Mitochondrial aminoacyl-tRNA synthetase disorders: an emerging group of developmental disorders of myelination.

Background: The mitochondrial aminoacyl-tRNA synthetase proteins (mt-aaRSs) are a group of nuclear-encoded enzymes that facilitate conjugation of each of the 20 amino acids to its cognate tRNA molecule. Mitochondrial diseases are a large, clinically heterogeneous group of disorders with diverse etiologies, ages of onset, and involved organ systems. Diseases related to mt-aaRS mutations are associated with specific syndromes that affect the central nervous system and produce highly characteristic MRI patterns, prototypically the DARS2, EARS, and AARS2 leukodystrophies, which are caused by mutations in mitochondrial aspartyl-tRNA synthetase, mitochondria glutamate tRNA synthetase, and mitochondrial alanyl-tRNA synthetase, respectively.

Injury characteristics across functional classes of self-injurious behavior.

Self-injurious behavior (SIB) is inherently problematic because it can lead to injuries, including those that are quite severe and may result in loss of function or permanent disfigurement. The current study replicated and extended Rooker et al. (2018) by classifying the physical characteristics of injuries across groups of individuals with automatically maintained SIB (ASIB Subtypes 2 and 3) and socially maintained SIB.

SYNGAP1 mutations: Clinical, genetic, and pathophysiological features.

SYNGAP1 is a gene that encodes the cytosolic protein SYNGAP1 (SYNaptic GTPase Activating Protein), an essential component of the postsynaptic density at excitatory glutamatergic neurons. SYNGAP1 plays critical roles in synaptic development, structure, function, and plasticity. Mutations in SYNGAP1 result in a neurodevelopmental disorder termed Mental retardation-type 5 (MRD5, OMIM #612621) with a phenotype consisting of intellectual disability, motor impairments, and epilepsy, attesting to the importance of this protein for normal brain development.

Interactions between motor exploration and reinforcement learning.

Motor exploration, a trial-and-error process in search for better motor outcomes, is known to serve a critical role in motor learning. This is particularly relevant during reinforcement learning, where actions leading to a successful outcome are reinforced while unsuccessful actions are avoided. Although early on motor exploration is beneficial to finding the correct solution, maintaining high levels of exploration later in the learning process might be deleterious.

What are neurodevelopmental disorders?

Purpose Of Review: The purpose of this review is to highlight the origin and evolution of the field of neurodevelopmental disabilities and describe the main construct(s) upon which the current classification of neurodevelopmental disorders is based.

Recent Findings: We address the following questions: Are neurodevelopmental disorders independent entities? Why is it desirable to understand the neurobiological substrate for these disorders? What new knowledge have we generated by leveraging advances in neuroscience, genetics, and neuroimaging? And finally, is the current construct, that is based on functional classification, still useful?

Summary: As our biological understanding of brain-behavior disorders evolves, we ought to re-evaluate the current classification system and expand it into a multidimensional classification that takes into account behavioral profiles and underlying mechanisms.

Loss of the sphingolipid desaturase DEGS1 causes hypomyelinating leukodystrophy.

Sphingolipid imbalance is the culprit in a variety of neurological diseases, some affecting the myelin sheath. We have used whole-exome sequencing in patients with undetermined leukoencephalopathies to uncover the endoplasmic reticulum lipid desaturase DEGS1 as the causative gene in 19 patients from 13 unrelated families. Shared features among the cases include severe motor arrest, early nystagmus, dystonia, spasticity, and profound failure to thrive.

Subtle Motor Signs in Children With Chronic Traumatic Brain Injury.

Objective: The aim of the study was to characterize subtle motor signs in children with moderate-severe traumatic brain injury in the chronic phase of injury.

Design: Fourteen children with moderate (n = 6) or severe (n = 8) traumatic brain injury, ages 11-18 yrs, who had sustained their injury at least 1-yr before study participation (range 1-14 yrs since injury), and 14 matched typically developing controls were examined using the Physical and Neurological Examination of Subtle Signs (PANESS). To examine the neural correlates of subtle motor signs, measures of total cerebral volume and motor/premotor volume were derived from magnetic resonance imaging.

