Imbalanced social-communicative and restricted repetitive behavior subtypes of autism spectrum disorder exhibit different neural circuitry

Social-communication (SC) and restricted repetitive behaviors (RRB) are autism diagnostic symptom domains. SC and RRB severity can markedly differ within and between individuals and may be underpinned by different neural circuitry and genetic mechanisms. Modeling SC-RRB balance could help identify how neural circuitry and genetic mechanisms map onto such phenotypic heterogeneity. Here, we developed a phenotypic stratification model that makes highly accurate (97-99%) out-of-sample SC = RRB, SC > RRB, and RRB > SC subtype predictions. Applying this model to resting state fMRI data from the EU-AIMS LEAP dataset (n = 509), we find that while the phenotypic subtypes share many commonalities in terms of intrinsic functional connectivity, they also show replicable differences within some networks compared to a typically-developing group (TD). Specifically, the somatomotor network is hypoconnected with perisylvian circuitry in SC > RRB and visual association circuitry in SC = RRB. The SC = RRB subtype show hyperconnectivity between medial motor and anterior salience circuitry. Genes that are highly expressed within these networks show a differential enrichment pattern with known autism-associated genes, indicating that such circuits are affected by differing autism-associated genomic mechanisms. These results suggest that SC-RRB imbalance subtypes share many commonalities, but also express subtle differences in functional neural circuitry and the genomic underpinnings behind such circuitry

Faecal calprotectin: factors affecting levels and its potential role as a surrogate marker for risk of development of Crohn's Disease.

BACKGROUND: Faecal calprotectin (FC) is one of the most widely used non-invasive tests for the diagnosis and assessment of Crohn's disease (CD) activity. Despite this, factors other than disease activity which affect levels have not been extensively reviewed. This is of importance when using FC in the diagnostic setting but also may be of utility in studying the aetiology of disease. OBJECTIVES: Our review outlines environmental risk factors that affect FC levels influencing diagnostic accuracy and how these may be associated with risk of developing CD. FC as a surrogate marker could be used to validate risk factors established in case control studies where prospective studies are not feasible. Proof of this concept is provided by our identification of obesity as being associated with elevated FC, our subsequent confirmation of obesity as risk factor for CD and the subsequent verification in prospective studies, as well as associations of lack of physical activity and dietary fibre intake with elevated FC levels and their subsequent confirmation as risk factors in prospective studies. CONCLUSION: We believe that FC is likely to prove a useful surrogate marker for risk of developing CD. This review has given a theoretical basis for considering the epidemiological determinants of CD which to date has been missing

Preference for biological motion is reduced in ASD: implications for clinical trials and the search for biomarkers

Background: The neurocognitive mechanisms underlying autism spectrum disorder (ASD) remain unclear. Progress has been largely hampered by small sample sizes, variable age ranges and resulting inconsistent findings. There is a pressing need for large definitive studies to delineate the nature and extent of key case/control differences to direct research towards fruitful areas for future investigation. Here we focus on perception of biological motion, a promising index of social brain function which may be altered in ASD. In a large sample ranging from childhood to adulthood, we assess whether biological motion preference differs in ASD compared to neurotypical participants (NT), how differences are modulated by age and sex and whether they are associated with dimensional variation in concurrent or later symptomatology. Methods: Eye-tracking data were collected from 486 6-to-30-year-old autistic (N = 282) and non-autistic control (N = 204) participants whilst they viewed 28 trials pairing biological (BM) and control (non-biological, CTRL) motion. Preference for the biological motion stimulus was calculated as (1) proportion looking time difference (BM-CTRL) and (2) peak look duration difference (BM-CTRL). Results: The ASD group showed a present but weaker preference for biological motion than the NT group. The nature of the control stimulus modulated preference for biological motion in both groups. Biological motion preference did not vary with age, gender, or concurrent or prospective social communicative skill within the ASD group, although a lack of clear preference for either stimulus was associated with higher social-communicative symptoms at baseline. Limitations: The paired visual preference we used may underestimate preference for a stimulus in younger and lower IQ individuals. Our ASD group had a lower average IQ by approximately seven points. 18% of our sample was not analysed for various technical and behavioural reasons. Conclusions: Biological motion preference elicits small-to-medium-sized case–control effects, but individual differences do not strongly relate to core social autism associated symptomatology. We interpret this as an autistic difference (as opposed to a deficit) likely manifest in social brain regions. The extent to which this is an innate difference present from birth and central to the autistic phenotype, or the consequence of a life lived with ASD, is unclear

Saccade dysmetria indicates attenuated visual exploration in autism spectrum disorder

