Pilot Feasibility Study of Cranial Electrotherapy Stimulation (CES) on Behavioral Regulation in a Mixed Clinical Cohort

Objective: Children and adolescents with neurodevelopmental disorders often report disturbances in autonomic nervous system (ANS) related behavioral regulation such as sensory sensitivity, anxiety, and emotion dysregulation. Cranial electrotherapy stimulation (CES) is a method of non-invasive transcranial current stimulation presumed to modify behavioral regulation abilities via ANS modulation. Methods: To begin to address this knowledge gap, we examined the feasibility and preliminary efficacy of a 4-week CES intervention on behavioral regulation in a mixed neurodevelopmental sample of children and adolescents currently receiving care at clinical centers operated by Cortica. We first aimed to evaluate adherence, side effects, and tolerance of CES device use. Second, we aimed to evaluate pre-post change in three PNS-associated behavioral regulation conditions: sensory sensitivities, emotion dysregulation, and anxiety. Results: Feasibility results demonstrated moderate adherence, tolerability, and satisfaction with CES usage. Further, preliminary efficacy results demonstrated a significant reduction in sensory sensitivity, anxiety, and emotion dysregulation. Conclusion: Results from this pilot study provide justification for future randomized control trials using CES in children and adolescents with behavioral dysregulation

Evaluating the Effectiveness of a Comprehensive, Personalized, Medically Based Care Model on Adaptive Behavior Outcomes in Autism

The purpose of this study was to examine the effects of a medically centered, interdisciplinary treatment model on adaptive behavior in children with Autism Spectrum Disorder (ASD). The Cortica model involves a comprehensive program including behavioral and developmental therapies, overseen by a neurodevelopmental physician. We investigated the research question, how do adaptive behaviors change over time during care at Cortica? We analyzed change in the Vineland Adaptive Behavior Scales, Third Edition, over the course of Cortica care compared to standard care, represented by longitudinal data from the National Database for Autism Research (NDAR). Using propensity score weights to match cohorts based on baseline functioning, multilevel growth curve models showed significant Cohort × Time interactions for the Adaptive Behavior Composite score and all subscale scores, indicating increased growth in adaptive behavior skills for children in the Cortica cohort relative to NDAR. Results of this study highlight the importance of using adaptive behaviors as a primary outcome in clinical research studies

A pilot study to determine the feasibility of enhancing cognitive abilities in children with sensory processing dysfunction.

Children with Sensory Processing Dysfunction (SPD) experience incoming information in atypical, distracting ways. Qualitative challenges with attention have been reported in these children, but such difficulties have not been quantified using either behavioral or functional neuroimaging methods. Furthermore, the efficacy of evidence-based cognitive control interventions aimed at enhancing attention in this group has not been tested. Here we present work aimed at characterizing and enhancing attentional abilities for children with SPD. A sample of 38 SPD and 25 typically developing children were tested on behavioral, neural, and parental measures of attention before and after a 4-week iPad-based at-home cognitive remediation program. At baseline, 54% of children with SPD met or exceeded criteria on a parent report measure for inattention/hyperactivity. Significant deficits involving sustained attention, selective attention and goal management were observed only in the subset of SPD children with parent-reported inattention. This subset of children also showed reduced midline frontal theta activity, an electroencephalographic measure of attention. Following the cognitive intervention, only the SPD children with inattention/hyperactivity showed both improvements in midline frontal theta activity and on a parental report of inattention. Notably, 33% of these individuals no longer met the clinical cut-off for inattention, with the parent-reported improvements persisting for 9 months. These findings support the benefit of a targeted attention intervention for a subset of children with SPD, while simultaneously highlighting the importance of having a multifaceted assessment for individuals with neurodevelopmental conditions to optimally personalize treatment

White Matter Microstructure is Associated with Auditory and Tactile Processing in Children with and without Sensory Processing Disorder

International audienceSensory processing disorders (SPDs) affect up to 16% of school-aged children, and contribute to cognitive and behavioral deficits impacting affected individuals and their families. While sensory processing differences are now widely recognized in children with autism, children with sensory-based dysfunction who do not meet autism criteria based on social communication deficits remain virtually unstudied. In a previous pilot diffusion tensor imaging (DTI) study, we demonstrated that boys with SPD have altered white matter microstructure primarily affecting the posterior cerebral tracts, which subserve sensory processing and integration. This disrupted microstructural integrity, measured as reduced white matter fractional anisotropy (FA), correlated with parent report measures of atypical sensory behavior. In this present study, we investigate white matter microstructure as it relates to tactile and auditory function in depth with a larger, mixed-gender cohort of children 8–12 years of age. We continue to find robust alterations of posterior white matter microstructure in children with SPD relative to typically developing children (TDC), along with more spatially distributed alterations. We find strong correlations of FA with both parent report and direct measures of tactile and auditory processing across children, with the direct assessment measures of tactile and auditory processing showing a stronger and more continuous mapping to the underlying white matter integrity than the corresponding parent report measures. Based on these findings of microstructure as a neural correlate of sensory processing ability, diffusion MRI merits further investigation as a tool to find biomarkers for diagnosis, prognosis and treatment response in children with SPD. To our knowledge, this work is the first to demonstrate associations of directly measured tactile and non-linguistic auditory function with white matter microstructural integrity – not just in children with SPD, but also in TDC

Burden of de novo mutations and inherited rare single nucleotide variants in children with sensory processing dysfunction

