The BTBR Mouse Model of Autism Spectrum Disorders Has Learning and Attentional Impairments and Alterations in Acetylcholine and Kynurenic Acid in Prefrontal Cortex

Autism is a complex spectrum of disorders characterized by core behavioral deficits in social interaction, communication, repetitive stereotyped behaviors and restricted interests. Autism frequently presents with additional cognitive symptoms, including attentional deficits and intellectual disability. Preclinical models are important tools for studying the behavioral domains and biological underpinnings of autism, and potential treatment targets. The inbred BTBR T+tf/J (BTBR) mouse strain has been used as an animal model of core behavioral deficits in autism. BTBR mice exhibit repetitive behaviors and deficits in sociability and communication, but other aspects of their cognitive phenotype, including attentional performance, are not well characterized. We examined the attentional abilities of BTBR mice in the 5-choice serial reaction time task (5-CSRTT) using an automated touchscreen testing apparatus. The 5-CSRTT is an analogue of the human continuous performance task of attention, and so both the task and apparatus have translational relevance to human touchscreen cognitive testing. We also measured basal extracellular levels of a panel of neurotransmitters within the medial prefrontal cortex, a brain region critically important for performing the 5-CSRTT. We found that BTBR mice have increased impulsivity, defined as an inability to withhold responding, and decreased motivation, as compared to C57Bl/6J mice. Both of these features characterize attentional deficit disorders in humans. BTBR mice also display decreased accuracy in detecting short stimuli, lower basal levels of extracellular acetylcholine and higher levels of kynurenic acid within the prefrontal cortex. Intact cholinergic transmission in prefrontal cortex is required for accurate performance of the 5-CSRTT, consequently this cholinergic deficit may underlie less accurate performance in BTBR mice. Based on our findings that BTBR mice have attentional impairments and alterations in a key neural substrate of attention, we propose that they may be valuable for studying mechanisms for treatment of cognitive dysfunction in individuals with attention deficits and autism.     

Moderate prenatal alcohol exposure impairs cognitive control,but not attention,on a rodent touchscreen continuous performance task

A common feature associated with fetal alcohol spectrum disorders is the inability to concentrate on a specific task while ignoring distractions. Human continuous performance tasks (CPT), measure vigilance and cognitive control simultaneously while these processes are traditionally measured separately in rodents. We recently established a touchscreen 5-choice CPT (5C-CPT) that measures vigilance and cognitive control simultaneously by incorporating both target and nontargets and showed it was sensitive to amphetamine-induced improvement in humans and mice. Here, we examined the effects of moderate prenatal alcohol exposure (PAE) in male and female mice on performance of the 5-choice serial reaction time task (5-CSRTT), which contained only target trials, and the 5C-CPT which incorporated both target and nontarget trials. In addition, we assessed gait and fine motor coordination in behavioral naïve PAE and control animals. We found that on the 5-CSRTT mice were able to respond to target presentations with similar hit rates regardless of sex or treatment. However, on the 5C-CPT PAE mice made significantly more false alarm responses vs controls. Compared with control animals, PAE mice had a significantly lower sensitivity index, a measure of ability to discriminate appropriate responses to stimuli types. During 5C-CPT, female mice, regardless of treatment, also had increased mean latency to respond when correct and omitted more target trials. Gait assessment showed no significant differences in PAE and SAC mice on any measure. These findings suggest that moderate exposure to alcohol during development can have long lasting effects on cognitive control unaffected by gross motor alterations.     

