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Sign and goal tracker animals show different behavioral patterns in response to conditioned stimuli, which may be driven by different neural circuits involved in processing stimuli. Here, we explored whether sign and goal-tracker profiles implicated different brain regions and responses to incentive salience of stimuli. We performed three experiments using male Wistar rats. Experiment 1 showed that lesioning the medial prefrontal cortex increased the prevalence of the goal-tracker phenotype. Experiment 2 assessed the developmental trajectory of the salience incentive attribution to a conditioned stimulus, showing that increased incentive salience of stimuli increased the prevalence of the sign-tracker phenotype in mature, but not preadolescent rats. In experiment 3, the functional impact of the medial prefrontal cortex circuits was analyzed with a latent inhibition procedure. Sign tracker rats showed a reduced latent inhibition to stimuli previously exposed when compared to goal tracker or intermediate rats. The overall results of this study highlight a key role of the medial prefrontal cortex for sign tracking behavior. The expression of sign and goal tracker phenotypes changed after lesion to the medial prefrontal cortex (experiment 1), differed across development (experiment 2), and showed differences in the attentional processes to previously exposed stimuli, as preexposure to CS was ineffective in sign tracker animals (experiment 3). These data indicate that the responses to the incentive salience of stimuli in sign tracker and goal tracker profiles are likely driven by different neural circuitry, with a different role of prefrontal cortical function.

The paraventricular nucleus of the thalamus (PVT) has been implicated in cue-induced motivated behaviors. Although reward-associated cues (conditioned stimuli, CSs) contain different types of information including predictive information of future reward delivery and incentive (motivational) value of the reward, it remains unknown whether PVT neurons represent predictive and incentive information of CSs. It is suggested that neural activity just after the onset of CSs (early activity) and that just before reward delivery (late activity) might more strongly represent predictive and incentive information, respectively. In this study, rats were trained to lick a tube, which was protruded close to their mouth just after a CS, to obtain a reward (sucrose or water) (cue-induced licking task). Auditory and visual CSs were used: each elemental cue (CS) predicted reward or non-reward outcome, while simultaneous presentation of the two elemental cues (configural cues) predicted the opposite reward outcome. We recorded PVT neurons in the cue-induced licking task, and report that half of the CS-responsive PVT neurons responded selectively to the CSs predicting reward outcome regardless of physical property of the cues (CS+-selective). In addition, the early activity of the CS+-selective neurons discriminated reward/non-reward association (predictive information) and was less sensitive to reward value and motivation reflected by lick latency (incentive information), while the late activity of the CS+-selective neurons was correlated with reward value and motivation rather than reward/non-reward association. Early and late population activity of the CS+-selective neurons also represented predictive and incentive information of the CSs, respectively. On the other hand, activity of more than half of the PVT neurons was correlated with individual licking during licking to acquire reward. Taken together, the results suggest that the PVT neurons engage in different neural processes involved in cue-induced motivated behaviors: CS encoding to determine reward availability and form motivation for reward-seeking behavior, and hedonic mouth movements during reward consumption.

Recent studies support the idea that stimulus processing in latent inhibition can vary during the course of preexposure. Controlled attentional mechanisms are said to be important in the early stages of preexposure, while in later stages animals adopt automatic processing of the stimulus to be used for conditioning. Given this distinction, it is possible that both types of processing are governed by different neural systems, affecting differentially the retrieval of information about the stimulus. In the present study we tested if a lesion to the dorso-lateral striatum or to the medial prefrontal cortex has a selective effect on exposure to the future conditioned stimulus (CS). With this aim, animals received different amounts of exposure to the future CS. The results showed that a lesion to the medial prefrontal cortex enhanced latent inhibition in animals receiving limited preexposure to the CS, but had no effect in animals receiving extended preexposure to the CS. The lesion of the dorso-lateral striatum produced a decrease in latent inhibition, but only in animals with an extended exposure to the future conditioned stimulus. These results suggest that the dorsal striatum and medial prefrontal cortex play essential roles in controlled and automatic processes. Automatic attentional processes appear to be impaired by a lesion to the dorso-lateral striatum and facilitated by a lesion to the prefrontal cortex.

Currently the model of associative memory in mammals most frequently used in neurobiological studies consists of acquisition of a conditioned reflex freezing reaction. As most studies address the mechanisms of learning in response to a sound stimulus, the question of the extent to which the patterns of forming associative memory are universal and apply to other conditioned stimuli remains open. The aim of the present work was to compare the dynamics of the formation and reproduction of a memory in mice on acquisition of a conditioned freezing reaction to light and sound conditioned stimuli. Training using a light stimulus was found to occur in this model significantly more slowly than using a sound signal. In addition, the dynamics of memory reproduction differed in animals trained using sound and light stimuli, being slower using light stimuli, which may reflect different consolidation or extraction processes for these types of memory. The results of this study are critically important for understanding the common and specific conditions for the formation of associative memory in this model.

