Sequential dependency for affective appraisal of food images

How we perceive the world is not solely determined by our experiences at a given moment in time, but also by what we have experienced in our immediate past. Here, we investigated whether such sequential effects influence the affective appraisal of food images. Participants from 16 different countries (N = 1278) watched a randomly presented sequence of 60 different food images and reported their affective appraisal of each image in terms of valence and arousal. For both measures, we conducted an inter-trial analysis, based on whether the rating on the preceding trial(s) was low or high. The analyses showed that valence and arousal ratings for a given food image are both assimilated towards the ratings on the previous trial (i.e., a positive serial dependence). For a given trial, the arousal rating depends on the arousal ratings up to three trials back. For valence, we observed a positive dependence for the immediately preceding trial only, while a negative (repulsive) dependence was present up to four trials back. These inter-trial effects were larger for males than for females, but independent of the participants’ BMI, age, and cultural background. The results of this exploratory study may be relevant for the design of websites of food delivery services and restaurant menus.

Choice-confirmation bias in reinforcement learning changes with age during adolescence

Confirmation bias, the widespread tendency to favour evidence that confirms rather than disconfirms one’s prior beliefs and choices, has been shown to play a role in the way decisions are shaped by rewards and punishment, known as confirmatory reinforcement learning. Given that exploratory tendencies change during adolescence, we investigated whether confirmatory learning also changes during this age. In an instrumental learning task, participants aged 11-33 years attempted to maximize monetary rewards by repeatedly sampling different pairs of novel options, which varied in their reward/punishment probabilities. Our results showed an age-related increase in accuracy with as long as learning contingencies remained stable across trials, but less so when they reversed halfway through the trials. Across participants, there was a greater tendency to stay with an option that had delivered a reward on the immediately preceding trial, more than to switch away from an option that had just delivered a punishment, and this behavioural asymmetry also increased with age. Younger participants spent more time assessing the outcomes of their choices than did older participants, suggesting that their learning inefficiencies were not due to reduced attention. At a computational level, these decision patterns were best described by a model that assumes that people learn very little from disconfirmatory evidence and that they vary in the extent to which they learn from confirmatory evidence. Such confirmatory learning rates also increased with age. Overall, these findings are consistent with the hypothesis that a discrepancy between confirmatory and disconfirmatory learning increases with age during adolescence.

Combined inhibition of CXCL12 and PD-1 in MSS colorectal and pancreatic cancer: modulation of the microenvironment and clinical effects

BackgroundImmunotherapy in microsatellite stable colorectal or pancreatic cancer has not shown promising results. It has been hypothesized that targeting immunosuppressive molecules like SDF1-alpha/CXCL12 could contribute to immunotherapy and animal models showed promising results on T cell activation and migration in combination with immune checkpoint inhibition.MethodsHere, we describe the successful application of anti-CXCL12 (NOX-A12) in patients with advanced stage pretreated metastatic colorectal and pancreatic cancer (OPERA trial). The treatment consisted of 2 weeks of anti-CXCL12 monotherapy with NOX-A12 followed by combination therapy with pembrolizumab (n=20 patients) until progression or intolerable toxicity had occurred.ResultsThe treatment was safe and well tolerated with 83.8% grade I/II, 15.5% grade III and 0.7% grade V adverse events. Of note, for a majority of patients, time on trial treatment was prolonged compared with their last standard treatment preceding trial participation. Systematic serial biopsies revealed distinct patterns of modulation. Tissue and clinical responses were associated with Th1-like tissue reactivity upon CXCL12 inhibition. A downregulation of a cytokine cassette of interleukin (IL)-2/IL-16/CXCL-10 was associated with tumor resistance and furthermore linked to a rare, CXCL12-associated CD14+CD15+promonocytic population. T cells showed aggregation and directed movement towards the tumor cells in responding tissues. Serum analyses detected homogeneous immunomodulatory patterns in all patients, regardless of tissue responses.ConclusionsWe demonstrate that the combination of CXCL12 inhibition and checkpoint inhibition is safe and grants further exploration of synergistic combinatorial strategies.