Alcohol-Preferring Rats Show Goal Oriented Behaviour to Food Incentives but Are Neither Sign-Trackers Nor Impulsive

Drug addiction is often associated with impulsivity and altered behavioural responses to both primary and conditioned rewards. Here we investigated whether selectively bred alcohol-preferring (P) and alcohol-nonpreferring (NP) rats show differential levels of impulsivity and conditioned behavioural responses to food incentives. P and NP rats were assessed for impulsivity in the 5-choice serial reaction time task (5-CSRTT), a widely used translational task in humans and other animals, as well as Pavlovian conditioned approach to measure sign- and goal-tracking behaviour. Drug-naïve P and NP rats showed similar levels of impulsivity on the 5-CSRTT, assessed by the number of premature, anticipatory responses, even when the waiting interval to respond was increased. However, unlike NP rats, P rats were faster to enter the food magazine and spent more time in this area. In addition, P rats showed higher levels of goal-tracking responses than NP rats, as measured by the number of magazine nose-pokes during the presentation of a food conditioned stimulus. By contrast, NP showed higher levels of sign-tracking behaviour than P rats. Following a 4-week exposure to intermittent alcohol we confirmed that P rats had a marked preference for, and consumed more alcohol than, NP rats, but were not more impulsive when re-tested in the 5-CSRTT. These findings indicate that high alcohol preferring and drinking P rats are neither intrinsically impulsive nor do they exhibit impulsivity after exposure to alcohol. However, P rats do show increased goal-directed behaviour to food incentives and this may be associated with their strong preference for alcohol.     

Deletion of alpha-synuclein decreases impulsivity in mice

The presynaptic protein alpha-synuclein, associated with Parkinson's Disease (PD), plays a role in dopaminergic neurotransmission and is implicated in impulse control disorders (ICDs) such as drug addiction. In this study we investigated a potential causal relationship between alpha-synuclein and impulsivity, by evaluating differences in motor impulsivity in the 5-choice serial reaction time task (5-CSRTT) in strains of mice that differ in the expression of the alpha-synuclein gene. C57BL/6JOlaHsd mice differ from their C57BL/6J ancestors in possessing a chromosomal deletion resulting in the loss of two genes, snca, encoding alpha-synuclein, and mmrn1, encoding multimerin-1. C57BL/6J mice displayed higher impulsivity (more premature responding) than C57BL/6JOlaHsd mice when the pre-stimulus waiting interval was increased in the 5-CSRTT. In order to ensure that the reduced impulsivity was indeed related to snca, and not adjacent gene deletion, wild type (WT) and mice with targeted deletion of alpha-synuclein (KO) were tested in the 5-CSRTT. Similarly, WT mice were more impulsive than mice with targeted deletion of alpha-synuclein. Interrogation of our ongoing analysis of impulsivity in BXD recombinant inbred mouse lines revealed an association of impulsive responding with levels of alpha-synuclein expression in hippocampus. Expression of beta- and gamma-synuclein, members of the synuclein family that may substitute for alpha-synuclein following its deletion, revealed no differential compensations among the mouse strains. These findings suggest that alpha-synuclein may contribute to impulsivity and potentially, to ICDs which arise in some PD patients treated with dopaminergic medication.     

Cannabinoid CB1 receptor activation mediates the opposing effects of amphetamine on impulsive action and impulsive choice

It is well known that acute challenges with psychostimulants such as amphetamine affect impulsive behavior. We here studied the pharmacology underlying the effects of amphetamine in two rat models of impulsivity, the 5-choice serial reaction time task (5-CSRTT) and the delayed reward task (DRT), providing measures of inhibitory control, an aspect of impulsive action, and impulsive choice, respectively. We focused on the role of cannabinoid CB1 receptor activation in amphetamine-induced impulsivity as there is evidence that acute challenges with psychostimulants activate the endogenous cannabinoid system, and CB1 receptor activity modulates impulsivity in both rodents and humans. Results showed that pretreatment with either the CB1 receptor antagonist/inverse agonist SR141716A or the neutral CB1 receptor antagonist O-2050 dose-dependently improved baseline inhibitory control in the 5-CSRTT. Moreover, both compounds similarly attenuated amphetamine-induced inhibitory control deficits, suggesting that CB1 receptor activation by endogenously released cannabinoids mediates this aspect of impulsive action. Direct CB1 receptor activation by Δ9-Tetrahydrocannabinol (Δ9-THC) did, however, not affect inhibitory control. Although neither SR141716A nor O-2050 affected baseline impulsive choice in the DRT, both ligands completely prevented amphetamine-induced reductions in impulsive decision making, indicating that CB1 receptor activity may decrease this form of impulsivity. Indeed, acute Δ9-THC was found to reduce impulsive choice in a CB1 receptor-dependent way. Together, these results indicate an important, though complex role for cannabinoid CB1 receptor activity in the regulation of impulsive action and impulsive choice as well as the opposite effects amphetamine has on both forms of impulsive behavior.     

