The nucleus accumbens shell (NAc-S) and its projections to the ventral pallidum (VP) are thought to be critical for stimulus-based decisions. The NAc-S is predominantly composed of spiny projection neurons (SPNs) that express either the dopamine D1 (D1-SPNs) or the dopamine D2 receptor (D2-SPNs). Yet, the role of these two neuronal subpopulations and their inputs to the VP in stimulus-based decisions remains unknown. Here, we used optogenetics in female and male knock-in rats to selectively silence D1- or D2-SPNs and their projections to the VP at a time when the rats were required to use predictive stimuli to choose between two instrumental actions. Silencing either population of NAc-S SPNs disrupted choice. Silencing NAc-S D1-SPNs terminals in the VP also disrupted choice. However, choice was left intact by silencing NAc-S D2-SPNs terminals in the VP. Together, these findings provide novel insights into the cellular mechanisms and circuitry underlying stimulus-based decisions. We discuss how these insights are consistent with a recent model proposing that these decisions are controlled by an opioid-based memory system residing in the NAc-S.

The nucleus accumbens shell (NAc-S) and its projections to the ventral pallidum (VP) are thought to be critical for stimulus-based decisions. The NAc-S is predominantly composed of spiny projection neurons (SPNs) that express either the dopamine D1 (D1-SPNs) or the dopamine D2 receptor (D2-SPNs). Yet, the role of these two neuronal subpopulations and their inputs to the VP in stimulus-based decisions remains unknown. Here, we used optogenetics in female and male knock-in rats to selectively silence D1- or D2-SPNs and their projections to the VP at a time when the rats were required to use predictive stimuli to choose between two instrumental actions. Silencing either population of NAc-S SPNs disrupted choice. Silencing NAc-S D1-SPNs terminals in the VP also disrupted choice. However, choice was left intact by silencing NAc-S D2-SPNs terminals in the VP. Together, these findings provide novel insights into the cellular mechanisms and circuitry underlying stimulus-based decisions. We discuss how these insights are consistent with a recent model proposing that these decisions are controlled by an opioid-based memory system residing in the NAc-S.

The nucleus accumbens shell (NAc-S) and its projections to the ventral pallidum (VP) are thought to be critical for stimulus-based decisions. The NAc-S is predominantly composed of spiny projection neurons (SPNs) that express either the dopamine D1 (D1-SPNs) or the dopamine D2 receptor (D2-SPNs). Yet, the role of these two neuronal subpopulations and their inputs to the VP in stimulus-based decisions remains unknown. Here, we used optogenetics in female and male knock-in rats to selectively silence D1- or D2-SPNs and their projections to the VP at a time when the rats were required to use predictive stimuli to choose between two instrumental actions. Silencing either population of NAc-S SPNs disrupted choice. Silencing NAc-S D1-SPNs terminals in the VP also disrupted choice. However, choice was left intact by silencing NAc-S D2-SPNs terminals in the VP. Together, these findings provide novel insights into the cellular mechanisms and circuitry underlying stimulus-based decisions. We discuss how these insights are consistent with a recent model proposing that these decisions are controlled by an opioid-based memory system residing in the NAc-S.

BackgroundThe cognitive control of action reflects our ability to extract and encode causal relationships between environmental events and to use that information to guide decision-making and, ultimately, our choice between different courses of action. Dysfunction in this capacity accompanies many major psychiatric conditions and neurodegenerative disorders. It is also powerfully affected by exposure to various drugs in a manner that precipitates the poor decision-making associated with addiction.Aims & ObjectivesTo understand this process at both a psychological and a neural level we have adopted a model of cognitive control in animals in which the influence of predictive learning on action selection is assessed in an instrumental choice situation: the Pavlovian-instrumental transfer paradigm. We have been systematically investigating the core neural systems and cellular circuits that mediate this effect, and, in this presentation, I will describe recent evidence for a key modulatory neural circuit in the brain involved in this process.MethodTo investigate this circuit we used circuit-specific tools, including DREADDs, ontogenetic and ex-vivo electrophysiology to characterise specific connectivity and its functional role in choice and decision-making.ResultsUsing these methods we established that this modulatory circuit links key structures involved in predictive learning with those that select and implement specific actions including infra limbic cortex, the ventral striatum, ventral palladium, mediodorsal thalamus and lateral orbitofrontal cortex in a cortico-striato-pallidal-thalamo-cortical feedback loop. Increasing and decreasing activity in this loop respectively caused an increase and decrease in the capacity for predictive learning to influence choice.Discussion & ConclusionsWe believe that this loop constitutes an essential component of the interface between cognition and emotion and that dysfunction, specifically in the modulatory function of this loop, underlies deficits in decision-making in a number of conditions, most notably obsessive compulsive disorder, addiction and psychosis.

