Visual illusions: An interesting tool to investigate developmental dyslexia and autism spectrum disorder

A visual illusion refers to a percept that is different in some aspect from the physical stimulus. Illusions are a powerful non-invasive tool for understanding the neurobiology of vision, telling us, indirectly, how the brain processes visual stimuli. There are some neurodevelopmental disorders characterized by visual deficits. Surprisingly, just a few studies investigated illusory perception in clinical populations. Our aim is to review the literature supporting a possible role for visual illusions in helping us understand the visual deficits in developmental dyslexia and autism spectrum disorder. Future studies could develop new tools – based on visual illusions – to identify an early risk for neurodevelopmental disorders

Age, dyslexia subtype and comorbidity modulate rapid auditory processing in developmental dyslexia

The nature of Rapid Auditory Processing (RAP) deficits in dyslexia remains debated, together with the specificity of the problem to certain types of stimuli and/or restricted subgroups of individuals. Following the hypothesis that the heterogeneity of the dyslexic population may have led to contrasting results, the aim of the study was to define the effect of age, dyslexia subtype and comorbidity on the discrimination and reproduction of nonverbal tone sequences.Participants were 46 children aged 8 - 14 (26 with dyslexia, subdivided according to age, presence of a previous language delay, and type of dyslexia). Experimental tasks were a Temporal Order Judgment (TOJ) (manipulating tone length, ISI and sequence length), and a Pattern Discrimination Task. Dyslexic children showed general RAP deficits. Tone length and ISI influenced dyslexic and control children’s performance in a similar way, but dyslexic children were more affected by an increase from 2 to 5 sounds. As to age, older dyslexic children’s difficulty in reproducing sequences of 4 and 5 tones was similar to that of normally reading younger (but not older) children. In the analysis of subgroup profiles, the crucial variable appears to be the advantage, or lack thereof, in processing long vs short sounds. Dyslexic children with a previous language delay obtained the lowest scores in RAP measures, but they performed worse with shorter stimuli, similar to control children, while dyslexic-only children showed no advantage for longer stimuli. As to dyslexia subtype, only surface dyslexics improved their performance with longer stimuli, while phonological dyslexics did not. Differential scores for short vs long tones and for long vs short ISIs predict nonword and word reading, respectively, and the former correlate with phonemic awareness.In conclusion, the relationship between nonverbal RAP, phonemic skills and reading abilities appears to be characterized by complex interactions with subgroup characteristics

Cellular residual disease (CRD) in early breast cancer –Expanding the concept of minimal residual disease monitoring?

Despite a significant evolution in treatment strategies for early breast cancer (EBC) patients, up to 30% of them experience recurrence due to occult micrometastasis. The minimal residual disease (minimal RD) in EBC patients after the treatment with curative intent cannot be easily detected by clinical examination and radiological imaging, as they are both burdened by limited sensitivity. A new frontier and promising approach to address this unmet need is the study of liquid biopsy (LB). The most studied tumor-derived analytes in the peripheral blood for minimal RD monitoring are currently: i) the circulating tumor DNA (ctDNA), for the detection of somatic DNA alterations, so referred to as molecular residual disease (MRD); ii) circulating tumor cells (CTCs), for the detection of cellular residual disease (CRD). MRD detection, while reaching a high specificity, is still presenting a number of limitations. On the other hand, CRD allows a real-time disease monitoring, detecting live cells, and possess the potential to provide an enormous amount of biological information. Indeed, CTCs can provide a multi-level portrait (i.e., DNA, RNA and proteins) of the tumor, longitudinally depicting its evolving landscape, and can be used for functional (in vitro/in vivo) characterization. Moreover, CRD goes beyond the association with the risk of recurrence: predictive biomarkers for treatment response can also be evaluated. Nevertheless, CTCs are less studied in this context, because of their need to be immediately processed and their limited detection in a small fraction of patients in the early and post-surgery setting. These limitations could however be overcome by the use of newly developed technologies that enable an increased CTC detection rate and retrospective studies. Here, we review the strengths and limitations of using MRD and CRD for minimal RD detection, focusing on the methodologies available for LB analysis in this setting, and on the main clinical studies investigating MRD and CRD in EBC. Considering the limits and the advantages of both MRD and CRD, we propose the integration of ctDNA and CTCs as complementary tools for minimal RD assessment to achieve a synergistic and novel approach for minimal RD analysis

Learning and Using Abstract Words: Evidence from Clinical Populations

Lorusso ML, Burigo M, Tavano A, et al. Learning and Using Abstract Words: Evidence from Clinical Populations. BioMed Research International. 2017;2017:1-8

