Hippocampal and lateral entorhinal cortex physiological activity during trace conditioning under urethane anesthesia.

Significant evidence shows that the acquisition of delay conditioning can occur in out-of-awareness states, such as under anesthesia. However, it is unclear to what extent and what type of conditioning animals may achieve during nonawake states. Trace conditioning is an appealing protocol to study under anesthesia, given the long empty gap separating the conditioned and unconditioned stimuli, which must be bridged for acquisition to happen. Here, we show evidence that rats develop physiological responses during the trace conditioning paradigm under anesthesia. We recorded the activity of the hippocampus (HPC) and lateral entorhinal cortex (LEC) in urethane-anesthetized rats, along with an electromyogram and an electrocardiogram. The protocol consisted of randomly presenting two distinct sound stimuli (CS- and CS+), where only one stimulus (CS+) was assigned to be trace-paired with a footshock. A trial-average analysis revealed that animals developed significant climbing heart rate activity initiating at the CS onset and persisting during the trace period. Such climbing arose for both CS- and CS+ with similar slopes but different intercepts, suggesting CS+ heart rates were typically above CS-. The power and coherence of HPC and LEC high-frequency bands (>100 Hz) significantly increased during CS presentation and trace, similarly to CS- and CS+ and insensitive to either activated or deactivated states. To the best of our knowledge, this is the first attempt to perform a trace conditioning protocol under anesthesia. Confirmation of this procedure acquisition can allow a new preparation for the exploration of brain mechanisms that bind time-discontinuous events.NEW & NOTEWORTHY Some forms of learning, such as some types of conditioning, can occur in anesthetized states. However, the extent to which memories can be formed in these states is still an open question. Here, we investigated the trace conditioning under urethane anesthesia and found heart rate, hippocampus, and lateral entorhinal cortex physiological changes to stimuli presentation. This new preparation may allow for exploration of memory acquisition of time-discontinuous events in the nonawake brain.

Low-cost open hardware system for behavioural experiments simultaneously with electrophysiological recordings.

A major frontier in neuroscience is to find neural correlates of perception, learning, decision making, and a variety of other types of behavior. In the last decades, modern devices allow simultaneous recordings of different operant responses and the electrical activity of large neuronal populations. However, the commercially available instruments for studying operant conditioning are expensive, and the design of low-cost chambers has emerged as an appealing alternative to resource-limited laboratories engaged in animal behavior. In this article, we provide a full description of a platform that records the operant behavior and synchronizes it with the electrophysiological activity. The programming of this platform is open source, flexible, and adaptable to a wide range of operant conditioning tasks. We also show results of operant conditioning experiments with freely moving rats with simultaneous electrophysiological recordings.

Rats can learn a temporal task in a single session.

Fixed interval, peak interval, and temporal bisection procedures have been used to assess cognitive functions and address questions such as how animals perceive, represent, and reproduce time intervals. They have also been extensively used to test the effects of drugs on behavior, and to describe the neural correlates of interval timing. However, those procedures usually require several weeks of training for behavior to stabilize. Here, we investigated a variation of the Differential Reinforcement of Response Duration (DRRD) task with a target time of 1.2 s. We compared three types of training protocols and reported a procedure in which performance by the end of the very first session nearly matches the performance of long-term training. We also showed that the initial distribution of the responses is uni-modal and, as training evolves (and rats improve their performance), a second peak emerges and progressively shifts toward longer times. This one-day training protocol can be used to investigate temporal learning and may be especially useful to electrophysiological and neuropharmacological studies.

A model for the peak-interval task based on neural oscillation-delimited states.

Specific mechanisms underlying how the brain keeps track of time are largely unknown. Several existing computational models of timing reproduce behavioral results obtained with experimental psychophysical tasks, but only a few tackle the underlying biological mechanisms, such as the synchronized neural activity that occurs throughout 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 - sets of neurons connected to the sequence of states. Later, during the peak-interval procedure, these downstream networks are reactivated by previously experienced neuronal ensembles, triggering behavioral responses 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, we provide a biological interpretation of the parameters of the model.

Low-frequency cortical oscillations are modulated by temporal prediction and temporal error coding.

