Elevated and accelerated: Locus coeruleus activity and visual search abilities in autistic children.

BACKGROUND: Autistic individuals excel at visual search, however, the neural mechanism(s) underlying this advantage remain unclear. The locus coeruleus-norepinephrine (LC-NE) system, which plays a critical role in sensory perception and selective attention, has been shown to function in a persistently elevated state in individuals on the spectrum. However, the relationship between elevated tonic LC-NE activity and accelerated search in autism has not been explored. OBJECTIVE: To examine the relationship between visual search abilities and resting pupil diameter (an indirect measure of tonic LC-NE activation) in autistic and neurotypical children. METHODS: Participants were 24 school-aged autistic children and 24 age- and IQ-matched neurotypical children aged 8-15 years. Children completed two tasks: a resting eye-tracking task and a visual search paradigm. For the resting eye-tracking task, pupil diameter was monitored while participants fixated a central crosshair. For the visual search paradigm, participants were instructed to find the target (vertical line) embedded within an array of tilted (10°) distractor lines. The target was present on 50% of trials, and displayed within set sizes of 18, 24, and 36 items. RESULTS: Consistent with previous studies, autistic children had significantly larger resting pupil size and searched faster and more efficiently compared to their neurotypical peers. Eye-tracking findings revealed that accelerated search was associated with fewer, not shorter, fixations in the autism group. Autistic children also showed reduced leftward search bias. Larger resting pupil size, indicative of increased tonic activation of the LC-NE system, was associated with greater search efficiency, longer fixation durations, and reduced leftward bias. Finally, within both groups reduced leftward bias was associated with increased autism symptomatology. DISCUSSION: Together, these findings add to the existing body of research highlighting superior search in autism, suggest that elevated tonic LC-NE activity may contribute to more efficient search, and link non-social visual-spatial processing strengths to autism symptoms.

Diagnostic Accuracy of Primary Care Clinicians Across a Statewide System of Autism Evaluation.

OBJECTIVES: To evaluate the diagnostic accuracy of the Early Autism Evaluation (EAE) Hub system, a statewide network that provides specialized training and collaborative support to community primary care providers in the diagnosis of young children at risk for autism spectrum disorder (ASD). METHODS: EAE Hub clinicians referred children, aged 14 to 48 months, to this prospective diagnostic study for blinded follow-up expert evaluation including assessment of developmental level, adaptive behavior, and ASD symptom severity. The primary outcome was agreement on categorical ASD diagnosis between EAE Hub clinician (index diagnosis) and ASD expert (reference standard). RESULTS: Among 126 children (mean age: 2.6 years; 77% male; 14% Latinx; 66% non-Latinx white), 82% (n = 103) had consistent ASD outcomes between the index and reference evaluation. Sensitivity was 81.5%, specificity was 82.4%, positive predictive value was 92.6%, and negative predictive value was 62.2%. There was no difference in accuracy by EAE Hub clinician or site. Across measures of development, there were significant differences between true positive and false negative (FN) cases (all Ps < .001; Cohen's d = 1.1-1.4), with true positive cases evidencing greater impairment. CONCLUSIONS: Community-based primary care clinicians who receive specialty training can make accurate ASD diagnoses in most cases. Diagnostic disagreements were predominately FN cases in which EAE Hub clinicians had difficulty differentiating ASD and global developmental delay. FN cases were associated with a differential diagnostic and phenotypic profile. This research has significant implications for the development of future population health solutions that address ASD diagnostic delays.

Diagnosis and treatment of children and adolescents with autism and ADHD.

Attention-deficit/hyperactivity disorder (ADHD) and autism are neurodevelopmental disorders that emerge in childhood. There is increasing recognition that ADHD and autism frequently co-occur. Yet, questions remain among clinicians regarding the best ways to evaluate and treat co-occurring autism and ADHD. This review outlines issues relevant to providing evidence-based practice to individuals and families who may be experiencing difficulties associated with co-occurring autism and ADHD. After describing the complexities of the co-occurrence of autism and ADHD, we present practical considerations for best practice assessment and treatment of co-occurring autism and ADHD. Regarding assessment, this includes considerations for interviewing parents/caregivers and youth, using validated parent and teacher rating scales, conducting cognitive assessments, and conducting behavior observations. Regarding treatment, consideration is given to behavioral management, school-based interventions, social skills development, and the use of medications. Throughout, we note the quality of evidence that supports a particular component of assessment or treatment, highlighting when evidence is most relevant to those with co-occurring autism and ADHD across stages of development. In light of the current evidence for assessment and treatment of co-occurring autism and ADHD, we conclude by outlining practical implications for clinical and educational practice.

