Impaired online control in children with developmental coordination disorder reflects development immaturity

The present study aimed to clarify whether a reduced ability to correct movements in-flight observed in children with developmental coordination disorder (DCD) reflects a developmental immaturity or deviance from the typical trajectory. Eighteen children with DCD (8–12 years), 18 age-matched controls, and 12 younger controls (5–7 years) completed a double-step reaching task. Compared to older controls, children with DCD and younger controls showed similarly prolonged reaching when the target unexpectedly shifted at movement onset and were equally slow to correct their reaching trajectory. These results suggest that impaired online control in DCD reflects developmental immaturity, possibly implicating the parietal-cerebellar cortices.

Online motor control in children with developmental coordination disorder: chronometric analysis of double-step reaching performance

Background
Although there are a number of plausible accounts to explain movement clumsiness in children [or developmental coordination disorder (DCD)], the cause(s) of the disorder remain(s) an issue of debate. One aspect of motor control that is particularly important to the fluid expression of skill is rapid online control (ROC). Data on DCD have been conflicting. While some recent work using double-step reaching suggests no difficulty in online control, others suggest deficits (e.g. based on sequential pointing). To help resolve this debate, we suggest two things: use of recent neuro-computational models as a framework for investigating motor control in DCD, and more rigorous investigation of double-step reaching. Our working assumption here is that ROC is only viable through the seamless integration of predictive (or forward) models of movement and feedback-based mechanisms.

Aim
The aim of this chronometric study was to explore ROC in children with DCD using a double-step reaching paradigm. We predicted slower online adjustments in DCD based on the argument that these children manifest a core difficulty in predictive control.

Methods
Participants were a group of 17 children with DCD and 27 typically developing children aged between 7 and 12 years. Visual targets were presented on a 17-inch LCD touch screen, inclined to an angle of 15° from horizontal. The children were instructed to press each target as it appeared as quickly and accurately as possible. For 80% of the trials, the central target location remained unchanged for the duration of the movement (non-jump trials), while for the remaining 20% of trials, the target jumped at movement onset to one of the two peripheral locations (jump trials). Reaction time (RT), movement time (MT) and reaching errors were recorded.

Results
For both groups, RT did not vary according to trial condition, while children with DCD were slower to initiate movement. Further, the MT of children with DCD was prolonged to a far greater extent on jump trials relative to controls, with a large effect size. As well, children with DCD committed significantly more errors, notably a reduced ability to inhibit central responses on jump trials.

Conclusion
Our findings help reconcile some disparate findings in the literature using similar tasks. The pattern of performance in children with DCD suggests impairment in the ability to make rapid online adjustments that are based on a predictive (or internal) model of the action. These results pave the way for future kinematic investigation.

Coupling online control and inhibitory systems in children with developmental coordination disorder: goal-directed reaching

For children with Developmental Coordination Disorder (DCD), the real-time coupling between frontal executive function and online motor control has not been explored despite reported deficits in each domain. The aim of the present study was to investigate how children with DCD enlist online control under task constraints that compel the need for inhibitory control. A total of 129 school children were sampled from mainstream primary schools. Forty-two children who met research criteria for DCD were compared with 87 typically developing controls on a modified double-jump reaching task. Children within each skill group were divided into three age bands: younger (6-7 years), mid-aged (8-9), and older (10-12). Online control was compared between groups as a function of trial type (non-jump, jump, anti-jump). Overall, results showed that while movement times were similar between skill groups under simple task constraints (non-jump), on perturbation (or jump) trials the DCD group were significantly slower than controls and corrected trajectories later. Critically, the DCD group was further disadvantaged by anti-jump trials where inhibitory control was required; however, this effect reduced with age. While coupling online control and executive systems is not well developed in younger and mid-aged children, there is evidence of age-appropriate coupling in older children. Longitudinal data are needed to clarify this intriguing finding. The theoretical and applied implications of these results are discussed.