Automatic classification of autism spectrum disorder in children using cortical thickness and support vector machine

Objective: Autism spectrum disorder (ASD) is a neurodevelopmental condition with a heterogeneous phenotype. The role of biomarkers in ASD diagnosis has been highlighted; cortical thickness has proved to be involved in the etiopathogenesis of ASD core symptoms. We apply support vector machine, a supervised machine learning method, in order to identify specific cortical thickness alterations in ASD subjects. Methods: A sample of 76 subjects (9.5 \ub1 3.4 years old) has been selected, 40 diagnosed with ASD and 36 typically developed subjects. All children underwent a magnetic resonance imaging (MRI) examination; T1-MPRAGE sequences were analyzed to extract features for the characterization and parcellation of regions of interests (ROI); average cortical thickness (CT) has been measured for each ROI. For the classification process, the extracted features were used as input for a classifier to identify ASD subjects through a "learning by example" procedure; the features with best performance was then selected by "greedy forward-feature selection." Finally, this model underwent a leave-one-out cross-validation approach. Results: From the training set of 68 ROIs, five ROIs reached accuracies of over 70%. After this phase, we used a recursive feature selection process in order to identify the eight features with the best accuracy (84.2%). CT resulted higher in ASD compared to controls in all the ROIs identified at the end of the process. Conclusion: We found increased CT in various brain regions in ASD subjects, confirming their role in the pathogenesis of this condition. Considering the brain development curve during ages, these changes in CT may normalize during development. Further validation on a larger sample is required

COMT Val158Met polymorphism and socioeconomic status interact to predict attention deficit/hyperactivity problems in children aged 10–14

The functional Val158Met COMT polymorphism appears to affect a host of behaviours mediated by the pre-frontal cortex, and has been found associated to the risk for disruptive behaviours including ADHD. Parental socioeconomic status (SES) has also been reported as a predictor for the same childhood disorders. In a general population sample of 575 Italian pre-adolescents aged 10–14, we examined the association of the functional Val158Met COMT polymorphism and SES—both as linear and interactive effects—with oppositional defiant problems, conduct problems, and attention deficit/hyperactivity problems, as defined by the newly established Child Behaviour Check-List/6-18 DSM oriented scales. Multivariate- and subsequent univariate-analysis of covariance showed a significant association of COMT × SES interaction with CBCL 6/18 DOS attention deficit/hyperactivity problems (p = 0.004), and revealed higher scores among those children with Val/Val COMT genotype who belonged to low-SES families. We also found a significant association of SES with attention deficit/hyperactivity problems and conduct problems DOS (p = 0.04 and 0.01, respectively). Our data are consistent with a bulk of recent literature suggesting a role of environmental factors in moderating the contribution of specific genetic polymorphisms to human variability in ADHD. While future investigations will refine and better clarify which specific environmental and genetic mechanisms are at work in influencing the individual risk to ADHD in pre-adolescence, these data may contribute to identify/prevent the risk for ADHD problems in childhood

Clinical Effects of an ACT-Group Training in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

Abstract Objective The aim of the present study is evaluate the effectiveness of an Acceptance and Commitment Therapy (ACT)-based training protocol, in adjunct to token economy and previous parent training, in a sample of children with Attention-Deficit/Hyperactivity Disorder (ADHD). By promoting the reduction of immediate responses to thoughts and feelings, we aimed to reduce the impulsive behaviour of children and to improve their self-regulation. Methods The protocol was centred on awareness of the present moment, defusion and acceptance of feelings and emotions. Behavioural (Conners' Parent Rating Scale -Revised: Long version, CPRS-R:L) and severity measures (Clinical Global Impression -Severity, CGI-S) were assessed before and after treatment in a clinical sample of 31 children aged 8–13 years. Results At the end of the ACT protocol, children showed significant improvement in global functioning and behavioural symptoms. There were significant improvements in the CPRS subscales Cognitive Problems (p = 0.005), Hyperactivity (p = 0.006), Perfectionism (p = 0.017), ADHD Index (p = 0.023), Global Index: Restless–Impulsive (p = 0.023), Global Index: Total (p = 0.036), DSM IV Inattentive (p = 0.029), DSM IV Hyperactive–Impulsive (p = 0.016), and DSM IV Total (p = 0.003). When controlling for the confounding effect of pharmacological therapy, comorbidities and socio-economic status, treatment maintained a significant effect on the CPRS subscales Perfectionism (partial η2 = 0.31, p < 0.01), Global Index: Restless–Impulsive (partial η2 = 0.29, p < 0.01), Global Index: Total (partial η2 = 0.31, p < 0.01), DSM IV Hyperactive–Impulsive (partial η2 = 0.20, p = 0.02). Symptom severity as rated by CGI-S scores decreased in 74.2% of the children. Conclusions This preliminary work on an Acceptance and Commitment Therapy-based child training in children affected by ADHD resulted in significant improvements, measured by a rating scale specific for ADHD

