Biology subjects

Caetano, M. S.

Publications and source records attributed to Caetano, M. S..

8 recordsLinked to original sources

bioRxiv2026

Evidence for timing in the midsession reversal task with rats in operant conditioning boxes

The midsession reversal (MSR) task is frequently used to study behavioral flexibility and decision strategies in animals. In a typical version of the task, subjects complete 80 trials in which they choose between two simultaneously presented stimuli, S1 and S2. During the first 40 trials, responses to S1 are reinforced, whereas responses to S2 are not. The contingencies then reverse without warning: From trial 41 to 80, only responses to S2 are reinforced. In birds, performance in this task is often characterized by anticipatory and perseverative errors around the reversal point, suggesting a reliance on elapsed time since the session began. In contrast, rats tested in operant conditioning chambers typically show near-optimal performance with few errors, a pattern often interpreted as evidence that rats rely primarily on local reinforcement cues rather than temporal information. The present study investigated whether rats exclusively rely on local cues in the MSR task or whether temporal information also contributes to the decision process. Two groups of rats were trained with different intertrial intervals (ITIs; 5 s or 10 s) while the reversal point remained fixed at Trial 41. During acquisition, both groups diplayed similar learning rates and near-optimal steady-state performance with minimal anticipatory or perseverative errors. However, when the ITI was manipulated in probe sessions, systematic shifts in switching behavior emerged. Rats adjusted their choices according to the temporal midpoint experienced during training rather than the nominal trial number of the reversal. These results suggest that rats rely on a mixed strategy that integrates local reinforcement cues with global timing information. Temporal control may therefore be present even when it is not expressed during standard training conditions.

animal behavior and cognition↗

bioRxiv2020

Time-Encoding Migrates from Prefrontal Cortex to Dorsal Striatum During Learning of a Self-Timed Response Duration Task

Although time is a fundamental dimension of life, we do not know how the brain encodes the temporal information. Several brain areas underlie the temporal information, such as the hippocampus, prefrontal cortex, and striatum, but evidence of how they cooperate to process temporal information is scarce. Notably, the analysis of neural activity during learning are rare, mainly because timing tasks usually take a long time to train. Here we investigated how the time encoding evolves when animals learn to time a 1.5 s interval. We designed a novel training protocol where rats go from naive- to proficient-level timing performance within a single session, allowing us to investigate neuronal activity from very early learning stages. We used pharmacological experiments and machine-learning algorithms to evaluate the level of time encoding in the medial prefrontal cortex and the dorsal striatum. Our results show a double dissociation between the roles of the medial prefrontal cortex and the dorsal striatum during temporal learning, where the former commits to early learning stages while the latter become more engaged as animals become more proficient in the task.

neuroscience↗

bioRxiv2020

Omics-Based Interaction Framework - a systems model to reveal molecular drivers of synergy

Bioactive molecule library screening strategies may empirically identify effective combination therapies. However, without a systems theory to interrogate synergistic responses, the molecular mechanisms underlying favorable drug-drug interactions remain unclear, precluding rational design of combination therapies. Here, we introduce Omics-Based Interaction Framework (OBIF) to reveal molecular drivers of synergy through integration of statistical and biological interactions in supra-additive biological responses. OBIF performs full factorial analysis of feature expression data from single vs. dual factor exposures to identify molecular clusters that reveal synergy-mediating pathways, functions and regulators. As a practical demonstration, OBIF analyzed a therapeutic dyad of immunostimulatory small molecules that induces synergistic protection against influenza A pneumonia. OBIF analysis of transcriptomic and proteomic data identified biologically relevant, unanticipated cooperation between RelA and cJun that we subsequently confirmed to be required for the synergistic antiviral protection. To demonstrate generalizability, OBIF was applied to data from a diverse array of Omics platforms and experimental conditions, successfully identifying the molecular clusters driving their synergistic responses. Hence, OBIF is a phenotype-driven systems model that supports multiplatform exploration of synergy mechanisms.

systems biology↗

bioRxiv2019

Temporal regularity and stimulus control in multiple fixed interval schedules

In multiple fixed interval schedules of reinforcement, different time intervals are signaled by different environmental stimuli which acquire control over behavior. Previous work has shown that temporal performance is controlled not only by external stimuli but also by temporal aspects of the task, depending on the order in which the different intervals are trained - intermixed across trials or in blocks of several trials. The aim of this study was to further describe the training conditions under which the stimuli acquire control over temporal performance. We manipulated the number of consecutive trials of each fixed interval (FI) per training block (Experiment I) and the number of FIs trained (Experiment II). The results suggest that when trained in blocks of several consecutive trials of the same FI, temporal performance is controlled by temporal regularities across trials and not by the visual stimuli that signal the FIs. One possible account for those data is that the temporal cues overshadow the visual stimuli for the control of temporal performance. Similar results have also been observed with humans, which suggest that temporal regularity overcomes the stimuli in the control of behavior in temporal tasks across species.