Do children with autism and Asperger's disorder have difficulty controlling handwriting size? A kinematic evaluation

Children with autism spectrum disorders (ASD) often show difficulties in controlling letter size and consistent letter formation during handwriting; however, there has been little research into the underlying nature of handwriting impairments in this group. The aim of this study was to assess the ability of children with ASD to regulate the size and consistency of fundamental handwriting movements when using writing guides, and determine whether the kinematic profile during writing is different to typically developing children. Twenty-six boys with ASD (16 with high-functioning autism, 10 with Asperger's disorder) aged 8-13 years (IQ > 75), and 17 typically developing children wrote a series of four cursive letter l's using 10 mm and 40 mm writing guides, using a graphics tablet and stylus. Movement size and consistency was comparable between groups when the writing guides were set at 10 mm; however, handwriting movements of children with ASD were significantly faster and more fluent than typically developing children when writing guides were set at 40 mm. Neuromotor noise was comparable to that of typically developing children across both writing sizes. Clinically, our findings indicate that children with ASD have a well-automated motor plan for simple handwriting movements when writing guides are present and that problems of handwriting legibility in ASD are likely to arise from other factors, such as complex motor chaining (i.e. writing whole words and sentences), or attentional, working memory and linguistic demands when writing.

Reduced motor imagery efficiency is associated with online control difficulties in children with probable developmental coordination disorder

Recent evidence indicates that the ability to correct reaching movements in response to unexpected target changes (i.e., online control) is reduced in children with developmental coordination disorder (DCD). Recent computational modeling of human reaching suggests that these inefficiencies may result from difficulties generating and/or monitoring internal representations of movement. This study was the first to test this putative relationship empirically. We did so by investigating the degree to which the capacity to correct reaching mid-flight could be predicted by motor imagery (MI) proficiency in a sample of children with probable DCD (pDCD). Thirty-four children aged 8 to 12 years (17 children with pDCD and 17 age-matched controls) completed the hand rotation task, a well-validated measure of MI, and a double-step reaching task (DSRT), a protocol commonly adopted to infer one's capacity for correcting reaching online. As per previous research, children with pDCD demonstrated inefficiencies in their ability to generate internal action representations and correct their reaching online, demonstrated by inefficient hand rotation performance and slower correction to the reach trajectory following unexpected target perturbation during the DSRT compared to age-matched controls. Critically, hierarchical moderating regression demonstrated that even after general reaching ability was controlled for, MI efficiency was a significant predictor of reaching correction efficiency, a relationship that was constant across groups. Ours is the first study to provide direct pilot evidence in support of the view that a decreased capacity for online control of reaching typical of DCD may be associated with inefficiencies generating and/or using internal representations of action.

Gaze pursuit and arm control of adolescent males diagnosed with attention deficit hyperactivity disorder (ADHD) and normal controls: evidence of a dissociation in processing visual information of short and long duration

Three-dimensional kinematic analysis of line of gaze, arm and ball was used to describe the visual and motor behaviour of male adolescents diagnosed with attention deficit hyperactivity disorder (ADHD). The ADHD participants were tested when both on (ADHD-On) and off (ADHD-Off) their medication and compared to age-matched normal controls in a modified table tennis task that required tracking the ball and hitting to cued right and left targets. Long-duration information was provided by a pre-cue, in which the target was illuminated approximately 2 s before the serve, and short-duration information by an early-cue illuminated about 350 ms after the serve, leaving -500 ms to select the target and perform the action. The ADHD groups differed significantly from the control group in both the pre-cue and early-cue conditions in being less accurate, in having a later onset and duration of pursuit tracking, and a higher frequency of gaze on and off the ball. The use of medication significantly reduced the gaze frequency of the ADHD participants, but surprisingly this did not lead to an increase in pursuit tracking, suggesting a barrier was reached beyond which ball flight information could not be processed. The control and ADHD groups did not differ in arm movement onset, duration and velocity in the short-duration early-cue condition; in the long-duration pre-cue condition, however, the ADHD group's movement time onset and arm velocity differed significantly from controls. The results show that the ADHD groups were able to process short-duration information without experiencing adverse effects on their motor behaviour; however, long-duration information contributed to irregular movement control.