Ventilation response thresholds do not change with age or self-reinforcement in workers of the bumble bee Bombus impatiens

The response threshold model is a potential mechanism for task allocation in social insects, and it assumes that workers vary in the levels of task stimuli to which they respond. Furthermore, response thresholds of individual workers may change over time through self-reinforcement (experience), such that workers become more sensitive to task stimuli. However, in addition to self-reinforcement, aging is another process that occurs through time. Distinguishing whether response thresholds change within workers due to self-reinforcement or aging may give insight into the flexibility of this task allocation mechanism. Using a ventilation paradigm, we manipulated workers of Bombus impatiens to have either repeated or lack of exposures to increases in nest air temperature, thereby allowing us to manipulate experience and thus self-reinforcement. Nest air temperature was the task stimulus, and ventilation (fanning) was the behavioral response. We found that ventilation response thresholds do not decrease either with age or experience in workers of B. impatiens, contrary to what has been reported for B. terrestris workers (Weidenmüller, 2004). Instead, we found high levels of intra-individual variation in response thresholds. Our results also show that workers with lower average response thresholds respond to heating events with higher probability than those with higher ventilation thresholds. These results provide insight into the role of the response threshold framework for task allocation; we also discuss how response probabilities may play a role in task allocation among workers.     

Prefrontal neurons predict choices during an auditory same-different task

The detection of stimuli is critical for an animal's survival [1]. However, it is not adaptive for an animal to respond automatically to every stimulus that is present in the environment [2-5]. Given that the prefrontal cortex (PFC) plays a key role in executive function [6-8], we hypothesized that PFC activity should be involved in context-dependent responses to uncommon stimuli. As a test of this hypothesis, monkeys participated in a same-different task, a variant of an oddball task [2]. During this task, a monkey heard multiple presentations of a "reference" stimulus that were followed by a "test" stimulus and reported whether these stimuli were the same or different. While they participated in this task, we recorded from neurons in the ventrolateral prefrontal cortex (vPFC; a cortical area involved in aspects of nonspatial auditory processing [9, 10]). We found that vPFC activity was correlated with the monkeys' choices. This finding demonstrates a direct link between single neurons and behavioral choices in the PFC on a nonspatial auditory task.     

Oscillatory Activity in the Medial Prefrontal Cortex and Nucleus Accumbens Correlates with Impulsivity and Reward Outcome

Actions expressed prematurely without regard for their consequences are considered impulsive. Such behaviour is governed by a network of brain regions including the prefrontal cortex (PFC) and nucleus accumbens (NAcb) and is prevalent in disorders including attention deficit hyperactivity disorder (ADHD) and drug addiction. However, little is known of the relationship between neural activity in these regions and specific forms of impulsive behaviour. In the present study we investigated local field potential (LFP) oscillations in distinct sub-regions of the PFC and NAcb on a 5-choice serial reaction time task (5-CSRTT), which measures sustained, spatially-divided visual attention and action restraint. The main findings show that power in gamma frequency (50–60 Hz) LFP oscillations transiently increases in the PFC and NAcb during both the anticipation of a cue signalling the spatial location of a nose-poke response and again following correct responses. Gamma oscillations were coupled to low-frequency delta oscillations in both regions; this coupling strengthened specifically when an error response was made. Theta (7–9 Hz) LFP power in the PFC and NAcb increased during the waiting period and was also related to response outcome. Additionally, both gamma and theta power were significantly affected by upcoming premature responses as rats waited for the visual cue to respond. In a subgroup of rats showing persistently high levels of impulsivity we found that impulsivity was associated with increased error signals following a nose-poke response, as well as reduced signals of previous trial outcome during the waiting period. Collectively, these in-vivo neurophysiological findings further implicate the PFC and NAcb in anticipatory impulsive responses and provide evidence that abnormalities in the encoding of rewarding outcomes may underlie trait-like impulsive behaviour.     