Monitoring and updating temporal predictions are critical abilities for adaptive behavior. Here, we investigated whether neural oscillations are related to violation and updating of temporal predictions. Human participants performed an experiment in which they had to generate a target at an expected time point, by pressing a button while taking into account a variable delay between the act and the stimulus occurrence. Our behavioral results showed that participants quickly adapted their temporal predictions in face of an error. Concurrent electrophysiological (EEG) data showed that temporal errors elicited markers that are classically related to error coding. Furthermore, intertrial phase coherence of frontal theta oscillations was modulated by error magnitude, possibly indexing the degree of surprise. Finally, we found that delta phase at stimulus onset was correlated with future behavioral adjustments. Together, our findings suggest that low frequency oscillations play a key role in monitoring and in updating temporal predictions.

Visual Causality Judgments Correlate with the Phase of Alpha Oscillations.

The detection of causality is essential for our understanding of whether distinct events relate. A central requirement for the sensation of causality is temporal contiguity: As the interval between events increases, causality ratings decrease; for intervals longer than approximately 100 msec, the events start to appear independent. It has been suggested that this effect might be due to perception relying on discrete processing. According to this view, two events may be judged as sequential or simultaneous depending on their temporal relationship within a discrete neuronal process. To assess if alpha oscillations underlie this discrete neuronal process, we investigated how these oscillations modulate the judgment of causality. We used the classic launching effect with concurrent recording of EEG signal. In each trial, a disk moved horizontally toward a second disk at the center of the screen and stopped when they touched each other. After a delay that varied between 0 and 400 msec after contact, the right disk began to move. Participants were instructed to judge whether or not they had a feeling that the first disk caused the movement of the second disk. We found that frontocentral alpha phase significantly biased causality estimates. Moreover, we found that alpha phase was concentrated around different angles for trials in which participants judged events as causally related versus not causally related. We conclude that alpha phase plays a key role in biasing causality judgments.

A modeling approach on why simple central pattern generators are built of irregular neurons.

The crustacean pyloric Central Pattern Generator (CPG) is a nervous circuit that endogenously provides periodic motor patterns. Even after about 40 years of intensive studies, the rhythm genesis is still not rigorously understood in this CPG, mainly because it is made of neurons with irregular intrinsic activity. Using mathematical models we addressed the question of using a network of irregularly behaving elements to generate periodic oscillations, and we show some advantages of using non-periodic neurons with intrinsic behavior in the transition from bursting to tonic spiking (as found in biological pyloric CPGs) as building components. We studied two- and three-neuron model CPGs built either with Hindmarsh-Rose or with conductance-based Hodgkin-Huxley-like model neurons. By changing a model's parameter we could span the neuron's intrinsic dynamical behavior from slow periodic bursting to fast tonic spiking, passing through a transition where irregular bursting was observed. Two-neuron CPG, half center oscillator (HCO), was obtained for each intrinsic behavior of the neurons by coupling them with mutual symmetric synaptic inhibition. Most of these HCOs presented regular antiphasic bursting activity and the changes of the bursting frequencies was studied as a function of the inhibitory synaptic strength. Among all HCOs, those made of intrinsic irregular neurons presented a wider burst frequency range while keeping a reliable regular oscillatory (bursting) behavior. HCOs of periodic neurons tended to be either hard to change their behavior with synaptic strength variations (slow periodic burster neurons) or unable to perform a physiologically meaningful rhythm (fast tonic spiking neurons). Moreover, 3-neuron CPGs with connectivity and output similar to those of the pyloric CPG presented the same results.

What is learned during simultaneous temporal acquisition? An individual-trials analysis.

The processes involved in the acquisition of simultaneous temporal processing are currently less understood. For example, it is unclear whether scalar property emerges early during simultaneous temporal acquisition. Using an information-processing model which accounts for the amount of information that each temporal process provides in regard to reward time, we predicted that scalar property would emerge early during the acquisition process, but that subjects should take about 27% longer (more trials) to acquire the long duration than the short duration. To evaluate these predictions, we performed individual-trials analyses to identify changes in timing behavior when rats simultaneously acquire two criterion durations, either 10s and 20s (group 10/20) or 20s and 40s (group 20/40). To analyze the individual trials we used a change-point algorithm to identify changes in rats' wait time. For each individual rat, and for each criterion duration, analyses indicated that simultaneous temporal acquisition is characterized by a sudden change in waiting to a wait-time proportional to the associated criterion. The results failed to indicate group differences in regard to the number of trials it takes for the change in wait-time to occur, but that in both groups, it took longer (more trials) to acquire the long duration than the shorter one, not significantly different from the theoretical prediction. These results are discussed in the framework of an information-processing model informing both associative and temporal learning, thus providing a bridge between the two fields. This article is part of a Special Issue entitled: Associative and Temporal Learning.