Patterns of sensory processing in young children with autism: Differences in autism characteristics, adaptive skills, and attentional problems.

LAY ABSTRACT: Research has found differences in responding to various sensory stimuli among autistic individuals, which are associated with social and adaptive skills. However, our understanding of sensory profiles in autism has been complicated due to the variable presentation of sensory symptoms. One way to better understand variability in sensory symptoms is to use advanced statistical approaches, such as latent profile analysis, that allow for the identification of more similar sensory classes in otherwise variable groups. We used the Short Sensory Profile to identify homogeneous classes of sensory reactivity in autistic children based on both severity and modality and examined whether sensory classes differed in terms of autism characteristics, adaptive skills, and attention-deficit/hyperactivity disorder symptoms. Based on the pattern of both severity and modality, four sensory classes emerged and were named Moderate/Mixed (35.5%; probable-to-definite differences in all modalities except in movement sensitivity and low energy/weakness), Severe/Mixed (8.5%; definite sensory differences in all modalities except in low energy/weakness), Moderate/Broad (14.6%; probable-to-definite differences in all modalities), and Low/Mixed (41.1%; typical scores in most modalities with probable differences in taste/smell sensitivity, under-responsive/seeks sensation, and auditory filtering). The Severe/Mixed class exhibited greater problems in a variety of areas such as social, adaptive, and attention-deficit/hyperactivity disorder symptoms, whereas the Low/Mixed class showed overall fewer problems. This may provide insight for clinicians and researchers aiming to understand whether autistic children who exhibit distinct sensory patterns are more or less likely to also experience social, adaptive, and/or attention/behavior-related difficulties.

Measures of tonic and phasic activity of the locus coeruleus-norepinephrine system in children with autism spectrum disorder: An event-related potential and pupillometry study.

A growing body of research suggests that locus coeruleus-norepinephrine (LC-NE) system may function differently in individuals with autism spectrum disorder (ASD). Understanding the dynamics of both tonic (resting pupil diameter) and phasic (pupil dilation response [PDR] and event-related potential [ERP]) indices may provide meaningful insights about the nature of LC-NE function in ASD. Twenty-four children with ASD and 27 age- and nonverbal-IQ matched typically developing (TD) children completed two experiments: (1) a resting eye-tracking task to measure tonic pupil diameter, and (2) a three-stimulus oddball paradigm to measure phasic responsivity using PDR and ERP. Consistent with prior reports, our results indicate that children with ASD exhibit increased tonic (resting pupil diameter) and reduced phasic (PDR and ERP) activity of the LC-NE system compared to their TD peers. For both groups, decreased phasic responsivity was associated with increased resting pupil diameter. Lastly, tonic and phasic LC-NE indices were primarily related to measures of attention-deficit/hyperactivity disorder (ADHD), and not ASD, symptomatology. These findings expand our understanding of neurophysiological differences present in ASD and demonstrate that aberrant LC-NE activation may be associated with atypical arousal and decreased responsivity to behaviorally-relevant information in ASD.

Attentional Disengagement and the Locus Coeruleus - Norepinephrine System in Children With Autism Spectrum Disorder.

BACKGROUND: Differences in non-social attentional functions have been identified as among the earliest features that distinguish infants later diagnosed with autism spectrum disorder (ASD), and may contribute to the emergence of core ASD symptoms. Specifically, slowed attentional disengagement and difficulty reorienting attention have been found across the lifespan in those at risk for, or diagnosed with, ASD. Additionally, the locus coeruleus-norepinephrine (LC-NE) system, which plays a critical role in arousal regulation and selective attention, has been shown to function atypically in ASD. While activity of the LC-NE system is associated with attentional disengagement and reorienting in typically developing (TD) individuals, it has not been determined whether atypical LC-NE activity relates to attentional disengagement impairments observed in ASD. OBJECTIVE: To examine the relationship between resting pupil diameter (an indirect measure of tonic LC-NE activation) and attentional disengagement in children with ASD. METHODS: Participants were 21 school-aged children with ASD and 20 age- and IQ-matched TD children. The study consisted of three separate experiments: a resting eye-tracking task and visual and auditory gap-overlap paradigms. For the resting eye-tracking task, pupil diameter was monitored while participants fixated a central crosshair. In the gap-overlap paradigms, participants were instructed to fixate on a central stimulus and then move their eyes to peripherally presented visual or auditory targets. Saccadic reaction times (SRT), percentage of no-shift trials, and disengagement efficiency were measured. RESULTS: Children with ASD had significantly larger resting pupil size compared to their TD peers. The groups did not differ for overall SRT, nor were there differences in SRT for overlap and gap conditions between groups. However, the ASD group did evidence impairments in disengagement (larger step/gap effects, higher percentage of no-shift trials, and reduced disengagement efficiency) compared to their TD peers. Correlational analyses showed that slower, less efficient disengagement was associated with increased pupil diameter. CONCLUSION: Consistent with prior reports, children with ASD show significantly larger resting pupil diameter, indicative of atypically elevated tonic LC-NE activity. Associations between pupil size and measures of attentional disengagement suggest that atypically increased tonic activation of the LC-NE system may be associated with poorer attentional disengagement in children with ASD.

