Distributed coding of duration in rodent prefrontal cortex during time reproduction

As we interact with the external world, we judge magnitudes from sensory information. The estimation of magnitudes has been characterized in primates, yet it is largely unexplored in non-primate species. Here we use time interval reproduction to study rodent behavior and its neural correlates in the context of magnitude estimation. We show that gerbils display primate-like magnitude estimation characteristics in time reproduction. Most prominently their behavioral responses show a systematic overestimation of small stimuli and an underestimation of large stimuli, often referred to as regression effect. We investigated the underlying neural mechanisms by recording from medial prefrontal cortex and show that the majority of neurons respond either during the measurement or the reproduction of a time interval. Cells that are active during both phases display distinct response patterns. We categorize the neural responses into multiple types and demonstrate that only populations with mixed responses can encode the bias of the regression effect. These results help unveil the organizing neural principles of time reproduction and perhaps magnitude estimation in general.

Estimating COVID-19 pandemic severity in Indian context

The case fatality rate (CFR) represents one of the most vital factors in demonstrating the severity of novel infectious disease, COVID-19. Various estimates of COVID-19 fatalities (based on the publicly and published information and data in Indian context of COVID-19): confirmed CFR, asymptomatic CFR, symptomatic CFR, and hospitalized CFR were 2.32% (2.05-2.59), 0.14% (0.12-0.16), 0.32% (0.27-0.36), 1.86% (1.64-2.07) respectively. The relative susceptibility of developing symptoms (RSODS) and relative susceptibility of developing infection (RSODI) of COVID-19 were ~33 times higher among people aged <45 years. The RSODS estimates were 1.97 (0.47-3.47), 0.62 (0.15-1.09), 0.29 (0.07-0.52), 0.06 (0.02-0.10) respectively, for patients <45 years, 45-60, 60-75, >75 years. Similar trend, for RSODI were found, with relatively higher value, compared to RSODS, which decreased with the increase of age. The 14-day lag estimate of CFR were 18.07 (15.67-20.47), and outcome (deaths plus recoveries)-based estimate of CFR were 16.57 (14.65-18.49). The growth rate, serial interval, reproduction number and average time from onset of COVID-19 infection to death were 6.12% (5.30%-6.99%), 11.4 days (9.91-12.85), 1.03 (1.01-1.05), and 11.85 days (10.55-13.15), respectively. Among 1,673,688 samples tested, 62,939 (3.76%) were positive for COVID-19 accounting 1,228 tests per million population of India, as of May 10, 2020. The average daily recovery was 19.45% (14.75- 24.15) and average cumulative recovery was 12.68% (10.70- 14.66) among COVID-19 patients. As per our belief and knowledge, this is the first study of its kind in reporting COVID-19 severity in Indian context during pandemic.

Distributed coding of stimulus magnitude across the rodent prefrontal cortex

As we interact with the external world, we judge magnitudes from sensory information. The estimation of magnitudes has been characterized in primates, yet it is largely unexplored in non-primate species. Here, we show that gerbils that solve a time-interval reproduction task display primate-like magnitude estimation characteristics, most prominently a systematic overestimation of small stimuli and an underestimation of large stimuli, often referred to as regression effect. We investigated the underlying neural mechanisms by recording from medial prefrontal cortex and show that the majority of neurons respond either during the measurement or the reproduction of a time-interval. Cells that are active during both phases display distinct response patterns. We categorize the neural responses into multiple types and demonstrate that only populations with mixed responses can encode the bias of the regression effect. These results reveal the organizing neural principles of an important higher cognitive function.

Temporal context actively shapes EEG signatures of time perception

Our subjective perception of time is optimized to temporal regularities in the environment. This is illustrated by the central tendency effect: when estimating a range of intervals, short intervals are overestimated whereas long intervals are underestimated to reduce the overall estimation error. Most models of interval timing ascribe this effect to the weighting of the current interval with previous memory traces after the interval has been perceived. Alternatively, the perception of the duration could already be flexibly tuned to its temporal context. We investigated this hypothesis using an interval reproduction task with a shorter and longer interval range. As expected, reproductions were biased towards the subjective mean of each presented range. EEG analysis showed that temporal context affected neural dynamics during the perception phase. Specifically, longer previous durations decreased CNV and P2 amplitude and increased beta power. In addition, multivariate pattern analysis showed that it is possible to decode context from the transient EEG signal quickly after the onset and offset of the perception phase. Together, these results suggest that temporal context creates dynamic expectations which actively affect the perception of duration.Significance StatementThe subjective sense of duration does not arise in isolation, but is informed by previous experiences. This is demonstrated by abundant evidence showing that duration estimates are biased towards previously perceived time intervals. However, it is yet unknown whether this temporal context actively affects perception or asserts its influence in later, post-perceptual stages as proposed by most current formal models of this task. Using an interval reproduction task, we here show that EEG signatures flexibly adapt to the temporal context during perceptual encoding. Furthermore, interval history could be decoded from the transient EEG signal even when the current duration was identical. All in all, our results suggest that context actively influences perception.

A neural circuit model for human sensorimotor timing

ABSTRACTHumans can rapidly and flexibly coordinate their movements with external stimuli. Theoretical considerations suggest that this flexibility can be understood in terms of how sensory responses reconfigure the neural circuits that control movements. However, because external stimuli can occur at unexpected times, it is unclear how the corresponding sensory inputs can be used to exert flexible control over the ongoing activity of recurrent neural circuits. Here, we tackle this problem in the domain of sensorimotor timing and develop a circuit-level model that provides insight into how the brain coordinates movement times with expected and unexpected temporal events. The model consists of two interacting modules, a motor planning module that controls movement times and a sensory anticipation module that anticipates external events. Both modules harbor a reservoir of latent dynamics and their interaction forms a control system whose output is adjusted adaptively to minimize timing errors. We show that the model’s output matches human behavior in a range of tasks including time interval production, periodic production, synchronization/continuation, and Bayesian time interval reproduction. These results demonstrate how recurrent interactions in a simple and modular neural circuit could create the dynamics needed to control temporal aspects of behavior.

Differences in auditory timing between human and nonhuman primates

The gradual audiomotor evolution hypothesis is proposed as an alternative interpretation to the auditory timing mechanisms discussed in Ackermann et al.'s article. This hypothesis accommodates the fact that the performance of nonhuman primates is comparable to humans in single-interval tasks (such as interval reproduction, categorization, and interception), but shows differences in multiple-interval tasks (such as entrainment, synchronization, and continuation).