Shift in the intrinsic excitability of medial prefrontal cortex neurons following training in impulse control and cued-responding tasks

Impulse control is an executive process that allows animals to inhibit their actions until an appropriate time. Previously, we reported that learning a simple response inhibition task increases AMPA currents at excitatory synapses in the prelimbic region of the medial prefrontal cortex (mPFC). Here, we examined whether modifications to intrinsic excitability occurred alongside the synaptic changes. To that end, we trained rats to obtain a food reward in a response inhibition task by withhold responding on a lever until they were signaled to respond. We then measured excitability, using whole-cell patch clamp recordings in brain slices, by quantifying action potentials generated by the injection of depolarizing current steps. Training in this task depressed the excitability of layer V pyramidal neurons of the prelimbic, but not infralimbic, region of the mPFC relative to behavioral controls. This decrease in maximum spiking frequency was significantly correlated with performance on the final session of the task. This change in intrinsic excitability may represent a homeostatic mechanism counterbalancing increased excitatory synaptic inputs onto those neurons in trained rats. Interestingly, subjects trained with a cue that predicted imminent reward availability had increased excitability in infralimbic, but not the prelimbic, pyramidal neurons. This dissociation suggests that both prelimbic and infralimbic neurons are involved in directing action, but specialized for different types of information, inhibitory or anticipatory, respectively.     

Alpha adrenergic modulation on effects of norepinephrine transporter inhibitor reboxetine in five-choice serial reaction time task

The study examined the effects of a norepinephrine transporter (NET) inhibitor reboxetine (RBX) on an attentional performance test. Adult SD rats trained with five-choice serial reaction time task (5-CSRTT) were administered with RBX (0, 3.0 and 10 mg/kg) in the testing day. Alpha-1 adrenergic receptor antagonist PRA and alpha-2 adrenergic receptor antagonist RX821002 were used to clarify the RBX effect. Results revealed that rat received RBX at 10 mg/kg had an increase in the percentage of the correct response and decreases in the numbers of premature response. Alpha-1 adrenergic receptor antagonist Prazosin (PRA) at 0.1 mg/kg reversed the RBX augmented correct responding rate. However, alpha-2 adrenergic receptor antagonist RX821002 at 0.05 and 0.1 mg/kg dose dependently reversed the RBX reduced impulsive responding. Our results suggested that RBX as a norepinephrine transporter inhibitor can be beneficial in both attentional accuracy and response control and alpha-1 and alpha-2 adrenergic receptors might be involved differently.     

Latitudinal variation in thermal ecology of North American ratsnakes and its implications for the effect of climate warming on snakes

Behavioral thermoregulation is expected to be critical in determining the capacity of reptiles to respond to climate warming and how that response will vary with latitude. We used radio-telemetry to compare behavioral thermoregulation among ratsnake (Elaphe obsoleta) populations in Texas, Illinois, and Ontario, a latitudinal distance of >1500 km. Despite numerous specific differences among populations, overall the thermal ecology was surprisingly similar during the months that snakes in all three populations were active. Preferred temperatures varied only slightly across the snakes’ range, the extent of thermoregulation was similar, and by varying when during the day and season they thermoregulated, snakes in all three populations realized body temperatures within their preferred temperature range 15–20% of the time. The ability to use fine-scale behavioral thermoregulation (i.e., selective use of habitats and microclimates) to a similar extent and achieve similar outcomes across such a wide latitudinal and climatic gradient is made possible by large-scale differences in timing of activity (ratsnakes in Texas switch to nocturnal activity during summer, whereas in Illinois and Ontario activity is exclusively diurnal and hibernation lasts 5–7 months). Modeling indicated that a 3 °C increase in ambient temperature will generally improve thermal conditions for all three populations. Our empirical analyses suggest that the snakes’ ability to respond to climate warming will be determined more by their capacity to adjust when they are active than by changes in the extent of fine-scale behavioral thermoregulation. The ability to adjust timing of activity appears to make many snakes fundamentally different from lizards. As such, the consequences of climate warming may be very different for these two groups of reptiles.     

