Investigating the development of the autonomic nervous system in infancy through pupillometry

Vries, Lyssa de; Amelynck, Steffie; Nyström, Pär; Esch, Lotte van; Lierde, Thijs Van; Warreyn, Petra; Roeyers, Herbert; Noens, Ilse; Naulaers, Gunnar; Boets, Bart; Steyaert, Jean; Moerman, Floor; Erdogan, Maide; Mađarević, Melinda; Segers, Julie

doi:10.1007/s00702-023-02616-7

Cited by 3 publications

(4 citation statements)

References 47 publications

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“…Additionally, prospective, longitudinal studies of infants at elevated likelihood for autism have also yielded potential biomarkers. These include less efficient nonsocial attentional disengagement, 33 , 34 , 35 amplitude and latency differences of the pupillary light reflex (PLR), 36 , 37 larger tonic baseline 38 , 39 or resting 40 pupil diameter, and differences in basic oculomotor measures, such as fixation duration 41 and saccade amplitude. 42 Although these are almost exclusively laboratory-based studies with effect sizes that suggest limited diagnostic utility, 43 these results indicate that multiple eye-tracking indices may be combined to increase discriminative power 44 and have promise for identifying autism in toddlers and young children.…”

Section: Introductionmentioning

confidence: 99%

Eye-Tracking Biomarkers and Autism Diagnosis in Primary Care

Keehn,

Monahan,

Enneking

et al. 2024

JAMA Netw Open

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ImportanceFinding effective and scalable solutions to address diagnostic delays and disparities in autism is a public health imperative. Approaches that integrate eye-tracking biomarkers into tiered community-based models of autism evaluation hold promise for addressing this problem.ObjectiveTo determine whether a battery of eye-tracking biomarkers can reliably differentiate young children with and without autism in a community-referred sample collected during clinical evaluation in the primary care setting and to evaluate whether combining eye-tracking biomarkers with primary care practitioner (PCP) diagnosis and diagnostic certainty is associated with diagnostic outcome.Design, Setting, and ParticipantsEarly Autism Evaluation (EAE) Hub system PCPs referred a consecutive sample of children to this prospective diagnostic study for blinded eye-tracking index test and follow-up expert evaluation from June 7, 2019, to September 23, 2022. Participants included 146 children (aged 14-48 months) consecutively referred by 7 EAE Hubs. Of 154 children enrolled, 146 provided usable data for at least 1 eye-tracking measure.Main Outcomes and MeasuresThe primary outcomes were sensitivity and specificity of a composite eye-tracking (ie, index) test, which was a consolidated measure based on significant eye-tracking indices, compared with reference standard expert clinical autism diagnosis. Secondary outcome measures were sensitivity and specificity of an integrated approach using an index test and PCP diagnosis and certainty.ResultsAmong 146 children (mean [SD] age, 2.6 [0.6] years; 104 [71%] male; 21 [14%] Hispanic or Latine and 96 [66%] non-Latine White; 102 [70%] with a reference standard autism diagnosis), 113 (77%) had concordant autism outcomes between the index (composite biomarker) and reference outcomes, with 77.5% sensitivity (95% CI, 68.4%-84.5%) and 77.3% specificity (95% CI, 63.0%-87.2%). When index diagnosis was based on the combination of a composite biomarker, PCP diagnosis, and diagnostic certainty, outcomes were concordant with reference standard for 114 of 127 cases (90%) with a sensitivity of 90.7% (95% CI, 83.3%-95.0%) and a specificity of 86.7% (95% CI, 70.3%-94.7%).Conclusions and RelevanceIn this prospective diagnostic study, a composite eye-tracking biomarker was associated with a best-estimate clinical diagnosis of autism, and an integrated diagnostic model including PCP diagnosis and diagnostic certainty demonstrated improved sensitivity and specificity. These findings suggest that equipping PCPs with a multimethod diagnostic approach has the potential to substantially improve access to timely, accurate diagnosis in local communities.

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Section: Introductionmentioning

confidence: 99%

Eye-Tracking Biomarkers and Autism Diagnosis in Primary Care

Keehn,

Monahan,

Enneking

et al. 2024

JAMA Netw Open

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“…Two common simple methods for assessing vegetative balance are based on the pupillary and orthostatic reflexes. Pupillometry involves measuring the diameter of the pupils using a pupillometer and observing changes in pupil size when exposed to light [13][14][15]. Since the degree of pupil constriction depends on parasympathetic tone, while dilation depends on sympathetic tone, changes in pupil width reflect the balance of autonomic regulation.…”

Section: Introductionmentioning

confidence: 99%

“…This method is particularly useful for examining newborns: in full-term infants, it indicates the state of vegetative balance, and asymmetric reactions may suggest possible traumatic cerebral problems [16]. In preterm infants during the perinatal and postnatal periods, it assesses the degree of development of the autonomic nervous system since there are specific timeframes, a «critical window,» for the atypical formation of the autonomic regulation system [13]. According to Ishikawa M., pupillometry also correlates well with heart rate variability in infants [17].…”

Section: Introductionmentioning

confidence: 99%

Comparative Characteristics of Autonomic Imbalance Diagnostic Methods in School-Age Children

Buriak,

Nechytailo

2023

Clin. and prev. med.