Chewing in temporomandibular disorder patients: an exploratory study of an association with some psychological variables

Aims: To compare kinematic parameters (ie, amplitude, velocity, cycle frequency) of chewing and pain characteristics in a group of female myofascial temporomandibular disorder (TMD) patients with an age-matched control female group, and to study correlations between psychological variables and kinematic variables of chewing. Methods: Twenty-nine female participants were recruited. All participants were categorized according to the Research Diagnostic Criteria for TMD (RDC/TMD) into control (n = 14, mean age 28.9 years, SD 5.0 years) or TMD (n = 15, mean age 31.3 years, SD 10.7) groups. Jaw movements were recorded during free gum chewing and chewing standardized for timing. Patients completed the Depression, Anxiety, and Stress Scales (DASS-42), the Pain Catastrophizing Scale (PCS), the Fear of Pain Questionnaire-III (FPQ-III), and the Pain Self-Efficacy Questionnaire (PSEQ). Statistical analyses involved evaluation for group differences, and correlations between kinematic variables and psychological questionnaire scores (eg, depression, anxiety, stress) and pain intensity ratings. Results: Velocity and amplitude of standardized (but not free) chewing were significantly greater (P < .05) in the TMD group than the control group. There were significant (P < .05) positive correlations between pain intensity ratings and velocity and amplitude of standardized chewing but not free chewing. There were significant (P < .05) positive correlations between depression and jaw amplitude and stress and jaw velocity for standardized but not free chewing. Conclusion: This exploratory study has provided data suggesting that psychological factors, manifesting in depression and stress, play a role in influencing the association between pain and motor activity. J OROFAC PAIN 2011;25:56-67

Integrated analysis environment for the Movement Assessment Battery for Children

Developmental Coordination Disorder (DCD), a chronic and usually permanent condition found in children, is characterized by motor impairment that interferes with a child's activities of daily living and with academic achievement. One of the most popular tests for the quantitative diagnosis of DCD is the Movement Assessment Battery for Children (MABC). Based on the Battery's standardized scores, it is possible to identify children with typical development, children at risk of developing DCD, and children with DCD. This article describes a computational system we developed to assist with the analysis of results obtained in the MABC test. The tool was developed for the web environment and its database provides integration of MABC data. Thus, researchers around the world can share data and develop collaborative work in the DCD field. In order to help analysis processes, our system provides services for filtering data to show more specific sets of information and present the results in textual, table, and graphic formats, allowing easier and more comprehensive evaluation of the results.

Sensory phenomena associated with repetitive behaviors in obsessive-compulsive disorder: An exploratory study of 1001 patients

A substantial number of patients with obsessive-compulsive disorder (OCD) report compulsions that are preceded not by obsessions but by subjective experiences known as sensory phenomena. This study aimed to investigate the frequency, severity, and age at onset of sensory phenomena in OCD, as well as to compare OCD patients with and without sensory phenomena in terms of clinical characteristics. We assessed 1,001 consecutive OCD patients, using instruments designed to evaluate the frequency/severity of OC symptoms, tics, anxiety, depression, level of insight and presence/severity of sensory phenomena. All together, 651 (65.0%) subjects reported at least one type of sensory phenomena preceding the repetitive behaviors. Considering the sensory phenomena subtypes, 371 (57.0%) patients had musculoskeletal sensations, 519 (79.7%) had externally triggered "just-right" perceptions, 176 (27.0%) presented internally triggered "just right," 144 (22.1%) had an "energy release," and 240 (36.9%) patients had an "urge only" phenomenon. Sensory phenomena were described as being as more severe than were obsessions by 102(15.7%) patients. Logistic regression analysis showed that the following characteristics were associated with the presence of sensory phenomena: higher frequency and greater severity of the symmetry/ordering/arranging and contamination/washing symptom dimensions; comorbid Tourette syndrome, and a family history of tic disorders. These data suggest that sensory phenomena constitute a poorly understood psychopathological aspect of OCD that merits further investigation. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Severity of restless legs syndrome is inversely correlated with echogenicity of the substantia nigra in different neurodegenerative movement disorders. A preliminary observation

Objective: Hyperechogenicity of the substantia nigra is a frequent observation on transcranial sonography in Parkinson's disease and Machado-Joseph disease patients. Additionally, restless legs syndrome is a sleep disorder that is also frequently found in both diseases. Autopsy studies have demonstrated increased SN iron content in hyperechogenic substantia nigra. Iron storage is also known to be involved in restless legs syndrome. We formally compared echogenicity of the substantia nigra with restless legs syndrome in Parkinson's disease and Machado-Joseph disease patients. Methods: Transcranial brain sonography was performed in a sample of Parkinson's disease and Machado-Joseph disease patients, and findings then correlated with the presence and severity of restless legs syndrome. Results: There was a continuum of substantia nigra echogenicity among groups (Parkinson's disease versus Machado-Joseph disease versus controls) and sub-groups (Parkinson's disease with and without restless legs syndrome versus Machado-Joseph disease with and without restless legs syndrome) as well as a statistically significant negative correlation between restless legs syndrome severity and substantia nigra echogenicity (p<0.001). Conclusions: These preliminary observations demonstrate that the severity of RLS may be influenced by nigral iron load reflected by substantia nigra echogenicity in different neurodegenerative movement disorders. (C) 2012 Elsevier B.V. All rights reserved.

