The role of uncertainty in regulating associative change.

Rescorla (2000, 2001) interpreted his compound test results to show that both common and individual error terms regulate associative change such that the element of a conditioned compound with the greater prediction error undergoes greater associative change than the one with the smaller prediction error. However, it has recently been suggested that uncertainty, not prediction error, is the primary determinant of associative change in people (Spicer et al., 2020, 2022). The current experiments use the compound test in a continuous outcome allergist task to assess the role of uncertainty in associative change, using two different manipulations of uncertainty: outcome uncertainty (where participants are uncertain of the level of the outcome on a particular trial) and causal uncertainty (where participants are uncertain of the contribution of the cue to the level of the outcome). We replicate Rescorla's compound test results in the case of both associative gains (Experiment 1) and associative losses (Experiment 3) and then provide evidence for greater change to more uncertain cues in the case of associative gains (Experiments 2 and 4), but not associative losses (Experiments 3 and 5). We discuss the findings in terms of the notion of theory protection advanced by Spicer et al., and other ways of thinking about the compound test procedure, such as that proposed by Holmes et al. (2019). (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Encoding of Predictive Associations in Human Prefrontal and Medial Temporal Neurons During Pavlovian Appetitive Conditioning.

Pavlovian conditioning is thought to involve the formation of learned associations between stimuli and values, and between stimuli and specific features of outcomes. Here, we leveraged human single neuron recordings in ventromedial prefrontal, dorsomedial frontal, hippocampus, and amygdala while patients of both sexes performed an appetitive Pavlovian conditioning task probing both stimulus-value and stimulus-stimulus associations. Ventromedial prefrontal cortex encoded predictive value along with the amygdala, and also encoded predictions about the identity of stimuli that would subsequently be presented, suggesting a role for neurons in this region in encoding predictive information beyond value. Unsigned error signals were found in dorsomedial frontal areas and hippocampus, potentially supporting learning of non-value related outcome features. Our findings implicate distinct human prefrontal and medial temporal neuronal populations in mediating predictive associations which could partially support model-based mechanisms during Pavlovian conditioning.

Optogenetic activation of dopamine D1 receptors in island cells of medial entorhinal cortex inhibits temporal association learning.

A critical feature of episodic memory formation is to associate temporally segregated events as an episode, called temporal association learning. The medial entorhinal cortical-hippocampal (EC-HPC) networks is essential for temporal association learning. We have previously demonstrated that pyramidal cells in the medial EC (MEC) layer III project to the hippocampal CA1 pyramidal cells and are necessary for trace fear conditioning (TFC), which is an associative learning between tone and aversive shock with the temporal gap. On the other hand, Island cells in MECII, project to GABAergic neurons in hippocampal CA1, suppress the MECIII input into the CA1 pyramidal cells through the feed-forward inhibition, and inhibit TFC. However, it remains unknown about how Island cells activity is regulated during TFC. In this study, we report that dopamine D1 receptor is preferentially expressed in Island cells in the MEC. Optogenetic activation of dopamine D1 receptors in Island cells facilitate the Island cell activity and inhibited hippocampal CA1 pyramidal cell activity during TFC. The optogenetic activation caused the impairment of TFC memory recall without affecting contextual fear memory recall. These results suggest that dopamine D1 receptor in Island cells have a crucial role for the regulation of temporal association learning.

Chinese character unitization enhances recollection-based associative recognition: Evidence from fMRI.

Previous research has suggested that familiarity can enhance associative memory after unitization, but the cognitive mechanisms underlying unitization remain debated. To explore the neural mechanisms of associative memory after unitization in the absence of semantic relations, we used Chinese characters as stimuli and recorded participants' blood oxygen level-dependent signals during recognition. Behavioral results showed that after Chinese character unitization, not only the associative performance of recognition (Pr, hit rate minus false alarm rate) and general Pr but also the hit rate and correct rejection rate increased. Neuroimaging results revealed activation of the hippocampus and parahippocampal gyrus during associative recognition in both the unitized and the non-unitized condition, and hippocampal activation increased after unitization. However, activation of the perirhinal cortex was not observed in either condition. These findings, in contrast to those from previous studies on unitization, suggest that Chinese character unitization enhances recollection-based, rather than familiarity-based, associative recognition. This suggests that the encoding of semantic relations during unitization is critical for subsequent familiarity-based associative recognition.