Comprehensive genomic characterization uncovers maintained and gained alterations during evolution from intestinal metaplasia to gastric cancer, which could serve as predictive biomarkers to identify individuals at high risk of developing cancer.

The mental condition is closely linked with peoples instrumental behavior, which allows us to adapt to the external environment. Rely on the positive valence system, the habits and goal or value seeking behavior is linked with the instrumental behavior and the influence of environmental cues. While depression patients build up an aversive Pavlovian-instrumental transfer and form a biased emotional state. The Pavlovian-to-instrumental transfer (PIT) was influenced by the environment and was reflected in biological chemistry level. Also, in the safety learning and exposure therapy, instrumental behavior has become a fundamental factor of generation of safety signals to help ease fear and anxiety. It makes exposure therapy possible. All of them are revealing that by changing instrumental behavior, it may be able to change patients mental condition and contribute to depression therapy. In the future, simple and effective instrumental behavior may be able to get into therapy and recover procedure of all kinds of mental disorders.

Anticipating rewards is fundamental for decision-making. Animals often use cues to assess reward availability and to make predictions about future outcomes. The gustatory region of the insular cortex (IC), the so-called gustatory cortex, has a well-established role in the representation of predictive cues, such that IC neurons encode both a general form of outcome expectation and anticipatory outcome-specific knowledge. Here, we used pavlovian-instrumental transfer (PIT) in male rats to assess if the IC is also required for predictive cues to exert both a general and specific influence over instrumental actions. Chemogenetic inhibition of IC impaired the ability of a reward-predictive stimulus to energize instrumental responding for reward. This deficit in general transfer was evident whether the same or different outcomes were used in the pavlovian and instrumental conditioning phases. We observed a similar deficit in specific PIT, such that rats with IC inhibition failed to use a reward-predictive stimulus to guide choice toward actions that deliver the same food reward. Finally, we show that rats with IC inhibition also fail to show outcome-selective reinstatement. Together, these data suggest a crucial role for IC in the representation of appetitive outcomes and particularly in using this representation to guide instrumental action.

A stimulus that predicts the delivery of a specific food outcome can bias performance towards instrumental actions that earn that same outcome in a phenomenon known as specific Pavlovian-instrumental transfer (PIT). The precise mechanism by which the specific instrumental action is selected under these circumstances has remained elusive. The present set of experiments explored whether treatments that undermine the response-outcome (R-O) association also affect the expression of specific PIT. Consistent with previous work, in Experiment 1 we showed that specific PIT remains intact after an instrumental degradation treatment that attempted to undermine R-O associations. However, we additionally demonstrated that outcome-devaluation sensitivity also persisted after degradation, suggesting that R-O associations were impervious to the degradation treatment, and precluding any conclusions about the necessity of R-O associations for specific PIT expression. Nevertheless, given the two-lever two-outcome design of this experiment it is possible that R-O associations were indeed undermined by degradation and that the devaluation effect was driven by distinct, incidental Pavlovian lever-outcome associations. To nullify the obscuring effects of these incidental Pavlovian associations, we used a bidirectional lever for instrumental conditioning that could be pushed to the left or the right for distinct outcomes. In Experiment 2 we demonstrated that specific PIT could be observed on this bidirectional manipulandum whether the subjects were hungry or sated, consistent with the literature. The critical third Experiment used an identical design to Experiment 1 except that the two instrumental responses were made on the single bidirectional manipulanda. Here, specific PIT was intact after instrumental degradation and, crucially, we saw no evidence of outcome devaluation sensitivity in these same subjects, suggesting that the R-O associations were weakened or undermined by this treatment. We conclude that the expression of specific PIT is resistant to treatments that undermine R-O associations and disrupt value based choice, and discuss how these findings contribute to our understanding of the associative framework supporting behavioral control.

