NIH Toolbox Cognition Battery Feasibility in Individuals With Williams Syndrome.

The NIH Toolbox Cognition Battery (NIHTB-CB) was developed for epidemiological and longitudinal studies across a wide age span. Such a tool may be useful for intervention trials in conditions characterized by intellectual disability (ID), such as Williams syndrome (WS). Three NIHTB-CB tasks, including two executive functioning (Flanker, Dimensional Change Card Sort) and one episodic memory (Picture Sequence Memory) task, were given to 47 individuals with WS, ages 4 to 50, to evaluate feasibility (i.e., proportion of valid administrations) in this population. Findings indicated that NIHTB-CB tests showed good feasibility. Flanker and DCCS age-corrected scores were negatively correlated with age and showed floor effects, indicating these scores may not be useful for quantifying performance on these NIHTB-CB tests in ID.

Structured sparse multiset canonical correlation analysis of simultaneous fNIRS and EEG provides new insights into the human action-observation network.

The action observation network (AON) is a network of brain regions involved in the execution and observation of a given action. The AON has been investigated in humans using mostly electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI), but shared neural correlates of action observation and action execution are still unclear due to lack of ecologically valid neuroimaging measures. In this study, we used concurrent EEG and functional Near Infrared Spectroscopy (fNIRS) to examine the AON during a live-action observation and execution paradigm. We developed structured sparse multiset canonical correlation analysis (ssmCCA) to perform EEG-fNIRS data fusion. MCCA is a generalization of CCA to more than two sets of variables and is commonly used in medical multimodal data fusion. However, mCCA suffers from multi-collinearity, high dimensionality, unimodal feature selection, and loss of spatial information in interpreting the results. A limited number of participants (small sample size) is another problem in mCCA, which leads to overfitted models. Here, we adopted graph-guided (structured) fused least absolute shrinkage and selection operator (LASSO) penalty to mCCA to conduct feature selection, incorporating structural information amongst the variables (i.e., brain regions). Benefitting from concurrent recordings of brain hemodynamic and electrophysiological responses, the proposed ssmCCA finds linear transforms of each modality such that the correlation between their projections is maximized. Our analysis of 21 right-handed participants indicated that the left inferior parietal region was active during both action execution and action observation. Our findings provide new insights into the neural correlates of AON which are more fine-tuned than the results from each individual EEG or fNIRS analysis and validate the use of ssmCCA to fuse EEG and fNIRS datasets.

Cerebral hemodynamic response during a live action-observation and action-execution task: A fNIRS study.

Although many studies have examined the location of the action observation network (AON) in human adults, the shared neural correlates of action-observation and action-execution are still unclear partially due to lack of ecologically valid neuroimaging measures. In this study, we aim to demonstrate the feasibility of using functional near infrared spectroscopy (fNIRS) to measure the neural correlates of action-observation and action execution regions during a live task. Thirty adults reached for objects or observed an experimenter reaching for objects while their cerebral hemodynamic responses including oxy-hemoglobin (HbO) and deoxy-hemoglobin (HbR) were recorded in the sensorimotor and parietal regions. Our results indicated that the parietal regions, including bilateral superior parietal lobule (SPL), bilateral inferior parietal lobule (IPL), right supra-marginal region (SMG) and right angular gyrus (AG) share neural activity during action-observation and action-execution. Our findings confirm the applicability of fNIRS for the study of the AON and lay the foundation for future work with developmental and clinical populations.

Comparison of Functional Connectivity in the Prefrontal Cortex during a Simple and an Emotional Go/No-Go Task in Female versus Male Groups: An fNIRS Study.

Inhibitory control is a cognitive process to suppress prepotent behavioral responses to stimuli. This study aimed to investigate prefrontal functional connectivity during a behavioral inhibition task and its correlation with the subject's performance. Additionally, we identified connections that are specific to the Go/No-Go task. The experiment was performed on 42 normal, healthy adults who underwent a vanilla baseline and a simple and emotional Go/No-Go task. Cerebral hemodynamic responses were measured in the prefrontal cortex using a 16-channel near infrared spectroscopy (NIRS) device. Functional connectivity was calculated from NIRS signals and correlated to the Go/No-Go performance. Strong connectivity was found in both the tasks in the right hemisphere, inter-hemispherically, and the left medial prefrontal cortex. Better performance (fewer errors, faster response) is associated with stronger prefrontal connectivity during the simple Go/No-Go in both sexes and the emotional Go/No-Go connectivity in males. However, females express a lower emotional Go/No-Go connectivity while performing better on the task. This study reports a complete prefrontal network during a simple and emotional Go/No-Go and its correlation with the subject's performance in females and males. The results can be applied to examine behavioral inhibitory control deficits in population with neurodevelopmental disorders.