Inter-trial effects in priming of pop-out: Comparison of computational updating models

In visual search tasks, repeating features or the position of the target results in faster response times. Such inter-trial ‘priming’ effects occur not just for repetitions from the immediately preceding trial but also from trials further back. A paradigm known to produce particularly long-lasting inter-trial effects–of the target-defining feature, target position, and response (feature)–is the ‘priming of pop-out’ (PoP) paradigm, which typically uses sparse search displays and random swapping across trials of target- and distractor-defining features. However, the mechanisms underlying these inter-trial effects are still not well understood. To address this, we applied a modeling framework combining an evidence accumulation (EA) model with different computational updating rules of the model parameters (i.e., the drift rate and starting point of EA) for different aspects of stimulus history, to data from a (previously published) PoP study that had revealed significant inter-trial effects from several trials back for repetitions of the target color, the target position, and (response-critical) target feature. By performing a systematic model comparison, we aimed to determine which EA model parameter and which updating rule for that parameter best accounts for each inter-trial effect and the associated n-back temporal profile. We found that, in general, our modeling framework could accurately predict the n-back temporal profiles. Further, target color- and position-based inter-trial effects were best understood as arising from redistribution of a limited-capacity weight resource which determines the EA rate. In contrast, response-based inter-trial effects were best explained by a bias of the starting point towards the response associated with a previous target; this bias appeared largely tied to the position of the target. These findings elucidate how our cognitive system continually tracks, and updates an internal predictive model of, a number of separable stimulus and response parameters in order to optimize task performance.

A Bayesian Mixture Modelling of Stop Signal Reaction Time Distributions: The Second Contextual Solution for the Problem of Aftereffects of Inhibition on SSRT Estimations

The distribution of single Stop Signal Reaction Times (SSRT) in the stop signal task (SST) has been modelled with two general methods: a nonparametric method by Hans Colonius (1990) and a Bayesian parametric method by Dora Matzke, Gordon Logan and colleagues (2013). These methods assume an equal impact of the preceding trial type (go/stop) in the SST trials on the SSRT distributional estimation without addressing the relaxed assumption. This study presents the required model by considering a two-state mixture model for the SSRT distribution. It then compares the Bayesian parametric single SSRT and mixture SSRT distributions in the usual stochastic order at the individual and the population level under ex-Gaussian (ExG) distributional format. It shows that compared to a single SSRT distribution, the mixture SSRT distribution is more varied, more positively skewed, more leptokurtic and larger in stochastic order. The size of the results’ disparities also depends on the choice of weights in the mixture SSRT distribution. This study confirms that mixture SSRT indices as a constant or distribution are significantly larger than their single SSRT counterparts in the related order. This result offers a vital improvement in the SSRT estimations.

Between Joy and Sympathy: Smiling and Sad Recipient Faces Increase Prosocial Behavior in the Dictator Game

In human interactions, the facial expression of a bargaining partner may contain relevant information that affects prosocial decisions. We were interested in whether facial expressions of the recipient in the dictator game influence dictators’ behavior. To test this, we conducted an online study (n = 106) based on a modified version of a dictator game. The dictators allocated money between themselves and another person (recipient), who had no possibility to respond to the dictator. Importantly, before the allocation decision, the dictator was presented with the facial expression of the recipient (angry, disgusted, sad, smiling, or neutral). The results showed that dictators sent more money to recipients with sad or smiling facial expressions and less to recipients with angry or disgusted facial expressions compared with a neutral facial expression. Moreover, based on the sequential analysis of the decision and the interaction partner in the preceding trial, we found that decision-making depends upon previous interactions.

A Signal-seeking Phase Iia Trial of Palbociclib in Advanced Cancers With Cell Cycle Pathway Alterations – A Substudy of the Molecular Screening and Therapeutics (Most) Program