Retardation of acquisition after conditioned inhibition and latent inhibition training in human causal learning.

Inhibitory stimuli are slow to acquire excitatory properties when paired with the outcome in a retardation test. However, this pattern is also seen after simple nonreinforced exposure: latent inhibition. It is commonly assumed that retardation would be stronger for a conditioned inhibitor than for a latent inhibitor, but there is surprisingly little empirical evidence comparing the two in either animals or humans. Thus, retardation after inhibitory training could in principle be attributable entirely to latent inhibition. We directly compared the speed of excitatory acquisition after conditioned inhibition and matched latent inhibition training in human causal learning. Conditioned inhibition training produced stronger transfer in a summation test, but the two conditions did not differ substantially in a retardation test. We offer two explanations for this dissociation. One is that learned predictiveness attenuated the latent inhibition that otherwise would have occurred during conditioned inhibition training, so that retardation in that condition was primarily due to inhibition. The second explanation is that inhibitory learning in these experiments was hierarchical in nature, similar to negative occasion-setting. By this account, the conditioned inhibitor was able to negatively modulate the test excitor in a summation test, but was no more retarded than a latent inhibitor in its ability to form a direct association with the outcome. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The opportunity to compare similar stimuli can reduce the effectiveness of features they hold in common.

In three experiments, rats were given experience of flavored solutions AX and BX, where A and B represent distinctive flavors and X a flavor common to both solutions. In one condition, AX and BX were presented on the same trial separated by a 5-min interval (intermixed preexposure). In another condition, each daily trial consisted of presentations of only AX or only BX (blocked preexposure). The properties acquired by stimulus X were then tested. Experiment 1 showed that after intermixed preexposure X was less able to interfere with a conditioned response established to a different flavor. Experiment 2 showed that X was less effective at overshadowing when trained in compound with another flavor. Simple conditioning, with X as the conditioned stimulus, was not sensitive to the form of preexposure (Experiment 3). These results indicate that the opportunity to compare similar stimuli that is provided by presenting them in close succession can change the properties of features they hold in common, making these features less effective when tested in compound with other stimuli. A loss of effectiveness by such features would contribute to the perceptual learning effect, the enhancement of subsequent discrimination, that is generated by prior exposure to closely spaced similar stimuli. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Neural distinctiveness and reinstatement of hippocampal representations support unitization for associations.

The medial temporal lobe (MTL) is critical to associative memory success, yet not all types of associations may be processed in a similar manner within MTL subregions. In particular, previous work suggests intra- and inter-item associations not only exhibit differences in overall rates of recollection, but also recruit different MTL subregions. Whereas intra-item associations, akin to unitization, take advantage of associations between within-item features, inter-item associations form links across discrete items. The current work examines the neural differences between these two types of associations using fMRI and multivoxel analyses. Specifically, the current study examines differences across face-occupation as a function of whether the pairing was viewed as a person performing the given job (intra-item binding) or a person saying they knew someone who had a particular job (inter-item binding). The results show that at encoding, successfully recollected neural patterns related to intra- and inter-item associations are distinct from one another in the hippocampus, parahippocampal and perirhinal cortex. Additionally, the two trial types are reinstated distinctly such that inter-item trials have higher neural reinstatement from encoding to retrieval compared to intra-item trials in the hippocampus. We conclude that intra- and inter- associative pairs may utilize similar neural regions that represent patterns of activation differentially at encoding. However, to reinstate information to the same degree (i.e., subsequently successfully recollected) inter-item associations, that are all encoded in the same manner, may be reinstated more similarly compared to intra-item associations that are encoded by imagining pairs differently and occupation specific. This may indicate that intra-item associations promote more efficient reinstatement.

Perceptual learning after rapidly alternating exposure to taste compounds: Assessment with different indices of generalization.