Reproducibility of brain MRS in older healthy adults at 7T.

To date, the majority of MRS reproducibility studies have been conducted in healthy younger adults, with only a few conducted in older adults at 3 T. With the growing interest in applying MRS methods to study the longitudinal course and effects of treatments in neurodegenerative disease, it is important to establish reproducibility in age-matched controls, especially in older individuals. In this study, spectroscopic data were acquired using a stimulated echo acquisition mode (STEAM) localization technique in two regions (anterior and posterior cingulate cortices-ACC, PCC, respectively) in 10 healthy, cognitively normal older adults (64 ± 8.

Addressing Medical Students' Negative Bias Toward Patients With Obesity Through Ethics Education.

Context: Negative bias toward patients with obesity is an ethical challenge in patient care. Several interventions to mitigate medical students' negative weight bias have been tried but none with an explicit focus on ethics. Here we describe first-year medical students' attitudes toward obesity and our effort to improve their attitudes through an innovative ethics session embedded within the required course, "Obesity, Nutrition, and Behavior Change," at Johns Hopkins University School of Medicine.

Post hoc analyses of asenapine treatment in pediatric patients with bipolar I disorder: efficacy related to mixed or manic episode, stage of illness, and body weight.

Background: Patient characteristics and disease progression may affect response to pharmacologic intervention in bipolar I disorder. Asenapine is approved for acute treatment of manic/mixed episodes of bipolar I disorder in patients 10-17 years old. Post hoc analyses assessed asenapine efficacy in pediatric patients by current manic or mixed episode, number of lifetime episodes, and baseline body mass index (BMI).

Classification of injuries observed in functional classes of self-injurious behaviour.

Background: Limited research has examined how the functions of self-injurious behaviour (SIB) relate to the production of injuries and the location, type or severity of those injuries.

Methods: Clinical and medical records were coded for 64 individuals hospitalised for SIB. When injuries were present, the physical properties of SIB and injuries were assessed across groups of individuals with automatically and socially maintained SIB.

Behavioral treatment of automatically reinforced SIB: 1982 - 2015.

Some individuals diagnosed with intellectual and developmental disabilities engage in automatically reinforced self-injurious behavior (SIB). For these individuals, identifying effective treatments may be difficult due to the nature of the reinforcement contingency. The purpose of this study was to review the literature on the treatment of automatically reinforced SIB to determine commonalities in procedures that produced effective and ineffective treatment outcomes, as well as historical trends in the treatment of this class of SIB.

Identifying predictive behavioral markers: A demonstration using automatically reinforced self-injurious behavior.

Predictive biomarkers (PBioMs) are objective biological measures that predict response to medical treatments for diseases. The current study translates methods used in the field of precision medicine to identify PBioMs to identify parallel predictive behavioral markers (PBMs), defined as objective behavioral measures that predict response to treatment. We demonstrate the utility of this approach by examining the accuracy of two PBMs for automatically reinforced self-injurious behavior (ASIB).

Preliminary Use of the Physical and Neurological Examination of Subtle Signs for Detecting Subtle Motor Signs in Adolescents With Sport-Related Concussion.

Sensitive examination tools are needed to optimize evaluation after sports-related concussion. The Physical and Neurological Examination of Subtle Signs was preliminarily examined for sensitivity to motor changes in a pilot cohort of adolescents aged 13-17 yrs with sports-related concussion. A total of 15 adolescents (5 female adolescents) with sports-related concussion were evaluated up to three times: within 2 wks of injury, approximately 1 mo later (mean, 35 days between visits), and for those not recovered at the second visit, again after clinical recovery (mean, 70 days between the first and last visits for all participants).

Treating Bipolar Disorder in Adolescents.

