Prenatal ethanol exposure impairs sensory processing and habituation to visual stimuli, effects normalized by enrichment of postnatal environmental.

BACKGROUND: Individuals with fetal alcohol spectrum disorders (FASD) often show processing deficits in all sensory modalities. Using an operant light reinforcement model, we tested whether prenatal ethanol exposure (PE) alters operant responding to elicit a contingent sensory stimulus-light onset (turning on the light) and habituation to this behavior in rats. We also explored whether postnatal environmental enrichment could ameliorate PE-induced deficits. METHODS: Pregnant Sprague Dawley rats were gavaged twice/day with 0 or 3 g/kg/treatment ethanol (15% w/v) during gestational days 8-20, mimicking second-trimester heavy PE in humans. The offspring were reared in a standard housing condition or an enriched condition. Adult male and female offspring underwent an operant light reinforcement experiment with either a short-access or a long-access procedure. A dishabituation test was also conducted to characterize the habituation process. RESULTS: In the short-access procedure, PE led to increased operant responding to the contingent light onset in both sexes reared in the standard housing condition. Such an effect was not observed in rats reared in enriched conditions due to an overall decrease in responding. Moreover, rats reared in enriched conditions showed greater short-term habituation. In the long access procedure, PE rats showed increased responding and impaired long-term habituation. The long-access procedure facilitated both short-term and long-term habituation in control and PE rats. CONCLUSION: Prenatal ethanol exposure increases responding to contingent light onset and impairs the long-term habituation process. The PE-induced deficits were ameliorated by rearing in the enriched environment and increasing the duration and frequency of exposure to light onset. The PE-induced effects are like increased sensation-seeking, a subtype of sensory-processing deficit that is often observed in individuals with FASD. Our findings could inform a suitable animal model for investigating the underlying mechanisms and possible intervention strategies for sensory deficits in FASD.

Stimulus generalization as a mechanism for learning to trust.

How do humans learn to trust unfamiliar others? Decisions in the absence of direct knowledge rely on our ability to generalize from past experiences and are often shaped by the degree of similarity between prior experience and novel situations. Here, we leverage a stimulus generalization framework to examine how perceptual similarity between known individuals and unfamiliar strangers shapes social learning. In a behavioral study, subjects play an iterative trust game with three partners who exhibit highly trustworthy, somewhat trustworthy, or highly untrustworthy behavior. After learning who can be trusted, subjects select new partners for a second game. Unbeknownst to subjects, each potential new partner was parametrically morphed with one of the three original players. Results reveal that subjects prefer to play with strangers who implicitly resemble the original player they previously learned was trustworthy and avoid playing with strangers resembling the untrustworthy player. These decisions to trust or distrust strangers formed a generalization gradient that converged toward baseline as perceptual similarity to the original player diminished. In a second imaging experiment we replicate these behavioral gradients and leverage multivariate pattern similarity analyses to reveal that a tuning profile of activation patterns in the amygdala selectively captures increasing perceptions of untrustworthiness. We additionally observe that within the caudate adaptive choices to trust rely on neural activation patterns similar to those elicited when learning about unrelated, but perceptually familiar, individuals. Together, these findings suggest an associative learning mechanism efficiently deploys moral information encoded from past experiences to guide future choice.

Neutral but not in the middle: cross-cultural comparisons of negative bias of "neutral" emotional stimuli.

Previous studies have shown that the perception of neutral emotion stimuli can be negative rather than absolutely neutral. In the current study, we examined the negative bias of both neutral faces and scenes, cross-culturally between East Asians (e.g. Koreans) and Caucasian Americans. In all experiments, participants performed a Go/No-go task, by either executing or withholding a response toward neutral stimuli presented in the context of positive or negative stimuli. Differentiating neutral stimuli from negative stimuli was less accurate, measured in d', than doing so from positive stimuli. This negative bias was evident with both faces (Experiments 1 and 2) and scenes (Experiment 3). In all experiments, while both ethnic groups demonstrated significant negative biases, there was a subtle modulation of the bias by cultural background. For example, for Korean faces and IAPS scenes, Koreans showed a mitigated negative bias and Caucasian Americans demonstrated a greater negative bias. However, for Caucasian faces, bias was comparable between the two groups. With the possibility of cultural modulation, the prevalent negative bias of neutral emotion questions the validity of the neutrality assumption of the neutral emotion. The study discusses the necessity of methodological and theoretical reconsiderations for the utilisation of neutral emotion stimuli.

