Working Memory In Individuals With Fragile X Syndrome

The present research tests the hypothesis that fragile X syndrome (FXS) is associated with a deficit in working memory (WM) and the deficit is more pronounced the higher the control requirements of the task. To this purpose, 15 boys with FXS and 15 typically developing children, matched for mental age, assessed with Logical Operation Test, were tested with batteries of 4 verbal and 4 visuospatial WM tasks requiring different levels of control. Children with FXS showed a performance equal to controls, in WM tasks requiring low and medium-low control but significant impairment in correspondence with greater control requirements. Results show that boys with FXS present a WM deficit only when high control is required by the task, supporting the hypothesis that control can be a critical variable distinguishing WM functions and explaining intellectual differences. On the contrary the hypothesis that the FXS is associated with a visuospatial deficit was not supported.     

Do women with fragile X syndrome have problems in switching attention: preliminary findings from ERP and fMRI

Fragile X syndrome (FXS) is a neurodevelopmental disorder that represents the most common known cause of developmental delay. Recent neuropsychological findings indicate that females with FXS present with a specific pattern of cognitive deficits and that these difficulties primarily involve skills requiring executive control. The present study is the first to examine the extent to which neural activity of females with FXS can be observed on a task that specifically taps two core deficits, namely switching and response inhibition. Brain activity was measured using both event-related electrical potentials (ERPs) and event-related functional MRI (fMRI) neuroimaging in separate studies using the same cognitive paradigm. Compared to controls, females with FXS were significantly slower and made more errors on trials that required an immediate response (Go) to stimulus onset but were comparable on trials that required a delayed response (Wait) to stimulus onset. At the brain level, several areas showed significantly greater activation for females with FXS compared with controls, including the cingulate cortex and left and right ventral prefrontal areas. In contrast, no areas were found to show significantly greater activation for controls compared with females with FXS.     

Language development and fragile X syndrome: profiles, syndrome-specificity, and within-syndrome differences

Fragile X syndrome (FXS) is the leading inherited cause of mental retardation. In this article, we review what is known about the language and related problems of individuals with FXS. In doing so, we focus on the syndrome-specific features of the language phenotype and on the organismic (i.e., genetic and individual neurocognitive and behavioral) and environmental factors associated with within-syndrome variation in the phenotype. We also briefly review those aspects of the behavioral phenotype of FXS that are relevant for understanding syndrome-specific features of, and within-syndrome variability in, language. The review includes summaries of research on the prelinguistic foundations for language development and on each of the major components of language (i.e., vocabulary, morphosyntax, and pragmatics). Throughout the review, we point out implications of existing research for intervention as well as directions for future research.     

Previous reward decreases errors of commission on later ‘No‐Go’ trials in children 4 to 12 years of age: evidence for a context monitoring account

Inhibitory control is widely hypothesized to be the cornerstone of executive function in childhood and the central deficit in a number of developmental disorders, including attention‐deficit/hyperactivity disorder (ADHD). However, recent evidence from adults indicates that performance on response inhibition tasks may primarily reflect non‐inhibitory attentional control (context monitoring) processes. Yet it may be that inhibition plays a more central role in childhood – a time when the architecture of cognitive processes might be more transparent due to wide variability in skill level. Here we directly test inhibitory and context monitoring explanations of task performance on a Go/No‐Go task in a large group of children 4–12 years of age. We conclude that traditional inhibitory conceptualizations of task performance on the Go/No‐Go task cannot account for our findings, calling into question evidence supporting a central role for inhibitory control in cognitive development or developmental psychopathology.     

What can autism and dyslexia tell us about intelligence?

This paper argues that understanding developmental disorders requires developing theories and models that explicitly represent the role of general intelligence in the cognitive phenotype of the disorder. In the case of autism it is argued that the low-IQ scores of people with autism are not likely to be due to a deficit in the cognitive process that is arguably the major cause of mental retardation - namely, speed of processing - but rather low IQ reflects the pervasive and cascading effects of the deficit in the information-processing module that causes autism. In the case of dyslexia, two radically different models of reading disorder (ability = disability and a modular deficit model) are likely to be influenced by the effect of general intelligence on reading performance in ways that will remain unclear without an explicit model of how general intelligence influences reading.     