How do you select among treatments for bipolar disorder in adolescents? Check out this brief report activity to explore the efficacy and safety of lithium, anticonvulsants, and atypical antipsychotics in the treatment of adolescent bipolar disorder. Plus, receive guidance for monitoring for common adverse effects, such as weight gain and fatigue.

Closing the Loop: From Motor Neuroscience to Neurorehabilitation.

The fields of human motor control, motor learning, and neurorehabilitation have long been linked by the intuition that understanding how we move (and learn to move) leads to better rehabilitation. In reality, these fields have remained largely separate. Our knowledge of the neural control of movement has expanded, but principles that can directly impact rehabilitation efficacy remain somewhat sparse.

Improving the Diagnosis and Treatment of Pediatric Bipolar Disorder.

Awareness of the prevalence and impact of bipolar disorder in pediatric patients has grown in recent years. Youths with this disorder are at risk for poor long-term outcomes, but with careful screening, clinicians may be able to detect early signs or subthreshold symptoms and provide a timely diagnosis and effective treatment. Although several pharmacologic options are available for patients aged 10 years and up, they differ in their safety and tolerability profiles.

Pediatric Multiple Sclerosis in the United Arab Emirates: Characteristics From a Multicenter Study and Global Comparison.

We delineate the clinical characteristics, incidence, and prevalence of pediatric-onset multiple sclerosis in Abu Dhabi, United Arab Emirates, from 2010 to 2014. Eighty-two patients (65% female) were identified. Fifty-three (64.

Accelerating locomotor savings in learning: compressing four training days to one.

Acquiring new movements requires the capacity of the nervous system to remember previously experienced motor patterns. The phenomenon of faster relearning after initial learning is termed "savings." Here we studied how savings of a novel walking pattern develops over several days of practice and how this process can be accelerated.

Does preference rank predict substitution for the reinforcer for problem behavior? a behavioral economic analysis.

Predictions made under low response requirements inherent in most preference assessments (PAs) do not guarantee the utility of stimuli in treatments. We examined whether PA rank would predict how well stimuli supported compliance for children with escape-maintained problem behavior by examining the relation between PA rank and demand elasticity across five fixed-ratio values. Three patterns were observed: All stimuli were selected equally across values, higher ranked stimuli were selected more at higher values, and something other than the highest ranked stimulus was selected more at higher values (i.

Neuronal pentraxin 1: A synaptic-derived plasma biomarker in Alzheimer's disease.

Synaptic neurodegeneration is thought to be an early event initiated by soluble β-amyloid (Aβ) aggregates that closely correlates with cognitive decline in Alzheimer disease (AD). Apolipoprotein ε4 (APOE4) is the most common genetic risk factor for both familial AD (FAD) and sporadic AD; it accelerates Aβ aggregation and selectively impairs glutamate receptor function and synaptic plasticity. However, its molecular mechanisms remain elusive and these synaptic deficits are difficult to monitor.

Alterations in the Plasma Levels of Specific Choline Phospholipids in Alzheimer's Disease Mimic Accelerated Aging.

Alzheimer's disease (AD) is the most common neurodegenerative disease and of continuously rising prevalence. The identification of easy-to-measure biomarkers capable to assist in the prediction and early diagnosis of AD is currently a main research goal. Lipid metabolites in peripheral blood of human patients have recently gained major attention in this respect.

Additional free reinforcers increase persistence of problem behavior in a clinical context: A partial replication of laboratory findings.

Behavioral momentum theory is a quantitative framework used to characterize the persistence of behavior during response disruptors as a function of baseline stimulus-reinforcer relations. Results of several investigations have shown that alternative reinforcement can increase the resistance to change of a target response during extinction. In the present study, concomitant variable-interval fixed-time schedules of reinforcement for problem behavior were employed to simulate naturalistic situations involving the superimposition of response-independent reinforcers on a baseline schedule of reinforcement for problem behavior, as in the common use of noncontingent reinforcement treatments.