Cortico-cortical white matter motor pathway microstructure is related to psychomotor retardation in major depressive disorder

Alterations of brain structure and function have been associated with psychomotor retardation in major depressive disorder (MDD). However, the association of motor behaviour and white matter integrity of motor pathways in MDD is unclear. The aim of the present study was to first investigate structural connectivity of white matter motor pathways in MDD. Second, we explore the relation of objectively measured motor activity and white matter integrity of motor pathways in MDD. Therefore, 21 patients with MDD and 21 healthy controls matched for age, gender, education and body mass index underwent diffusion tensor imaging and 24 hour actigraphy (measure of the activity level) the same day. Applying a probabilistic fibre tracking approach we extracted connection pathways between the dorsolateral prefrontal cortex (dlPFC), the rostral anterior cingulate cortex (rACC), the pre-supplementary motor area (pre-SMA), the SMA-proper, the primary motor cortex (M1), the caudate nucleus, the putamen, the pallidum and the thalamus. Patients had lower activity levels and demonstrated increased mean diffusivity (MD) in pathways linking left pre-SMA and SMA-proper, and right SMA-proper and M1. Exploratory analyses point to a positive association of activity level and mean-fractional anisotropy in the right rACC-pre-SMA connection in MDD. Only MDD patients with low activity levels had a negative linear association of activity level and mean-MD in the left dlPFC-pre-SMA connection. Our results point to structural alterations of cortico-cortical white matter motor pathways in MDD. Altered white matter organisation of rACC-pre-SMA and dlPFC-pre-SMA pathways may contribute to movement initiation in MDD.

Eye Movement Measures of Cognitive Control in Children with Tourette Syndrome

Tourette Syndrome begins in childhood and is characterized by uncontrollable repetitive actions like neck craning or hopping and noises such as sniffing or chirping. Worst in early adolescence, these tics wax and wane in severity and occur in bouts unpredictably, often drawing unwanted attention from bystanders. Making matters worse, over half of children with Tourette Syndrome also suffer from comorbid, or concurrent, disorders such as attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). These disorders introduce anxious thoughts, impulsivity, inattention, and mood variability that further disrupt children with Tourette Syndrome from focusing and performing well at school and home. Thus, deficits in the cognitive control functions of response inhibition, response generation, and working memory have long been ascribed to Tourette Syndrome. Yet, without considering the effect of medication, age, and comorbidity, this is a premature attribution. This study used an infrared eye tracking camera and various computer tasks requiring eye movement responses to evaluate response inhibition, response generation, and working memory in Tourette Syndrome. This study, the first to control for medication, age, and comorbidity, enrolled 39 unmedicated children with Tourette Syndrome and 29 typically developing peers aged 10-16 years who completed reflexive and voluntary eye movement tasks and diagnostic rating scales to assess symptom severities of Tourette Syndrome, ADHD, and OCD. Children with Tourette Syndrome and comorbid ADHD and/or OCD, but not children with Tourette Syndrome only, took longer to respond and made more errors and distracted eye movements compared to typically-developing children, displaying cognitive control deficits. However, increasing symptom severities of Tourette Syndrome, ADHD, and OCD correlated with one another. Thus, cognitive control deficits were not specific to Tourette Syndrome patients with comorbid conditions, but rather increase with increasing tic severity, suggesting that a majority of Tourette Syndrome patients, regardless of a clinical diagnosis of ADHD and/or OCD, have symptoms of cognitive control deficits at some level. Therefore, clinicians should evaluate and counsel all families of children with Tourette Syndrome, with or without currently diagnosed ADHD and/or OCD, about the functional ramifications of comorbid symptoms and that they may wax and wane with tic severity.