Serial conditional discrimination and temporal bisection in rats selectively lesioned in the dentate gyrus

In positive serial conditional discrimination, animals respond during a target stimulus when it is preceded by a feature stimulus, but they do not respond when the same target stimulus is presented alone. Moreover, the feature and target stimuli are separated from each other by an empty interval. The present work aimed to investigate if two durations (4 or 16 s) of the same feature stimulus (light) could modulate the operant responses of rats to different levers (A and B) during a 5-s target stimulus (tone). In the present study, lever A was associated with the 4-s light, and lever B was associated with the 16-s light. A 5-s empty interval was included between the light and the tone. In the same training procedure, the rats were also presented with the 5-s tone without the preceding light stimuli. In these trials, the responses were not reinforced. We evaluated the hippocampal involvement of these behavioral processes by selectively lesioning the dentate gyrus with colchicine. Once trained, the rats were submitted to a test using probe trials without reinforcement. They were presented with intermediate durations of the feature stimulus (light) to obtain a temporal bisection curve recorded during the exposure to the target stimuli. The rats from both groups learned to respond with high rates during tones preceded by light and with low rates during tones presented alone, which indicated acquisition of the serial conditional discrimination. The rats were able to discriminate between the 4- and 16-s lights by correctly choosing lever A or B. In the test, the temporal bisection curves from both experimental groups showed a bisection point at the arithmetic mean between 4 and 16 s. Such processes were not impaired by the dentate gyrus lesion. Thus, our results showed that different durations of a feature stimulus could result in conditional properties. However, this processing did not appear to depend on the dentate gyrus alone.     

Socially biased learning among adult cottontop tamarins (Saguinus oedipus)

We presented adult cottontop tamarins (Saguinus oedipus) with a novel foraging task that had been used previously to examine socially biased learning of juvenile observers [Humle & Snowdon, Animal Behaviour 75:267–277, 2008]. The task could be solved in one of two ways, and thus allowed for an analysis of behavioral matching between an observer and a skilled demonstrator (trained to use one of the two methods exclusively). Because the demonstrator was an adult in both this study and the juvenile study, the influence of the observer's age could be isolated and examined, as well as the behavior of demonstrators toward observers of different ages. Our main goals were to (1) compare adults and juveniles acquiring the same task to identify how the age of the observer affects socially biased learning and (2) examine the relationship between socially biased learning and behavioral matching in adults. Although adults spent less time observing the trained demonstrators than did juveniles, the adults were more proficient at solving the task. Furthermore, even though observers did not overtly match the behavior of the demonstrator, observation remained an important factor in the success of these individuals. The findings suggested that adult observers could extract information needed to solve a novel foraging task without explicitly matching the behavior of the demonstrator. Adult observers begged much less than juveniles and demonstrators did not respond to begging from adult. Skill acquisition and the process of socially biased learning are, therefore, age‐dependent and are influenced by the behavioral interactions between observer and demonstrator. To what extent this holds true for other primates or animal species still needs to be more fully investigated and considered when designing experiments and interpreting results. Am. J. Primatol. 72:287–295, 2010. © 2009 Wiley‐Liss, Inc.     