Modern living is characterized by easy access to highly palatable energy-dense foods. Environmental cues associated with palatable foods increase seeking of those foods (specific transfer) and other palatable foods (general transfer). We conducted a series of studies testing the boundaries of food cue-reactivity by evaluating the impact of broader flavor associations (i.e. saltiness, sweetness) in eliciting general transfer effects. Experiment 1 was an online experiment with fictive rewards that tested if two actions associated with different food rewards (chip and chocolate points) could be provoked by images of other foods that were either similar or distinct in flavor from the foods associated with these instrumental actions. We observed that response excitation was only elicited by similarly flavored food cues, whereas distinctly flavored food cues inhibited response rates relative to control cues. Experiment 2 confirmed this observation in a classroom setting where real food rewards were contingent on task performance. Experiment 3 was an online study that further confirmed the reliability of the effects with a well powered sample. There were moderate-to-strong associations between specific and general transfer effects across all studies, suggesting overlapping cognitive processes are responsible for both transfer effects. These data improve the mechanistic understanding of how broad category associations can moderate the impact of food cues on food choices. This knowledge could be helpful for improving the precision of psychological interventions that seek to mitigate the impact of food cue-reactivity.

Post-mortem fetal extrusion, also known as "coffin birth", refers to the phenomenon where a fetus is pushed out of a deceased female due to pressure from decomposing gas in the abdominal cavity. While post-mortem fetal extrusion has been documented in humans at several archaeological sites, there are few reports of it occurring in non-human animals. In this study, we present a case of post-mortem fetal extrusion in equids observed in a chariot-horse pit (CMK2) at the Western Zhou period site of Yaoheyuan in northwestern China, dating to the early first millennium BC. This specific pit, one of four excavated at the site, contained at least 29 horses and 3 wooden chariots. Most of these horses were young adults aged between 4 and 12 years. Out of the 22 horses with sex estimates, 21 were males. Among these individuals, one adult female horse (Horse 6) and one infantile horse (Horse 10) were of particular importance. Based on the age-at-death, sex, and head orientation of the two individuals, alongside their spatial relationships, it is highly likely that Horse 6 was the fetus of Horse 10 and was extruded in the pit. According to the parturition stage of Horse 10, Horse 6 was likely interred in CMK2 in late spring or early summer of the year, during which the relatively high temperature may have generated gas that led to the extrusion of the fetus. Although the specific reason for the inclusion of a pregnant mare in a chariot-horse pit at Yaoheyuan remains a topic for future research, this case marks the first report of post-mortem fetal extrusion in archaeological horses. The findings offer insights into the timing of horse interment as part of ritual practices among the settled elites during the Bronze Age in China and provide valuable reference data for contemporary equine veterinary science.

Recent research suggests that insufficient sleep elevates the risk of obesity. Although the mechanisms underlying the relationship between insufficient sleep and obesity are not fully understood, preliminary evidence suggests that insufficient sleep may intensify habitual control of behavior, leading to greater cue-elicited food-seeking behavior that is insensitive to satiation. The present study tested this hypothesis using a within-individual, randomized, crossover experiment. Ninety-six adults underwent a one-night normal sleep duration (NSD) condition and a one-night total sleep deprivation (TSD) condition. They also completed the Pavlovian-instrumental transfer paradigm in which their instrumental responses for food in the presence and absence of conditioned cues were recorded. The sleep × cue × satiation interaction was significant, indicating that the enhancing effect of conditioned cues on food-seeking responses significantly differed across sleep × satiation conditions. However, this effect was observed in NSD but not TSD, and it disappeared after satiation. This finding contradicted the hypothesis but aligned with previous literature on the effect of sleep disruption on appetitive conditioning in animals—sleep disruption following learning impaired the expression of appetitive behavior. The present finding is the first evidence for the role of sleep in Pavlovian-instrumental transfer effects. Future research is needed to further disentangle how sleep influences motivational mechanisms underlying eating.

