Enhanced learning and sensory salience in a cerebellar mouse autism model

Among the impairments manifested by autism spectrum disorder (ASD) are sometimes islands of enhanced function. Although neuronal mechanisms for enhanced functions in ASD are unknown, the cerebellum is a major site of developmental alteration, and early-life perturbation to it leads to ASD with higher likelihood than any other brain region. Here we report that a cerebellum-specific transgenic mouse model of ASD shows faster learning on a sensory evidence-accumulation task. In addition, transgenic mice showed enhanced sensitivity to touch and auditory cues, and prolonged electrophysiological responses in Purkinje-cell complex spikes and associative neocortical regions. These findings were replicated by pairing cues with optogenetic stimulation of Purkinje cells. Computational latent-state analysis of behavior revealed that both groups of mice with cerebellar perturbations exhibited enhanced focus on current rather than past information, consistent with a role for the cerebellum in retaining information in memory. We conclude that cerebellar perturbation can activate neocortex via complex spike activity and reduce reliance on prior experience, consistent with a weak-central-coherence account in which ASD traits arise from enhanced detail-oriented processing. This recasts ASD not so much as a disorder but as a variation that, in particular niches, can be adaptive.

Lesson study as a way of improving school-day navigation for pupils with severe intellectual disability and autism

PurposeThis research explores lesson study as a way to enhance the quality of teaching for pupils with learning disabilities and autism spectrum disorder by observing changes to one pupil's (Wilma) active educational participation. The study also investigates if and in what ways the professional development impacted teaching practices.Design/methodology/approachFive teachers met with the author on four occasions. Between these meetings, the teachers delivered the lessons they had planned together. The author video recorded the meetings to discern how the teachers' expressions developed. The author shared their thoughts with another researcher to enable an interrater validity examination.FindingsThe implementation of the lesson study vehicle enabled the teachers to transform their thinking from mainly focusing on pupils' deficiencies to instead focusing on their strengths. A relationship was found between teachers' understanding of central coherence, their skills in adapting received instructions and pupils' abilities to process and contextualize information or discern the whole picture.Research limitations/implicationsResearch that involves teachers in the learning process emphasizes the relation between teachers’ thinking and their potential to enable the contextualized inclusion of pupils with learning disabilities.Originality/valueThis research offers important insights into how school-day navigation for pupils with severe intellectual disability and autism can be understood through the lens of variation theory; the teachers' repeated and adjusted use of the frame on the schedule strip enabled Wilma to discern what would happen next during the school day.

Autistic-like traits and Positive Schizotypy as Diametric Specializations of the Predictive Mind

The predictive processing (PP) framework suggests that the mind works by making and testing predictions. According to PP, only prediction errors (rather than all sensory inputs) are processed by an organism’s perceptual system. Prediction errors can be weighted such that some errors (usually those deemed more reliable) will be more influential in updating prior beliefs. It has recently been argued that autism spectrum disorders (ASD) result from an underlying predictive processing mechanism. The weight given to sensory prediction errors is thought to be inflexibly high in ASD, meaning that the perceptual system utilizes even relatively small prediction errors to update prior beliefs. Deficits in executive functioning, theory of mind, and central coherence are all argued to flow naturally from this core underlying mechanism. The diametric model of autism and psychosis suggests that these disorders result from opposite cognitive tendencies. Building on the diametric model, others have argued that autistic-like traits and positive schizotypy represent diametric cognitive-perceptual and behavioral traits that exist on a continuum in normal, non-clinical populations. In this paper I argue that positive schizotypy (which consists of magical thinking, unusual experiences, and ideas of reference) can be explained by the opposite mechanism to that of autism, namely an inflexibly low weight given to sensory prediction errors. This mechanism can potentially explain such disparate features of positive schizotypy as increased exploratory behavior, hyper-theory of mind, attentional differences, idiosyncratic worldviews, and a hyper-active imagination.

