Brainstem as a developmental gateway to social attention

Geva, Ronny; Dital, Ayelet; Ramon, Dan; Yarmolovsky, Jessica; Gidron, Maor; Kuint, Jacob

doi:10.1111/jcpp.12746

Cited by 21 publications

(25 citation statements)

References 62 publications

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“…The link between social function and brainstem neurocircuitry is further supported by the recent findings in both typically developing children and children with ASD. For example, typically developing pre-term neonates who had abnormal ABRs also exhibited deficits in social engagement ( Geva et al, 2013 ), which then developed into impaired social attention at 7–8 years of age ( Geva et al, 2017 ). Concurrently, abnormal ABR of the pre-term neonates who later were diagnosed with ASD predicted the severity of the core autism symptoms such as social and linguistic competence ( Cohen et al, 2013 ).…”

Section: Human Evidence For Brainstem Contributions To Asdmentioning

confidence: 99%

Evidence for Brainstem Contributions to Autism Spectrum Disorders

Dadalko

Travers

2018

Front. Integr. Neurosci.

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Autism spectrum disorder (ASD) is a neurodevelopmental condition that affects one in 59 children in the United States. Although there is a mounting body of knowledge of cortical and cerebellar contributions to ASD, our knowledge about the early developing brainstem in ASD is only beginning to accumulate. Understanding how brainstem neurotransmission is implicated in ASD is important because many of this condition’s sensory and motor symptoms are consistent with brainstem pathology. Therefore, the purpose of this review was to integrate epidemiological, behavioral, histological, neuroimaging, and animal evidence of brainstem contributions to ASD. Because ASD is a neurodevelopmental condition, we examined the available data through a lens of hierarchical brain development. The review of the literature suggests that developmental alterations of the brainstem could have potential cascading effects on cortical and cerebellar formation, ultimately leading to ASD symptoms. This view is supported by human epidemiology findings and data from animal models of ASD, showing that perturbed development of the brainstem substructures, particularly during the peak formation of the brainstem’s monoaminergic centers, may relate to ASD or ASD-like behaviors. Furthermore, we review evidence from human histology, psychophysiology, and neuroimaging suggesting that brainstem development and maturation may be atypical in ASD and may be related to key ASD symptoms, such as atypical sensorimotor features and social responsiveness. From this review there emerges the need of future research to validate early detection of the brainstem-based somatosensory and psychophysiological behaviors that emerge in infancy, and to examine the brainstem across the life span, while accounting for age. In all, there is preliminary evidence for brainstem involvement in ASD, but a better understanding of the brainstem’s role would likely pave the way for earlier diagnosis and treatment of ASD.

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Section: Human Evidence For Brainstem Contributions To Asdmentioning

confidence: 99%

Evidence for Brainstem Contributions to Autism Spectrum Disorders

Dadalko

Travers

2018

Front. Integr. Neurosci.

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“…It also plays a pivotal role in sensory information processing, in eliciting goal-oriented behavior, in the regulation of social attention, and in the modulation of emotions (Berntson & Micco, 1976;Geva et al, 2017;Venkatraman, Edlow, & Immordino-Yang, 2017). Structural MRI studies of ASD individuals have demonstrated the potential role of the brainstem in the pathophysiology of ASD (Gaffney, Kuperman, Tsai, & Minchin, 1988) (Jou et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Brainstem enlargement in preschool children with autism: Results from an intermethod agreement study of segmentation algorithms

Bosco

Giuliano

Delafield‐Butt

et al. 2018

Human Brain Mapping

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The intermethod agreement between automated algorithms for brainstem segmentation is investigated, focusing on the potential involvement of this structure in Autism Spectrum Disorders (ASD). Inconsistencies highlighted in previous studies on brainstem in the population with ASD may in part be a result of poor agreement in the extraction of structural features between different methods. A sample of 76 children with ASD and 76 age-, gender-, and intelligence-matched controls was considered. Volumetric analyses were performed using common tools for brain structures segmentation, namely FSL-FIRST, FreeSurfer (FS), and Advanced Normalization Tools (ANTs). For shape analysis SPHARM-MAT was employed. Intermethod agreement was quantified in terms of Pearson correlations between pairs of volumes obtained by the different methods. The degree of overlap between segmented masks was quantified in terms of the Dice index. Both Pearson correlations and Dice indices, showed poor agreement between FSL-FIRST and the other methods (ANTs and FS), which by contrast, yielded Pearson correlations greater than 0.93 and average Dice indices greater than 0.76 when compared with each other. As with volume, shape analyses exhibited discrepancies between segmentation methods, with particular differences noted between FSL-FIRST and the others (ANT and FS), with under- and over-segmentation in specific brainstem regions. These data suggest that research on brain structure alterations should cross-validate findings across multiple methods. We consistently detected an enlargement of brainstem volume in the whole sample and in the male cohort across multiple segmentation methods, a feature particularly driven by the subgroup of children with idiopathic intellectual disability associated with ASD.

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“…No one has demonstrated essential and consistent evidence of indicators for onset of ASD mainly due to heterogeneity of ASD diagnosis and the possibility of the developing trajectory of the brain and compensatory structural changes [23][24][25]. Some researchers have reported brainstem dysfunction in children with ASD by administrating auditory brainstem evoked responses or by the polyvagal theory [26][27][28].…”

Section: Discussionmentioning

confidence: 99%

Primitive Reflexes in Very Low Birth Weight Infants Later Diagnosed with Autism Spectrum Disorder

Nagai

Nomura

Uemura

2019

Preprint

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Background: As early screening and diagnosis is very important in treatment of Autism Spectrum Disorder, we investigated the relationship between primitive reflexes and Autism Spectrum Disorder (ASD). Methods: Of 88 very low birth weight infants born from April 2010 to March 2012, subjects comprised 38 examined for 18 primitive reflexes between age 38 and 45 wks corrected age and followed-up over 6 yrs. ASD was diagnosed using Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5) and Autism Diagnostic Observation Schedule Second Edition (ADOS-2). We compared the number of abnormal primitive reflexes between two groups (11 children with and 19 without ASD) after excluding eight children with cerebral palsy in this case-control study. Results: The number of abnormal primitive reflexes differed significantly between groups, with hypoactive reflexes markedly higher in the ASD group (p=0.001). Conclusion: The result suggests primitive reflexes can be one of the key elements to identify ASD in low birth weight infants. Abnormal primitive reflexes of low birth weight infants with ASD in very early infancy may inform future research of the pathogenesis of ASD.

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Brainstem as a developmental gateway to social attention

Cited by 21 publications

References 62 publications

Evidence for Brainstem Contributions to Autism Spectrum Disorders

Evidence for Brainstem Contributions to Autism Spectrum Disorders

Brainstem enlargement in preschool children with autism: Results from an intermethod agreement study of segmentation algorithms

Primitive Reflexes in Very Low Birth Weight Infants Later Diagnosed with Autism Spectrum Disorder

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