Concrete compressive strength (CS) is a crucial performance parameter in concrete structure design. Reliable strength prediction reduces costs and time in design and prevents material waste from extensive mixture trials. Machine learning techniques solve structural engineering challenges such as CS prediction. This study used Machine Learning (ML) models to enhance the prediction of CS, analyzing 1030 experimental CS data ranging from 2.33 to 82.60 MPa from previous research databases. The ML models included both non-ensemble and ensemble types. The non-ensemble models were regression-based, evolutionary, neural network, and fuzzy-inference-system. Meanwhile, the ensemble models consisted of adaptive boosting, random forest, and gradient boosting. There were eight input parameters: cement, blast-furnace-slag, aggregates (coarse and fine), fly ash, water, superplasticizer, and curing days, with the CS as the output. Comprehensive performance evaluations include visual and quantitative methods and k-fold cross-validation to assess the study’s reliability and accuracy. A sensitivity analysis using Shapley-Additive-exPlanations (SHAP) was conducted to understand better how each input variable affects CS. The findings showed that the Categorical-Gradient-Boosting (CatBoost) model was the most accurate prediction during the testing stage. It had the highest determination-coefficient (R 2 ) of 0.966 and the lowest Root-Mean-Square-Error (RMSE) of 3.06 MPa. The SHAP analysis showed that the age of the concrete was the most critical factor in the predictive accuracy. Finally, a Graphical User Interface (GUI) was offered for designers to predict concrete CS quickly and economically instead of costly computational or experimental tests.

Rationale Sensitization of the incentive and dopamine (DA) stimulant properties of drug-conditioned stimuli (CSs) by repeated exposure to drugs of abuse has been assigned an important role in the genesis of drug addiction. Objective To test in rats if morphine-induced sensitization potentiates incentive and DA-releasing properties in the nucleus accumbens (NAc) shell and core elicited by presentation of a morphine-conditioned stimulus(CS) and if this property generalizes to a non-drug-(palatable food, Fonzies)-CS. Methods Controls and rats previously sensitized by morphine were trained via three daily sessions consisting of a 10-min presentation of CS (Fonzies filled box, FB) followed by s.c. saline and morphine (1 mg/kg) or by standard food and Fonzies. Rats were implanted with microdialysis probes and the next-day incentive reactions and NAc shell and core DA were monitored during CS presentation and subsequent morphine (1 mg/kg) administration or Fonzies feeding. Results Morphine sensitization increased incentive and NAc shell and core DA responses to morphine-CS. Morphine conditioning per se increased incentive reactions and NAc shell but not core DA responses to FB presentation. Morphine sensitization potentiated incentive responses but did not affect NAc shell and core DA responses to Fonzies-CS. Fonzies conditioning increased incentive reactions and NAc core but not shell DA responses to FB presentation. Conclusions These observations confirm the prediction of the incentive sensitization theory in the case of drug-CS but not of non-drug-CS. NAc DA might be differentially involved in the expression of incentive sensitization of drug- and non-drug-CSs, thus providing a clue for the abnormal incentive properties of drug CSs.

Caesarean section (CS) rates continue to evoke worldwide concern because of their steady increase, lack of consensus on the appropriate CS rate and the associated additional short- and long-term risks and costs. We present the latest CS rates and trends over the last 24 years. We collected nationally-representative data on CS rates between 1990 to 2014 and calculated regional and subregional weighted averages. We conducted a longitudinal analysis calculating differences in CS rates as absolute change and as the average annual rate of increase (AARI). According to the latest data from 150 countries, currently 18.6% of all births occur by CS, ranging from 6% to 27.2% in the least and most developed regions, respectively. Latin America and the Caribbean region has the highest CS rates (40.5%), followed by Northern America (32.3%), Oceania (31.1%), Europe (25%), Asia (19.2%) and Africa (7.3%). Based on the data from 121 countries, the trend analysis showed that between 1990 and 2014, the global average CS rate increased 12.4% (from 6.7% to 19.1%) with an average annual rate of increase of 4.4%. The largest absolute increases occurred in Latin America and the Caribbean (19.4%, from 22.8% to 42.2%), followed by Asia (15.1%, from 4.4% to 19.5%), Oceania (14.1%, from 18.5% to 32.6%), Europe (13.8%, from 11.2% to 25%), Northern America (10%, from 22.3% to 32.3%) and Africa (4.5%, from 2.9% to 7.4%). Asia and Northern America were the regions with the highest and lowest average annual rate of increase (6.4% and 1.6%, respectively). The use of CS worldwide has increased to unprecedented levels although the gap between higher- and lower-resource settings remains. The information presented is essential to inform policy and global and regional strategies aimed at optimizing the use of CS.

