Yves Chaix

Behavioural and cognitive phenotypes in children with neurofibromatosis type 1 (NF1): The link with the neurobiological level

Neurofibromatosis type 1 (NF1) is one of the most frequent monogenetic disorder encountered in children. Approximately 50% of children with NF1 develop learning disabilities notably for reading. Understanding the reasons of reading impairment in this context may lead to improve therapeutic methods in NF1 and more generally in reading developmental disorders. An interesting challenge is to disentangle the connections between the different levels of description proposed in the etiological approach. This is the aim of this review based on recent advances in analysis of cognitive deficits observed in children with NF1 and on results of recent brain imaging (structural and functional) or animal model studies.

Neural Signature of DCD: A Critical Review of MRI Neuroimaging Studies

The most common neurodevelopmental disorders (e.g., developmental dyslexia (DD), autism, attention-deficit hyperactivity disorder (ADHD)) have been the subject of numerous neuroimaging studies, leading to certain brain regions being identified as neural correlates of these conditions, referring to a neural signature of disorders. Developmental coordination disorder (DCD), however, remains one of the least understood and studied neurodevelopmental disorders. Given the acknowledged link between motor difficulties and brain features, it is surprising that so few research studies have systematically explored the brains of children with DCD. The aim of the present review was to ascertain whether it is currently possible to identify a neural signature for DCD, based on the 14 magnetic resonance imaging neuroimaging studies that have been conducted in DCD to date. Our results indicate that several brain areas are unquestionably linked to DCD: cerebellum, basal ganglia, parietal lobe, and parts of the frontal lobe (medial orbitofrontal cortex and dorsolateral prefrontal cortex). However, research has been too sparse and studies have suffered from several limitations that constitute a serious obstacle to address the question of a well-established neural signature for DCD.

A study of EEG coherence in DCD children during motor synchronization task

This paper investigates the hypothesis that the coordination difficulties of DCD children are associated with an increased coherence in the cortical motor regions, which persists with age. Forty-eight children participated in the study (24 DCD and 24 Controls). Their ages ranged from 8 to 13 years, divided into three groups (8-9, 10-11, and 12-13 years old). Children were required to perform finger flexion or extension either in synchrony or in syncopation with a rhythmic metronome, while a 32-channel EEG was recorded. Along with stability measures of motor performance, we analyzed the spectral EEG coherence between intrahemispheric (left frontal/left central; left central/left parietal) and interhemispheric (left central/right central) sites. Spectral coherence assesses functional coupling between distant areas of the brain. Two frequency bands related to sensorimotor activation were chosen: alpha (8-12 Hz) and beta (12-30 Hz). The synchrony task was chosen as a rest condition against which the two syncopation conditions at 0.5 Hz and 1.3 Hz were contrasted. For intrahemispheric comparison, 8-9-year-old DCD children showed that coherence between fronto-central regions increased for both rhythms and conditions, as compared to controls. No difference was found for interhemispheric comparisons. As frontal sites are related to motor planning, our results suggest that youngest DCD children were forced to maintain a high level of pre-programming to compensate for the difficulties caused by the perceptual-motor requirements of the task in light of their coordination disorder.

Procedural learning and automatization process in children with developmental coordination disorder and/or developmental dyslexia.

OBJECTIVE There is increasing evidence to suggest that developmental dyslexia (DD) and developmental coordination disorder (DCD) actually form part of a broader disorder. Their frequent association could be justified by a deficit of the procedural memory system, that subtends many of the cognitive, motor and linguistic abilities that are impaired in both DD and DCD. However, studies of procedural learning in these two disorders have yielded divergent results, and in any case no studies have so far addressed the issue of automatization (dual-task paradigm). METHODS We administered a finger tapping task to participants aged 8-12 years (19 DCD, 18 DD, and 22 with both DD and DCD) to explore procedural learning and automatic movements in these three groups of children, comparing motor performances at the prelearning stage, after 2 weeks of training, and in a post-training dual-task condition. RESULTS First, results indicated that all the children were able to learn a sequence of movements and even automatize their movements. Second, they revealed between-groups differences in procedural/automatization learning abilities, setting the DCD group apart from the other two. Third, contrary to our expectations concerning comorbidity, they suggested that the DD+DCD association does not have an additional impact on behavioral performances.

Motor impairment in children with Neurofibromatosis type 1: Effect of the comorbidity with language disorders.

BACKGROUND There is a body of evidence demonstrating comorbidity of motor and cognitive deficit in «idiopathic» developmental disorders. These associations are also found in developmental disorders secondary to monogenic disorders as in Neurofibromatosis type 1 for which the principal complication during childhood is learning disabilities. The comparison of motor impairment between developmental disorders either idiopathic or secondary as in NF1 could help us to better understand the cause of the combined language/motor deficit in these populations. AIM The aim of this current study was to investigate motor impairment in children with NF1 for which oral language had been specified and then to compare the motors skills of the NF1 group to motor performance of children with Specific Language Disorder (SLD). METHOD Two groups of 49 children between 5 and 12years old were included and compared, the NF1 group and the SLD (Specific Language Disorder) group. Each child completed evaluation involving cognitive, language and motor assessment. RESULTS In NF1 group, motor impairment was more frequent and more severe and concerned specifically balance rather than manual dexterity or ball skills, compared to a group of children with SLD. This motor impairment was independent of language status in the NF1 group. CONCLUSIONS These results as well as other studies on the same topic could suggest that in NF1 children, fine motor skills impairment would be dependent on the existence of comorbidity with language disorders. Also, that gross motor skills impairment, and more precisely the balance deficit would be characteristic of NF1. This issue encourages studies of procedural learning that can involve the fronto-striatal or the fronto-cerebellar loops according to the type of motor tasks and the stage of learning.