Weak Central Coherence in Adults With ASD: Evidence From Eye-Tracking And Thematic Content Analysis Of Social Scenes

Central coherence theory proposes that a specific perceptual-cognitive process that limits the ability to derive overall meaning from details underlies the central disturbance in autism spectrum disorder (ASD). In a social context, it may interfere with the ability of individuals with ASD to understand interactions between people by recognizing emotional clues or attributing a particular mental state, and to play a role in the social difficulties associated with ASD. A sample of 28 adults diagnosed with ASD Level 1 and 25 controls were submitted to a cartoon-like task with the instruction to describe social scenes and a Navon letter task. Both quantitative measures and qualitative (thematic content analysis) procedures were used to assess performance. Heatmap and fixation preferences according to the stimuli quadrants were used to investigate eye-tracking patterns. A tendency to local processing, independently of the stimuli type, in the ASD participants was seen. In social scenes, quadrants with components such as characters' faces were neglected, resulting in a loss of implicit content related to interactions, as evidenced by verbal reports. A significantly longer reaction times and response durations in ASD. The findings corroborate the idea that weak central coherence may be part of the cognitive phenotype in ASD.

The Neuropsychological Profile of Severe and Enduring Anorexia Nervosa: A Systematic Review

Characteristics of Severe and Enduring Anorexia Nervosa (SE-AN) are being investigated to differentiate the patients experiencing SE-AN from those at earlier stages of the AN disease. The current systematic review was the first step in exploring neuropsychological functioning as a potentially identifying characteristic for long-term presentations. With a subgroup of AN patients reflecting a unique neuropsychological profile that is proportionate to the quantity of patients that go on to develop SE-AN, it was the aim of this review to assess neuropsychological functioning in the later stage of the disease. In accordance with PRISMA guidelines, a literature search was conducted using four electronic databases (PsycINFO, MEDLINE, Web of Science, and Scopus) for neuropsychological research on AN participants with a seven or more year illness duration. Datasets that met inclusion criteria were screened for SE-AN participants (N = 166) and neuropsychological data extracted together with potentially confounding variables and information required to conduct a quality assessment. In research investigating decision-making, participants with a SE-AN presentation demonstrated significantly lower functioning compared to healthy controls. There was conflicting evidence for differences in intellectual functioning and set-shifting abilities with no variability indicated in central coherence, memory, attention, reasoning, or processing speed. If findings from this preliminary analysis are confirmed through empirical research, implications include earlier identification of SE-AN patients and more effective treatment development.

What’s the Link Between Theory of Mind and Other Cognitive Abilities – A Co-twin Control Design of Neurodevelopmental Disorders

Theory of mind (ToM), or the ability to attribute mental states to oneself and others, is a core element of social cognition (SC). Even though its importance for social functioning in general, and neurodevelopmental disorders (NDDs), in particular, is well established, the links between ToM and other cognitive functions are not. Especially the familial underpinnings of such links remain unclear. Using a co-twin control design, we examined N = 311 twins (mean age M = 17.19 years, 47% females) diagnosed with autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), other NDDs, or typically developing individuals. We used the Reading the Mind in the Eyes Test to operationalize ToM, the Fragmented Pictures Test for central coherence (CC), the Tower Test for executive functioning (EF), and the general ability index in the Wechsler Intelligence Scales for IQ. In the linear regressions, weak CC and a lower IQ were associated with a reduced ToM ability across pairs. Female sex and higher age were robustly associated with increased ToM ability, whereas EF was not associated with ToM. In the within-pair analyses, where unmeasured familial confounders are implicitly adjusted, the associations between ToM and other cognitive functions, were attenuated and the association with CC was non-significant. The result suggests that familial factors shared by the twins, such as genetic and shared environment, influence the association between CC, IQ, and ToM. Future studies need to include a larger sample of monozygotic twins, who are genetically identical, in order to draw more firm conclusions regarding the influence of familial factors, and to differentiate between shared environmental and genetic effects on the associations between cognitive functions.

