Intradimensional Shift Research Articles

Automation at the service of the study of executive functions in preclinical models

Cognitive flexibility involves the capability to switch between different perspectives and implement novel strategies upon changed circumstances. The Wisconsin Card Sorting Test (in humans) and the Attentional Set-Shifting Task (ASST, in rodents) evaluate individual capability to acquire a reward-associated rule and subsequently disregard it in favour of a new one. Both tasks entail consecutive stages wherein subjects discriminate between: two stimuli of a given category (simple discrimination, SD); the stimuli of SD confounded by an irrelevant stimulus of a different category (compound discrimination, CD); different stimuli belonging to the SD category (intradimensional shift, IDS); and two stimuli of the confounding category (extradimensional shift, EDS). The ASST is labour intensive, not sufficiently standardised, and prone to experimental error. Here, we tested the validity of a new, commercially available, automated version of ASST (OPERON) in two independent experiments conducted in: different mouse strains (C57BL/6 and CD1 mice) to confirm their differential cognitive capabilities (Experiment 1); and an experimental model of chronic stress (administration of corticosterone in the drinking water; Experiment 2). In both experiments, OPERON confirmed the findings obtained through the manual version. Just as in Experiment 1 both versions captured the deficit of C57BL/6 mice on the reversal of the CD (CDR), so also in Experiment 2 they provided analogous evidence that corticosterone treated mice have a remarkable impairment in the IDS. Thus, OPERON capitalises upon automated phenotyping to overcome the limitation of the manual version of the ASST while providing comparable results.

Rules and metarules: Adult cotton-top tamarins (Saguinus oedipus) and 5-year-old children (Homo sapiens) can master both.

Developmental psychologists have noted a similar timeline of change for children's use of different perspectives about the same objects or events, as in the use of different labels for the same object, an aspect of language, and in understanding other's knowledge or beliefs, an aspect of social cognition as reviewed in the study by Neiworth et al. Comparative psychologists are interested to know what cognitive flexibility looks like in other species and how such variation relates to life history, ecology, and phylogeny. The general pattern of results to date indicates that monkeys can master both intra- and interdimensional shifts, but intradimensional shifts are learned far more quickly than interdimensional shifts (reviewed in the study by Neiworth et al, 2022). Neiworth et al. report that they have conducted exactly this kind of comparative study: They examined cognitive flexibility in adult cotton-top tamarins and human children in three age groups as they participated in a modified version of the Dimensional Change Card Sort (DCCS). Neiworth et al.'s study offers an example of careful consideration of one such possibility: that of using the experimenter's postural orientation to the cards as an inadvertent aid. Here the authors had the benefit of prior work showing that tamarins follow human-provided cues to make a spatially discriminated choice only if the experimenter's head, body, and eyes oriented to a particular location. Thus, in this study, the experimenter kept their head and body centered in the testing space between the two cards and looked at a point on the wall directly behind the midpoint of the testing tray. But the DCCS task, in abstract form, has potentially broader comparative value than to examine cognitive flexibility in primates alone. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A modified version of the dimensional change card sort task tests cognitive flexibility in children (Homo sapiens) and cotton-top tamarins (Saguinus oedipus).

A modified Dimensional Change Card Sort (DCCS) task was used to test cognitive flexibility in adult cotton-top tamarins and children aged 19 months to 60 months. Subjects had to infer a rule from the experience of selecting between two cards to earn a reward, and the pairs of stimuli defined the rule (e.g., pick blue ones, not red ones, or pick trucks, not boats). Two different tests measured subjects' ability to shift to a reversal of the rule (intradimensional shift) and to shift to a new rule defined by a dimension previously irrelevant (interdimensional shift). Both adult tamarins and children aged 49-60 months were able to learn the initial rule and switch to a reversal and to a rule based on a different dimension. In contrast, the two younger groups of children, aged 19-36 months and aged 37-48 months, could switch when a reversal was imposed but took significantly longer to learn a new rule on a former irrelevant dimension. Experiment 2 presented a wider set of novel stimuli which shared some features with the original set to further explore the basis of rule learning. The result was that tamarins and 52- to 60-month-old children both chose novel stimuli that fit the rule and had no a priori associative strength, suggesting a rule application not solely based on associative strength. Importantly, novel items introduced some risk for choice, and children showed themselves to be risk-averse, whereas tamarins were risk-prone within a novel context. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Exploring the development of attentional set shifting in young children with a novel Intradimensional/Extradimensional shift task