animal behavior and cognition↗

bioRxiv2019

Differences in perceived duration between plausible biological and non-biological stimuli

Visual motion stimuli can sometimes distort our perception of time. This effect is dependent on the apparent speed of the moving stimulus, where faster stimuli are usually perceived lasting longer than slower stimuli. Although it has been shown that neural and cognitive processing of biological motion stimuli differ from non-biological motion stimuli, no study has yet investigated whether perceived durations of biological stimuli differ from non-biological stimuli across different speeds. Here, a prospective temporal reproduction task was used to assess that question. Biological motion stimuli consisted in a human silhouette running in place. Non-biological motion stimuli consisted in a rectangle moving in a pendular way. Amount and plausibility of movement for each stimulus and frame-rate (speed) were evaluated by an independent group of participants. Although amount of movement was positively correlated to frame rate, movie clips involving biological motion stimuli were judged to last longer than non-biological motion stimuli only at frame rates in which movement was rated as plausible. These results suggest that plausible representations of biomechanical movement induce additional temporal distortions to those modulated by increases in stimulus speed. Moreover, most studies that have reported neural and cognitive differences in the processing of biological and non-biological motion stimuli acquired neurophysiological data using fMRI. The present study aimed additionally to report differences in the processing of biological and non-biological motion stimuli across different speeds using functional near infrared spectroscopy (fNIRS), a less costly and portable form of neurophysiological data acquisition.

neuroscience↗

bioRxiv2019

Dissociating decisional and temporal information in interval categorisation

Interval timing is fundamental for humans and non-human animals to interact with their environment. Several studies that investigate temporal processing combine behavioural tasks with neurophysiological methods, such as electrophysiological recordings (EEG). However, in the majority of these studies, it is hard to dissociate whether EEG activity reflects temporal or decisional information. In the present study, we investigated how time and decision is encoded in the EEG signal while human participants performed a temporal categorisation task with two different temporal references. Using a combination of evoked potentials and multivariate pattern analysis, we show that: (1) During the interval to-be-timed, both temporal and decisional information are encoded; (2) Activity evoked by the end of the interval encodes almost exclusively decisional information. These results suggest that decisional aspects of the task better explain EEG activity commonly related to temporal processing. The interplay between the encoding of time and decision is consistent with recent proposals that approximate temporal processing with decisional models.

neuroscience↗

bioRxiv2018

A Model for the Peak-Interval Task Based on Neural Oscillation Delimited States

Timing mechanisms in the brain are still an open issue. Several existing computational models for timing can reproduce properties of experimental psychophysical responses. Still, only a few consider the underlying biological mechanisms, such as the synchronized neural activity that occurs in several brain areas. In this paper, we introduce a model for the peak-interval task based on neuronal network properties. We consider that Local Field Potential (LFP) oscillation cycles specify a sequence of states, represented as neuronal ensembles. Repeated presentation of time intervals during training reinforces the connections of specific ensembles to downstream networks. Later, during the peak-interval procedure, these downstream networks are reactivated by previously experienced neuronal ensembles, triggering actions at the learned time intervals. The model reproduces experimental response patterns from individual rats in the peak-interval procedure, satisfying relevant properties such as the Weber law. Finally, the model provides a biological interpretation of its parameters.

animal behavior and cognition↗

bioRxiv2017

A common representation of time across visual andauditory modalities

Humans and non-human animals ability to process time on the scale of milliseconds and seconds is essential for adaptive behaviour. A central question of how brains keep track of time is how specific temporal information across different sensory modalities is. In the present study, we show that encoding of temporal intervals in auditory and visual modalities are qualitatively similar. Human participants were instructed to reproduce intervals in the range from 750 ms to 1500 ms marked by auditory or visual stimuli. Our behavioural results suggest that, although participants were more accurate in reproducing intervals marked by auditory stimuli, there was a strong correlation in performance between modalities. Using multivariate pattern analysis in scalp EEG, we show that activity during late periods of the intervals was similar within and between modalities. Critically, we show that a multivariate pattern classifier was able to accurately predict the elapsed interval, even when trained on an interval marked by a stimulus of a different sensory modality. Taken together, our results suggest that, while there are differences in the processing of intervals marked by auditory and visual stimuli, they also share a common neural representation.

neuroscience↗