Memory is coded by patterns of neural activity in distinct circuits. Therefore, it should be possible to reverse engineer a memory by artificially creating these patterns of activity in the absence of a sensory experience. In olfactory conditioning, an odor conditioned stimulus (CS) is paired with an unconditioned stimulus (US; for example, a footshock), and the resulting CS–US association guides future behavior. Here we replaced the odor CS with optogenetic stimulation of a specific olfactory glomerulus and the US with optogenetic stimulation of distinct inputs into the ventral tegmental area that mediate either aversion or reward. In doing so, we created a fully artificial memory in mice. Similarly to a natural memory, this artificial memory depended on CS–US contingency during training, and the conditioned response was specific to the CS and reflected the US valence. Moreover, both real and implanted memories engaged overlapping brain circuits and depended on basolateral amygdala activity for expression.Pairing an odor conditioned stimulus (CS) with an unconditioned stimulus (US) induces memory formation. Vetere et al. replace the real CS and US with direct optogenetic stimulation of the brain and create a fully artificial odor memory in mice.

Adding hooked industrial steel fibers (ISF) to concrete boosts its tensile and flexural strength. However, the understanding of ISF’s influence on the compressive strength (CS) behavior of concrete is still questioned by the scientific society. The presented paper aims to use machine learning (ML) and deep learning (DL) algorithms to predict the CS of steel fiber reinforced concrete (SFRC) incorporating hooked ISF based on the data collected from the open literature. Accordingly, 176 sets of data are collected from different journals and conference papers. Based upon the initial sensitivity analysis, the most influential parameters like water-to-cement (W/C) ratio and content of fine aggregates (FA) tend to decrease the CS of SFRC. Meanwhile, the CS of SFRC could be enhanced by increasing the amount of superplasticizer (SP), fly ash, and cement (C). The least contributing factors include the maximum size of aggregates (D max ) and the length-to-diameter ratio of hooked ISFs (L/D ISF ). Several statistical parameters are also used as metrics to evaluate the performance of implemented models, such as coefficient of determination (R 2 ), mean absolute error (MAE), and mean of squared error (MSE). Among different ML algorithms, convolutional neural network (CNN) with R 2  = 0.928, RMSE = 5.043, and MAE = 3.833 shows higher accuracy. On the other hand, K-nearest neighbor (KNN) algorithm with R 2  = 0.881, RMSE = 6.477, and MAE = 4.648 results in the weakest performance.

The conditioning of cocaine's pharmacological actions with environmental stimuli is thought to be a critical factor in long-lasting relapse risk associated with cocaine addiction. To study the significance of environmental stimuli in enduring vulnerability to relapse, the resistance to extinction of drug-seeking behavior elicited by a cocaine-related stimulus was examined. Male Wistar rats were trained to associate discriminative stimuli (SD) with the availability of intravenous cocaine (S+) vs. the availability of non-rewarding (S−) saline solution, and then placed on extinction conditions during which intravenous solutions and SD were withheld. The rats were then presented with the S+ or S− alone in 60-min reinstatement sessions conducted at 3-day intervals. To examine the long-term persistence of the motivating effects of the cocaine S+, a subgroup of rats was re-tested following an additional three months of abstinence during which time the rats remained confined to their home cages. Re-exposure to the cocaine S+ selectively elicited robust responding at the previously active lever. The efficacy and selectivity of this stimulus to elicit responding remained unaltered throughout a 34-day phase of repeated testing as well as following the additional extended abstinence period. In pharmacological tests, conducted in a separate group of rats, the dopamine (DA) D1 antagonist SCH 39166 (10 μg/kg), the D2/3 antagonist nafadotride (1 mg/kg), and the D2/3 agonist PD 128907 (0.3 mg/kg) suppressed the cue-induced response reinstatement while the D1 agonist SKF 81297 (1.0 mg/kg) produced a variable behavioral profile attenuating cue-induced responding in some rats while exacerbating this behavior in others. The results suggest that the motivating effects of cocaine-related stimuli are highly resistant to extinction. The undiminished efficacy of the cocaine S+ to induce drug-seeking behavior both with repeated testing and following long-term abstinence parallels the long-lasting nature of conditioned cue reactivity and cue-induced cocaine craving in humans, and confirms a significant role of learning factors in long-lasting vulnerability to relapse associated with cocaine addiction. Finally, the results support a role of DA neurotransmission in cue-induced cocaine-seeking behavior.