Attentional set shifting is a core part of cognition, allowing quick and flexible adaption to new demands. The study of its development during early childhood has been hampered by a shortage of measures not requiring language. This article argues for a revival of the Intradimensional/Extradimensional (ID/ED) shift task by presenting a new nonverbal version of the task (Shifting Tray task). Children (N = 95 3- to 5-year-olds; 49 girls; predominantly European White) were presented with pairs of trays, each filled with a substrate and an upside-down cup on top, and were asked to find stickers. In the pre-switch phase, children learned (through trial and error) which dimension (substrate or cup) was predictive of the rewards. In the post-switch phase, all stimuli were exchanged. For children in the intradimensional shift condition, the dimension predictive of the sticker was the same as the one predictive in the pre-switch phase. For children in the extradimensional shift condition, the previously irrelevant dimension was now relevant. Results showed that most 3-year-olds were able to switch, and older children did not outperform younger children. The easy and flexible nature of the task allows researchers to investigate the impact of labels and instructions and to use it in cross-cultural and comparative research.

Orexin deficiency modulates cognitive flexibility in a sex-dependent manner.

Cognitive flexibility is an important executive function and refers to the ability to adapt behaviors in response to changes in the environment. Of note, many brain disorders are associated with impairments in cognitive flexibility. Several classical neurotransmitter systems including dopamine, acetylcholine and noradrenaline are shown to be important for cognitive flexibility, however, there is not much known about the role of neuropeptides. The neuropeptide orexin, which is brain-widely released by neurons in the lateral hypothalamus, is a major player in maintaining sleep/wake cycle, feeding behavior, arousal, and motivational behavior. Recent studies showed a role of orexin in attention, cognition and stress-induced attenuation of cognitive flexibility by disrupting orexin signaling locally or systemically. However, it is not known so far whether brain-wide reduction or loss of orexin affects cognitive flexibility. We investigated this question by testing male and female orexin-deficient mice in the attentional set shifting task (ASST), an established paradigm of cognitive flexibility. We found that orexin deficiency impaired the intra-dimensional shift phase of the ASST selectively in female homozygous orexin-deficient mice and improved the first reversal learning phase selectively in male homozygous orexin-deficient mice. We also found that these orexin-mediated sex-based modulations of cognitive flexibility were not correlated with trait anxiety, narcoleptic episodes, and reward consumption. Our findings highlight a sexually dimorphic role of orexin in regulating cognitive flexibility and the need for further investigations of sex-specific functions of the orexin circuitry.

Impaired Cognitive Flexibility After Neonatal Perirhinal Lesions in Rhesus Macaques.

Previous research indicated that monkeys with neonatal perirhinal lesions (Neo-PRh) were impaired on working memory (WM) tasks that generated proactive interference, but performed normally on WM tasks devoid of interference (Weiss et al., 2016). This finding suggested that the early lesions disrupted cognitive processes important for resolving proactive interference, such as behavioral inhibition and cognitive flexibility. To distinguish between these possibilities, the same Neo-PRh monkeys and their controls were tested using the Intradimensional/Extradimensional attentional set-shifting task (Roberts et al., 1988; Dias et al., 1997). Neo-PRh monkeys completed the Simple and Compound Discrimination stages, the Intradimensional Shift stage, and all Reversal stages comparably to controls, but made significantly more errors on the Extradimensional Shift stage of the task. These data indicate that impaired cognitive flexibility was the likely source of increased perseverative errors made by Neo-PRh monkeys when performing WM tasks, rather than impaired behavioral inhibition, and imply that the perirhinal cortex and its interactions with the PFC may play a unique and critical role in the development of attentional set shifting abilities.

