Reversal learning assays are commonly used across a wide range of taxa to investigate associative learning and behavioural flexibility. In serial reversal learning, the reward contingency in a binary discrimination is reversed multiple times. Performance during serial reversal learning varies greatly at the interspecific level, as some animals adopt a rule-based strategy that enables them to switch quickly between reward contingencies. A larger relative brain size, generating enhanced learning ability and increased behavioural flexibility, has been proposed to be an important factor underlying this variation. Here, we experimentally tested this hypothesis at the intraspecific level. We used guppies (Poecilia reticulata) artificially selected for small and large relative brain size, with matching differences in neuron number, in a serial reversal learning assay. We tested 96 individuals over 10 serial reversals and found that learning performance and memory were predicted by brain size, whereas differences in efficient learning strategies were not. We conclude that variation in brain size and neuron number is important for variation in learning performance and memory, but these differences are not great enough to cause the larger differences in efficient learning strategies observed at higher taxonomic levels.

Progressively improving performance in a serial reversal learning (SRL) test has been associated with higher cognitive abilities and has served as a measure for cognitive/behavioral flexibility. Although the cognitive and sensory abilities of marine mammals have been subject of extensive investigation, and numerous vertebrate and invertebrate species were tested, SRL studies in aquatic mammals are sparse. Particularly in pinnipeds, a high degree of behavioral flexibility seems probable as they face a highly variable environment in air and underwater. Thus, we tested four harbor seals in a visual two-alternative forced-choice discrimination task and its subsequent reversals. We found significant individual differences in performance. One individual was able to solve 37 reversals showing progressive improvement of performance with a minimum of 6 errors in reversal 33. Two seals mastered two reversals, while one animal had difficulties in learning the discrimination task and failed to complete a single reversal. In conclusion, harbor seals can master an SRL experiment; however, the performance is inferior to results obtained in other vertebrates in comparable tasks. Future experiments will need to assess whether factors such as the modality addressed in the experiment have an influence on reversal learning performance or whether indeed, during evolution, behavioral flexibility has not specifically been favored in harbor seals.

The effects of chronic adolescent fluoxetine (FLX, Prozac®) exposure on adult cognition are largely unknown. We used a serial multiple choice (SMC) task to characterize the effects of adolescent FLX exposure on rat serial pattern learning in adulthood. Male rats were exposed to either 1.0, 2.0, or 4.0 mg/kg/day FLX for five consecutive days each week for five weeks during adolescence, followed by a 35-day drug-free period. As adults, the rats were trained in a task that required them to learn a highly structured sequential pattern of responses in an octagonal chamber for water reinforcement. In a transfer phase, the terminal element of the pattern was replaced by a violation element that was inconsistent with previously learned pattern structure. Results indicated that adolescent FLX exposure caused differential learning deficits for different types of elements in the serial pattern. Adolescent exposure to 1.0 or 4.0 mg/kg/day FLX, but not 2.0 mg/kg/day FLX, impaired chunk-boundary element learning, which is known to be mediated by stimulus-response (S-R) learning. All three doses of FLX impaired violation element learning, which is known to be mediated by multiple-cue learning. FLX did not impair within-chunk element learning, which is known to be mediated by rule-learning mechanisms. The results indicate that adolescent FLX exposure produced multiple cognitive impairments that were detectable in adulthood long after drug exposure ended.

Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy and the most common neuromuscular disorder. In addition to neuromuscular consequences, some individuals with DMD experience global intellectual dysfunction and executive dysfunction of unknown mechanistic origin. The cognitive profile of the mdx mouse, the most commonly used mouse model of DMD, has been incompletely characterized and has never been assessed using the touchscreen operant conditioning paradigm. The touchscreen paradigm allows the use of protocols that are virtually identical to those used in human cognitive testing and may, therefore, provide the most translational paradigm for quantifying mouse cognitive function. In the present study, we used the touchscreen paradigm to assess the effects of the mdx mutation on visual discrimination learning, serial reversal learning, and extinction learning. To enable measuring task-dependent learning and memory processes while holding demands on sensory-driven information processing constant, we developed equally salient visual stimuli and used them on all experimental stages. Acquisition of the initial pairwise visual discrimination was facilitated in mdx mice relative to wildtype littermates; this effect was not explained by genotypic differences in impulsivity, motivation, or motor deficits. The mdx mutation had no effect on serial reversal or extinction learning. Together, findings from this study and previous studies suggest that mdx effects on cognitive function are task-specific and may be influenced by discrimination type (spatial, visual), reward type (food, escape from a non-preferred environment), sex, and genetic background.