Effects of chronic video game use on time perception: differences between sub- and multi-second intervals.

Even though video game players frequently report losing track of time while playing, few studies have addressed whether there are long-lasting effects of such activity on time perception. We compared the performance of chronic and occasional video game players in sub- and multi-second time perception tasks. Temporal Discrimination and Temporal Bisection tasks, in the range of 100 to 1,000 milliseconds, and Time estimation and Time production tasks, in the range of 5 to 60 seconds, were used to assess sub- and multi-second time perceptions, respectively. Chronic video game players performed significantly better than occasional players on sub-second tasks, but no group difference was found for the multi-second tasks used. Sub- and multi-second time perceptions are associated to different underlying systems: automatic and cognitive controlled for sub- and multi-second tasks, respectively. We argue that video game use seems to induce more efficient implicit, rather than cognitive controlled, processing of time.

Uso do procedimento de bissecção temporal na avaliação de idosos com doença de Alzheimer: uma revisão sistemática / Using the temporal bisection procedure in the evaluation of elderly with Alzheimer's disease: a systematic review

OBJETIVO: Realizar revisão sistemática de artigos que utilizaram o método de bissecção, para avaliar a percepção de tempo em idosos com doença de Alzheimer e analisar seus parâmetros. MÉTODO: As buscas dos artigos foram conduzidas no período de março a maio de 2011, nas seguintes bases de dados: Web of Science, Science Direct on Line, Biological Abstracts, PsychoInfo e Medline. As palavras-chave e operadores booleanos foram: "interval timing" ou "perception of time" ou "time discrimination" ou "reproduction of time" e "Alzheimer's disease". Também foram realizadas buscas manuais nas referências dos artigos selecionados. RESULTADOS: Quatro artigos contemplavam todos os critérios de inclusão, nos quais foram encontradas grandes variações nos parâmetros utilizados no método. CONCLUSÃO: Pacientes com doença de Alzheimer apresentam prejuízos nas tarefas de bissecção de tempo, que podem ser explicados pelo declínio gradual nas habilidades que são utilizadas no teste de percepção de tempo. Há grandes variações nos intervalos de tempo utilizados. Neste contexto, há necessidade de mais estudos, controlados e randomizados, para investigar potenciais efeitos das variações nos intervalos de tempo do método de bissecção. Os resultados de tais estudos poderão contribuir para o estabelecimento de parâmetros mais adequados e fidedignos.

OBJECTIVE: Perform a systematic review of articles that used the bisection time method to assess the perception of time in patients with Alzheimer's disease by means of the bisection-of-time method, and to analyze its parameters. METHOD: Searches were conducted from March to May, 2011, in the following databases: Web of Science, Science Direct On Line, Biological Abstracts, Medline and PsychoInfo. Keywords and boolean operators were: "interval timing" or "perception of time" or "time discrimination" or "reproduction of time" and "Alzheimer's disease". Additionally, a manual search was conducted in the references of the selected articles. RESULTS: Four studies fulfilled all inclusion criteria, and large variations in the parameters of the method were found. CONCLUSION: Patients with Alzheimer's disease show difficulty in performing the task of bisection of time, which can be explained by the gradual decline on the abilities required in the perception of time test. There are large variations regarding the time intervals applied in the method. In such context, controlled-and-randomized future studies are required, in order to investigate the potential effects of time-intervals variations in the bisection-of-time method. The results of such studies would contribute to establish most suitable and reliable parameters.

Connection topology selection in central pattern generators by maximizing the gain of information.

A study of a general central pattern generator (CPG) is carried out by means of a measure of the gain of information between the number of available topology configurations and the output rhythmic activity. The neurons of the CPG are chaotic Hindmarsh-Rose models that cooperate dynamically to generate either chaotic or regular spatiotemporal patterns. These model neurons are implemented by computer simulations and electronic circuits. Out of a random pool of input configurations, a small subset of them maximizes the gain of information. Two important characteristics of this subset are emphasized: (1) the most regular output activities are chosen, and (2) none of the selected input configurations are networks with open topology. These two principles are observed in living CPGs as well as in model CPGs that are the most efficient in controlling mechanical tasks, and they are evidence that the information-theoretical analysis can be an invaluable tool in searching for general properties of CPGs.