Perspectives on fear generalization and its implications for emotional disorders.

Although generalization to conditioned stimuli is not a new phenomenon, renewed interest in understanding its biological underpinning has stemmed from its association with a number of anxiety disorders. Generalization as it relates to fear processing is a temporally dynamic process in which animals, including humans, display fear in response to similar yet distinct cues or contexts as the time between training and testing increases. This Review surveys the literature on contextual fear generalization and its relation to several views of memory, including systems consolidation, forgetting, and transformation hypothesis, which differentially implicate roles of the hippocampus and neocortex in memory consolidation and retrieval. We discuss recent evidence on the neurobiological mechanisms contributing to the increase in fear generalization over time and how generalized responding may be modulated by acquisition, consolidation, and retrieval mechanisms. Whereas clinical perspectives of generalization emphasize a lack of fear inhibition to CS- cues or fear toward intermediate CS cues, the time-dependent nature of generalization and its relation to traditional views on memory consolidation and retrieval are often overlooked. Understanding the time-dependent increase in fear generalization has important implications not only for understanding how generalization contributes to anxiety disorders but also for understanding basic long-term memory function. © 2016 Wiley Periodicals, Inc.

Asymmetry in the discrimination of quantity by rats: The role of the intertrial interval.

In three experiments, rats were trained to discriminate between 20 and five (Exps. 1 and 2), or between 40 and five (Exp. 3), black squares. The squares were randomly distributed in the center of a white background and displayed on a computer screen. For one group, the patterns containing the higher quantity of squares signaled the delivery of sucrose (+), whilst patterns with the lower quantity of squares did not (-). For the second group, sucrose was signaled by the lower, but not by the higher, quantity of squares. In Experiment 1, the intertrial interval (ITI) was a white screen, and the 20+/5- discrimination was acquired more readily than the 5+/20- discrimination. For Experiment 2, the ITI was made up of 80 black squares on a white background. In this instance, the 5+/20- discrimination was acquired more successfully than the 20+/5- discrimination. In Experiment 3, two groups were trained with a 40+/5- discrimination, and two with a 5+/40- discrimination. For one group from each of these pairs, the training trials were separated by a white ITI, and the 40+/5- discrimination was acquired more readily than the 5+/40- discrimination. For the remaining two groups, the training trials were not separated by an ITI, and the two groups acquired the task at approximately the same rate. The results indicate that the cues present during the ITI play a role in the asymmetrical acquisition of magnitude discriminations based on quantity.

Dried bonito dashi: taste qualities evaluated using conditioned taste aversion methods in wild-type and T1R1 knockout mice.

The primary taste of dried bonito dashi is thought to be umami, elicited by inosine 5'-monphosphate (IMP) and L-amino acids. The present study compared the taste qualities of 25% dashi with 5 basic tastes and amino acids using conditioned taste aversion methods. Although wild-type C57BL/6J mice with compromised olfactory systems generalized an aversion of dashi to all 5 basic tastes, generalization was greater to sucrose (sweet), citric acid (sour), and quinine (bitter) than to NaCl (salty) or monosodium L-glutamate (umami) with amiloride. At neutral pH (6.5-6.9), the aversion generalized to l-histidine, L-alanine, L-proline, glycine, L-aspartic acid, L-serine, and monosodium L-glutamate, all mixed with IMP. Lowering pH of the test solutions to 5.7-5.8 (matching dashi) with HCl decreased generalization to some amino acids. However, adding lactic acid to test solutions with the same pH increased generalization to 5'-inosine monophosphate, L-leucine, L-phenylalanine, L-valine, L-arginine, and taurine but eliminated generalization to L-histidine. T1R1 knockout mice readily learned the aversion to dashi and generalized the aversion to sucrose, citric acid, and quinine but not to NaCl, glutamate, or any amino acid. These results suggest that dashi elicits a complex taste in mice that is more than umami, and deleting T1R1 receptor altered but did not eliminate their ability to taste dashi. In addition, lactic acid may alter or modulate taste transduction or cell-to-cell signaling.