Learning is a central ability for human development. Many skills we learn, such as language, are learned through observation or imitation in social contexts. Likewise, many skills are learned implicitly, that is, without an explicit intent to learn and without full awareness of the acquired knowledge. Here, we asked whether performance in a motor learning task is modulated by social vs. object cues of varying validity. To address this question, we asked participants to carry out a serial reaction time (SRT) task in which, on each trial, people have to respond as fast and as accurately as possible to the appearance of a stimulus at one of four possible locations. Unbeknownst to participants, the sequence of successive locations was sequentially structured, so that knowledge of the sequence facilitates anticipation of the next stimulus and hence faster motor responses. Crucially, each trial also contained a cue pointing to the next stimulus location. Participants could thus learn based on the cue, or on learning about the sequence of successive locations, or on a combination of both. Results show an interaction between cue type and cue validity for the motor responses: social cues (vs. object cues) led to faster responses in the low validity (LV) condition only. Concerning the extent to which learning was implicit, results show that in the cued blocks only, the highly valid social cue led to implicit learning. In the uncued blocks, participants showed no implicit learning in the highly valid social cue condition, but did in all other combinations of stimulus type and cueing validity. In conclusion, our results suggest that implicit learning is context-dependent and can be influenced by the cue type, e.g., social and object cues.

Impairments in reversal learning have been attributed to orbitofrontal cortex (OFC) dysfunction in many species. However, the role of subcortical areas interconnected with the OFC such as the striatum remains poorly understood. This study directly evaluated the contribution of core and shell sub-regions of the nucleus accumbens (NAc), dorsomedial (DMS) and dorsolateral (DLS) striatum to reversal learning of an instrumental two-lever spatial discrimination task in rats. Selective NAc core, DMS and DLS lesions were achieved with microinjections of quinolinic acid and NAc shell lesions with ibotenic acid. Damage to NAc core or shell did not affect retention of a previously acquired instrumental spatial discrimination. In contrast, DLS and DMS lesions produced changes in aspects of discrimination performance such as the latency to collect earned food pellets. Neither NAc core or shell lesions nor DLS lesions affected the main indices of reversal performance. Conversely, DMS lesion rats showed a significant impairment in reversal learning. DMS damage increased the number of errors to reach criteria that were perseverative in nature. The deficit in reversal learning in DMS lesion rats was not associated with an impairment to extinguish instrumental responding. There were no effects on spontaneous locomotor activity. Our data are in agreement with recent work showing that lesions of the medial striatum in marmoset monkeys produce perseverative impairments during a serial visual discrimination reversal task and support the hypothesis that dorsomedial striatal dysfunction contributes to pathological perseveration, which is a common feature of many psychiatric disorders.

Corticostriatal circuits, particularly the dorsomedial striatum (DMS) and lateral orbitofrontal cortex, are critical for navigating reversal learning under probabilistic uncertainty. These same areas are implicated in the reversal learning impairments observed in individuals with psychosis as well as their psychotic symptoms, suggesting that they may share a common neurobiological substrate. To address this question, we used psychostimulant exposure and specific activation of the DMS during reversal learning in mice to assess corticostriatal activity.

Animals are proposed to learn the latent rules governing their environment in order to maximize their chances of survival. However, rules may change without notice, forcing animals to keep a memory of which one is currently at work. Rule switching can lead to situations in which the same stimulus/response pairing is positively and negatively rewarded in the long run, depending on variables that are not accessible to the animal. This fact raises questions on how neural systems are capable of reinforcement learning in environments where the reinforcement is inconsistent. Here we address this issue by asking about which aspects of connectivity, neural excitability and synaptic plasticity are key for a very general, stochastic spiking neural network model to solve a task in which rules change without being cued, taking the serial reversal task (SRT) as paradigm. Contrary to what could be expected, we found strong limitations for biologically plausible networks to solve the SRT. Especially, we proved that no network of neurons can learn a SRT if it is a single neural population that integrates stimuli information and at the same time is responsible of choosing the behavioural response. This limitation is independent of the number of neurons, neuronal dynamics or plasticity rules, and arises from the fact that plasticity is locally computed at each synapse, and that synaptic changes and neuronal activity are mutually dependent processes. We propose and characterize a spiking neural network model that solves the SRT, which relies on separating the functions of stimuli integration and response selection. The model suggests that experimental efforts to understand neural function should focus on the characterization of neural circuits according to their connectivity, neural dynamics, and the degree of modulation of synaptic plasticity with reward.