Effects of Hormonal Contraception Use on Cognitive Functions in Patients With Bulimia Nervosa

Background: Growing evidences indicate that sex hormones have an effect on cognitive functions, and that Bulimia Nervosa (BN) is associated with cognitive impairment. The aim of this study was to determine the effect of hormonal contraception (HC) use on four cognitive functions that are impaired in patients with BN.Methods: This retrospective exploratory study included 103 women with a diagnosis of BN based on the DSM-5 criteria. Their age ranged from 15 to 45 years, and 46.6% were taking HC (oral, transdermal, or intrauterine). Cognition was assessed with the d2 test (attention), Iowa gambling task (IGT; decision making), Brixton spatial anticipation test (set shifting), and Rey-Osterrieth complex figure test (central coherence). Data were analyzed with logistic regression models to estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) of HC effect on the neuropsychological test scores.Results: In the multivariate model, HC use was significantly associated with better scores for two d2 test indices: F-score [OR = 0.98, 95% CI = (0.95; 0.99)] and final total score ratio [OR = 0.87, 95% CI = (0.77; 0.99)]. HC was also associated with a better understanding of the IGT explicit rules. No difference between the two groups (HC and non-HC use) was detected for set shifting and central coherence.Conclusions: This exploratory study suggests that HC could have effects on the sustained attention and concentration in women with BN. More studies are needed to confirm these results.

The Lost Neural Hierarchy of the Autistic Self—Locked-Out of the Mental Self and Its Default-Mode Network

Autism spectrum disorder (ASD) is characterized by a fundamental change in self-awareness including seemingly paradoxical features like increased ego-centeredness and weakened self-referentiality. What is the neural basis of this so-called “self-paradox”? Conducting a meta-analytic review of fMRI rest and task studies, we show that ASD exhibits consistent hypofunction in anterior and posterior midline regions of the default-mode network (DMN) in both rest and task with decreased self–non-self differentiation. Relying on a multilayered nested hierarchical model of self, as recently established (Qin et al. 2020), we propose that ASD subjects cannot access the most upper layer of their self, the DMN-based mental self—they are locked-out of their own DMN and its mental self. This, in turn, results in strong weakening of their self-referentiality with decreases in both self-awareness and self–other distinction. Moreover, this blocks the extension of non-DMN cortical and subcortical regions at the lower layers of the physical self to the DMN-based upper layer of the mental self, including self–other distinction. The ASD subjects remain stuck and restricted to their intero- and exteroceptive selves as manifested in a relative increase in ego-centeredness (as compared to self-referentiality). This amounts to what we describe as “Hierarchical Model of Autistic Self” (HAS), which, characterizing the autistic self in hierarchical and spatiotemporal terms, aligns well with and extends current theories of ASD including predictive coding and weak central coherence.

Are poor set-shifting and central coherence associated with everyday function in anorexia nervosa? A systematic review

Background There is increasing interest in associations between cognitive impairments and clinical symptoms in Anorexia Nervosa (AN), however, the relationship with everyday function is unclear. The current review synthesizes existing data regarding associations between scores on tests of set-shifting and central coherence and functional outcome measures for individuals with AN. Method A systematic electronic database search yielded 13 studies which included participants with current or lifetime AN where scores on a neuropsychological test of set-shifting or central coherence were directly or indirectly compared to a functional outcome measure. Results Associations between set-shifting and central coherence performance measures and functional outcomes were limited in number and noted only in adult or mixed-age cohorts. Associations were noted at subscale level, suggesting they are specific in nature. In younger cohorts, assessments of executive functioning in everyday life appear sensitive to cognitive-behavioral flexibility issues. Conclusions Associations between cognitive performance and functional outcome have not been as systematically assessed in AN as in other psychiatric disorders. Key factors to address in future research include: (a) the use of function measures which are sensitive to both the level of impairment, and specific rather than general impairments (b) the ecological validity of measures, (c) the task impurity problem, especially in regard to cognitive flexibility assessment, and (d) the need to measure both cognitive deficits and strengths, because tests of specific cognitive processes may underestimate the ability to function in daily life due to compensatory strategies.