underlying mechanisms that give rise to cognition. However, if subjects are able to accurately perform such a task by using a strategy that doesn't involve the targeted cognitive process, data from those experiments becomes more difficult to interpret. A number of perceptual decision-making tasks have been designed to study the accumulation of evidence, i.e. how noisy information presented over time is used to form a decision. Recent work, however, has highlighted how a variety of non-integration strategies can by some measures yield strikingly near-optimal performance on such tasks, raising the possibility that past conclusions from these experiments may be incorrect. Here we assemble the largest data set of animals performing one such task - the "Poisson Clicks" task - which is optimally solved by the gradual integration of pulsatile auditory noise. To investigate whether rats are in fact using this strategy, we compiled data from 515 rats performing over 35 million trials. We compare performance of 3 degenerate strategies (that circumvent the need to integrate evidence) to the optimal (integration) strategy. We demonstrate that the pulsatile nature of the stimuli used in the Poisson Clicks Task makes it possible to distinguish which strategy subjects use. Overwhelmingly, we find the rats are using an integration strategy when performing the Poisson Clicks Task.

Decision-making is thought to involve two phases: first, evidence accumulation, then, decision commitment. Accumulation is represented broadly in the brain, but whether this best matches single versus multiple accumulator models is unknown. Here, analysis of simultaneous, bilateral recordings across sensory, association, and motor regions, in both cortex and subcortical structures, strongly supports a single accumulator, and suggests that accumulated noise (diffusion) originates frontally. Decision commitment can occur internally, without an overt report. Long-standing competing models of covert commitment disagree as to whether it is abrupt or continuous. Temporally aligning data on a single-trial estimator of internal, covert commitment ("nTc") revealed a rapid (50 ms) drop in the accumulator's sensitivity to incoming sensory evidence, favoring abrupt transition models, and indicating a discrete cross-brain state change at nTc that was first detectable in motor regions. These data discriminate between decades-old models of accumulation, and between decades-old models of the transition to commitment.

Perceptual decision-making is the process by which an animal uses sensory stimuli to choose an action or mental proposition. This process is thought to be mediated by neurons organized as attractor networks ^1,2 . However, whether attractor dynamics underlie decision behavior and the complex neuronal responses remains unclear. Here we use simultaneous recordings from hundreds of neurons, together with an unsupervised, deep learning-based method, to discover decision-related neural dynamics in frontal cortex and striatum of rats while the subjects accumulate pulsatile auditory evidence. We found that trajectories evolved along two sequential regimes, the first dominated by sensory inputs, and the second dominated by the autonomous dynamics, with flow in a direction (i.e., “neural mode”) largely orthogonal to that in the first regime. We propose that the transition to the second regime corresponds to the moment of decision commitment. We developed a simplified model that approximates the coupled transition in dynamics and neural mode and allows precise inference, from each trial’s large-scale neural population activity, of a putative neurally-inferred time of commitment (“nTc”) on that trial. The simplified model captures diverse and complex single-neuron temporal profiles, such as ramping and stepping ^3–5 , as well as trial-averaged curved trajectories ^6–8 , and reveals distinctions between brain regions. The estimated nTc times were not time-locked to stimulus onset or offset, or to response onset, but were instead broadly distributed across trials. If nTc marks the moment of decision commitment, sensory evidence before nTc should affect the decision, while evidence afterward should not. Behavioral analysis of trials aligned to their estimated nTc times confirmed this prediction. Our results show that the formation of a perceptual choice involves a rapid, coordinated transition in both the dynamical regime and the neural mode of the decision process that corresponds to commitment to a decision, and suggest this moment as a useful entry point for dissecting mechanisms underlying rapid changes in internal state.

SUMMARY: Historically, cognitive processing has been thought to rely on cortical areas such as prefrontal cortex (PFC), with the outputs of these areas modulating activity in lower, putatively simpler spatiomotor regions, such as the midbrain superior colliculus (SC). Using a rat task in which subjects switch rapidly between task contexts that demand changes in sensorimotor mappings, we report a surprising role for the SC in non-spatial cognitive processes. Before spatial response choices could be formed, neurons in SC encoded task context more strongly than neurons in PFC, and bilateral SC silencing impaired behavioral performance. Once spatial choices could begin to be formed, SC neurons encoded the choice faster than PFC, while bilateral SC silencing no longer impaired choices. A set of dynamical models of the SC replicates our findings. Our results challenge cortically-focused views of cognition, and suggest that ostensibly spatiomotor structures can play central roles in non-spatiomotor cognitive processes.

How our brains measure the passage of time is still largely open for debate. One behavioral task commonly used to study how durations are perceived is the Temporal Bisection Task, in which subjects categorize time durations as either “short” or “long.” The duration equally likely to be categorized as short or long is known as the bisection point. It has been consistently demonstrated that for humans, the bisection point is near the arithmetic mean of the longest and shortest durations the subject was trained on. In contrast, for non-human subjects it has been consistently found near the geometric mean. This difference implies that humans may process or represent temporal durations differently than other species. Here we present a behavioral model that reconciles the differences by demonstrating that rats’ performance on this task is driven not only by their noisy estimates of duration, but also by the temporally-discounted value of future rewards. The model correctly predicts shifts in the bisection point induced by unequal rewards and explains otherwise-paradoxical psychometric reversals documented three decades ago. Furthermore, as predicted by the model, we found that modifying the Temporal Bisection Task to eliminate the temporally-discounted reward component shifted the rats’ bisection point from the geometric mean to the arithmetic mean, thus bringing the rat results into line with the human results. We therefore propose that humans and rats (and perhaps other non-human subjects as well) process temporal information similarly, and that the difference between them in the Temporal Bisection Task may be simply due to rats weighing temporal discounting of future rewards more strongly than humans.

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.

Many models of cognition and of neural computations posit the use and estimation of prior stimulus statistics ^1–4 : it has long been known that working memory and perception are strongly impacted by previous sensory experience, even when that sensory history is irrelevant for the current task at hand. Nevertheless, the neural mechanisms and brain regions necessary for computing and using such priors are unknown. Here we report that the posterior parietal cortex (PPC) is a critical locus for the representation and use of prior stimulus information. We trained rats in an auditory Parametric Working Memory (PWM) task, and found that rats displayed substantial and readily quantifiable behavioral effects of sensory stimulus history, similar to those observed in humans ^5,6 and monkeys ⁷ . Earlier proposals that PPC supports working memory ^8,9 predict that optogenetic silencing of this region would impair behavior in our working memory task. Contrary to this prediction, silencing PPC significantly improved performance. Quantitative analyses of behavior revealed that this improvement was due to the selective reduction of the effects of prior sensory stimuli. Electrophysiological recordings showed that PPC neurons carried far more information about sensory stimuli of previous trials than about stimuli of the current trial. Furthermore, the more information about previous trial sensory history in the neural firing rates of a given rat’s PPC, the greater the behavioral effect of sensory history in that rat, suggesting a tight link between behavior and PPC representations of stimulus history. Our results indicate that the PPC is a central component in the processing of sensory stimulus history, and open a window for neurobiological investigation of long-standing questions regarding how perception and working memory are affected by prior sensory information.

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.