Using Functional Connectivity to Examine the Correlation between Mirror Neuron Network and Autistic Traits in a Typically Developing Sample: A fNIRS Study.

Mirror neuron network (MNN) is associated with one's ability to recognize and interpret others' actions and emotions and has a crucial role in cognition, perception, and social interaction. MNN connectivity and its relation to social attributes, such as autistic traits have not been thoroughly examined. This study aimed to investigate functional connectivity in the MNN and assess relationship between MNN connectivity and subclinical autistic traits in neurotypical adults. Hemodynamic responses, including oxy- and deoxy-hemoglobin were measured in the central and parietal cortex of 30 healthy participants using a 24-channel functional Near-Infrared spectroscopy (fNIRS) system during a live action-observation and action-execution task. Functional connectivity was derived from oxy-hemoglobin data. Connections with significantly greater connectivity in both tasks were assigned to MNN connectivity. Correlation between connectivity and autistic traits were performed using Pearson correlation. Connections within the right precentral, right supramarginal, left inferior parietal, left postcentral, and between left supramarginal-left angular regions were identified as MNN connections. In addition, individuals with higher subclinical autistic traits present higher connectivity in both action-execution and action-observation conditions. Positive correlation between MNN connectivity and subclinical autistic traits can be used in future studies to investigate MNN in a developing population with autism spectrum disorder.

Characterizing the Action-Observation Network Through Functional Near-Infrared Spectroscopy: A Review.

Functional near-infrared spectroscopy (fNIRS) is a neuroimaging technique that has undergone tremendous growth over the last decade due to methodological advantages over other measures of brain activation. The action-observation network (AON), a system of brain structures proposed to have "mirroring" abilities (e.g., active when an individual completes an action or when they observe another complete that action), has been studied in humans through neural measures such as fMRI and electroencephalogram (EEG); however, limitations of these methods are problematic for AON paradigms. For this reason, fNIRS is proposed as a solution to investigating the AON in humans. The present review article briefly summarizes previous neural findings in the AON and examines the state of AON research using fNIRS in adults. A total of 14 fNIRS articles are discussed, paying particular attention to methodological choices and considerations while summarizing the general findings to aid in developing better protocols to study the AON through fNIRS. Additionally, future directions of this work are discussed, specifically in relation to researching AON development and potential multimodal imaging applications.

Probing Neurovisceral Integration via Functional Near-Infrared Spectroscopy and Heart Rate Variability.

The neurovisceral integration model (NVM) proposes that an organism's ability to flexibly adapt to its environment is related to biological flexibility within the central autonomic network (CAN). One important aspect of this flexibility is behavioral inhibition (Thayer and Friedman, 2002). During a behavioral inhibition task, the CAN, which comprises a series of feedback loops, must be able to integrate information and react to these inputs flexibly to facilitate optimal performance. The functioning of the CAN is shown to be associated with respiratory sinus arrhythmia (RSA), as the vagus nerve is part of this feedback system. Although the NVM has been examined through neural imaging and RSA, only a few studies have examined these measures simultaneously during the neuroimaging procedure. Furthermore, these studies were done at rest or used tasks that were not targeted at processes associated with the NVM, such as behavioral inhibition and cognitive flexibility. For this reason, the present study assessed RSA and neural activation in the pre-frontal cortex simultaneously while participants completed a behavior inhibition task. RSA and functional near-infrared spectroscopy were collected in 38 adults, and resting levels of pre-frontal activation were negatively related to RSA, but pre-frontal activation during the behavior inhibition task was not. The negative relationship between RSA and oxygenated hemoglobin is consistent with previous functional magnetic resonance imaging work examining the NVM at baseline and should be further studied. Additional research investigating how this relationship may change based on task demands or environmental contexts would help clarify the applicability of the model.

Maternal Affect During a Challenging Mother-Child Interaction: The Effects of Broad Autism Phenotype and Respiratory Sinus Arrhythmia Reactivity in Mothers of Children With and Without Autism Spectrum Disorder.

Respiratory sinus arrhythmia (RSA) is proposed to index cognitive and behavioral inflexibility. Broad autism phenotype (BAP) traits are prevalent in family members of children with autism spectrum disorder (ASD). The study investigated whether RSA and BAP traits in mothers of typically developing (TD) children and mothers of children with ASD influence maternal affect. It was hypothesized that these factors would interact to influence mother-child interactions. Twenty-three mother-child dyads participated in a challenging interaction while measuring mother's RSA. Results indicated that mothers of children with ASD show different RSA reactivity than mothers of TD children. Furthermore, preliminary analyses revealed RSA reactivity moderated the relationship between mothers' rigidity and maternal affect during this interaction. Implications for future research and interventions are discussed.

Restricted repetitive behaviors in autism spectrum disorder: A systematic review from the neurovisceral integration perspective.