Abstract Background In children with sensory processing dysfunction (SPD), who do not meet criteria for autism spectrum disorder (ASD) or intellectual disability, the contribution of de novo pathogenic mutation in neurodevelopmental genes is unknown and in need of investigation. We hypothesize that children with SPD may have pathogenic variants in genes that have been identified as causing other neurodevelopmental disorders including ASD. This genetic information may provide important insight into the etiology of sensory processing dysfunction and guide clinical evaluation and care. Methods Eleven community-recruited trios (children with isolated SPD and both biological parents) underwent WES to identify candidate de novo variants and inherited rare single nucleotide variants (rSNV) in genes previously associated with ASD. Gene enrichment in these children and their parents for transmitted and non-transmitted mutation burden was calculated. A comparison analysis to assess for enriched rSNV burden was then performed in 2377 children with ASD and their families from the Simons Simplex Collection. Results Of the children with SPD, 2/11 (18%), were identified as having a de novo loss of function or missense mutation in genes previously reported as causative for neurodevelopmental disorders (MBD5 and FMN2). We also found that the parents of children with SPD have significant enrichment of pathogenic rSNV burden in high-risk ASD candidate genes that are inherited by their affected children. Using the same approach, we confirmed enrichment of rSNV burden in a large cohort of children with autism and their parents but not unaffected siblings. Conclusions Our findings suggest that SPD, like autism, has a genetic basis that includes both de novo single gene mutations as well as an accumulated burden of rare inherited variants from their parents

Diffusion tensor tractography in children with sensory processing disorder: Potentials for devising machine learning classifiers.

The "sensory processing disorder" (SPD) refers to brain's inability to organize sensory input for appropriate use. In this study, we determined the diffusion tensor imaging (DTI) microstructural and connectivity correlates of SPD, and apply machine learning algorithms for identification of children with SPD based on DTI/tractography metrics. A total of 44 children with SPD and 41 typically developing children (TDC) were prospectively recruited and scanned. In addition to fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD), we applied probabilistic tractography to generate edge density (ED) and track density (TD) from DTI maps. For identification of children with SPD, accurate classification rates from a combination of DTI microstructural (FA, MD, AD, and RD), connectivity (TD) and connectomic (ED) metrics with different machine learning algorithms - including naïve Bayes, random forest, support vector machine, and neural networks - were determined. In voxel-wise analysis, children with SPD had lower FA, ED, and TD but higher MD and RD compared to TDC - predominantly in posterior white matter tracts including posterior corona radiata, posterior thalamic radiation, and posterior body and splenium of corpus callosum. In stepwise penalized logistic regression, the only independent variable distinguishing children with SPD from TDC was the average TD in the splenium (p < 0.001). Among different combinations of machine learning algorithms and DTI/connectivity metrics, random forest models using tract-based TD yielded the highest accuracy in classification of SPD - 77.5% accuracy, 73.8% sensitivity, and 81.6% specificity. Our findings demonstrate impaired microstructural and connectivity/connectomic integrity in children with SPD, predominantly in posterior white matter tracts, and with reduced TD of the splenium of corpus callosum as the most distinctive pattern. Applying machine learning algorithms, these connectivity metrics can be used to devise novel imaging biomarkers for neurodevelopmental disorders

A pilot study to determine the feasibility of enhancing cognitive abilities in children with sensory processing dysfunction

<div><p>Children with Sensory Processing Dysfunction (SPD) experience incoming information in atypical, distracting ways. Qualitative challenges with attention have been reported in these children, but such difficulties have not been quantified using either behavioral or functional neuroimaging methods. Furthermore, the efficacy of evidence-based cognitive control interventions aimed at enhancing attention in this group has not been tested. Here we present work aimed at characterizing and enhancing attentional abilities for children with SPD. A sample of 38 SPD and 25 typically developing children were tested on behavioral, neural, and parental measures of attention before and after a 4-week iPad-based at-home cognitive remediation program. At baseline, 54% of children with SPD met or exceeded criteria on a parent report measure for inattention/hyperactivity. Significant deficits involving sustained attention, selective attention and goal management were observed only in the subset of SPD children with parent-reported inattention. This subset of children also showed reduced midline frontal theta activity, an electroencephalographic measure of attention. Following the cognitive intervention, only the SPD children with inattention/hyperactivity showed both improvements in midline frontal theta activity and on a parental report of inattention. Notably, 33% of these individuals no longer met the clinical cut-off for inattention, with the parent-reported improvements persisting for 9 months. These findings support the benefit of a targeted attention intervention for a subset of children with SPD, while simultaneously highlighting the importance of having a multifaceted assessment for individuals with neurodevelopmental conditions to optimally personalize treatment.</p></div

Comparison of neural activity during perceptual discrimination task.

<p>Bar graphs represent averaged MFT power between 280-320ms post target stimulus. Circles on heat maps present neural activity at the location and time of interest (4–7 Hz; 280-320ms). Error bars indicated standard error of the mean. * = p≤ .05).</p

Transfer effect on behavioral and parent report measures.

<p>Pre and post (A) response time (B) and response time variability on behavioral tasks revealing within group change. Error bars indicate standard error of the mean. Within group main effects of session are designated as significant by stars: * = p≤ .05, ** =.p≤ .01. Sun symbols indicate statistically significant instances where SPD_+IA post-training performance was equivalent to or better than the TDC group prior to training. (C) Vanderbilt parent report inattention change bar plot (calculated by pre-post marginal means) and line plots revealing the significant group x session interaction. Error bars indicate standard error of the mean. All group x session interaction effects are designated as significant by stars (* = p≤ .05, ** =.p≤ .01) on bar graph.</p

Multiple regression of baseline assessment response times in predicting Vanderbilt improvement.

<p>Multiple regression of baseline assessment response times in predicting Vanderbilt improvement.</p