Effects of Serial Multiple Exemplar Training on Bidirectional Naming in Children with Autism.

This study examined the effect of a serial multiple exemplar training (S-MET) procedure on bidirectional naming (BiN) in four preschool children diagnosed with autism spectrum disorder (ASD). A non-concurrent multiple baseline design was used to evaluate the effects of training listener and speaker behavior for one stimulus at a time until BiN occurred. When BiN occurred, probes were conducted to measure whether generalization occurred across settings and people. Three out of four participants' responding met the mastery criterion for BiN, while the fourth participant improved her performance. The results of this study suggest that S-MET may be a promising intervention and contribute to our knowledge about learning histories required for BiN.

Gamma band plasticity in sensory cortex is a signature of the strongest memory rather than memory of the training stimulus.

Gamma oscillations (∼30-120Hz) are considered to be a reflection of coordinated neuronal activity, linked to processes underlying synaptic integration and plasticity. Increases in gamma power within the cerebral cortex have been found during many cognitive processes such as attention, learning, memory and problem solving in both humans and animals. However, the specificity of gamma to the detailed contents of memory remains largely unknown. We investigated the relationship between learning-induced increased gamma power in the primary auditory cortex (A1) and the strength of memory for acoustic frequency. Adult male rats (n=16) received three days (200 trials each) of pairing a tone (3.66 kHz) with stimulation of the nucleus basalis, which implanted a memory for acoustic frequency as assessed by associatively-induced disruption of ongoing behavior, viz., respiration. Post-training frequency generalization gradients (FGGs) revealed peaks at non-CS frequencies in 11/16 cases, likely reflecting normal variation in pre-training acoustic experiences. A stronger relationship was found between increased gamma power and the frequency with the strongest memory (peak of the difference between individual post- and pre-training FGGs) vs. behavioral responses to the CS training frequency. No such relationship was found for the theta/alpha band (4-15 Hz). These findings indicate that the strength of specific increased neuronal synchronization within primary sensory cortical fields can determine the specific contents of memory.

Modeling relational responding with artificial neural networks.

Relational responding refers to behavior that conforms to a rule for com- paring stimuli. Lazareva et al. (2014) trained pigeons to choose either the smaller or the larger of two circles, using 1-3 pairs of circles for training and 17-19 new pairs for testing. The pigeons showed relational responding on some test pairs and systematic failures on others. We present a simple artificial neural network model that reproduces the animals' behavior well, similarly to Lazareva et al.'s (2014) statistical model based on stimulus features and stimulus relationships. We analyze how the network model gener- alizes from training to test stimuli, and show that it can reconcile contrasting ideas about relational responding from the seminal works by Köhler (1929, 1918/1938, 1924), positing that animals can learn relational rules such as "choose the larger stimulus," and Spence (1937), positing that relational re- sponding can be explained based on stimulus generalization.

Behavioral and anatomical evidence for electroreception in the bottlenose dolphin (Tursiops truncatus).

