Oral motor deficits in speech-impaired children with autism

Absence of communicative speech in autism has been presumed to reflect a fundamental deficit in the use of language, but at least in a subpopulation may instead stem from motor and oral motor issues. Clinical reports of disparity between receptive vs. expressive speech/language abilities reinforce this hypothesis. Our early-intervention clinic develops skills prerequisite to learning and communication, including sitting, attending, and pointing or reference, in children below 6 years of age. In a cohort of 31 children, gross and fine motor skills and activities of daily living as well as receptive and expressive speech were assessed at intake and after 6 and 10 months of intervention. Oral motor skills were evaluated separately within the first 5 months of the child's enrolment in the intervention programme and again at 10 months of intervention. Assessment used a clinician-rated structured report, normed against samples of 360 (for motor and speech skills) and 90 (for oral motor skills) typically developing children matched for age, cultural environment and socio-economic status

Harnessing Repetitive Behaviours to Engage Attention and Learning in a Novel Therapy for Autism: An Exploratory Analysis

Rigorous, quantitative examination of therapeutic techniques anecdotally reported to have been successful in people with autism who lack communicative speech will help guide basic science toward a more complete characterisation of the cognitive profile in this underserved subpopulation, and show the extent to which theories and results developed with the high-functioning subpopulation may apply. This study examines a novel therapy, the “Rapid Prompting Method” (RPM). RPM is a parent-developed communicative and educational therapy for persons with autism who do not speak or who have difficulty using speech communicatively. The technique aims to develop a means of interactive learning by pointing amongst multiple-choice options presented at different locations in space, with the aid of sensory “prompts” which evoke a response without cueing any specific response option. The prompts are meant to draw and to maintain attention to the communicative task – making the communicative and educational content coincident with the most physically salient, attention-capturing stimulus – and to extinguish the sensory–motor preoccupations with which the prompts compete. Video-recorded RPM sessions with nine autistic children ages 8–14 years who lacked functional communicative speech were coded for behaviours of interest. An analysis controlled for age indicates that exposure to the claimed therapy appears to support a decrease in repetitive behaviours and an increase in the number of multiple-choice response options without any decrease in successful responding. Direct gaze is not related to successful responding, suggesting that direct gaze might not be any advantage for this population and need not in all cases be a precondition to communication therapies

Anatomic dissociation of selective and suppressive processes in visual attention

Visual spatial attention is associated with activation in parietal regions as well as with modulation of visual activity in ventral occipital cortex. Within the parietal lobe, localisation of activity has been hampered by variation in individual anatomy. Using fMRI within regions of interest derived from individual functional maps, we examined the response of superior parietal lobule, intraparietal sulcus, and ventral occipital cortex in 11 normal adults as attention was directed to the left and right visual hemifields during bilateral visual stimulation. Activation in ventral occipital cortex was augmented contralateral to the attended hemifield (p < 0.006), while intraparietal activation was augmented ipsilaterally (p < 0.009), and superior parietal lobule showed no modulation of activity as a function of attended hemifield. These findings suggest that spatial enhancement of relevant stimuli in ventral occipital cortex is complemented by an intraparietal response associated with suppression of, or preparation of a reflexive shift of attention towards, irrelevant stimuli. The spatial attention system in superior parietal cortex, in contrast, may be driven to equal degrees by currently attended stimuli and by stimuli that are potential targets of attention

Detail-oriented cognitive style and social communicative deficits, within and beyond the autism spectrum: independent traits that grow into developmental interdependence

At the heart of debates over underlying causes of autism is the "Kanner hypothesis" that autistic deficits in social reciprocity, and a cognitive/perceptual 'style' favouring detail-oriented cognition, co-vary in autistic individuals. A separate line of work indicates these two domains are normally distributed throughout the population, with autism representing an extremity. This realisation brings the Kanner debate into the realm of normative co-variation, providing more ways to test the hypothesis, and insights into typical development; for instance, in the context of normative functioning, the Kanner hypothesis implies social costs to spatial/numerical prowess

Development of frataxin gene expression measures for the evaluation of experimental treatments in Friedreich\u27s ataxia.

BACKGROUND: Friedreich ataxia is a progressive neurodegenerative disorder caused by GAA triplet repeat expansions or point mutations in the FXN gene and, ultimately, a deficiency in the levels of functional frataxin protein. Heterozygous carriers of the expansion express approximately 50% of normal frataxin levels yet manifest no clinical symptoms, suggesting that therapeutic approaches that increase frataxin may be effective even if frataxin is raised only to carrier levels. Small molecule HDAC inhibitor compounds increase frataxin mRNA and protein levels, and have beneficial effects in animal models of FRDA. METHODOLOGY/PRINCIPAL FINDINGS: To gather data supporting the use of frataxin as a therapeutic biomarker of drug response we characterized the intra-individual stability of frataxin over time, determined the contribution of frataxin from different components of blood, compared frataxin measures in different cell compartments, and demonstrated that frataxin increases are achieved in peripheral blood mononuclear cells. Frataxin mRNA and protein levels were stable with repeated sampling over four and 15 weeks. In the 15-week study, the average CV was 15.6% for protein and 18% for mRNA. Highest levels of frataxin in blood were in erythrocytes. As erythrocytes are not useful for frataxin assessment in many clinical trial situations, we confirmed that PBMCs and buccal swabs have frataxin levels equivalent to those of whole blood. In addition, a dose-dependent increase in frataxin was observed when PBMCs isolated from patient blood were treated with HDACi. Finally, higher frataxin levels predicted less severe neurological dysfunction and were associated with slower rates of neurological change. CONCLUSIONS/SIGNIFICANCE: Our data support the use of frataxin as a biomarker of drug effect. Frataxin levels are stable over time and as such a 1.5 to 2-fold change would be detectable over normal biological fluctuations. Additionally, our data support buccal cells or PBMCs as sources for measuring frataxin protein in therapeutic trials