Exposure to two similar stimuli (AX and BX; e.g., two tastes) reduces the extent to which a conditioned response later established to BX generalizes to AX. This example of perceptual learning is more evident when AX and BX are exposed in an alternating manner (AX, BX, AX, BX,…) than when AX and BX occur in separate blocks (e.g., AX, AX,…BX, BX,…). We examined in male rats (N = 126) the impact of rapid alternation to AX and BX on generalization of a taste aversion from BX to AX. Experiment 1 showed that such alternating presentations (with 5-min intervals between AX and BX) reduced generalization relative to blocked exposure; but only as assessed by consumption levels and not by lick cluster size (an index of hedonic reactions). Experiment 1 also showed that the nature of exposure did not affect how A influenced performance to a novel conditioned taste, Y. Experiment 2 replicated the pattern of results involving the different influences of rapidly alternating and blocked exposure on generalization from BX to AX, and showed that this effect was only evident when rats received access to water during the 5-min intervals between AX and BX. These results reinforce parallels between perceptual learning effects in rats and humans, both at empirical and theoretical levels. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The role of prediction in learned predictiveness.

Learning permits even relatively uninteresting stimuli to capture attention if they are established as predictors of important outcomes. Associative theories explain this "learned predictiveness" effect by positing that attention is a function of the relative strength of the association between stimuli and outcomes. In three experiments we show that this explanation is incomplete: learned overt visual-attention is not a function of the relative strength of the association between stimuli and an outcome. In three experiments, human participants were exposed to triplets of stimuli that comprised (a) a target (that defined correct responding), (b) a stimulus that was perfectly correlated with the presentation of the target, and (c) a stimulus that was uncorrelated with the presentation of the target. Participants' knowledge of the associative relationship between the correlated or uncorrelated stimuli and the target was always good. However, eye-tracking revealed that an attentional bias toward the correlated stimulus only developed when it and target-relevant responding preceded the target stimulus. We propose a framework in which attentional changes are modulated during learning as a function the relative strength of the association between stimuli and the task-relevant response, rather than an association between stimuli and the task-relevant outcome. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Association learning: Dopamine and the formation of backward associations.

The activity of dopamine neurons is critical for the ability to learn and update cue-reward associations. New work in rats shows that dopamine transients are also critical for the formation of backward associations in which the reward precedes the neutral stimulus.

A response function that maps associative strengths to probabilities.

Bridging associative and normative theories of animal learning, I show that an associative system can behave as if performing probabilistic inference by using the function f(V) = 1 - e-cV to transform associative strengths (V) into response probabilities. For example, using this function, an associative system can respond normatively to a compound stimulus AB, given previous separate experiences with the components A and B. The CR probability formulae that result from the proposed function have a normative interpretation in terms of statistical decision theory. The formulae also suggest a normative interpretation of stimulus generalization as a heuristic to infer whether different stimuli are likely to convey redundant or independent information about reinforcement. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Reversal of inhibition by no-modulation training but not by extinction in human causal learning.

One of the many strengths of the Rescorla and Wagner (1972) model is that it accounts for both excitatory and inhibitory learning using a single error-correction mechanism. However, it makes the counterintuitive prediction that nonreinforced presentations of an inhibitory stimulus will lead to extinction of its inhibitory properties. Zimmer-Hart and Rescorla (1974) provided the first of several animal conditioning studies that contradicted this prediction. However, the human data are more mixed. Accordingly, we set out to test whether extinction of an inhibitor occurs in human causal learning after simultaneous feature negative training with a conventional unidirectional outcome. In 2 experiments with substantial sample sizes, we found no evidence of extinction after presentations of the inhibitory stimulus alone in either a summation test or causal ratings. By contrast, 2 "no-modulation" procedures that contradicted the original training contingencies successfully reversed inhibition. These results did not differ substantially as a function of participants' self-reported causal structures (configural/modulation/prevention). We hypothesize that inhibitory learning may be intrinsically modulatory, analogous to negative occasion-setting, even with simultaneous training. This hypothesis would explain why inhibition is reversed by manipulations that contradict modulation but not by simple extinction, as well as other properties of inhibitory learning such as imperfect transfer to another excitor. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Pavlovian summation: Data and theory.