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Introduction. An imbalance in the autonomic nervous system regulation, known as dysautonomia, is one of the most common clinical syndromes that accompany several diseases. The balance between sympathetic and parasympathetic influences on the body can rapidly change during dynamic processes, especially in cases of infectious and acute diseases, where autonomic regulation plays an active role in shaping the immune response. In children with respiratory diseases, the influence of the vagus nerve (n.vagus) on the frequency and depth of breathing is also important but remains relatively understudied. Assessment of vegetative balance in pediatrics is carried out using various methods depending on the child's age and condition, with commonly used approaches including questionnaires, calculation of the Kerdo autonomic index, and orthostatic testing. The aim. To compare the diagnostic capabilities of different methods for assessment of the autonomic nervous system state in school-age children on the model of acute bronchitis. Materials and methods. The paper presents data from a study that assessed the state of the autonomic nervous system in 52 school-age children (12-16 years old) divided into two groups: 30 children with acute bronchitis in the convalescent period and 22 clinically healthy individuals. Three different methods were used: the A.M. Wayne scale, the Kerdo index, and the orthostatic test. Results. The survey based on Wayne's questionnaire did not reveal a significant difference between the groups of healthy children and those affected by bronchitis. Dynamic tests proved to be more suitable for assessing acute pathology, such as Kerdo's autonomic index and the orthostatic test. The autonomic Kerdo index in children with bronchitis was significantly higher (14.2±2.38 points) than in healthy children (6.4±3.18 points, p<0.05). In children with acute bronchitis, dysautonomia with a predominance of sympathicotonia was recorded, which may be attributed to insufficient vagal innervation and a decrease in parasympathetic influence on the formation of an adequate immune response to the inflammatory process in the respiratory tract. Conclusions. Determining the autonomic Kerdo index and conducting the orthostatic test is suitable for diagnosing dysautonomia in children with acute respiratory pathology. These tests are dynamic, functionally based, and easy to perform and evaluate.

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“…Indeed, recent studies examining the heart rate variability confirmed dysregulation of the ANS in adult [207] and adolescent [208] ASD patients with reduced parasympathetic and increased sympathetic activity. The dysregulation of the ANS might lead to both hypo-and hyperarousal [209]. As social abilities are optimal when arousal is normal, when arousal increases due to misinterpretation of danger signals from the environment, social behaviors are compromised.…”

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confidence: 99%

Vasopressin as Possible Treatment Option in Autism Spectrum Disorder

László,

Vörös,

Correia

et al. 2023

Biomedicines

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Autism spectrum disorder (ASD) is rather common, presenting with prevalent early problems in social communication and accompanied by repetitive behavior. As vasopressin was implicated not only in salt-water homeostasis and stress-axis regulation, but also in social behavior, its role in the development of ASD might be suggested. In this review, we summarized a wide range of problems associated with ASD to which vasopressin might contribute, from social skills to communication, motor function problems, autonomous nervous system alterations as well as sleep disturbances, and altered sensory information processing. Beside functional connections between vasopressin and ASD, we draw attention to the anatomical background, highlighting several brain areas, including the paraventricular nucleus of the hypothalamus, medial preoptic area, lateral septum, bed nucleus of stria terminalis, amygdala, hippocampus, olfactory bulb and even the cerebellum, either producing vasopressin or containing vasopressinergic receptors (presumably V1a). Sex differences in the vasopressinergic system might underline the male prevalence of ASD. Moreover, vasopressin might contribute to the effectiveness of available off-label therapies as well as serve as a possible target for intervention. In this sense, vasopressin, but paradoxically also V1a receptor antagonist, were found to be effective in some clinical trials. We concluded that although vasopressin might be an effective candidate for ASD treatment, we might assume that only a subgroup (e.g., with stress-axis disturbances), a certain sex (most probably males) and a certain brain area (targeting by means of virus vectors) would benefit from this therapy.

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Investigating the development of the autonomic nervous system in infancy through pupillometry

Cited by 3 publications

References 47 publications

Eye-Tracking Biomarkers and Autism Diagnosis in Primary Care

Eye-Tracking Biomarkers and Autism Diagnosis in Primary Care

Comparative Characteristics of Autonomic Imbalance Diagnostic Methods in School-Age Children

Vasopressin as Possible Treatment Option in Autism Spectrum Disorder

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