Diagnosis of Fragile X Syndrome: A Qualitative Study of African American Families

Fragile X syndrome (FXS) is an inherited genetic condition with critical consequences to the proband and family members at all levels in the generations. Although evidence demonstrates that the rates of diagnosis for FXS are the same in all racial groups, age of diagnosis in African American children has been reported to occur later than in Caucasian children. Additionally, African American families are seriously under-represented in existing FXS research studies. As such, it is important to understand the possible disparities in the underlying factors to receiving a diagnosis in African American families with FXS. Herein, a qualitative approach was adopted to describe the overall FXS diagnosis experiences (pre-diagnosis, diagnosis, and post-diagnosis stages) of a convenience sample of 10 African American mothers. We identified three major findings among our participants: (1) FXS testing is not ordered immediately once a parent expresses concerns of developmental delays to the pediatricians, (2) the diagnosis is sometimes delivered in an insensitive manner with information often being outdated and unbalanced towards negative aspects, (3) communication issues among family members exists once the diagnosis is discovered. Although these qualitative data may not be representative of the whole group, these findings have significant implications for genetic counseling and our understanding in providing support and advocacy for African American families with FXS.     

Psychopharmacology in fragile X syndrome--present and future

In addition to cognitive disability, fragile X syndrome (FXS) is associated with behavioral problems that are often functionally limiting. There are few controlled trials to guide treatment; however, available information does suggest that medications can be quite helpful for a number of categories of behavioral disturbance in FXS. Specifically, stimulants appear to be quite useful for management of distractibility, hyperactivity, and impulsive behavior; antidepressants help with anxiety, obsessive-compulsive behaviors and mood dysregulation; and antipsychotics can reduce aggression. These medications are supportive and help minimize dysfunctional behaviors and maximize functioning. As more is learned about the neural functions of FMRP, medications in the future will be expected to target specific synaptic mechanisms dysregulated in FXS brain and thus ameliorate the cognitive deficit with resultant behavioral improvements. This article summarizes knowledge about effectiveness and approaches to management of currently available psychopharmacology for behavior in FXS and discusses early leads to future treatments for cognition.     

The evidence for a temporal processing deficit linked to dyslexia: A review

The existence of a phonemic deficit that is predictive of, and probably causal to, many cases of reading difficulty is well established. Tallal (1984) has suggested that this phonemic deficit is in fact a symptom of an underlying auditory temporal processing deficit. Our purpose in this paper is to evaluate the plausibility of this hypothesis. The various components that might constitute sequential (or temporal) processing are described. Our review of the literature reveals considerable evidence for a deficit in dyslexics in stimulus individuation tasks (e.g., gap detection) and temporal order judgments in both the auditory and visual modalities. The possibility that a general temporal processing deficit is associated with dyslexia, as suggested by Tallal (1984), is explored, and possible etiologies for such a deficit are discussed. The possibility of a causal link between temporal processing deficits and some reading disabilities is demonstrated, and converging evidence from morphological studies is reviewed. It is concluded that a temporal processing deficit does appear to be present in many developmental dyslexics, and strategies are suggested for further research aimed at evaluating the hypothesis that this deficit may be the root cause of a number of cases of dyslexia itself.     

Attentional set-shifting in fragile X syndrome

The ability to flexibly adapt to the changing demands of the environment is often reported as a core deficit in fragile X syndrome (FXS). However, the cognitive processes that determine this attentional set-shifting deficit remain elusive. The present study investigated attentional set-shifting ability in fragile X syndrome males with the well-validated intra/extra dimensional set-shifting paradigm (IED) which offers detailed assessment of rule learning, reversal learning, and attentional set-shifting ability within and between stimulus dimensions. A novel scoring method for IED stage errors was employed to interpret set-shifting failure in terms of repetitive decision-making, distraction to irrelevance, and set-maintenance failure. Performance of FXS males was compared to typically developing children matched on mental age, adults matched on chronological age, and individuals with Down syndrome matched on both mental and chronological age. Results revealed that a significant proportion of FXS males already failed prior to the intra-dimensional set-shift stage, whereas all control participants successfully completed the stages up to the crucial extra-dimensional set-shift. FXS males showed a specific weakness in reversal learning, which was characterized by repetitive decision-making during the reversal of newly acquired stimulus-response associations in the face of simple stimulus configurations. In contrast, when stimulus configurations became more complex, FXS males displayed increased distraction to irrelevant stimuli. These findings are interpreted in terms of the cognitive demands imposed by the stages of the IED in relation to the alleged neural deficits in FXS.     

Is Theory of Mind Understanding Impaired in Males with Fragile X Syndrome?