Serial electrocardiography aims to contribute to electrocardiogram (ECG) diagnosis by comparing the ECG under consideration with a previously made ECG in the same individual. Here, we present a novel algorithm to construct dedicated deep-learning neural networks (NNs) that are specialized in detecting newly emerging or aggravating existing cardiac pathology in serial ECGs.

The learning capacities of males and females may differ with sex-specific behavioural requirements. Bumblebees provide a useful model system to explore how different lifestyles are reflected in learning abilities, because their (female but sterile) workers and males engage in fundamentally different behaviour routines. Bumblebee males, like workers, embark on active flower foraging but in contrast to workers they have to trade off their feeding with mate search, potentially affecting their abilities to learn and utilize floral cues efficiently during foraging. We used a serial colour-learning task with freely flying males and workers to compare their ability to flexibly learn visual floral cues with reward in a foraging scenario that changed over time. Male bumblebees did not differ from workers in both their learning speed and their ability to overcome previously acquired associations, when these ceased to predict reward. In all foraging tasks we found a significant improvement in choice accuracy in both sexes over the course of the training. In both sexes, the characteristics of the foraging performance depended largely on the colour difference of the two presented feeder types. Large colour distances entailed fast and reliable learning of the rewarding feeders whereas choice accuracy on highly similar colours improved significantly more slowly. Conversely, switching from a learned feeder type to a novel one was fastest for similar feeder colours and slow for highly different ones. Overall, we show that behavioural sex dimorphism in bumblebees did not affect their learning abilities beyond the mating context. We discuss the possible drivers and limitations shaping the foraging abilities of males and workers and implications for pollination ecology. We also suggest stingless male bumblebees as an advantageous alternative model system for the study of pollinator cognition.

The serial feature-positive discrimination task requires the subjects to respond differentially to the identical stimulus depending on the temporal context given by a preceding cue stimulus. In the present study, we examined the involvement of the M1 muscarinic acetylcholine receptors using a selective M1 antagonist VU0255035 in the serial feature-positive discrimination task of eyeblink conditioning in mice. In this task, mice received a 2-s light stimulus as the conditional cue 5 or 6 s before the presentation of a 350-ms tone conditioned stimulus (CS) paired with a 100-ms peri-orbital electrical shock (cued trials), while they did not receive the cue before the presentation of the CS alone (non-cued trials). Each day mice randomly received 30 cued and 30 non-cued trials. We found that VU0255035 impaired acquisition of the conditional discrimination as well as the overall acquisition of the conditioned response (CR) and diminished the difference in onset latency of the CR between the cued and non-cued trials. VU0255035 administration to the control mice after sufficient learning did not impair the pre-acquired conditional discrimination or the CR expression itself. These effects of VU0255035 were almost similar to those with the scopolamine in our previous study, suggesting that among the several types of muscarinic acetylcholine receptors, the M1 receptors may play an important role in the acquisition of the conditional discrimination memory but not in mediating the discrimination itself after the memory had formed in the eyeblink serial feature-positive discrimination learning.

Against the scourge of the COVID-19 pandemic, college students' learning engagement has become a key issue in universities and society. Guided by the theories of existential positive psychology and social perception, we explored the positive effect of a growth mindset on learning engagement during the COVID-19 pandemic. A total of 1,040 college students from universities in Henan Province of China effectively completed online questionnaires. The results showed that growth mindset was positively related to learning engagement and negatively associated with perceived COVID-19 event strength and perceived stress; perceived COVID-19 event strength was positively related to perceived stress, while perceived COVID-19 event strength and perceived stress were negatively associated with learning engagement. Growth mindset affected learning engagement through three indirect paths: the mediating role of perceived COVID-19 event strength, the mediating role of perceived stress, and the serial mediating role of both perceived COVID-19 event strength and perceived stress. The results indicated that the growth mindset could contribute to college students' learning engagement through the roles of perceived COVID-19 event strength and perceived stress during the COVID-19 pandemic. This study advances the understanding of the mechanism underlying the relationship between growth mindset and college students' learning engagement during the COVID-19 pandemic. Furthermore, the findings of the study have important implications for promoting college students' learning engagement during the pandemic.