Neuropsychological status of French children with developmental dyslexia and/or developmental coordination disorder: Are both necessarily worse than one?

ABSTRACT Developmental dyslexia (DD) and developmental coordination disorder (DCD) co-occur frequently, raising the underlying question of shared etiological bases. We investigated the cognitive profile of children with DD, children with DCD, and children with the dual association (DD + DCD) to determine the inherent characteristics of each disorder and explore the possible additional impact of co-morbidity on intellectual, attentional, and psychosocial functioning. The participants were 8- to 12-year-olds (20 DD, 22 DCD, and 23 DD + DCD). Cognitive abilities were assessed by the Wechsler Intelligence Scale for Children – Fourth Edition (WISC-IV) and the Continuous Performance Test – Second Edition (CPT-II) and behavioral impairments were evaluated by the Child Behavior Checklist (CBCL). No differences were found between the three groups on attention testing (CPT-II) or psychosocial characteristics (CBCL), but a higher percentage of DD + DCD children had pathological scores on psychosocial scales. Significant between-group differences were observed on Processing Speed Index scores and the block design and symbol search subtests, where DD children fared better than DCD children. No significant differences were evident between the co-morbid vs. the pure groups. Our results clearly show significant differences between children with DD only and children with DCD only. In particular, visuo-spatial disabilities and heterogeneity of intellectual profile seem to be good markers of DCD. However, it should be noted that despite these distinct and separate characteristics, a common cognitive profile (weaknesses and strengths) is likely shared by both neurodevelopmental disorders. Surprisingly, concerning co-morbidity, DD + DCD association is not associated with a decrease in intellectual or attentional capacities.

What Do We Really Know About Motor Learning in Children with Developmental Coordination Disorder

There is a general consensus that developmental coordination disorder (DCD) is characterized by impaired motor learning skills. However, actual studies of motor learning in DCD are scarce and, above all, inconsistent. The aims of the present study were therefore to explore the presumed presence of a motor learning deficit among individuals with DCD and to provide a synopsis of the current literature on motor learning in DCD. We begin by defining DCD (etiology, neuropsychology, and brain bases), motor learning (measurement of learning, methods for promoting skill acquisition, scheduling, practice, retention, and feedback) and, of course, the link between the two, focusing on the issue of a possible motor learning deficit in DCD. We then discuss dominant hypotheses and suggest directions for future research in this domain, in the light of research conducted thus far. Particular attention is paid throughout to guide the choice of intervention approaches.

Lack of Motor Inhibition as a Marker of Learning Difficulties of Bimanual Coordination in Teenagers With Developmental Coordination Disorder

ABSTRACT This study tested the learning of a new bimanual coordination in teenagers with and without Developmental Coordination Disorder (DCD). Both groups improved accuracy of the new coordination. No difference was found on stability. But DCD teenagers exhibited an overall higher number of additional taps, suggesting a persistent lack of motor inhibition during learning. Moreover, teenagers with the lowest scores of motor abilities present the highest number of additional taps. All these results suggest that this number of additional taps (rather than traditional measures of accuracy and stability) could be a good marker of perceptual-motor learning deficit in DCD.

Deficit in phonological processes: a characteristic of the neuropsychological profile of children with NF1

ABSTRACT Learning disabilities are one of the most frequent complications of neurofibromatosis type 1 (NF1) in children. Studies of the effects of the neurocognitive deficit on academic performance are relatively rare, owing to the small size of the populations concerned. However, research is needed to develop effective rehabilitation programs. In the present study, we explored the impact of a possible phonological deficit on the reading abilities of children with NF1. A multicenter, cross-sectional study was conducted in France on two groups of 75 children with or without NF1 aged 8–12 years, matched for age, sex, handedness, and reading level. All participants underwent a neuropsychological evaluation to assess their general cognitive level, reading skills, phonological processes, visuoperceptual abilities, and attentional capacity. Phonological skills were assessed by means of two phonological awareness tasks and one short-term memory task. In the group of children with NF1, 41% had reading difficulties. Phonological processes were impaired in this group, compared with the children without NF1. Similar differences were found for a phoneme deletion task after adjustment for reading difficulties, IQ level, and visuoperceptual abilities. Phonological awareness, but not phonological short-term memory, was impaired in children with NF1, and not just those whose reading was impaired. Results suggest that children with NF1 have a phonological awareness deficit, whatever their reading level. Identification of reduced phonological skills may warrant the implementation of a specific rehabilitation program before early reading difficulties emerge.

Effect of desipramine on patients with breathing disorders in RETT syndrome

Rett Syndrome (RTT) is a severe neurodevelopmental condition with breathing disorders, affecting around one in 10,000 female births. Desipramine, a noradrenaline reuptake inhibitor, reduced the number of apneas in Mecp2‐deficient mice, a model of RTT. We planned a phase 2 trial to test its efficacy and its safety on breathing patterns in 36 girls with RTT.