Males with fragile X syndrome (FXS) have difficulties with social interaction and many show autistic features. This study examined whether the social deficits characteristic of FXS are associated with theory of mind difficulties. Two groups of boys with FXS participated: a group with few autistic features and a group with many autistic features. An intellectual disability control group also participated. In addition to using standard theory of mind tasks, new techniques were used that were able to separate out the various processing demands of the task (e.g., memory, inhibitory control). Overall, the findings indicate that both groups of boys with FXS have difficulty with theory of mind tasks compared to an intellectual disability control group. However, both groups with FXS also performed worse on comparison trials that required working memory but not theory of mind. Theory of mind difficulties are likely to be an important aspect of the FXS clinical profile, but are most likely the result from a more basic difficulty with working memory.     

Developmental cognitive genetics: how psychology can inform genetics and vice versa

Developmental neuropsychology is concerned with uncovering the underlying basis of developmental disorders such as specific language impairment (SLI), developmental dyslexia, and autistic disorder. Twin and family studies indicate that genetic influences play an important part in the aetiology of all of these disorders, yet progress in identifying genes has been slow. One way forward is to cut loose from conventional clinical criteria for diagnosing disorders and to focus instead on measures of underlying cognitive mechanisms. Psychology can inform genetics by clarifying what the key dimensions are for heritable phenotypes. However, it is not a one-way street. By using genetically informative designs, one can gain insights about causal relationships between different cognitive deficits. For instance, it has been suggested that low-level auditory deficits cause phonological problems in SLI. However, a twin study showed that, although both types of deficit occur in SLI, they have quite different origins, with environmental factors more important for auditory deficit, and genes more important for deficient phonological short-term memory. Another study found that morphosyntactic deficits in SLI are also highly heritable, but have different genetic origins from impairments of phonological short-term memory. A genetic perspective shows that a search for the underlying cause of developmental disorders may be misguided, because they are complex and heterogeneous and are associated with multiple risk factors that only cause serious disability when they occur in combination.     

Developmental cognitive genetics: How psychology can inform genetics and vice versa

Developmental neuropsychology is concerned with uncovering the underlying basis of developmental disorders such as specific language impairment (SLI), developmental dyslexia, and autistic disorder. Twin and family studies indicate that genetic influences play an important part in the aetiology of all of these disorders, yet progress in identifying genes has been slow. One way forward is to cut loose from conventional clinical criteria for diagnosing disorders and to focus instead on measures of underlying cognitive mechanisms. Psychology can inform genetics by clarifying what the key dimensions are for heritable phenotypes. However, it is not a one-way street. By using genetically informative designs, one can gain insights about causal relationships between different cognitive deficits. For instance, it has been suggested that low-level auditory deficits cause phonological problems in SLI. However, a twin study showed that, although both types of deficit occur in SLI, they have quite different origins, with environmental factors more important for auditory deficit, and genes more important for deficient phonological short-term memory. Another study found that morphosyntactic deficits in SLI are also highly heritable, but have different genetic origins from impairments of phonological short-term memory. A genetic perspective shows that a search for the underlying cause of developmental disorders may be misguided, because they are complex and heterogeneous and are associated with multiple risk factors that only cause serious disability when they occur in combination.     

From single to multiple deficit models of developmental disorders

The emerging etiological model for developmental disorders, like dyslexia, is probabilistic and multifactorial while the prevailing cognitive model has been deterministic and often focused on a single cognitive cause, such as a phonological deficit as the cause of dyslexia. So there is a potential contradiction in our explanatory frameworks for understanding developmental disorders. This paper attempts to resolve this contradiction by presenting a multiple cognitive deficit model of developmental disorders. It describes how this model evolved out of our attempts to understand two comorbidities, those between dyslexia and attention deficit hyperactivity disorder (ADHD) and between dyslexia and speech sound disorder (SSD).     

化危为机：青少年学校转折期的过渡

从生命历程的角度看, 学校过渡是青少年成长过程中的重要发展转折点, 对个体的发展轨迹具有重要影响。先前研究多基于缺陷的视角, 将学校过渡视为充满挑战和风险的危机时期, 并发现青少年在这一时期伴随着各种消极的发展结果。但从青少年积极发展的视角来看, 学校过渡可能是青少年获得适应性的、健康发展的重要机遇, 也是发展可塑性表现最为充分的时期。如果青少年的内部和外部资源能够很好的融合, 他们就有可能获得积极的学校过渡。     

Children with developmental coordination disorder (DCD) and their ability to disengage ongoing attentional focus: more on inhibitory function