Background: Visual exploration in autism spectrum disorder (ASD) is characterized by attenuated social attention. The underlying oculomotor function during visual exploration is understudied, whereas oculomotor function during restricted viewing suggested saccade dysmetria in ASD by altered pontocerebellar motor modulation. Methods: Oculomotor function was recorded using remote eye tracking in 142 ASD participants and 142 matched neurotypical controls during free viewing of naturalistic videos with and without human content. The sample was heterogenous concerning age (6–30 years), cognitive ability (60–140 IQ), and male/female ratio (3:1). Oculomotor function was defined as saccade, fixation, and pupil-dilation features that were compared between groups in linear mixed models. Oculomotor function was investigated as ASD classifier and features were correlated with clinical measures. Results: We observed decreased saccade duration (∆M = −0.50, CI [−0.21, −0.78]) and amplitude (∆M = −0.42, CI [−0.12, −0.72]), which was independent of human video content. We observed null findings concerning fixation and pupil-dilation features (POWER =.81). Oculomotor function is a valid ASD classifier comparable to social attention concerning discriminative power. Within ASD, saccade features correlated with measures of restricted and repetitive behavior. Conclusions: We conclude saccade dysmetria as ASD oculomotor phenotype relevant to visual exploration. Decreased saccade amplitude and duration indicate spatially clustered fixations that attenuate visual exploration and emphasize endogenous over exogenous attention. We propose altered pontocerebellar motor modulation as underlying mechanism that contributes to atypical (oculo-)motor coordination and attention function in ASD

Valid and reliable instruments for arm-hand assessment at ICF activity level in persons with hemiplegia: a systematic review

Contains fulltext : 110141.pdf (publisher's version ) (Open Access)BACKGROUND: Loss of arm-hand performance due to a hemiparesis as a result of stroke or cerebral palsy (CP), leads to large problems in daily life of these patients. Assessment of arm-hand performance is important in both clinical practice and research. To gain more insight in e.g. effectiveness of common therapies for different patient populations with similar clinical characteristics, consensus regarding the choice and use of outcome measures is paramount. To guide this choice, an overview of available instruments is necessary. The aim of this systematic review is to identify, evaluate and categorize instruments, reported to be valid and reliable, assessing arm-hand performance at the ICF activity level in patients with stroke or cerebral palsy. METHODS: A systematic literature search was performed to identify articles containing instruments assessing arm-hand skilled performance in patients with stroke or cerebral palsy. Instruments were identified and divided into the categories capacity, perceived performance and actual performance. A second search was performed to obtain information on their content and psychometrics. RESULTS: Regarding capacity, perceived performance and actual performance, 18, 9 and 3 instruments were included respectively. Only 3 of all included instruments were used and tested in both patient populations. The content of the instruments differed widely regarding the ICF levels measured, assessment of the amount of use versus the quality of use, the inclusion of unimanual and/or bimanual tasks and the inclusion of basic and/or extended tasks. CONCLUSIONS: Although many instruments assess capacity and perceived performance, a dearth exists of instruments assessing actual performance. In addition, instruments appropriate for more than one patient population are sparse. For actual performance, new instruments have to be developed, with specific focus on the usability in different patient populations and the assessment of quality of use as well as amount of use. Also, consensus about the choice and use of instruments within and across populations is needed

Imbalanced social-communicative and restricted repetitive behavior subtypes of autism spectrum disorder exhibit different neural circuitry

Abstract: Social-communication (SC) and restricted repetitive behaviors (RRB) are autism diagnostic symptom domains. SC and RRB severity can markedly differ within and between individuals and may be underpinned by different neural circuitry and genetic mechanisms. Modeling SC-RRB balance could help identify how neural circuitry and genetic mechanisms map onto such phenotypic heterogeneity. Here, we developed a phenotypic stratification model that makes highly accurate (97–99%) out-of-sample SC = RRB, SC > RRB, and RRB > SC subtype predictions. Applying this model to resting state fMRI data from the EU-AIMS LEAP dataset (n = 509), we find that while the phenotypic subtypes share many commonalities in terms of intrinsic functional connectivity, they also show replicable differences within some networks compared to a typically-developing group (TD). Specifically, the somatomotor network is hypoconnected with perisylvian circuitry in SC > RRB and visual association circuitry in SC = RRB. The SC = RRB subtype show hyperconnectivity between medial motor and anterior salience circuitry. Genes that are highly expressed within these networks show a differential enrichment pattern with known autism-associated genes, indicating that such circuits are affected by differing autism-associated genomic mechanisms. These results suggest that SC-RRB imbalance subtypes share many commonalities, but also express subtle differences in functional neural circuitry and the genomic underpinnings behind such circuitry

Influence of task-oriented training content on skilled arm-hand performance in stroke: a systematic review

Objective. This review evaluates the underlying training components currently used in task-oriented training and assesses the effects of these components on skilled arm—hand performance in patients after a stroke. Methods. A computerized systematic literature search in 5 databases (PubMed, CINAHL, EMBASE, PEDro, and Cochrane) identified randomized clinical trials, published through March 2009, evaluating the effects of task-oriented training. Relevant article references listed in publications included were also screened. The methodological quality of the selected studies was assessed with the Van Tulder Checklist. For each functional outcome measure used, the effect size (bias corrected Hedges’s g) was calculated. Results. The intervention results in 528 patients (16 studies) were studied. From these, 15 components were identified to characterize task-oriented training. An average of 7.8 (standard deviation = 2.1) components were used in the included trials. There was no correlation between the number of task-oriented training components used in a study and the treatment effect size. “Distributed practice” and “feedback” were associated with the largest postintervention effect sizes. “Random practice” and “use of clear functional goals” were associated with the largest follow-up effect sizes. Conclusion. The task-oriented training was operationalized with 15 components. The number of components used in an intervention aimed at improving arm—hand performance after stroke was not associated with the posttreatment effect size. Certain components, which optimize storage of learned motor performance in the long-term memory, occurred more in studies with larger treatment effects