In summation experiments, responding to a compound stimulus is assessed after conditioning a response to each of its components. This simple experiment poses significant challenges to models of associative learning because of substantial variability in results. Here, I introduce a new method to quantify generalization from components to compound in summation experiments, which I apply to over 250 measurements of summation in rabbits, pigeons, rats, and humans. The analysis confirms that more summation occurs with stimuli from different rather than from the same sensory modality, although this is not the sole determinant of summation. A theoretical analysis shows that this finding is best accounted for by a model that includes both element sharing (Rescorla & Wagner, 1972) and element replacement (Brandon et al., 2000) in stimulus representations. I point out remaining gaps in our empirical and theoretical understanding of summation. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Inhibitory summation as a form of generalization.

Inhibitory learning after feature negative training (A+/AB-) is typically measured by combining the Feature B with a separately trained excitor (e.g., C) in a summation test. Reduced responding to C is taken as evidence that B has properties directly opposite to those of C. However, in human causal learning, transfer of B's inhibitory properties to another excitor is modest and depends on individual differences in inferred causal structure. Here we ask whether instead of opposing processes, a summation test might instead be thought of in terms of generalization. Using an allergist task, we tested whether inhibitory transfer would be influenced by similarity. We found that transfer was greater when the test stimuli were from the same semantic category as the training stimuli (Experiments 1 and 2) and when the test excitor had previously been associated with the same outcome (Experiment 3). We also found that the similarity effect applied across all self-reported causal structures. We conclude it may be more helpful to consider transfer of inhibition as a form of conceptual generalization rather than the arithmetic summation of opposing processes. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Social behavior mediates the use of social and personal information in wild jays.

The factors favoring the evolution of certain cognitive abilities in animals remain unclear. Social learning is a cognitive ability that reduces the cost of acquiring personal information and forms the foundation for cultural behavior. Theory predicts the evolutionary pressures to evolve social learning should be greater in more social species. However, research testing this theory has primarily occurred in captivity, where artificial environments can affect performance and yield conflicting results. We compared the use of social and personal information, and the social learning mechanisms used by wild, asocial California scrub-jays and social Mexican jays. We trained demonstrators to solve one door on a multi-door task, then measured the behavior of naïve conspecifics towards the task. If social learning occurs, observations of demonstrators will change the rate that naïve individuals interact with each door. We found both species socially learned, though personal information had a much greater effect on behavior in the asocial species while social information was more important for the social species. Additionally, both species used social information to avoid, rather than copy, conspecifics. Our findings demonstrate that while complex social group structures may be unnecessary for the evolution of social learning, it does affect the use of social versus personal information.

Increased associative interference under high cognitive load.

Associative processing is central for human cognition, perception and memory. But while associations often facilitate performance, processing irrelevant associations can interfere with performance, for example when learning new information. The aim of this study was to explore whether associative interference is influenced by contextual factors such as resources availability. Experiments 1-3 show that associative interference increases under high cognitive load. This result generalized to both long-term and short-term memory associations, and to both explicitly learned as well as incidentally learned associations in the linguistic and pictorial domains. Experiment 4 further revealed that attention to associative information can delay one's perceptual processing when lacking resources. Taken together, when resources diminish associative interference increases, and additionally, processing novel and ambiguous information is hindered. These findings bare relevance to other domains as well (e.g., social, educational), in which increased load or stress may prompt an undesirable bias towards prior, misleading information.

Serotonergic modulation of effective connectivity in an associative relearning network during task and rest.

An essential core function of one's cognitive flexibility is the use of acquired knowledge and skills to adapt to ongoing environmental changes. Animal models have highlighted the influence serotonin has on neuroplasticity. These effects have been predominantly demonstrated during emotional relearning which is theorized as a possible model for depression. However, translation of these mechanisms is in its infancy. To this end, we assessed changes in effective connectivity at rest and during associative learning as a proxy of neuroplastic changes in healthy volunteers. 76 participants underwent 6 weeks of emotional or non-emotional (re)learning (face-matching or Chinese character-German noun matching). During relearning participants either self-administered 10 mg/day of the selective serotonin reuptake inhibitor (SSRI) escitalopram or placebo in a double-blind design. Associative learning tasks, resting-state and structural images were recorded before and after both learning phases (day 1, 21 and 42). Escitalopram intake modulated relearning changes in a network encompassing the right insula, anterior cingulate cortex and right angular gyrus. Here, the process of relearning during SSRI intake showed a greater decrease in effective connectivity from the right insula to both the anterior cingulate cortex and right angular gyrus, with increases in the opposite direction when compared to placebo. In contrast, intrinsic connections and those at resting-state were only marginally affected by escitalopram. Further investigation of gray matter volume changes in these functionally active regions revealed no significant SSRI-induced structural changes. These findings indicate that the right insula plays a central role in the process of relearning and SSRIs further potentiate this effect. In sum, we demonstrated that SSRIs amplify learning-induced effective connections rather than affecting the intrinsic task connectivity or that of resting-state.