Less structured movement patterns predict severity of positive syndrome, excitement, and disorganization

Disorganized behavior is a key symptom of schizophrenia. The objective assessment of disorganized behavior is particularly challenging. Actigraphy has enabled the objective assessment of motor behavior in various settings. Reduced motor activity was associated with negative syndrome scores, but simple motor activity analyses were not informative on other symptom dimensions. The analysis of movement patterns, however, could be more informative for assessing schizophrenia symptom dimensions. Here, we use time series analyses on actigraphic data of 100 schizophrenia spectrum disorder patients. Actigraphy recording intervals were set at 2 s. Data from 2 defined 60-min periods were analyzed, and partial autocorrelations of the actigraphy time series indicated predictability of movements in each individual. Increased positive syndrome scores were associated with reduced predictability of movements but not with the overall amount of movement. Negative syndrome scores were associated with low activity levels but unrelated with predictability of movement. The factors disorganization and excitement were related to movement predictability but emotional distress was not. Thus, the predictability of objectively assessed motor behavior may be a marker of positive symptoms and disorganized behavior. This behavior could become relevant for translational research.

STXBP1 encephalopathy: A neurodevelopmental disorder including epilepsy

OBJECTIVE To give a comprehensive overview of the phenotypic and genetic spectrum of STXBP1 encephalopathy (STXBP1-E) by systematically reviewing newly diagnosed and previously reported patients. METHODS We recruited newly diagnosed patients with STXBP1 mutations through an international network of clinicians and geneticists. Furthermore, we performed a systematic literature search to review the phenotypes of all previously reported patients. RESULTS We describe the phenotypic features of 147 patients with STXBP1-E including 45 previously unreported patients with 33 novel STXBP1 mutations. All patients have intellectual disability (ID), which is mostly severe to profound (88%). Ninety-five percent of patients have epilepsy. While one-third of patients presented with Ohtahara syndrome (21%) or West syndrome (9.5%), the majority has a nonsyndromic early-onset epilepsy and encephalopathy (53%) with epileptic spasms or tonic seizures as main seizure type. We found no correlation between severity of seizures and severity of ID or between mutation type and seizure characteristics or cognitive outcome. Neurologic comorbidities including autistic features and movement disorders are frequent. We also report 2 previously unreported adult patients with prominent extrapyramidal features. CONCLUSION De novo STXBP1 mutations are among the most frequent causes of epilepsy and encephalopathy. Most patients have severe to profound ID with little correlation among seizure onset, seizure severity, and the degree of ID. Accordingly, we hypothesize that seizure severity and ID present 2 independent dimensions of the STXBP1-E phenotype. STXBP1-E may be conceptualized as a complex neurodevelopmental disorder rather than a primary epileptic encephalopathy.

Aceruloplasminemia: molecular characterization of this disorder of iron metabolism.

Ceruloplasmin is an abundant alpha 2-serum glycoprotein that contains 95% of the copper found in the plasma of vertebrate species. We report here on the identification of a genetic defect in the ceruloplasmin gene in a patient previously noted to have a total absence of circulating serum ceruloplasmin in association with late-onset retinal and basal ganglia degeneration. In this patient T2 (transverse relaxation time)-weighted magnetic resonance imaging of the brain revealed basal ganglia densities consistent with iron deposition, and liver biopsy confirmed the presence of excess iron. Although Southern blot analysis of the patient's DNA was normal, PCR amplification of 18 of the 19 exons composing the human ceruloplasmin gene revealed a distinct size difference in exon 7. DNA sequence analysis of this exon revealed a 5-bp insertion at amino acid 410, resulting in a frame-shift mutation and a truncated open reading frame. The validity of this mutation was confirmed by analysis of DNA from the patient's daughter, which revealed heterozygosity for this same 5-bp insertion. The presence of this mutation in conjunction with the clinical and pathologic findings demonstrates an essential role for ceruloplasmin in human biology and identifies aceruloplasminemia as an autosomal recessive disorder of iron metabolism. These findings support previous studies that identified ceruloplasmin as a ferroxidase and are remarkably consistent with recent studies on the essential role of a homologous copper oxidase in iron metabolism in yeast. The clinical and laboratory findings suggest that additional patients with movement disorders and nonclassical Wilson disease should be examined for ceruloplasmin gene mutations.