The neurovisceral integration model posits that cognitive-behavioral inflexibility arises from biological inflexibility of feedback loops within the central autonomic network. The parasympathetic nervous system (PNS) is integral in this network. Activity of the PNS, which is normally tonically inhibited, can be indexed through respiratory sinus arrhythmia (RSA). When the PNS becomes disinhibited, indicating decreased flexibility within the network, RSA is reduced and cognitive-behavioral flexibility is impaired. Using this theoretical framework, cognitive-behavioral inflexibility is discussed from the Research Domain Criteria (RDoC) perspective. Restricted repetitive behaviors in autism spectrum disorder (ASD) are proposed as exemplars of cognitive-behavioral inflexibility, and behavioral and RSA literature in ASD are reviewed. RSA differences and their relation to inflexibility in ASD are discussed to support the model and to propose RSA as a biomarker for cognitive-behavioral inflexibility. Considerations for future research are discussed, in addition to implications the model might have on assessment and transdiagnostic treatment practices.

Gender differences in restricted and repetitive behaviors and interests in youth with autism.

Previous work has found gender differences in restricted and repetitive behaviors and interests (RRBI) for autism spectrum disorder (ASD). Compared to girls, affected boys have increased stereotyped and restricted behaviors; however much less is known about gender differences in other areas of RRBI. This study aims to identify whether specific RRBI (i.e., stereotyped, self-injurious, compulsive, insistence on sameness, ritualistic, and restricted), as measured by item-level data on the Repetitive Behavior Scale-Revised (RBS-R), can distinguish girls from boys with ASD. Participants included 615 individuals with ASD (507 boys; 82.4%), ages 3-18 years of age (M = 10.26, SD = 4.20), who agreed to share data with the National Database for Autism Research (NDAR). Multivariate analysis of variance and discriminant function analysis (DFA) were used to determine whether item-level RBS-R data could correctly classify cases by gender. DFA results suggest that RBS-R items significantly differentiate gender. Strongly differentiating RBS-R items had greater success in correctly classifying affected boys (67.90%) than girls (61.00%). Items that best-discriminated gender were heightened stereotyped behaviors and restricted interests items in boys and compulsive, sameness, restricted, and self-injurious behavior items in girls. This study is the first to find that girls with ASD may have increased compulsive, sameness, and restricted RRBI compared to boys. Additionally, findings support heightened self-injurious behaviors in affected girls. Future research should disentangle whether elevated rates of RRBI in girls are central to the presentation of ASD in girls or an epiphenomenon of the high rates of co-occurring disorders (e.g., anxiety) noted in girls. Autism Res 2019, 12: 274-283 © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This study is the first to examine a comprehensive measure of repetitive behavior in children with autism, with findings of increased compulsive, insistence on sameness, and self-injurious behavior characterizing girls and increased stereotyped and restricted behavior characterizing boys. Future research should determine whether these elevated behaviors in girls are directly part of the autism presentation in girls or symptoms of co-occurring psychopathology. It is important for autism diagnostic measures to best capture the types of repetitive behavior girls may demonstrate.

Respiratory Sinus Arrhythmia Predicts Restricted Repetitive Behavior Severity.

In addition to social communication deficits, restricted repetitive behaviors (RRBs) are a key diagnostic feature of autism spectrum disorder (ASD). Dysfunction of the autonomic nervous system (ANS) in ASD has been posited as a mechanism of RRBs; however, most studies investigating ANS activity in ASD have focused on its relation to social functioning. This study used respiratory sinus arrhythmia (RSA) patterns to measure ANS functioning and analyze its relation to RRBs in children with and without an ASD diagnosis. Baseline RSA and RSA reactivity predicted RRB severity and exploratory analyses revealed these measures may be associated with RRB subgroups. These results are discussed in regards to the behavioral literature on RRBs and the benefits of finding biomarkers for these behaviors.

Brief Report: Insistence on Sameness, Anxiety, and Social Motivation in Children with Autism Spectrum Disorder.

While the function of restricted repetitive behaviors (RRBs) in autism spectrum disorder (ASD) is unclear, RRBs may function as anxiety reduction strategies (Joosten et al. J Autism Dev Disord 39(3):521-531, 2009. Moreover, anxiety in ASD is associated with low social motivation (Swain et al. J Autism Dev Disord, 2015. The present study examined social motivation as a mediator between anxiety and RRBs in a sample of 44 children (2-17 years old; 80 % male) with ASD. The relationship between anxiety and IS, but not other RRBs, was partially mediated by social motivation. These findings suggest anxiety is linked to social motivation deficits in children with ASD, which may increase ritualized behaviors and difficulties with changes in routine. Implications are discussed for differing functions and treatment of RRB domains.