Intrusion of stereotyped responding in pigeon spatial memory tasks

Pigeons appear predisposed to respond in stereotyped manners in multi-item spatial memory tasks in which the items are simultaneously presented. We discovered this when we attempted to study primacy and recency serial position effects using a delayed matching of key location task (Experiment 1) and when we attempted to develop a keypack analog of the radial-arm maze task (Experiment 4). In Experiment 1 matching accuracy for first-pecked sample was above chance, approximately chance for the second-pecked sample, and below chance for the third-pecked sample. Experiments 2 and 3 showed that the results of Experiment 1 were due to “superstitious” stereotyped responding: When pigeons were allowed to respond to two or three keys in any order and then respond to the same keys again, they responded in the same order on the second occasion. In Experiment 4, the pigeons successfully avoided pecking previously-pecked keys but did so by pecking the keys in a fixed sequence.     

Enhanced Memory for Scenes Presented at Behaviorally Relevant Points in Time

The ability to remember a briefly presented scene depends on a number of factors, such as its saliency, novelty, degree of threat, or behavioral relevance to a task. Here, however, we show that the encoding of a scene into memory may depend not only on what the scene contains but also when it occurs. Participants performed an attentionally demanding target detection task at fixation while also viewing a rapid sequence of full-field photographs of urban and natural scenes. Participants were then tested on whether they recognized a specific scene from the previous sequence. We found that scenes were recognized reliably only when presented concurrently with a target at fixation. This is evidence of a mechanism where traces of a visual scene are automatically encoded into memory at behaviorally relevant points in time regardless of the spatial focus of attention.     

Naloxone blocks the effect of 5-hydroxy-tryptophan on passive avoidance learning in rats: Implication of endogenous opioid peptides

The synthetic opioid peptide D-Ala²-met-enkephalinamide (DALA) impairs retention performance of rats on a one-trial passive avoidance task. The same effect is observed after administration of 5-hydroxy-tryptophan (5-HTP). Both drugs appear to impair learning by disrupting memory consolidation since similar effects are observed when they are given either peripherally before the acquisition test or intracerebroventricularly immediately after. A moderate dose of naloxone prevents the amnesia produced by DALA or 5-HTP. However, the opiate antagonist does not block the behavioral syndrome induced by clorgyline and 5-HTP. Moreover, bacitracin, a peptidase inhibitor, potentiates the effect of 5-HTP on the passive avoidance task. The results suggest that endogenous opioid peptides are involved in the amnesic effect of 5-HTP.     

Performance deficits of NK1 receptor knockout mice in the 5-choice serial reaction-time task: effects of d-amphetamine, stress and time of day

Background

The neurochemical status and hyperactivity of mice lacking functional substance P-preferring NK1 receptors (NK1R-/-) resemble abnormalities in Attention Deficit Hyperactivity Disorder (ADHD). Here we tested whether NK1R-/- mice express other core features of ADHD (impulsivity and inattentiveness) and, if so, whether they are diminished by d-amphetamine, as in ADHD. Prompted by evidence that circadian rhythms are disrupted in ADHD, we also compared the performance of mice that were trained and tested in the morning or afternoon.

Methods and Results

The 5-Choice Serial Reaction-Time Task (5-CSRTT) was used to evaluate the cognitive performance of NK1R-/- mice and their wildtypes. After training, animals were tested using a long (LITI) and a variable (VITI) inter-trial interval: these tests were carried out with, and without, d-amphetamine pretreatment (0.3 or 1 mg/kg i.p.). NK1R-/- mice expressed greater omissions (inattentiveness), perseveration and premature responses (impulsivity) in the 5-CSRTT. In NK1R-/- mice, perseveration in the LITI was increased by injection-stress but reduced by d-amphetamine. Omissions by NK1R-/- mice in the VITI were unaffected by d-amphetamine, but premature responses were exacerbated by this psychostimulant. Omissions in the VITI were higher, overall, in the morning than the afternoon but, in the LITI, premature responses of NK1R-/- mice were higher in the afternoon than the morning.

