EEG-Meta-Microstates: Towards a More Objective Use of Resting-State EEG Microstate Findings Across Studies.

Over the last decade, EEG resting-state microstate analysis has evolved from a niche existence to a widely used and well-accepted methodology. The rapidly increasing body of empirical findings started to yield overarching patterns of associations of biological and psychological states and traits with specific microstate classes. However, currently, this cross-referencing among apparently similar microstate classes of different studies is typically done by "eyeballing" of printed template maps by the individual authors, lacking a systematic procedure. To improve the reliability and validity of future findings, we present a tool to systematically collect the actual data of template maps from as many published studies as possible and present them in their entirety as a matrix of spatial similarity. The tool also allows importing novel template maps and systematically extracting the findings associated with specific microstate maps from ongoing or published studies. The tool also allows importing novel template maps and systematically extracting the findings associated with specific microstate maps in the literature. The analysis of 40 included sets of template maps indicated that: (i) there is a high degree of similarity of template maps across studies, (ii) similar template maps were associated with converging empirical findings, and (iii) representative meta-microstates can be extracted from the individual studies. We hope that this tool will be useful in coming to a more comprehensive, objective, and overarching representation of microstate findings.

Brief report: replication of the psychometric characteristics of the behavioral inflexibility scale in an independent sample.

The Behavioral Inflexibility Scale (BIS) is a recently developed measure of behavioral inflexibility, defined as rigid patterns of behavior that contrast with the need to be flexible when the situation calls for it. In this study, we sought to replicate previous findings on the psychometric properties of the BIS in a community sample. Data for this study were collected using in-person assessments of 163 autistic and 95 non-autistic children ages 3-17 and included the BIS, measures of social-communication ability and repetitive behaviors, and an assessment of cognitive ability. Our findings replicate the psychometric properties of the BIS, indicating that the measure is a valid measure of behavioral inflexibility in ASD.

Measuring the Functional Impact of Behavioral Inflexibility in Children with Autism Using the Behavioral Inflexibility Scale: Clinical Interview (BIS-CI).

For individuals with autism spectrum disorder (ASD), behavioral inflexibility can affect multiple domains of functioning and family life. The objective of this study was to develop and validate a clinical interview version of the Behavioral Inflexibility Scale. Trained interviewers conducted interviews with parents of 144 children with ASD and 70 typically developing children (ages: 3-17 years). Using exploratory factor analysis, the Behavioral Inflexibility Scale-Clinical Interview (BIS-CI) was found to be unidimensional. Reliability data indicated the measure was internally consistent (α = 0.80), achieved excellent inter-rater reliability (ICC = 0.97) and test-retest reliability (ICC = 0.87). These findings demonstrate that the BIS-CI is a reliable and valid measure to determine the functional impact of behavioral inflexibility.

Improved survival and reduced phenotypic severity following AAV9/MECP2 gene transfer to neonatal and juvenile male Mecp2 knockout mice.

Typical Rett syndrome (RTT) is a pediatric disorder caused by loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. The demonstrated reversibility of RTT-like phenotypes in mice suggests that MECP2 gene replacement is a potential therapeutic option in patients. We report improvements in survival and phenotypic severity in Mecp2-null male mice after neonatal intracranial delivery of a single-stranded (ss) AAV9/chicken ß-actin (CBA)-MECP2 vector. Median survival was 16.6 weeks for MECP2-treated versus 9.3 weeks for green fluorescent protein (GFP)-treated mice. ssAAV9/CBA-MECP2-treated mice also showed significant improvement in the phenotype severity score, in locomotor function, and in exploratory activity, as well as a normalization of neuronal nuclear volume in transduced cells. Wild-type (WT) mice receiving neonatal injections of the same ssAAV9/CBA-MECP2 vector did not show any significant deficits, suggesting a tolerance for modest MeCP2 overexpression. To test a MECP2 gene replacement approach in a manner more relevant for human translation, a self-complementary (sc) adeno-associated virus (AAV) vector designed to drive MeCP2 expression from a fragment of the Mecp2 promoter was injected intravenously (IV) into juvenile (4-5 weeks old) Mecp2-null mice. While the brain transduction efficiency in juvenile mice was low (~2-4% of neurons), modest improvements in survival were still observed. These results support the concept of MECP2 gene therapy for RTT.