In the order of cetacean, the ability to detect bioelectric fields has, up to now, only been demonstrated in the Guiana dolphin (Sotalia guianensis) and is suggested to facilitate benthic feeding. As this foraging strategy has also been reported for bottlenose dolphins (Tursiops truncatus), we studied electroreception in this species by combining an anatomical analysis of "vibrissal crypts" as potential electroreceptors from neonate and adult animals with a behavioral experiment. In the latter, four bottlenose dolphins were trained on a go/no-go paradigm with acoustic stimuli and afterward tested for stimulus generalization within and across modalities using acoustic, optical, mechanical, and electric stimuli. While neonates still possess almost complete vibrissal follicles including a hair shaft, hair papilla, and cavernous sinus, adult bottlenose dolphins lack these features. Thus, their "vibrissal crypts" show a similar postnatal morphological transformation from a mechanoreceptor to an electroreceptor as in Sotalia. However, innervation density was high and almost equal in both, neonate as well as adult animals. In the stimulus generalization tests the dolphins transferred the go/no-go response within and across modalities. Although all dolphins responded spontaneously to the first presentation of a weak electric field, only three of them showed perfect transfer in this modality by responding continuously to electric field amplitudes of 1.5 mV cm-1 , successively reduced to 0.5 mV cm-1 . Electroreception can explain short-range prey detection in crater-feeding bottlenose dolphins. The fact that this is the second odontocete species with experimental evidence for electroreception suggests that it might be widespread in this marine mammal group.

Stimulus generalization of behavioral history: Interspecies generality and persistence of generalization gradients.

Four pigeons were exposed to a tandem variable-interval (VI) fixed-ratio (FR) schedule in the presence of a 50-pixel (about 15 mm) square or an 80-pixel (about 24 mm) square and to a tandem VI differential-reinforcement-of-low-rate (DRL) schedule when a second 80-pixel or 50-pixel square was present. The values of the VI and FR schedules were adjusted to equate reinforcement rates in the two tandem schedules. Following this, a square-size continuum generalization test was administered under a fixed-interval (FI) schedule or extinction. In the first testing session, response frequency was a graded function of the similarity of the test stimuli to the training stimuli for all pigeons. These systematic generalization gradients persisted longer under the FI schedule than under extinction.

Generalization of conditioned disgust and the attendant maladaptive avoidance: Validation of a novel paradigm and effects of trait disgust-proneness.

Overgeneralization of conditioned fear to safe stimuli that resemble a previously-learned threat-cue is a well-studied correlate of clinical anxiety, yet whether conditioned disgust generalizes remains unknown, as does the extent to which such generalization is associated with disgust-related traits and maladaptive outcomes. The present study addresses this gap by adapting a validated fear-generalization paradigm to assess conditioned disgust and behavioral avoidance to a disgust-cue (CS+) paired with a disgusting video clip, and safe generalization stimuli parametrically varying in perceptual similarity to CS+. For comparison, levels of fear generalization were also assessed using the original fear-generalization paradigm. In both paradigms, costly and unnecessary avoidance to safe threat-cue approximations analogues maladaptive outcomes of generalization. In the disgust paradigm only, disgust-proneness was associated with elevated perceived risk to safe stimuli and increases in the extent to which such elevations were accompanied by maladaptive avoidance. Comparable levels of generalization, and positive associations between generalization and maladaptive avoidance, were found across disgust and fear paradigms. Results confirm that conditioned disgust is subject to generalization, implicate generalized disgust as a source of maladaptive avoidance particularly among those prone to disgust, and suggest a potential role for these processes in the etiology and maintenance of disgust-related disorders.

Knockout of the Serotonin Transporter in the Rat Mildly Modulates Decisional Anhedonia.

Serotonin transporter gene variance has long been considered an essential factor contributing to depression. However, meta-analyses yielded inconsistent findings recently, asking for further understanding of the link between the gene and depression-related symptoms. One key feature of depression is anhedonia. While data exist on the effect of serotonin transporter gene knockout (5-HTT-/-) in rodents on consummatory and anticipatory anhedonia, with mixed outcomes, the effect on decisional anhedonia has not been investigated thus far. Here, we tested whether 5-HTT-/- contributes to decisional anhedonia. To this end, we established a novel touchscreen-based go/go task of visual decision-making. During the learning of stimulus discrimination, 5-HTT+/+ rats performed more optimal decision-making compared to 5-HTT-/- rats at the beginning, but this difference did not persist throughout the learning period. During stimulus generalization, the generalization curves were similar between both genotypes and did not alter as the learning progress. Interestingly, the response time in 5-HTT+/+ rats increased as the session increased in general, while 5-HTT-/- rats tended to decrease. The response time difference might indicate that 5-HTT-/- rats altered willingness to exert cognitive effort to the categorization of generalization stimuli. These results suggest that the effect of 5-HTT ablation on decisional anhedonia is mild and interacts with learning, explaining the discrepant findings on the link between 5-HTT gene and depression.