Maternal caregiving moderates the impact of antenatal maternal cortisol on infant stress regulation

Background Emerging evidence suggests that antenatal exposure to maternal stress signals affects the development of the infant stress response systems. Animal studies indicate that maternal sensitive caregiving can reverse some of these effects. However, the generalizability of these findings to humans is unknown. This study investigated the role of maternal caregiving in the association between multiple markers of maternal antenatal stress and infant stress regulation. Methods The sample consisted of 94 mother-infant (N = 47 males, mean postnatal weeks = 12; SD = 1.84) dyads. Maternal levels of Interleukin-6, C-Reactive Protein (CRP), diurnal cortisol and alpha amylase, depressive and anxiety symptoms were assessed in late pregnancy (mean gestational age = 34.76; SD = 1.12), whereas postnatal symptomatology, caregiving, and infant cortisol response to the inoculation were evaluated at 3 months. Results Hierarchical linear models (HLMs) showed a significant interaction between maternal antenatal cortisol, caregiving, and time on infant cortisol reactivity, while controlling for gender, maternal age, and postnatal depression. Specifically, higher levels of maternal antenatal cortisol were associated with greater cortisol response only among infants of less emotionally available mothers. All other markers of antenatal stress were not significantly associated with infant cortisol reactivity either independently or in interaction with maternal caregiving. Conclusions Albeit preliminary, results provide the first evidence in humans that maternal sensitive caregiving may eliminate the association between antenatal maternal cortisol and infant cortisol regulation

Neuroendocrine and immune markers of maternal stress during pregnancy and infant cognitive development

Antenatal exposure to maternal stress is a factor that may impact on offspring cognitive development. While some evidence exists of an association between maternal antenatal depressive or anxiety symptoms and infants’ cognitive outcomes, less is known about the role of biological indices of maternal antenatal stress in relation to infant cognitive development. The current study investigated the association between maternal depressive and anxiety symptoms, stress and inflammatory markers during pregnancy and infant’s cognitive development in a sample of 104 healthy pregnant women (mean gestational age=34.76; SD=1.12) and their 12-week-old infants (mean postnatal weeks=11.96; SD=1.85). Maternal depressive and anxiety symptoms were evaluated during pregnancy, alongside measurements of serum Interleukin-6 (IL-6), C-Reactive Protein (CRP), salivary cortisol and alpha amylase (sAA) concentrations. Infant cognitive development, maternal caregiving and concurrent anxiety or depressive symptoms were assessed 12 weeks after delivery. Hierarchical linear regressions indicated that higher maternal diurnal cortisol and CRP levels were independently associated with lower infant cognitive development scores, while adjusting for infant gender and gestational age, maternal IQ, caregiving, depressive or anxiety symptoms. Though correlational, findings seem suggestive of a role for variation in maternal biological stress signals during pregnancy in influencing infants’ early cognitive development

Real-time assessment of HER2 status in circulating tumor cells of breast cancer patients: Methods of detection and clinical implications

The human epidermal growth factor receptor 2 (HER2) plays a central role in breast cancer (BC). Therefore, it is critical to develop a method that can capture its spatial and temporal heterogeneity. Nowadays, therapeutic decisions for BC patients relies on evaluation of HER2 status from tissue biopsies using immunohistochemistry and in situ hybridization. Nevertheless, considering the technical and logistical challenges associated with tissue biopsies, there is an unmet need for a non-invasive and accurate approach to obtain real-time assessment of HER2 status. In this context, circulating biomarkers, particularly circulating tumor cells (CTCs), emerged as promising candidates. HER2 assessment on CTCs can be performed at genomic, transcriptomic, and protein levels on both bulk CTCs and at the single-cell resolution. However, the main limitation of the literature to date is the lack of a consistent definition of HER2-positive CTCs, which poses a major challenge for both, future research and clinical applications. Several studies revealed discordance in HER2 status between the primary tumor and corresponding CTCs. For instance, HER2-positive CTCs have been detected among patients with HER2-negative BC and vice versa. As a result, researchers have evaluated the prognostic and predictive value of HER2 status in CTCs, both in the early and metastatic settings, to increase the possibility of using anti-HER2 therapy also for these patients and to dissect mechanisms of treatment resistance. This review aims to provide an overview of the methods to determine HER2 status in CTCs and to summarize the evidence and future perspective on how CTCs-HER2 assessment can be integrated into the clinical management of BC patients