The association between mnemonic discrimination ability and differential fear learning.

BACKGROUND AND OBJECTIVES: It is important to be able to learn which stimuli in our surroundings predict aversive outcomes. To maintain emotional well-being, it is similarly important to be able to learn which stimuli predict safety. The ability to discriminate between stimuli that predict danger and safety has been suggested to not only have an emotional component, but also a cognitive one. One such candidate mechanism is mnemonic discrimination (MD), the ability to differentiate between two memories that are similar but not identical. In the present study, we wanted to examine if MD performance helps to explain inter-individual differences in the ability to acquire a differentiated fear response during fear conditioning. METHODS: Participants performed a task assessing MD ability, and then underwent a fear conditioning procedure. Fear responses were measured using skin conductance responses (SCRs). RESULTS: Results revealed no support for MD ability being associated with to which degree a differentiated fear response was acquired, or with the time needed to acquire such a response. LIMITATIONS: Our only outcome measurement was SCRs. Future studies need to include fear ratings, expectancy ratings and neural responses. Future studies also need to examine this using a stimulus material where the conditioned stimulus and the safety stimulus are more difficult to distinguish from each other. CONCLUSIONS: If MD ability has a role in inhibiting overgeneralization of fear learning, this does not seem to be driven by MD already during the initial learning.

Associative recognition without hippocampal associations.

Whereas both human and animal lesion and human neuroimaging studies have implicated the hippocampus in memory for associations, some studies find preserved associative memory following hippocampal damage. Starting with a classic summed similarity model of item recognition, we can account for associative recognition without assuming a specific hippocampally-mediated associative process. We add one key assumption: that one item can influence activation of another item's features. Feature-strength patterns, evaluated for each probe item individually, are then diagnostic of whether an item was paired with one item versus another. We suggest that feature-level inference, without explicit storage of associations, may play a critical role in associative recognition tasks. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Selective expression of the neurexin substrate for presenilin in the adult forebrain causes deficits in associative memory and presynaptic plasticity.

Presenilins (PS) form the active subunit of the gamma-secretase complex, which mediates the proteolytic clearance of a broad variety of type-I plasma membrane proteins. Loss-of-function mutations in PSEN1/2 genes are the leading cause of familial Alzheimer's disease (fAD). However, the PS/gamma-secretase substrates relevant for the neuronal deficits associated with a loss of PS function are not completely known. The members of the neurexin (Nrxn) family of presynaptic plasma membrane proteins are candidates to mediate aspects of the synaptic and memory deficits associated with a loss of PS function. Previous work has shown that fAD-linked PS mutants or inactivation of PS by genetic and pharmacological approaches failed to clear Nrxn C-terminal fragments (NrxnCTF), leading to its abnormal accumulation at presynaptic terminals. Here, we generated transgenic mice that selectively recreate the presynaptic accumulation of NrxnCTF in adult forebrain neurons, leaving unaltered the function of PS/gamma-secretase complex towards other substrates. Behavioral characterization identified selective impairments in NrxnCTF mice, including decreased fear-conditioning memory. Electrophysiological recordings in medial prefrontal cortex-basolateral amygdala (mPFC-BLA) of behaving mice showed normal synaptic transmission and uncovered specific defects in synaptic facilitation. These data functionally link the accumulation of NrxnCTF with defects in associative memory and short-term synaptic plasticity, pointing at impaired clearance of NrxnCTF as a new mediator in AD.