Neonatal handling impairs intradimensional shift and alters plasticity markers in the medial prefrontal cortex of adult rats

Stress response can be modulated by neonatal/childhood events. Neonatal handling (NH) is an animal model in which the animals are subjected to brief separations from the dam during the first days of life, and it leads to lower emotionality and behavioral changes in adulthood. The aim of this study was to observe if early events, such as (NH), may program associative learning and behavioral flexibility in adult male rats and if these changes could be related to altered neurochemistry in the medial prefrontal cortex (mPFC). We evaluated proteins related to synaptic plasticity (brain-derived neurotrophic factor [BDNF] and synaptophysin [SYP]) as well as Na+/K+-ATPase activity. Additionally, we evaluated proteins related to the dopaminergic system (tyrosine hydroxylase [TH] and phosphorylated TH [pTH]), since this system appears to be affected in some neonatal interventions. Neonatally handled animals exhibited impairment in simple discrimination and intradimensional shift but not in reversal or compound discrimination; in addition, no alteration in switching from an egocentric spatial to a cued strategy was observed. These effects were accompanied by a decrease in SYP levels and Na+/K+-ATPase activity, suggesting reduced synaptic function. These results indicate that NH increases attention to irrelevant stimuli and/or impairs associative learning, and this is accompanied by neurochemical alterations in the (mPFC).

Environmental Enrichment Expedites Acquisition and Improves Flexibility on a Temporal Sequencing Task in Mice.

Environmental enrichment (EE) via increased opportunities for voluntary exercise, sensory stimulation and social interaction, can enhance the function of and behaviours regulated by cognitive circuits. Little is known, however, as to how this intervention affects performance on complex tasks that engage multiple, definable learning and memory systems. Accordingly, we utilised the Olfactory Temporal Order Discrimination (OTOD) task which requires animals to recall and report sequence information about a series of recently encountered olfactory stimuli. This approach allowed us to compare animals raised in either enriched or standard laboratory housing conditions on a number of measures, including the acquisition of a complex discrimination task, temporal sequence recall accuracy (i.e., the ability to accurately recall a sequences of events) and acuity (i.e., the ability to resolve past events that occurred in close temporal proximity), as well as cognitive flexibility tested in the style of a rule reversal and an Intra-Dimensional Shift (IDS). We found that enrichment accelerated the acquisition of the temporal order discrimination task, although neither accuracy nor acuity was affected at asymptotic performance levels. Further, while a subtle enhancement of overall performance was detected for both rule reversal and IDS versions of the task, accelerated performance recovery could only be attributed to the shift-like contingency change. These findings suggest that EE can affect specific elements of complex, multi-faceted cognitive processes.

Attentional deficits and altered neuronal activation in medial prefrontal and posterior parietal cortices in mice with reduced dopamine transporter levels.

The executive control function of attention is regulated by the dopaminergic (DA) system. Dopamine transporter (DAT) likely plays a role in controlling the influence of DA on cognitive processes. We examined the effects of DAT depletion on cognitive processes related to attention. Mice with the DAT gene genetically deleted (DAT+/- heterozygotes) were compared to wild type (WT) mice on the Attentional Set-Shifting Task (ASST). Changes in neuronal activity during the ASST were shown with early growth response genes 1 and 2 (egr-1 and egr-2) immunohistochemistry in the medial prefrontal cortex (mPFC) and in the posterior parietal cortex (PPC). Heterozygotes were impaired in tasks that tax reversal learning, attentional-set formation and set-shifting. Densities of egr-2 labeled cells in the mPFC were lower in mutant mice when compared with wild-types in intradimensional shift of attention (IDS), extradimensional shift of attention and extradimensional shift of attention-reversal phases of the ASST task, and in PPC in the IDS phase of the task. The results demonstrate impairments of the areas associated with attentional functions in DAT+/- mice and show that an imbalance of the dopaminergic system has an impact on the complex attention-related executive functions.

Attentional set-shifting and social abilities in children with schizotypal and comorbid autism spectrum disorders.

