Abnormal Speech Motor Control in Individuals with 16p11.2 Deletions.

Speech and motor deficits are highly prevalent (>70%) in individuals with the 600 kb BP4-BP5 16p11.2 deletion; however, the mechanisms that drive these deficits are unclear, limiting our ability to target interventions and advance treatment. This study examined fundamental aspects of speech motor control in participants with the 16p11.2 deletion. To assess capacity for control of voice, we examined how accurately and quickly subjects changed the pitch of their voice within a trial to correct for a transient perturbation of the pitch of their auditory feedback. When compared to controls, 16p11.2 deletion carriers show an over-exaggerated pitch compensation response to unpredictable mid-vocalization pitch perturbations. We also examined sensorimotor adaptation of speech by assessing how subjects learned to adapt their sustained productions of formants (speech spectral peak frequencies important for vowel identity), in response to consistent changes in their auditory feedback during vowel production. Deletion carriers show reduced sensorimotor adaptation to sustained vowel identity changes in auditory feedback. These results together suggest that 16p11.2 deletion carriers have fundamental impairments in the basic mechanisms of speech motor control and these impairments may partially explain the deficits in speech and language in these individuals

Comparison of artifacts between paste and collodion method of electrode application in pediatric EEG

© 2019 International Federation of Clinical Neurophysiology Objectives: Children pose challenges to obtain quality EEG data due to excessive artifact. Collodion is used in EEG electrodes due to its water resistance and strong adhesive qualities. This study was done to evaluate differences in artifacts between the collodion and paste method. Methods: 115 subjects (children age \u3e3 years) were randomized into paste and collodion groups and artifacts evaluated at baseline and every hour over 30 s increments. Age, sleep state, and number of electrodes with artifact were also documented. T-test was performed to determine differences in the various parameters between the two groups. Results: 61 subjects were in the paste group and 54 in the collodion group. Mean of total seconds of artifact from 0 to 24 h were 41.8 s in paste group versus 30.3 s in collodion group (P = 0.02). Children \u3e11 years old had less artifact than younger children from 0 to 24 h (24.3 versus 41.2 s, P = 0.03), and from 24 to 48 h (33.1 versus 43.1 s, P = 0.03). There was a significant effect of sleep vs. awake state recordings on artifact from 0 to 24 h (30.3 versus 50.2 s, P = 0.01). Conclusion: Electrode problems are common with both collodion and paste in prolonged AEEG monitoring. However, for studies less than 24 h, collodion may be a better alternative. Significance: Our study provides evidence that in some cases collodion may be a better alternative to paste in terms of decreased artifacts

Abnormal speech motor control in individuals with 16p11.2 deletions

Speech and motor deficits are highly prevalent (\u3e70%) in individuals with the 600 kb BP4-BP5 16p11.2 deletion; however, the mechanisms that drive these deficits are unclear, limiting our ability to target interventions and advance treatment. This study examined fundamental aspects of speech motor control in participants with the 16p11.2 deletion. To assess capacity for control of voice, we examined how accurately and quickly subjects changed the pitch of their voice within a trial to correct for a transient perturbation of the pitch of their auditory feedback. When compared to controls, 16p11.2 deletion carriers show an over-exaggerated pitch compensation response to unpredictable mid-vocalization pitch perturbations. We also examined sensorimotor adaptation of speech by assessing how subjects learned to adapt their sustained productions of formants (speech spectral peak frequencies important for vowel identity), in response to consistent changes in their auditory feedback during vowel production. Deletion carriers show reduced sensorimotor adaptation to sustained vowel identity changes in auditory feedback. These results together suggest that 16p11.2 deletion carriers have fundamental impairments in the basic mechanisms of speech motor control and these impairments may partially explain the deficits in speech and language in these individuals

Robust constrained model predictive control based on parameter-dependent Lyapunov functions