BACKGROUND: The D-type cyclin and cyclin dependent kinase 4/6 (CDK) complex phosphorylates retinoblastoma protein, thereby driving cell cycle progression. This process is blocked by inhibitors of CDK4/6. As part of the Molecular Screening and Therapeutics program, this phase IIa trial tested the clinical activity of CDK4/6 inhibitor monotherapy in tumors with cell cycle pathway alterations.PATIENTS AND METHODS: Eligible patients ≥ 18 years old, with advanced or metastatic solid cancers, along with amplification of CDK4/6, CCND1/2/3, or loss of function alterations in CDKN2A were recruited. The primary objective of this signal-seeking trial was to evaluate the clinical activity of palbociclib – a composite of objective responses and the ratio of time to progression (TTP) on palbociclib, to TTP on treatment preceding trial entry.RESULTS: Ten patients had CDK4/CDK6 or Cyclin D1 amplifications, six patients had CDKN2A deletions. After a median follow-up of 35 months, there were no objective responses. Seven patients had stable disease and one had non-complete response/non-progressive disease (non-CR/non-PD) based on evaluation of a non-target lesion. Two of these seven patients maintained stable disease for at least 6 months, as did the patient with non-CR/non-PD. Median PFS and OS were 3.5 and 11.0 months respectively. No unexpected toxicities were observed. Translational correlates yielded strategies for targeting cell cycle interactions with other molecular pathways and the immune system.CONCLUSION: Palbociclib monotherapy was not associated with any objective responses, but stable disease lasting at least 6 months was observed in 19% of patients. There was no clear relationship with alteration type or histotype. The signals of immune activation provide insights into the design of future trials, with a combination approach adding checkpoint blockade to CDK4/6 inhibition.

The Role of Haptic Expectations in Reaching to Grasp: From Pantomime to Natural Grasps and Back Again

When we reach to pick up an object, our actions are effortlessly informed by the object’s spatial information, the position of our limbs, stored knowledge of the object’s material properties, and what we want to do with the object. A substantial body of evidence suggests that grasps are under the control of “automatic, unconscious” sensorimotor modules housed in the “dorsal stream” of the posterior parietal cortex. Visual online feedback has a strong effect on the hand’s in-flight grasp aperture. Previous work of ours exploited this effect to show that grasps are refractory to cued expectations for visual feedback. Nonetheless, when we reach out to pretend to grasp an object (pantomime grasp), our actions are performed with greater cognitive effort and they engage structures outside of the dorsal stream, including the ventral stream. Here we ask whether our previous finding would extend to cued expectations for haptic feedback. Our method involved a mirror apparatus that allowed participants to see a “virtual” target cylinder as a reflection in the mirror at the start of all trials. On “haptic feedback” trials, participants reached behind the mirror to grasp a size-matched cylinder, spatially coincident with the virtual one. On “no-haptic feedback” trials, participants reached behind the mirror and grasped into “thin air” because no cylinder was present. To manipulate haptic expectation, we organized the haptic conditions into blocked, alternating, and randomized schedules with and without verbal cues about the availability of haptic feedback. Replicating earlier work, we found the strongest haptic effects with the blocked schedules and the weakest effects in the randomized uncued schedule. Crucially, the haptic effects in the cued randomized schedule was intermediate. An analysis of the influence of the upcoming and immediately preceding haptic feedback condition in the cued and uncued random schedules showed that cuing the upcoming haptic condition shifted the haptic influence on grip aperture from the immediately preceding trial to the upcoming trial. These findings indicate that, unlike cues to the availability of visual feedback, participants take advantage of cues to the availability of haptic feedback, flexibly engaging pantomime, and natural modes of grasping to optimize the movement.

Perceptual inference is impaired in individuals with ASD and intact in individuals who have lost the autism diagnosis

Beyond the symptoms which characterize their diagnoses, individuals with autism spectrum disorder (ASD) show enhanced performance in simple perceptual discrimination tasks. Often attributed to superior sensory sensitivities, enhanced performance may also reflect a weaker bias towards previously perceived stimuli. This study probes perceptual inference in a group of individuals who have lost the autism diagnosis (LAD); that is, they were diagnosed with ASD in early childhood but have no current ASD symptoms. Groups of LAD, current ASD, and typically developing (TD) participants completed an auditory discrimination task. Individuals with TD showed a bias towards previously perceived stimuli—a perceptual process called “contraction bias”; that is, their representation of a given tone was contracted towards the preceding trial stimulus in a manner that is Bayesian optimal. Similarly, individuals in the LAD group showed a contraction bias. In contrast, individuals with current ASD showed a weaker contraction bias, suggesting reduced perceptual inferencing. These findings suggest that changes that characterize LAD extend beyond the social and communicative symptoms of ASD, impacting perceptual domains. Measuring perceptual processing earlier in development in ASD will tap the causality between changes in perceptual and symptomatological domains. Further, the characterization of perceptual inference could reveal meaningful individual differences in complex high-level behaviors.