While diagnostically independent, autism and schizotypal disorders can co-occur. Their concurrent impact on outcomes and phenotypes has not been investigated. We investigated the impact of comorbid autism and schizotypal disorders in children on executive functioning and socio-pragmatic skills - core features of both disorders. Executive functioning (assessed with the Cambridge Neuropsychological Test Automated Battery) and socio-pragmatic skills (assessed using the Melbourne Assessment of Schizotypy in Kids) were investigated in a total of 67 (6-12 year old) children with autism ( n = 15; M/F = 10/5), schizotypal disorder ( n = 8; M/F = 5/3) and comorbid autism and schizotypal disorder ( n = 12; M/F = 5/7) and typically developing children ( n = 32; M/F = 17/15). Both the autism and schizotypal disorder groups performed more poorly than the typically developing group on socio-pragmatic skills and overall performance (i.e. number of stages completed) of the intra-/extra-dimensional set-shifting task (all ps < 0.001). Clear distinctions between the autism and schizotypal groups were present in the intra-/extra-dimensional task relative to the typically developing group - the autism group had difficulties with extra-dimensional shifts ( p < 0.001), and the schizotypal disorder group with intra-dimensional shifts ( p = 0.08). Interestingly, the overall performance of the comorbid group on the intra-/extra-dimensional task was not significantly different from the typically developing group, and they were superior to both the autism ( p = 0.019) and schizotypal disorder ( p = 0.042) groups on socio-pragmatic skills. The phenotypical overlap between autism and schizotypal disorders may be precipitated by different cognitive styles and/or mechanisms associated with attention and information processing. We propose that sustaining and switching attention represent two poles of irregularities across the autism and schizotypal spectra, which appear to converge in a compensatory manner in the comorbid group. Our findings highlight the importance of investigating children with a dual diagnosis of autism and schizotypal disorders, and raise intriguing questions about possible mechanisms to explain the attenuated impairment observed in the group of children with comorbid autism and schizotpyal disorders.

Potential role of dopamine transporter in behavioral flexibility

Behavioral flexibility is subserved by the prefrontal cortex and the basal ganglia. Orbitofrontal cortex (OFC) and dorsomedial striatum (DMS) form a functional frontocorticostriatal circuit crucial for the mediation of flexibility during reversal learning via dopamine (DA) neurotransmission. The regulatory control in maintaining DA homeostasis and function is provided by the dopamine transporter (DAT), which therefore likely plays a significant role in controlling the influence of DA on cognitive processes. Here we used a gene knockout mouse model to investigate the role of DAT in the performance on the Attentional Set-Shifting Task (ASST) stages dependent upon the OFC and the DMS. Additionally, behavior of mice after repeated administration of selective DAT inhibitor, GBR 12909, was examined. The animals were treated with the inhibitor to elicit a compensatory DAT up-regulation following withdrawal. Learning was slower and the number of errors during reversal learning and intra-dimensional shift stages was higher in DAT+/- mutant mice than in WT mice. GBR 12909-treated mice had deficits in reversal stages of the ASST. Neuronal activation in the OFC and DMS during the ASST was examined with early growth response proteins 1 and 2 (egr-1, egr-2) immunohistochemistry. Density of egr-2 labeled cells in the OFC was lower in mutant mice than in wild-types during reversal learning and the expression of the egr-1 was lower in mutant mice in the OFC and DMS during reversal and intra-dimensional shift stages. Mice with decreased DAT levels displayed behavioral difficulties that were accompanied by a lower task-induced activation of neurons in brain regions involved in the reversal learning. Altogether, these data indicate the role of the DAT in the behavioral flexibility.