A number of studies have investigated procedural learning in dyslexia using serial reaction time (SRT) tasks. Overall, the results have been mixed, with evidence of both impaired and intact learning reported. We undertook a systematic search of studies that examined procedural learning using SRT tasks, and synthesized the data using meta-analysis. A total of 14 studies were identified, representing data from 314 individuals with dyslexia and 317 typically developing control participants. The results indicate that, on average, individuals with dyslexia have worse procedural learning abilities than controls, as indexed by sequence learning on the SRT task. The average weighted standardized mean difference (the effect size) was found to be 0.449 (CI95: .204, .693), and was significant (p<.001). However, moderate levels of heterogeneity were found between study-level effect sizes. Meta-regression analyses indicated that studies with older participants that used SRT tasks with second order conditional sequences, or with older participants that used sequences that were presented a large number of times, were associated with smaller effect sizes. These associations are discussed with respect to compensatory and delayed memory systems in dyslexia.

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability in males and the most common genetic cause of autism. Although executive dysfunction is consistently found in humans with FXS, evidence of executive dysfunction in Fmr1 KO mice, a mouse model of FXS, has been inconsistent. One possible explanation for this is that executive dysfunction in Fmr1 KO mice, similar to humans with FXS, is only evident when cognitive demands are high. Using touchscreen operant conditioning chambers, male Fmr1 KO mice and their male wildtype littermates were tested on the acquisition of a pairwise visual discrimination followed by four serial reversals of the response rule. We assessed reversal learning performance under two different conditions. In the first, the correct stimulus was salient and the incorrect stimulus was non-salient. In the second and more challenging condition, the incorrect stimulus was salient and the correct stimulus was non-salient; this increased cognitive load by introducing conflict between sensory-driven (i.e., bottom-up) and task-dependent (i.e., top-down) signals. Fmr1 KOs displayed two distinct impairments relative to wildtype littermates. First, Fmr1 KOs committed significantly more learning-type errors during the second reversal stage, but only under high cognitive load. Second, during the first reversal stage, Fmr1 KOs committed significantly more attempts to collect a reward during the timeout following an incorrect response. These findings indicate that Fmr1 KO mice display executive dysfunction that, in some cases, is only evident under high cognitive load.

In current clinical practice, tumor response assessment is usually based on tumor size change on serial computerized tomography (CT) scan images. However, evaluation of tumor response to anti-vascular endothelial growth factor therapies in metastatic colorectal cancer (mCRC) is limited because morphological change in tumor may occur earlier than tumor size change. Here we present an analysis utilizing a deep learning (DL) network to characterize tumor morphological change for response assessment in mCRC patients. We retrospectively analyzed 1,028 mCRC patients who were prospectively included in the VELOUR trial (NCT00561470). We found that DL network was able to predict early on-treatment response in mCRC and showed better performance than its size-based counterpart with C-Index: 0.649 (95% CI: 0.619,0.679) vs. 0.627 (95% CI: 0.567,0.638), p = 0.009, z-test. The integration of DL network with size-based methodology could further improve the prediction performance to C-Index: 0.694 (95% CI: 0.661,0.720), which was superior to size/DL-based-only models (all p < 0.001, z-test). Our study suggests that DL network could provide a noninvasive mean for quantitative and comprehensive characterization of tumor morphological change, which may potentially benefit personalized early on-treatment decision making.

Tumors are continuously evolving biological systems which can be monitored by medical imaging. Previous studies only focus on single timepoint images, whether the performance could be further improved by using serial noncontrast CT imaging obtained during nodule follow-up management remains unclear. In this study, we evaluated DL model for predicting tumor invasiveness of GGNs through analyzing time series CT images.