Equivalent Behavioral Facilitation to Tactile Cues in Children with Autism Spectrum Disorder.

The alerting network, a subcomponent of attention, enables humans to respond to novel information. Children with ASD have shown equivalent alerting in response to visual and/or auditory stimuli compared to typically developing (TD) children. However, it is unclear whether children with ASD and TD show equivalent alerting to tactile stimuli. We examined (1) whether tactile cues affect accuracy and reaction times in children with ASD and TD, (2) whether the duration between touch-cues and auditory targets impacts performance, and (3) whether behavioral responses in the tactile cueing task are associated with ASD symptomatology. Six- to 12-year-olds with ASD and TD participated in a tactile-cueing task and were instructed to respond with a button press to a target sound /a/. Tactile cues were presented at 200, 400, and 800 ms (25% each) prior to the auditory target. The remaining trials (25%) were presented without tactile cues. Findings suggested that both groups showed equivalent alerting responses to tactile cues. Additionally, all children were faster to respond to auditory targets at longer cue-target intervals. Finally, there was an association between rate of facilitation and RRB scores in all children, suggesting that patterns of responding to transient phasic cues may be related to ASD symptomatology.

Associations between sensory processing and electrophysiological and neurochemical measures in children with ASD: an EEG-MRS study.

BACKGROUND: Autism spectrum disorder (ASD) is associated with hyper- and/or hypo-sensitivity to sensory input. Spontaneous alpha power, which plays an important role in shaping responsivity to sensory information, is reduced across the lifespan in individuals with ASD. Furthermore, an excitatory/inhibitory imbalance has also been linked to sensory dysfunction in ASD and has been hypothesized to underlie atypical patterns of spontaneous brain activity. The present study examined whether resting-state alpha power differed in children with ASD as compared to TD children, and investigated the relationships between alpha levels, concentrations of excitatory and inhibitory neurotransmitters, and atypical sensory processing in ASD. METHODS: Participants included thirty-one children and adolescents with ASD and thirty-one age- and IQ-matched typically developing (TD) participants. Resting-state electroencephalography (EEG) was used to obtain measures of alpha power. A subset of participants (ASD = 16; TD = 16) also completed a magnetic resonance spectroscopy (MRS) protocol in order to measure concentrations of excitatory (glutamate + glutamine; Glx) and inhibitory (GABA) neurotransmitters. RESULTS: Children with ASD evidenced significantly decreased resting alpha power compared to their TD peers. MRS estimates of GABA and Glx did not differ between groups with the exception of Glx in the temporal-parietal junction. Inter-individual differences in alpha power within the ASD group were not associated with region-specific concentrations of GABA or Glx, nor were they associated with sensory processing differences. However, atypically decreased Glx was associated with increased sensory impairment in children with ASD. CONCLUSIONS: Although we replicated prior reports of decreased alpha power in ASD, atypically reduced alpha was not related to neurochemical differences or sensory symptoms in ASD. Instead, reduced Glx in the temporal-parietal cortex was associated with greater hyper-sensitivity in ASD. Together, these findings may provide insight into the neural underpinnings of sensory processing differences present in ASD.

Electrophysiological Measures of Tactile and Auditory Processing in Children With Autism Spectrum Disorder.