EP 56. Optogenetic control of the locus coeruleus in mice: Behavioral and electrophysiological data

The locus coeruleus (LC) is the sole source of noradrenergic projections to the cortex and to better understand its essential role for attention-dependent cognitive processes, we first expressed the halorhodopsin eNpHR3.0 to reversibly silence LC activity in naive male B6.Cg-Tg(Th-cre)1Tmd/J hemizygous mice (Th-cre mice) that express Cre-recombinase under the control of the tyrosine hydroxylase (TH) promoter. Unilateral optogenetic silencing of the LC during the performance of an attentional set-shifting task (ASST) selectively impaired learning of those parts of the ASST that most strongly rely on cognitive flexibility. In particular, extra-dimensional set-shifting (EDS) and reversal learning was impaired. However, those parts of the task that are less dependent on cognitive flexibility, i.e. compound discrimination (CD) and the intra-dimensional shifts (IDS), as well as attentional set formation were unaffected by LC silencing. Therefore, our results suggest a modulatory influence of the LC on cognitive flexibility, mediated by different frontal networks. Subsequently, we used AAV8-Ef1a-DIO-Chronos-eYFP to stimulate LC activity in Th-cre mice and performed electrophysiological recordings during optogenetic stimulation by using an optetrode. Laser pulses of different intensities (0.5, 1, 2, 5, and 10 mW) and different pulse durations (5, 10, 20, 50, 100, 200, and 500 ms) were tested. Results showed that pulses at 5 mW of 5 ms pulse duration are optimal and that those laser pulses are able to induce bursts of 20 Hz discharges and sustained 10 Hz discharges of LC neurons.

How does Estrogen Influence Attention? Impact of 17‐beta Estradiol on Performance in an Attentional Set Shifting Task

Estrogens have been shown to affect learning and memory in female rats. ADHD is 3–9× more prevalent in males, suggesting that gonadal hormones may be in part responsible for the observed disparity between the sexes. In this disorder dopamine and norepinephrine levels in the ventromedial prefrontal cortex may be deficient, as evidenced by the use of stimulants to treat this disorder. Estrogen has been shown to inhibit dopamine reuptake in the prefrontal cortex this increasing extracellular levels of dopamine. Our previous work has suggested that in ovariectomized female rats, estradiol supplementation yielded higher levels of dopamine in the PFC than in male rats (1). The purpose of the present study was to evaluate the effect of estrogen in ovariectomized (OVX) female Long‐Evans rats in the attentional set‐shifting task (ASST)(2), a measure of attention which is strongly associated with monoamine levels in the vmPFC. Adult female rats were ovariectomized (OVX) or underwent a sham surgery. OVX rats were then randomized into two groups and given injections of 21 ug/kg 17‐B‐estradiol or vehicle every other day for the remainder of the study, while sham surgery animals were given vehicle injections. Rats were then tested in the ASST, wherein rats are trained to dig in pots for food reward. Pots are labeled with three dimensions, scent, digging material and texture of the pot and trained to dig for a food reward. Once the animal reaches criteria performance in a simple discrimination (SD) and then a complex discrimination (CD), the animal is then tested for performance in the intradimensional shift (ID), followed by a reversal (IDR). The animal is then exposed to an extradimensional shift (odor to digging material) (ED), followed by the reversal within this ED (EDR). This study found that OVX rats performed better in the ASST than sham or OVX + E animals, possibly reflecting a complicated dose‐response relationship to 17‐B‐estradiol administration. Further studies are underway to assess the levels of dopamine, norepinephrine, and serotonin in the ventromedial prefrontal cortex of these animals using in vivo microdialysis.Support or Funding InformationSC supported by a Morgane Research Fellowship from UNECOM.

Optogenetic silencing of locus coeruleus activity in mice impairs cognitive flexibility in an attentional set-shifting task.

The locus coeruleus (LC) is the sole source of noradrenergic projections to the cortex and essential for attention-dependent cognitive processes. In this study we used unilateral optogenetic silencing of the LC in an attentional set-shifting task (ASST) to evaluate the influence of the LC on prefrontal cortex-dependent functions in mice. We expressed the halorhodopsin eNpHR 3.0 to reversibly silence LC activity during task performance, and found that silencing selectively impaired learning of those parts of the ASST that most strongly rely on cognitive flexibility. In particular, extra-dimensional set-shifting (EDS) and reversal learning was impaired, suggesting an involvement of the medial prefrontal cortex (mPFC) and the orbitofrontal cortex. In contrast, those parts of the task that are less dependent on cognitive flexibility, i.e., compound discrimination (CD) and the intra-dimensional shifts (IDS) were not affected. Furthermore, attentional set formation was unaffected by LC silencing. Our results therefore suggest a modulatory influence of the LC on cognitive flexibility, mediated by different frontal networks.