Conclusion

In addition to locomotor hyperactivity, NK1R-/- mice express inattentiveness, perseveration and impulsivity in the 5-CSRTT, thereby matching core criteria for a model of ADHD. Because d-amphetamine reduced perseveration in NK1R-/- mice, this action does not require functional NK1R. However, the lack of any improvement of omissions and premature responses in NK1R-/- mice given d-amphetamine suggests that beneficial effects of this psychostimulant in other rodent models, and ADHD patients, need functional NK1R. Finally, our results reveal experimental variables (stimulus parameters, stress and time of day) that could influence translational studies.     

Neuroimaging evidence for processes underlying repetition of ignored stimuli

Prolonged response times are observed with targets having been presented as distractors immediately before, called negative priming effect. Among others, inhibitory and retrieval processes have been suggested underlying this behavioral effect. As those processes would involve different neural activation patterns, a functional magnetic resonance imaging (fMRI) study including 28 subjects was conducted. Two tasks were used to investigate stimulus repetition effects. One task focused on target location, the other on target identity. Both tasks are known to elicit the expected response time effects. However, there is less agreement about the relationship of those tasks with the explanatory accounts under consideration. Based on within-subject comparisons we found clear differences between the experimental repetition conditions and the neutral control condition on neural level for both tasks. Hemodynamic fronto-striatal activation patterns occurred for the location-based task favoring the selective inhibition account. Hippocampal activation found for the identity-based task suggests an assignment to the retrieval account; however, this task lacked a behavioral effect.     

Processing Irrelevant Location Information: Practice and Transfer Effects in a Simon Task

How humans produce cognitively driven fine motor movements is a question of fundamental importance in how we interact with the world around us. For example, we are exposed to a constant stream of information and we must select the information that is most relevant by which to guide our actions. In the present study, we employed a well-known behavioral assay called the Simon task to better understand how humans are able to learn to filter out irrelevant information. We trained subjects for four days with a visual stimulus presented, alternately, in central and lateral locations. Subjects responded with one hand moving a joystick in either the left or right direction. They were instructed to ignore the irrelevant location information and respond based on color (e.g. red to the right and green to the left). On the fifth day, an additional testing session was conducted where the task changed and the subjects had to respond by shape (e.g. triangle to the right and rectangle to the left). They were instructed to ignore the color and location, and respond based solely on the task relevant shape. We found that the magnitude of the Simon effect decreases with training, however it returns in the first few trials after a break. Furthermore, task-defined associations between response direction and color did not significantly affect the Simon effect based on shape, and no significant associative learning from the specific stimulus-response features was found for the centrally located stimuli. We discuss how these results are consistent with a model involving route suppression/gating of the irrelevant location information. Much of the learning seems to be driven by subjects learning to suppress irrelevant location information, however, this seems to be an active inhibition process that requires a few trials of experience to engage.     

Falling Out of Time: Enhanced Memory for Scenes Presented at Behaviorally Irrelevant Points in Time in Posttraumatic Stress Disorder (PTSD)

Spontaneous encoding of the visual environment depends on the behavioral relevance of the task performed simultaneously. If participants identify target letters or auditory tones while viewing a series of briefly presented natural and urban scenes, they demonstrate effective scene recognition only when a target, but not a behaviorally irrelevant distractor, appears together with the scene. Here, we show that individuals with posttraumatic stress disorder (PTSD), who witnessed the red sludge disaster in Hungary, show the opposite pattern of performance: enhanced recognition of scenes presented together with distractors and deficient recognition of scenes presented with targets. The recognition of trauma-related and neutral scenes was not different in individuals with PTSD. We found a positive correlation between memory for scenes presented with auditory distractors and re-experiencing symptoms (memory intrusions and flashbacks). These results suggest that abnormal encoding of visual scenes at behaviorally irrelevant events might be associated with intrusive experiences by disrupting the flow of time.