Behavioral differences in responding to tactile and auditory stimuli are widely reported in individuals with autism spectrum disorder (ASD). However, the neural mechanisms underlying distinct tactile and auditory reactivity patterns in ASD remain unclear with theories implicating differences in both perceptual and attentional processes. The current study sought to investigate (1) the neural indices of early perceptual and later attentional factors underlying tactile and auditory processing in children with and without ASD, and (2) the relationship between neural indices of tactile and auditory processing and ASD symptomatology. Participants included 14, 6-12-year-olds with ASD and 14 age- and non-verbal IQ matched typically developing (TD) children. Children participated in an event-related potential (ERP) oddball paradigm during which they watched a silent video while being presented with tactile and auditory stimuli (i.e., 80% standard speech sound/a/; 10% oddball speech sound/i/; 10% novel vibrotactile stimuli on the fingertip with standard speech sound/a/). Children's early and later ERP responses to tactile (P1 and N2) and auditory stimuli (P1, P3a, and P3b) were examined. Non-parametric analyses showed that children with ASD displayed differences in early perceptual processing of auditory (i.e., lower amplitudes at central region of interest), but not tactile, stimuli. Analysis of later attentional components did not show differences in response to tactile and auditory stimuli in the ASD and TD groups. Together, these results suggest that differences in auditory responsivity patterns could be related to perceptual factors in children with ASD. However, despite differences in caregiver-reported sensory measures, children with ASD did not differ in their neural reactivity to infrequent touch-speech stimuli compared to TD children. Nevertheless, correlational analyses confirmed that inter-individual differences in neural responsivity to tactile and auditory stimuli were related to social skills in all children. Finally, we discuss how the paradigm and stimulus type used in the current study may have impacted our results. These findings have implications for everyday life, where individual differences in responding to tactile and auditory stimuli may impact social functioning.

Does Human Touch Facilitate Object Categorization in 6-to-9-Month-Old Infants?

Infants form object categories in the first months of life. By 3 months and throughout the first year, successful categorization varies as a function of the acoustic information presented in conjunction with category members. Here we ask whether tactile information, delivered in conjunction with category members, also promotes categorization. Six- to 9-month-olds participated in an object categorization task in either a touch-cue or no-cue condition. For infants in the touch-cue condition, familiarization images were accompanied by precisely-timed light touches from their caregivers; infants in the no-cue condition saw the same images but received no touches. Only infants in the touch-cue condition formed categories. This provides the first evidence that touch may play a role in supporting infants' object categorization.

Brief Report: Reduced Heart Rate Variability in Children with Autism Spectrum Disorder.

Dysregulation of the autonomic nervous system (ANS), which can be indexed by heart rate variability (HRV), has been posited to contribute to core features of autism spectrum disorder (ASD). However, the relationship between ASD and HRV remains uncertain. We assessed tonic and phasic HRV of 21 children with ASD and 21 age- and IQ-matched typically developing (TD) children and examined (1) group differences in HRV and (2) associations between HRV and ASD symptomatology. Children with ASD showed significantly lower tonic HRV, but similar phasic HRV compared to TD children. Additionally, reduced tonic HRV was associated with atypical attentional responsivity in ASD. Our findings suggest ANS dysregulation is present in ASD and may contribute to atypical attentional responses to sensory stimulation.

Caregiver Touch-Speech Communication and Infant Responses in 12-Month-Olds at High Risk for Autism Spectrum Disorder.

Multimodal communication may facilitate attention in infants. This study examined the presentation of caregiver touch-only and touch + speech input to 12-month-olds at high (HRA) and low risk for ASD. Findings indicated that, although both groups received a greater number of touch + speech bouts compared to touch-only bouts, the duration of overall touch that overlapped with speech was significantly greater in the HRA group. Additionally, HRA infants were less responsive to touch-only bouts compared to touch + speech bouts suggesting that their mothers may use more touch + speech communication to elicit infant responses. Nonetheless, the exact role of touch in multimodal communication directed towards infants at high risk for ASD warrants further exploration.

Auditory Attentional Disengagement in Children with Autism Spectrum Disorder.

Despite early differences in orienting to sounds, no study to date has investigated whether children with ASD demonstrate impairments in attentional disengagement in the auditory modality. Twenty-one 9-15-year-old children with ASD and 20 age- and IQ-matched TD children were presented with an auditory gap-overlap paradigm. Evidence of impaired disengagement in ASD was mixed. Differences in saccadic reaction time for overlap and gap conditions did not differ between groups. However, children with ASD did show increased no-shift trials in the overlap condition, as well as reduced disengagement efficiency compared to their TD peers. These results provide further support for disengagement impairments in ASD, and suggest that these deficits include disengaging from and shifting to unimodal auditory information.

Atypical Response to Caregiver Touch in Infants at High Risk for Autism Spectrum Disorder.

Atypical response to tactile input is associated with greater socio-communicative impairments in individuals with autism spectrum disorder (ASD). The current study examined overt orienting to caregiver-initiated touch in 12-month-olds at high risk for ASD (HRA) with (HRA+) and without (HRA-) a later diagnosis of ASD compared to low-risk comparison infants. Findings indicate that infants that go on to receive a diagnosis of ASD may more frequently fail to shift their attention in response to caregiver touch and when they do, they may be more likely to orient away from touch. Additionally, failure to respond to touch predicts ADOS severity scores at outcome suggesting that atypical response to touch may be an early indicator of autism severity.