A New Spectroscopic and Photometric Analysis of the Transiting Planet Systems TrES-3 and TrES-4

We report new spectroscopic and photometric observations of the parent stars of the recently discovered transiting planets TrES-3 and TrES-4. A detailed abundance analysis based on high-resolution spectra yields [Fe/H] = –0.19 ± 0.08, T_(eff) = 5650 ± 75 K, and log g = 4.4 ± 0.1 for TrES-3, and [Fe/H] = +0.14 ± 0.09, T_(eff) = 6200 ± 75 K, and log g = 4.0 ± 0.1 for TrES-4. The accuracy of the effective temperatures is supported by a number of independent consistency checks. The spectroscopic orbital solution for TrES-3 is improved with our new radial velocity measurements of that system, as are the light-curve parameters for both systems based on newly acquired photometry for TrES-3 and a reanalysis of existing photometry for TrES-4. We have redetermined the stellar parameters taking advantage of the strong constraint provided by the light curves in the form of the normalized separation a/R_* (related to the stellar density) in conjunction with our new temperatures and metallicities. The masses and radii we derive are M_* = 0.928^(+0.028)_(–0.048) M_⊙, R_* = 0.829^(+0.015)_(–0.022) R_⊙, and M_* = 1.404^(+0.066)_(–0.134) M_⊙, R_* = 1.846^(+0.096)_(–0.087) R_⊙ for TrES-3 and TrES-4, respectively. With these revised stellar parameters, we obtain improved values for the planetary masses and radii. We find M_p = 1.910^(+0.075)_(–0.080) M_(Jup), R_p = 1.336^(+0.031)_(–0.036) R_(Jup) for TrES-3, and M_p = 0.925 ± 0.082 M_(Jup), R_p = 1.783^(+0.093)_(–0.086) R_(Jup) for TrES-4. We confirm TrES-4 as the planet with the largest radius among the currently known transiting hot Jupiters

Point OutWords: protocol for a feasibility randomised controlled trial of a motor skills intervention to promote communicative development in non-verbal children with autism

Abstract: Background: Point OutWords is a caregiver-delivered, iPad-assisted intervention for non-verbal or minimally verbal children with autism. It aims to develop prerequisite skills for communication such as manual and oral motor skills, sequencing, and symbolic representation. This feasibility trial aims to determine the viability of evaluating the clinical efficacy of Point OutWords. Methodology: We aim to recruit 46 non-verbal or minimally verbal children with autism and their families, approximately 23 per arm. Children in the intervention group will use Point OutWords for half an hour, five times a week, for 8 weeks. Children in the control group will have equal caregiver-led contact time with the iPad using a selection of control apps (e.g. sensory apps, drawing apps). Communication, motor, and daily living skills are assessed at baseline and post-intervention. Parents will keep diaries during the intervention period and will take part in focus groups when the intervention is completed. Discussion: Point OutWords was developed in collaboration with children with autism and their caregivers, to provide an intervention for a subgroup of autism that has been historically underserved. As autism is a heterogeneous condition, it is unlikely that one style of intervention will address all aspects of its symptomatology; the motor skills approach of Point OutWords can complement other therapies that address core autistic symptoms of social cognition and communication more directly. The current feasibility trial can inform the selection of outcome measures and design for future full-scale randomised controlled trials of Point OutWords and of other early interventions in autism. Trial registration: ISRCTN, ISRCTN12808402. Prospectively registered on 12 March 2019

Overcoming hurdles to intervention studies with autistic children with profound communication difficulties and their families.

Autistic children who speak few or no words or who have an intellectual disability are the most in need of new understandings and treatments, but the most often left out of the research that can bring these benefits. Researchers perceive difficulties around compliance with instructions, testing, challenging behaviours and family stress. Although research with these children can indeed be difficult, their continuing exclusion is unethical and unacceptable. Drawing on our experiences testing a possible treatment for children with profound autism, we provide 10 practical guidelines related to (1) interacting physically, (2) combining play and testing, (3) responding to challenging behaviour, (4) finding suitable tests, (5) relationships with parents, (6) relationships with siblings, (7) involving stakeholders, (8) planning the testing times, (9) the role of the clinical supervisor and (10) recruiting and retaining participants. We hope that these guidelines will prepare and embolden other research teams to work with profoundly autistic children, ending their historical exclusion from research. These guidelines also could be useful for conducting research with children with intellectual disabilities