A Hierarchical Reinforcement Learning Model Explains Individual Differences in Attentional Set Shifting

Attentional set shifting refers to the ease with which the focus of attention is directed and switched. Cognitive tasks such as CANTAB IED reveal great variation in set shifting ability in the general population, with notable impairments in those with psychiatric diagnoses. The attentional and learning processes underlying this cognitive ability, and how they lead to the observed variation remain unknown. To directly test this, we used a modelling approach on two independent large-scale online general-population samples performing CANTAB IED and psychiatric symptom assessment. We found a hierarchical model that learnt both feature values and dimension attention best explained the data, and that compulsive symptoms were associated with slower learning and higher attentional bias to the first relevant stimulus dimension. This data showcase a new methodology to analyse data from the CANTAB IED task, and suggest a possible mechanistic explanation for the variation in set shifting performance, and its relationship to compulsive symptoms.

Automatic Intra-/Extra-Dimensional Attentional Set-Shifting Task in Adolescent Mice

Adolescence is a developmental period crucial for the maturation of higher-order cognitive functions. Indeed, adolescence deficits in executive functions are strong predictors of increased vulnerability to several mental disabilities later in life. Here, we tested adolescent mice in a fully-automated attentional set-shifting task equivalent to the humans’ Wisconsin Card Sorting Test (WCST) and the Cambridge Neuropsychological Test Automated Battery Intra-/Extra-Dimensional set-shift task (ID/ED). Compared to an adult, adolescent mice required more time to complete the task (≈16 days), and a higher percentage failed to finish the entire task. Nevertheless, adolescent mice completing this demanding task showed an increased effort in solving the extradimensional shift stage (EDS) compared to previous stages. Moreover, we found that this paradigm can be used to detect early cognitive dysfunctions in adolescent genetically modified mice. Thus, this automatic paradigm provides a further tool to assess attentional control in adolescent mice, and the development of dysfunctional executive functions from adolescence to adulthood.

BDNF haploinsufficiency induces behavioral endophenotypes of schizophrenia in male mice that are rescued by enriched environment

Brain-derived neurotrophic factor (BDNF) is implicated in a number of processes that are crucial for healthy functioning of the brain. Schizophrenia is associated with low BDNF levels in the brain and blood, however, not much is known about BDNF’s role in the different symptoms of schizophrenia. Here, we used BDNF-haploinsufficient (BDNF+/−) mice to investigate the role of BDNF in different mouse behavioral endophenotypes of schizophrenia. Furthermore, we assessed if an enriched environment can prevent the observed changes. In this study, male mature adult wild-type and BDNF+/− mice were tested in mouse paradigms for cognitive flexibility (attentional set shifting), sensorimotor gating (prepulse inhibition), and associative emotional learning (safety and fear conditioning). Before these tests, half of the mice had a 2-month exposure to an enriched environment, including running wheels. After the tests, BDNF brain levels were quantified. BDNF+/− mice had general deficits in the attentional set-shifting task, increased startle magnitudes, and prepulse inhibition deficits. Contextual fear learning was not affected but safety learning was absent. Enriched environment housing completely prevented the observed behavioral deficits in BDNF+/− mice. Notably, the behavioral performance of the mice was negatively correlated with BDNF protein levels. These novel findings strongly suggest that decreased BDNF levels are associated with several behavioral endophenotypes of schizophrenia. Furthermore, an enriched environment increases BDNF protein to wild-type levels and is thereby able to rescue these behavioral endophenotypes.

Mediodorsal thalamus is critical for updating during extra-dimensional shifts but not reversals in the attentional set-shifting task

Cognitive flexibility, attributed to frontal cortex, is vital for navigating the complexities of everyday life. The mediodorsal thalamus (MD), interconnected to frontal cortex, may influence cognitive flexibility. Here rats performed an attentional set-shifting task measuring intra-dimensional and extra-dimensional shifts in sensory discriminations. MD lesion rats needed more trials to learn the rewarded sensory dimension. However, once the choice response strategy was established, learning further two-choice discriminations in the same sensory dimension, and reversals of the reward contingencies in the same dimension, were unimpaired. Critically though, MD lesion rats were impaired during the extra-dimensional shift, when they must rapidly update the optimal choice response strategy. Behavioral analyses showed MD lesion rats had significantly reduced ‘on-the-fly’ correct second choice responses. Diminshed c-Fos expression in the prelimbic and orbitofrontal cortex was also documented. This evidence shows transfer of information via the MD is critical when monitoring and rapid updates in established choice response strategies are required.

Cortisol to Dehydroepiandrosterone Sulphate Ratio and Executive Function in Bipolar Disorder

<b><i>Introduction:</i></b> Bipolar disorder (BD) is associated with impairment in cognitive domains such as verbal memory and executive functions. Very few studies have assessed dehydroepiandrosterone sulphate (DHEA-S) in BD and its relation to cognitive functioning despite evidence showing its regulatory effects on glucocorticoid action. The aim of our study was to explore the association of cortisol, DHEA-S, and cortisol to DHEA-S ratio with visuospatial memory and executive functioning in BD. <b><i>Methods:</i></b> Cognitive performance of 60 bipolar I patients and 30 healthy subjects was evaluated by using Cambridge Neuropsychological Test Automated Battery tasks targeting visuospatial memory (spatial recognition memory) and executive functions (planning [Stockings of Cambridge; SOC] and attentional set shifting [ID/ED]). Morning serum cortisol and DHEA-S levels were measured in patients. Main effects of cortisol, DHEA-S, and cortisol/DHEA-S ratio for each neurocognitive task were explored in multiple regression analyses correcting for demographic and clinical parameters as well as treatment-related factors (current use of antipsychotic and mood stabilizer medication). <b><i>Results:</i></b> Bipolar patients showed poorer performance than healthy subjects in planning and attentional set shifting but not in visuospatial memory. Cortisol to DHEA-S ratio predicted worse performance in planning (SOC). <b><i>Conclusions:</i></b> This is the first study to assess memory and executive function in BD in relation to DHEA-S and cortisol to DHEA-S ratio. We report an association of cortisol to DHEA-S ratio with worse performance in planning in bipolar I patients, which warrants further investigation.