A series of experiments employed a specific Pavlovian-instrumental transfer (PIT) task in rats to determine the capacity of various treatments to undermine two outcome-specific stimulus-outcome (S-O) associations. Experiment 1 tested a random treatment, which involved uncorrelated presentations of the two stimuli and their predicted outcomes. This treatment disrupted the capacity of the outcome-specific S-O associations to drive specific PIT. Experiment 2 used a negative-contingency treatment during which the predicted outcomes were exclusively delivered in the absence of their associated stimulus. This treatment spared specific PIT, suggesting that it left the outcome-specific S-O associations relatively intact. The same outcome was obtained in Experiment 3, which implemented a zero-contingency treatment consisting of delivering the predicted outcomes in the presence and absence of their associated stimulus. Experiment 4 tested a mixed treatment, which distributed the predicted outcomes at an equal rate during each stimulus. This treatment disrupted the capacity of the outcome-specific S-O associations to drive specific PIT. We suggest that the mixed treatment disrupted specific PIT by generating new and competing outcome-specific S-O associations. By contrast, we propose that the random treatment disrupted specific PIT by undermining the original outcome-specific S-O associations, indicating that these associations must be retrieved to express specific PIT. We discuss how these findings inform our theoretical understanding of the mechanisms underlying this phenomenon. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Supplemental Material for Stimulus–Outcome Associations Are Required for the Expression of Specific Pavlovian-Instrumental Transfer

In this study on healthy male mice using confocal imaging of dye spreading in the brain and its further accumulation in the peripheral lymphatics, we demonstrate stronger effects of photobiomodulation (PBM) on the brain's drainage system in sleeping vs. awake animals. Using the Pavlovian instrumental transfer probe and the 2-objects-location test, we found that the 10-day course of PBM during sleep vs. wakefulness promotes improved learning and spatial memory in mice. For the first time, we present the technology for PBM under electroencephalographic (EEG) control that incorporates modern state of the art facilities of optoelectronics and biopotential detection and that can be built of relatively cheap and commercially available components. These findings open a new niche in the development of smart technologies for phototherapy of brain diseases during sleep.

Ghrelin receptor antagonism and satiety attenuate Pavlovian-instrumental transfer

The mining planning and design were carried out in PT. Tanjung Alam Jaya, a coal mining company in South Kalimantan. The company intends to re-mine the Pit X area and requires a comprehensive mine planning approach to achieve its mining objectives. The study focuses on long-term planning, specifically optimizing the pit design while considering the company's specified stripping ratio limit and calculating the potential reserve volumes. The research aims to develop an optimized pit design and estimate the quantity of mineable reserves based on the optimization results. The findings include a mining layout design drawing and the calculated coal reserves that can be extracted from the optimized pit design. The excavation area spans 38.1 hectares, with excavation limits reaching a depth of -56 meters above sea level. The shape of the excavation extends from northeast to southwest, with a length of 1,065 meters and a variable width of 310 to 460 meters. The excavation features a slope height of 10 meters and a single slope angle of 65 degrees. Moreover, the haul road measures 21 meters in width with a 10% grade. The pit design indicates a total mineable coal reserve of 1,400,263.48 tons across all seams. Additionally, it reveals that 21,565,312.42 bcm of overburden / interburden must be stripped, resulting in a stripping ratio of 15.40 for the specific pit design. The haul road measures 21 meters in width with a 10% grade. In conclusion, this research demonstrates PT Tanjung Alam Jaya's efforts to optimize their pit design for re-mining in the Pit X area. The study provides valuable insights through a comprehensive mine planning approach, aiding the company in achieving their mining objectives while adhering to specified limits.