In radiological screening, clinicians scan myriads of radiographs with the intent of recognizing and differentiating lesions. Even though they are trained experts, radiologists' human search engines are not perfect: average daily error rates are estimated around 3-5%. A main underlying assumption in radiological screening is that visual search on a current radiograph occurs independently of previously seen radiographs. However, recent studies have shown that human perception is biased by previously seen stimuli; the bias in our visual system to misperceive current stimuli towards previous stimuli is called serial dependence. Here, we tested whether serial dependence impacts radiologists' recognition of simulated lesions embedded in actual radiographs. We found that serial dependence affected radiologists' recognition of simulated lesions; perception on an average trial was pulled 13% toward the 1-back stimulus. Simulated lesions were perceived as biased towards the those seen in the previous 1 or 2 radiographs. Similar results were found when testing lesion recognition in a group of untrained observers. Taken together, these results suggest that perceptual judgements of radiologists are affected by previous visual experience, and thus some of the diagnostic errors exhibited by radiologists may be caused by serial dependence from previously seen radiographs.

Up to now, serial NETest measurements in individuals assessing the disease course of gastroenteropancreatic neuroendocrine tumors (GEPNETs) at long-term follow-up and treatment response were not studied.

Precisely estimating event timing is essential for survival, yet temporal distortions are ubiquitous in our daily sensory experience. Here, we tested whether the relative position, duration, and distance in time of two sequentially-organized events-standard S, with constant duration, and comparison C, with duration varying trial-by-trial-are causal factors in generating temporal distortions. We found that temporal distortions emerge when the first event is shorter than the second event. Importantly, a significant interaction suggests that a longer inter-stimulus interval (ISI) helps to counteract such serial distortion effect only when the constant S is in the first position, but not if the unpredictable C is in the first position. These results imply the existence of a perceptual bias in perceiving ordered event durations, mechanistically contributing to distortion in time perception. We simulated our behavioral results with a Bayesian model and replicated the finding that participants disproportionately expand first-position dynamic (unpredictable) short events. Our results clarify the mechanisms generating time distortions by identifying a hitherto unknown duration-dependent encoding inefficiency in human serial temporal perception, something akin to a strong prior that can be overridden for highly predictable sensory events but unfolds for unpredictable ones.

Electrocardiogram (ECG) studies of drug-induced prolongation of the interval between the J point and the peak of the T wave (JTp interval) distinguished QT prolonging drugs that predominantly block the delayed potassium rectifier current from those affecting multiple cardiac repolarisation ion channel currents. Since the peak of the T wave depends on ECG lead, a "global" T peak requires to combine ECG leads into one-dimensional signal in which the T wave peak can be measured. This study aimed at finding the optimum one-dimensional representation of 12-lead ECGs for the most stable JTp measurements. Seven different one-dimensional representations were investigated including the vector magnitude of the orthogonal XYZ transformation, root mean square of all 12 ECG leads, and the vector magnitude of the 3 dominant orthogonal leads derived by singular value decomposition. All representations were applied to the median waveforms of 660,657 separate 10-s 12-lead ECGs taken from repeated day-time Holter recordings in 523 healthy subjects aged 33.5 ± 8.4 years (254 women). The JTp measurements were compared with the QT intervals and with the intervals between the J point and the median point of the area under the T wave one-dimensional representation (JT50 intervals) by means of calculating the residuals of the subject-specific curvilinear regression models relating the measured interval to the hysteresis-corrected RR interval of the underlying heart rate. The residuals of the regression models (equal to the intra-subject standard deviations of individually heart rate corrected intervals) expressed intra-subject stability of interval measurements. For both the JTp intervals and the JT50 intervals, the curvilinear regression residuals of measurements derived from the orthogonal XYZ representation were marginally but statistically significantly lower compared to the other representations. Using the XYZ representation, the residuals of the QT/RR, JTp/RR and JT50/RR regressions were 5.6 ± 1.1 ms, 7.2 ± 2.2 ms, and 4.9 ± 1.2 ms, respectively (all statistically significantly different; p < 0.0001). The study concludes that the orthogonal XYZ ECG representation might be proposed for future investigations of JTp and JT50 intervals. If the ability of classifying QT prolonging drugs is further confirmed for the JT50 interval, it might be appropriate to replace the JTp interval since with JT50 it appears more stable.