Learning Channels: The Role of Compound Stimuli in the Emergence of Intraverbal Relations in Children on the Autism Spectrum.

Teaching tact and intraverbal responses based on function-feature-class to children with language delays can result in the emergence of untrained relational responses. The purpose of this study was to compare the effects of compound stimuli in discriminated operants (i.e., different combinations of hear, see, touch, and taste) on the acquisition of object-attribute relations, on the emergence of untrained attribute-object relations, and on the acquisition and emergence of same-different relations between objects and their attributes. All the participants were on the autism spectrum and between 4 and 12 years old. Participants who did not meet the mastery criterion or show emergent intraverbal responses during initial training trials completed a fluency-based practice phase. Overall results showed that all six participants required fewer trials to meet the criterion in the condition involving compound stimuli (e.g., HearSeeSay plus Touch, Taste, or Sniff) as compared to the HearSeeSay-alone condition. In addition, participants required fewer fluency practice timings in the condition involving compound stimuli to meet fluency aim.

The influence of correlations between noncritical features and reinforcement on stimulus generalization.

One strategy to program for generalization is to vary noncritical features in teaching exemplars, thereby avoiding noncritical features from being highly correlated with reinforcement and thus gaining faulty stimulus control. In the current translational evaluation, 2 groups of adults of typical development were taught to respond to arbitrary stimuli with experimenter-defined critical and noncritical features in a matching-to-sample task. The teaching arrangement used for 1 group programmed for low correlation between noncritical features and reinforcement; the teaching arrangement used for the other group programmed for high correlation between noncritical features and reinforcement. Participants in the former group displayed (a) faster acquisition of matching, (b) less variability in correct responding, and (c) a decreased likelihood of faulty stimulus control developing during training. The results contribute towards advancing the study of stimulus control and developing an explicit technology of generalization to better serve consumers of the application of our science.

Generalization of response patterns in a multiple peak procedure.

Stimulus generalization is typically assessed by analyzing overall response rates. Studies of generalization of response-rate patterns across time are less common, despite the ubiquitous nature of time and the strong temporal control over behavior in the natural world. Thus, we investigated generalization of response-rate patterns across time using a multiple peak procedure in pigeons. The frequency (fast or slow) at which the color of a keylight changed signaled a fixed-interval (FI) 5-s or 20-s schedule, counterbalanced across subjects. In peak trials, the frequency of keylight-color changes was varied. For the fast and slow training stimuli, response rates in peak trials were controlled by the arranged FI schedule value; they increased as the arranged reinforcer time approached, and decreased thereafter. Response-rate patterns to all test stimuli were similar to response-rate patterns to the slow training stimulus for all subjects. Thus, overall, strong generalization from the slow training stimulus to all test stimuli was evident, whereas there was little to no generalization from the fast training stimulus. These findings extend past research examining generalization of temporally controlled response-rate patterns, and provide a useful starting point for future investigations of generalization of fixed-interval responding. A thorough understanding of generalization processes requires analysis of dependent variables other than overall response rates, especially when responding is likely to be temporally controlled.

Improving the Reliability of Tinnitus Screening in Laboratory Animals.

Behavioral screening remains a contentious issue for animal studies of tinnitus. Most paradigms base a positive tinnitus test on an animal's natural tendency to respond to the "sound" of tinnitus as if it were an actual sound. As a result, animals with tinnitus are expected to display sound-conditioned behaviors when no sound is present or to miss gaps in background sounds because tinnitus "fills in the gap." Reliable confirmation of the behavioral indications of tinnitus can be problematic because the reinforcement contingencies of conventional discrimination tasks break down an animal's tendency to group tinnitus with sound. When responses in silence are rewarded, animals respond in silence regardless of their tinnitus status. When responses in silence are punished, animals stop responding. This study introduces stimulus classification as an alternative approach to tinnitus screening. Classification procedures train animals to respond to the common perceptual features that define a group of sounds (e.g., high pitch or narrow bandwidth). Our procedure trains animals to drink when they hear tinnitus and to suppress drinking when they hear other sounds. Animals with tinnitus are revealed by their tendency to drink in the presence of unreinforced probe sounds that share the perceptual features of the tinnitus classification. The advantages of this approach are illustrated by taking laboratory rats through a testing sequence that includes classification training, the experimental induction of tinnitus, and postinduction screening. Behavioral indications of tinnitus are interpreted and then verified by simulating a known tinnitus percept with objective sounds.