Impairment of intradimensional shift in an attentional set-shifting task in rats with chronic bilateral common carotid artery occlusion

Studies of rats with chronic bilateral common carotid artery occlusion (BCCAo), an animal model for vascular dementia (VaD), have reported hippocampus-dependent memory impairment and associated neuropathologies. Patients with VaD also experience attentional shifting dysfunction. However, animal models of VaD have not been used to study attentional function. Therefore, the present study examined attentional function in rats with BCCAo, using attentional set-shifting task (ASST) that required rats to choose a food-baited pot from 2 possible pots. ASST included 6 consecutive sessions including simple discrimination, compound discrimination, intradimensional shifting, extradimensional shifting, and reversals. The BCCAo rats were significantly slower at learning the intradimensional set-shifting task compared to control rats. Previous studies have demonstrated that the cingulate cortex and medial prefrontal cortex are critical to intradimensional and extradimensional set-shifting, respectively. Additionally, inflammatory responses and neuronal dysfunction were observed in rats with chronic BCCAo. In addition, OX-6 positive microglia significantly increased in the forceps minor white matter of BCCAo rats, and glutamate decarboxylase signals co-localized with NeuN were reduced in the anterior cingulate cortex of BCCAo rats, compared to control rats. Impaired neuronal and GABAergic neuronal integrity in the anterior cingulate cortex, damage to white matter, and attentional impairments observed in BCCAo rats suggest dysfunction of brain structures that are associated with attentional impairments observed in patients with VaD.

A critical role for the anterior thalamus in directing attention to task-relevant stimuli.

The prefrontal cortex mediates adaption to changing environmental contingencies. The anterior thalamic nuclei, which are closely interconnected with the prefrontal cortex, are important for rodent spatial memory, but their potential role in executive function has received scant attention. The current study examined whether the anterior thalamic nuclei are involved in attentional processes akin to those of prefrontal regions. Remarkably, the results repeatedly revealed attentional properties opposite to those of the prefrontal cortex. Two separate cohorts of rats with anterior thalamic lesions were tested on an attentional set-shifting paradigm that measures not only the ability of stimuli dimensions that reliably predict reinforcement to gain attention ("intradimensional shift"), but also their ability to shift attention to another stimulus dimension when contingencies change ("extradimensional shift"). In stark contrast to the effects of prefrontal damage, anterior thalamic lesions impaired intradimensional shifts but facilitated extradimensional shifts. Anterior thalamic lesion animals were slower to acquire discriminations based on the currently relevant stimulus dimension but acquired discriminations involving previously irrelevant stimulus dimensions more rapidly than controls. Subsequent tests revealed that the critical determinant of whether anterior thalamic lesions facilitate extradimensional shifts is the degree to which the stimulus dimension has been established as an unreliable predictor of reinforcement over preceding trials. This pattern of performance reveals that the anterior thalamic nuclei are vital for attending to those stimuli that are the best predictors of reward. In their absence, unreliable predictors of reward usurp attentional control.

C19 Track Tghd Minipigs - A Discrimination Test As Part Of An Assessment Battery For Tghd Minipigs