The problem of robust constrained model predictive control (MPC) of systems with polytopic uncertainties is considered in this paper. New sufficient conditions for the existence of parameter-dependent Lyapunov functions are proposed in terms of linear matrix inequalities (LMIs), which will reduce the conservativeness resulting from using a single Lyapunov function. At each sampling instant, the corresponding parameter-dependent Lyapunov function is an upper bound for a worst-case objective function, which can be minimized using the LMI convex optimization approach. Based on the solution of optimization at each sampling instant, the corresponding state feedback controller is designed, which can guarantee that the resulting closed-loop system is robustly asymptotically stable. In addition, the feedback controller will meet the specifications for systems with input or output constraints, for all admissible time-varying parameter uncertainties. Numerical examples are presented to demonstrate the effectiveness of the proposed techniques

D2 receptor occupancy of olanzapine pamoate depot using positron emission tomography : an open-label study in patients with schizophrenia

A long-acting depot formulation of olanzapine that sustains plasma olanzapine concentrations for over a month after a single injection is currently under development. This multicenter, open-label study explored D2 receptor occupancy of a fixed dose of olanzapine pamoate (OP) depot given every 4 weeks. Patients (nine male, five female) with schizophrenia or schizoaffective disorder previously stabilized on oral olanzapine were switched to OP depot 300 mg by intramuscular injection every 4 weeks for 6 months. No visitwise within-group significant changes were found in Brief Psychiatric Rating Scale Total or Clinical Global Impressions-Severity of Illness scores, although seven patients received oral olanzapine supplementation during the first four injection cycles. To minimize impact on D2 occupancy, positron emission tomography (PET) scans were not completed during injection cycles that required supplemental oral olanzapine. Two patients reported transient injection site adverse events, which did not result in discontinuation. The most frequently reported treatment-emergent adverse events were insomnia, aggravated psychosis, and anxiety. Mean striatal D2 receptor occupancy, as measured by [11C]-raclopride PET, was 69% on oral olanzapine (5–20 mg/day) and 50% (trough) on OP depot at steady state. Following an initial decline, occupancy returned to 84% of baseline oral olanzapine occupancy after six injections. Over the study period, D2 receptor occupancy and plasma olanzapine concentrations were significantly correlated (r=0.76, Pless than or equal to0.001). OP depot resulted in mean D2 receptor occupancy of approximately 60% or higher at the end of the 6-month study period, a level consistent with antipsychotic efficacy and found during treatment with oral olanzapine. However, supplemental oral olanzapine or another dosing strategy may be necessary to maintain adequate therapeutic response during the first few injection cycles.peer-reviewe

Delivery of epilepsy care to adults with intellectual and developmental disabilities

Epilepsy is common in people with intellectual and developmental disabilities (IDD). In adulthood, patients with IDD and epilepsy (IDD-E) have neurologic, psychiatric, medical, and social challenges compounded by fragmented and limited care. With increasing neurologic disability, there is a higher frequency of epilepsy, especially symptomatic generalized and treatment-resistant epilepsies. The causes of IDD-E are increasingly recognized to be genetic based on chromosomal microarray analysis to identify copy number variants, gene panels (epilepsy, autism spectrum disorder, intellectual disability), and whole-exome sequencing. A specific genetic diagnosis may guide care by pointing to comorbid disorders and best therapy. Therapy to control seizures should be individualized, with drug selection based on seizure types, epilepsy syndrome, concomitant medications, and comorbid disorders. There are limited comparative antiepileptic drug data in the IDD-E population. Vagus nerve and responsive neural stimulation therapies and resective surgery should be considered. Among the many comorbid disorders that affect patients with IDD-E, psychiatric and sleep disorders are common but often unrecognized and typically not treated. Transition from holistic and coordinated pediatric to adult care is often a vulnerable period. Communication among adult health care providers is complex but essential to ensure best care when these patients are seen in outpatient, emergency room, and inpatient settings. We propose specific recommendations for minimum care standards for people with IDD-E