The Pavlovian-instrumental transfer (PIT) paradigm is widely used to assay the motivational influence of reward-predictive cues, reflected by their ability to invigorate instrumental behavior. Leading theories assume that a cue's motivational properties are tied to predicted reward value. We outline an alternative view that recognizes that reward-predictive cues may suppress rather than motivate instrumental behavior under certain conditions, an effect termed positive conditioned suppression. We posit that cues signaling imminent reward delivery tend to inhibit instrumental behavior, which is exploratory by nature, in order to facilitate efficient retrieval of the expected reward. According to this view, the motivation to engage in instrumental behavior during a cue should be inversely related to the value of the predicted reward, since there is more to lose by failing to secure a high-value reward than a low-value reward. We tested this hypothesis in rats using a PIT protocol known to induce positive conditioned suppression. In Experiment 1, cues signaling different reward magnitudes elicited distinct response patterns. Whereas the one-pellet cue increased instrumental behavior, cues signaling three or nine pellets suppressed instrumental behavior and elicited high levels of food-port activity. Experiment 2 found that reward-predictive cues suppressed instrumental behavior and increased food-port activity in a flexible manner that was disrupted by post-training reward devaluation. Further analyses suggest that these findings were not driven by overt competition between the instrumental and food-port responses. We discuss how the PIT task may provide a useful tool for studying cognitive control over cue-motivated behavior in rodents. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

We analyzed groundwater collected from 42 subdrain pits (wells) located around the reactor buildings of plant units #1 to #4 of the Tokyo Electric Power Company Fukushima Daiichi Nuclear Power Plant (F1-NPP) to understand the groundwater dynamics and water flows around F1-NPP. Since water samples collected from this small area exhibit very similar water quality, there are difficulties in understanding the flow dynamics of the groundwater using conventional chemical analyses. In this study, we clarified the groundwater flows using an altitude-modified principal component analysis (PCA) with a total of 798 data items (19 factors × 42 pits) in the chemical analyses. The PCA results showed that six specific pits deviated from the common values and that the others contained contributions from both the natural elements and radioactive nuclides. The groundwater flows under units #1–#4 into two flow lines originating from two main water sources were classified, and these lines merged around the bayside of unit #2 due to the lower groundwater head. This method proved suitable for elucidating the groundwater dynamics and water flows in this small area by the proposed altitude-modified PCA.

The Motivational Determinants of Human Action, Their Neural Bases and Functional Impact in Adolescents With Obsessive-Compulsive Disorder

Obsessive-compulsive disorder (OCD) is characterized by uncontrollable repetitive actions thought to rely on abnormalities within fundamental instrumental learning systems. We investigated cognitive and computational mechanisms underlying Pavlovian biases on instrumental behavior in both clinical OCD patients and healthy controls using a Pavlovian-Instrumental Transfer (PIT) task. PIT is typically evidenced by increased responding in the presence of a positive (previously rewarded) Pavlovian cue, and reduced responding in the presence of a negative cue. Thirty OCD patients and thirty-one healthy controls completed the Pavlovian Instrumental Transfer test, which included instrumental training, Pavlovian training for positive, negative and neutral cues, and a PIT phase in which participants performed the instrumental task in the presence of the Pavlovian cues. Modified Rescorla-Wagner models were fitted to trial-by-trial data of participants to estimate underlying computational mechanism and quantify individual differences during training and transfer stages. Bayesian hierarchical methods were used to estimate free parameters and compare the models. Behavioral and computational results indicated a weaker Pavlovian influence on instrumental behavior in OCD patients than in HC, especially for negative Pavlovian cues. Our results contrast with the increased PIT effects reported for another set of disorders characterized by compulsivity, substance use disorders, in which PIT is enhanced. A possible reason for the reduced PIT in OCD may be impairment in using the contextual information provided by the cues to appropriately adjust behavior, especially when inhibiting responding when a negative cue is present. This study provides deeper insight into our understanding of deficits in OCD from the perspective of Pavlovian influences on instrumental behavior and may have implications for OCD treatment modalities focused on reducing compulsive behaviors.