Similar to the category, but not the exemplars: A study of generalization.

Reference point approaches have dominated the study of categorization for decades by explaining classification learning in terms of similarity to stored exemplars or averages of exemplars. The most successful reference point models are firmly grounded in the associative learning tradition-treating categorization as a stimulus generalization process based on inverse exponential distance in psychological space augmented by a dimensional selective attention mechanism. We present experiments that pose a significant challenge to popular reference point accounts which explain categorization in terms of stimulus generalization from exemplars, prototypes, or adaptive clusters. DIVA, a similarity-based alternative to the reference point framework, provides a successful account of the human data. These findings suggest that a successful psychology of categorization may need to look beyond stimulus generalization and toward a view of category learning as the induction of a richer model of the data.

Generalization of the disruptive effects of alternative stimuli when combined with target stimuli in extinction.

Differential-reinforcement treatments reduce target problem behavior in the short term but at the expense of making it more persistent long term. Basic and translational research based on behavioral momentum theory suggests that combining features of stimuli governing an alternative response with the stimuli governing target responding could make target responding less persistent. However, changes to the alternative stimulus context when combining alternative and target stimuli could diminish the effectiveness of the alternative stimulus in reducing target responding. In an animal model with pigeons, the present study reinforced responding in the presence of target and alternative stimuli. When combining the alternative and target stimuli during extinction, we altered the alternative stimulus through changes in line orientation. We found that (1) combining alternative and target stimuli in extinction more effectively decreased target responding than presenting the target stimulus on its own; (2) combining these stimuli was more effective in decreasing target responding trained with lower reinforcement rates; and (3) changing the alternative stimulus reduced its effectiveness when it was combined with the target stimulus. Therefore, changing alternative stimuli (e.g., therapist, clinical setting) during behavioral treatments that combine alternative and target stimuli could reduce the effectiveness of those treatments in disrupting problem behavior.

Distraction/Suppression and Distress Endurance diminish the extent to which generalized conditioned fear is associated with maladaptive behavioral avoidance.

A central conditioning correlate of clinical anxiety is the over-generalization of Pavlovian fear to safe stimuli resembling conditioned danger cues (CS+). Though much of the pathogenic influence of such generalization may lie in the unnecessary behavioral avoidance it evokes, few studies have examined maladaptive avoidance associated with Pavlovian generalization. Lab-based assessments of this process, here referred to as instrumental avoidance from Pavlovian generalization (IAP-G), have recently begun. The current study represents a next step in this line of work by examining personality factors that may reduce maladaptive IAP-G. This is a clinically relevant effort, as such traits may reflect resilience factors, with high levels reducing the likelihood of maladaptive generalized avoidance following Pavlovian generalization. Here we focus on the effects of Distraction/Suppression (DS) and Distress Endurance (DE) on IAP-G. Results indicate that both DS and DE moderate IAP-G by weakening relations between Pavlovian generalization of fear-potentiated startle and maladaptive generalized avoidance. Further, moderating effects of DS were most pronounced for more ambiguous cues of threat (i.e., stimuli moderately resembling CS+), while moderating effects of DE were most pronounced for more certain cues of threat (i.e., stimuli highly resembling CS+, as well as the CS + itself). Results implicate DS and DE as protective factors against the maladaptive behavioral consequences of Pavlovian generalization, and further indicate that the protective influence of these traits may depend on the ambiguity of the threat at hand.