Children with developmental coordination disorder (DCD), along with their Control counterparts, completed two endogenous, spatial precue tasks. When the precue arrow was informative (.80) with respect to target location, the spatial precue effect results demonstrated that children with DCD take significantly longer than Control individuals to volitionally disengage (inhibit) attention from an endogenously cued location (i.e., a disengagement inhibition deficit). When the precue was uninformative (.25), we found, contrary to a common assumption, that the precue arrow automatically moved attention in the direction of the arrow, and, in addition, that DCD children may also be less able to inhibit the precued-induced urge to move attention (i.e., an initiation inhibition deficit). This type of inhibitory difficulty was also indicated for manual response inclinations produced on catch trials. Overall, DCD children appeared to have an elevated difficulty suppressing the initiation of incorrect, stimulus-provoked movement urges, be they manual or attention in nature.     

Atypical epigenesis

It is becoming increasingly clear that little in development is predetermined or permanently fixed. Rather, gene expression is activity dependent, and epigenesis is probabilistic. So, the study of genetic disorders needs to change from the still widely held view that developmental disorders can be accounted for in terms of intact versus impaired modules, to one which takes serious account of the fact that the infant cortex passes from an initial state of high regional interconnectivity to a subsequent state of increasing specialization and localization of function. With such early interconnectivity in mind, developmental neuroscientists must consider the possibility that an early deficit in one part of the brain may have subtle effects on other parts of the developing brain, even when scores fall 'in the normal range'. In studying developmental disorders, it is thus crucial to examine not only domains of clear-cut deficit, but also domains of behavioural proficiency. Atypical epigenesis may often involve a lack of specialization and localization of brain function over developmental time, even in cases of behavioural proficiency.     

Cortisol response to behavior problems in FMR1 premutation mothers of adolescents and adults with fragile X syndrome: A diathesis-stress model

Mothers of adolescents and adults with fragile X syndrome (FXS) are faced with high levels of parenting stress. The extent to which mothers are negatively impacted by this stress, however, may be influenced by their own genetic status. The present study uses a diathesis-stress model to examine the ways in which a genetic vulnerability in mothers with the premutation of the FMR1 gene interacts with child-related environmental stress to predict their morning cortisol levels. Seventy-six mothers of an adolescent or adult with FXS participated in an 8-day telephone diary study in which they reported on the behavior problems of their son or daughter with FXS each day. We analyzed salivary cortisol collected from mothers at awakening and 30 minutes after awakening on 4 of these days. The results indicated that mothers with greater genetic vulnerability had a lower level of cortisol on mornings following days when their son or daughter with FXS manifested more episodes of behavior problems, whereas mothers with less genetic risk evinced the opposite pattern of higher morning cortisol in response to their child's behavior problems. This finding contributes to our understanding of gene-by-environment interactions and highlights the importance of interventions to alleviate parenting stress in mothers raising children with FXS.     

汉语发展性阅读障碍儿童心理机制的初步研究

本研究采用真假字判断与同音判断任务考察了汉语发展性阅读障碍儿童的心理机制。结果显示,对于真假字判断任务,阅读障碍儿童与正常儿童没有显著差异,而在同音判断任务中表现出了显著差异。本研究说明汉语阅读障碍儿童在整体字形表征方面是正常的,同时还支持了阅读障碍为语音表征缺陷的观点。     

Attitude of Medical School Students in China Towards Genetic Testing and Counseling Issues in FXS

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. However, genetic testing protocols and genetic counseling guidelines for FXS are not yet established in mainland China. In the present study, we conducted a comprehensive analysis using a self-administered questionnaire among students at the Xiangya medical school to investigate their attitude towards genetic testing and counseling issues of FXS. We have gained a general understanding of the attitudes of medical students towards these FXS issues in China. This information is of immense importance to develop appropriate genetic tests and to train counselors for FXS. As the medical school students surveyed are prospective physicians who will be a part of the Chinese health system, our survey was focused on the basic knowledge of FXS, population-based FXS screening, confidentiality and reproductive options for mutation carriers. The study demonstrated that only less than one third of the participants had heard about FXS. 94.6 % of participants were in favor of FXS screening for women in their reproductive age who had a genetic history of FXS. Furthermore, only half of the participants would inform their families about their genetic status in case of positive test results, and more than half of the participants supported natural conception and prenatal diagnosis for FXS mutation carriers. Additional findings and research implications are also discussed. This survey targeting potential doctors provides important information for the development of FXS genetic test and counselor training for the Chinese health system.