Influence of Task-Oriented Training Content on Skilled Arm-Hand Performance in Stroke: A Systematic Review

Objective. This review evaluates the underlying training components currently used in task-oriented training and assesses the effects of these components on skilled arm—hand performance in patients after a stroke. Methods. A computerized systematic literature search in 5 databases (PubMed, CINAHL, EMBASE, PEDro, and Cochrane) identified randomized clinical trials, published through March 2009, evaluating the effects of task-oriented training. Relevant article references listed in publications included were also screened. The methodological quality of the selected studies was assessed with the Van Tulder Checklist. For each functional outcome measure used, the effect size (bias corrected Hedges’s g) was calculated. Results. The intervention results in 528 patients (16 studies) were studied. From these, 15 components were identified to characterize task-oriented training. An average of 7.8 (standard deviation = 2.1) components were used in the included trials. There was no correlation between the number of task-oriented training components used in a study and the treatment effect size. “Distributed practice” and “feedback” were associated with the largest postintervention effect sizes. “Random practice” and “use of clear functional goals” were associated with the largest follow-up effect sizes. Conclusion. The task-oriented training was operationalized with 15 components. The number of components used in an intervention aimed at improving arm—hand performance after stroke was not associated with the posttreatment effect size. Certain components, which optimize storage of learned motor performance in the long-term memory, occurred more in studies with larger treatment effects

Influence of Task-Oriented Training Content on Skilled Arm-Hand Performance in Stroke: A Systematic Review

Objective. This review evaluates the underlying training components currently used in task-oriented training and assesses the effects of these components on skilled arm-hand performance in patients after a stroke. Methods. A computerized systematic literature search in 5 databases (PubMed, CINAHL, EMBASE, PEDro, and Cochrane) identified randomized clinical trials, published through March 2009, evaluating the effects of task-oriented training. Relevant article references listed in publications included were also screened. The methodological quality of the selected studies was assessed with the Van Tulder Checklist. For each functional outcome measure used, the effect size (bias corrected Hedges's g) was calculated. Results. The intervention results in 528 patients (16 studies) were studied. From these, 15 components were identified to characterize task-oriented training. An average of 7.8 (standard deviation = 2.1) components were used in the included trials. There was no correlation between the number of task-oriented training components used in a study and the treatment effect size. "Distributed practice" and "feedback" were associated with the largest postintervention effect sizes. "Random practice" and "use of clear functional goals" were associated with the largest follow-up effect sizes. Conclusion. The task-oriented training was operationalized with 15 components. The number of components used in an intervention aimed at improving arm-hand performance after stroke was not associated with the posttreatment effect size. Certain components, which optimize storage of learned motor performance in the long-term memory, occurred more in studies with larger treatment effects

Reference values for the transformed Van Lieshout hand function test for tetraplegia.

Item does not contain fulltextSTUDY DESIGN: Longitudinal cohort study. OBJECTIVES: Previously, the Van Lieshout hand function test for tetraplegia (short form)(VLT-SF) has been transformed into an interval scale (r_VLT-SF) using the Rasch analysis, thereby fulfilling the requirements of an objective measurement. The present study aims (1) to transform r_VLT-SFlogit scores (r_VLT-SFlogit) into 0-100 scores (r_VLT-SF100) in order to facilitate communication amongst its users and (2) to describe r_VLT-SF100 reference values in order to refine the prediction of upper extremity skilled performance in persons with tetraplegia. SETTING: Eight Dutch rehabilitation centres. METHODS: The VLT-SF data of tetraplegic patients from eight Dutch rehabilitation centres, gathered at the start of the active rehabilitation (t1), 3 months after t1 (t2) and at the time of discharge (t3), have been used. The r_VLT-SF100 total score for t1 and t3 were computed, anchored on the data for t2. Reference values (medians and interquartiles) for different subgroups were calculated at different moments during the rehabilitation. RESULTS: Data at t1 (n=64), t2 (n=73) and t3 (n=69) were used. The r_VLT-SFlogit scores (-4.78-6.32) were transformed into r_VLT-SF100 (0-100) at t2. Reference values were established for persons with motor complete or incomplete lesions with either a high (C1-C6) or a low (C7-T1) lesion level at t1, t2 and t3. Significant differences (P<0.025) in r_VLT-SF100 were found for most subgroups and different time intervals. CONCLUSIONS: The r_VLT-SFlogit scores were converted into r_VLT-SF100 scores, and reference values of the r_VLT-SF100 have been established for different subgroups of tetraplegic patients at different stages during rehabilitation. The r_VLT-SF100 has been proven to be able to detect improvement over time.1 oktober 201