<h3>Background</h3> The TRACK tgHD minipig study aims to evaluate the potential of the Libechov tgHD minipig model for pre-clinical studies by studying the phenotype of these animals. Established tests for assessing different domains of possible phenotype manifestation in minipigs are lacking. The “Discrimination Test” introduced here is thought to primarily target cognitive dysfunction. <h3>Aim</h3> To assess the feasibility and tolerability of the application of the “Discrimination Test” in minipigs and explore the tgHD minipigs’ performance compared with that of wildtype (wt) minipigs. <h3>Methods/techniques</h3> Thirty-two minipigs – 18 wt and 14 tg (with an N-terminal fragment of the huntingtin gene coding for 548aa with 124Q) – were included in the study. The minipigs were housed in six mixed groups (wt and tg) at the animal facility of the University of Muenster, Germany. The “Discrimination Test” was performed using a special setup. During initial training, the minipigs learnt to leave a startbox (SB A), enter a walkway, open a blue plastic box (bB) as opposed to red and yellow box (rB/yB), and return to SB A. The boxes’ position was changed clockwise in subsequent runs. During testing 1, time to leave SB A and open bB, and time to leave bB and return to SB A was recorded and a score was given based on attempts to open and/or investigate bB and/or rB and yB. During testing 2, yB had to be opened instead of bB and yB (intradimensional shift). Each pig completes training, testing 1 and testing 2 biannually. <h3>Results/outcome</h3> The animals show a good tolerance of the method. Cross sectional and longitudinal data analysis is in progress using SPSS 22.0. <h3>Conclusion</h3> The data collected to date shows that implementation of the “Discrimination Test” is feasible and well tolerated. It is hypothesised that performance of the test is impaired in tgHD minipigs compared to controls. We expect to report first between group comparisons at the meeting. <h3>Acknowledgement</h3> This study was funded by the CHDI foundation.

Evidence that the attentional set shifting test in rats can be applied in repeated testing paradigms.

The attentional set shifting task (ASST) can be used to assess aspects of executive function, including reversal learning and set shifting. It has frequently been employed in between-subjects experimental designs: however, the clear advantages of within-subjects designs (reduction in variance, animal numbers, and cost) mean that investigation of the suitability of the ASST for within subjects designs is warranted. Rats were tested three times: test 1 (24 h after training), test 2 (24 h later), and test 3 (seven days later). On all three test days, animals showed the expected pattern of performance across the seven task stages with evidence of normal reversal learning (significant increase in trials to criterion when the rule was reversed) and intact set formation (significantly more trials to criterion for an extradimensional shift than for an intradimensional shift). There was a small decrease in total trials required to complete the task between test 1 and test 3 but this was not specific to any stage of the task. Latency to dig decreased on repeated testing suggesting some facilitation of associative learning. In conclusion, the rodent ASST is suitable for within-subject design longitudinal studies, increasing the utility and the translational value of this test and reducing numbers of animals needed in studies.

P.2.020 Deletion of contactin-4 leads to cognitive rigidity and aberrant motor cortex development in mice

Exposure to acetylcholinesterase inhibitors during development was shown in the past to induce sex-dependent changes in locomotion and specific cognitive and emotional tests in rodents. Adult mice that had been treated with 0.5 mg/kg diisopropylfluorphosphate (DFP), on post-natal days 14–20 were tested on active avoidance and a set-shifting task. DFP pre-treatment did not affect the active avoidance task, but impaired performance on the extra-dimensional shift task. DFP-treated females showed more general deficits in the acquisition of simple discrimination, intra-dimensional shift, extra-dimensional shift and reversal learning. These data suggest that pre-weanling exposure to cholinesterase inhibitors may have long-term consequences on attentional capabilities.

Shape shifting: Local landmarks interfere with navigation by, and recognition of, global shape.

An influential theory of spatial navigation states that the boundary shape of an environment is preferentially encoded over and above other spatial cues, such that it is impervious to interference from alternative sources of information. We explored this claim with 3 intradimensional–extradimensional shift experiments, designed to examine the interaction of landmark and geometric features of the environment in a virtual navigation task. In Experiments 1 and 2, participants were first required to find a hidden goal using information provided by the shape of the arena or landmarks integrated into the arena boundary (Experiment 1) or within the arena itself (Experiment 2). Participants were then transferred to a different-shaped arena that contained novel landmarks and were again required to find a hidden goal. In both experiments, participants who were navigating on the basis of cues that were from the same dimension that was previously relevant (intradimensional shift) learned to find the goal significantly faster than participants who were navigating on the basis of cues that were from a dimension that was previously irrelevant (extradimensional shift). This suggests that shape information does not hold special status when learning about an environment. Experiment 3 replicated Experiment 2 and also assessed participants’ recognition of the global shape of the navigated arenas. Recognition was attenuated when landmarks were relevant to navigation throughout the experiment. The results of these experiments are discussed in terms of associative and non-associative theories of spatial learning.