The Brainstem-Informed Autism Framework: Early Life Neurobehavioral Markers

Burstein, Or; Geva, Ronny

doi:10.3389/fnint.2021.759614

Cited by 18 publications

(23 citation statements)

References 131 publications

(169 reference statements)

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“…Basic neurological functions such as abnormalities in autonomic processing (Hirstein et al, 2001 ; Eilam-Stock et al, 2014 ) and circadian dysfunctions (Lorsung et al, 2021 ) are frequently found in ASD individuals, and these have also been pointed to as responsible for disruptions of emotional/social development. The cluster of abnormalities in autonomic/arousal regulation, sleep-wake homeostasis, and sensorimotor integration during the first months of life, reflect brainstem involvement and have been proposed as a very early risk factor for ASD (Burstein and Geva, 2021 ).…”

Section: Autism Theoriesmentioning

confidence: 99%

The “Primitive Brain Dysfunction” Theory of Autism: The Superior Colliculus Role

Jure

2022

Front. Integr. Neurosci.

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A better understanding of the pathogenesis of autism will help clarify our conception of the complexity of normal brain development. The crucial deficit may lie in the postnatal changes that vision produces in the brainstem nuclei during early life. The superior colliculus is the primary brainstem visual center. Although difficult to examine in humans with present techniques, it is known to support behaviors essential for every vertebrate to survive, such as the ability to pay attention to relevant stimuli and to produce automatic motor responses based on sensory input. From birth to death, it acts as a brain sentinel that influences basic aspects of our behavior. It is the main brainstem hub that lies between the environment and the rest of the higher neural system, making continuous, implicit decisions about where to direct our attention. The conserved cortex-like organization of the superior colliculus in all vertebrates allows the early appearance of primitive emotionally-related behaviors essential for survival. It contains first-line specialized neurons enabling the detection and tracking of faces and movements from birth. During development, it also sends the appropriate impulses to help shape brain areas necessary for social-communicative abilities. These abilities require the analysis of numerous variables, such as the simultaneous evaluation of incoming information sustained by separate brain networks (visual, auditory and sensory-motor, social, emotional, etc.), and predictive capabilities which compare present events to previous experiences and possible responses. These critical aspects of decision-making allow us to evaluate the impact that our response or behavior may provoke in others. The purpose of this review is to show that several enigmas about the complexity of autism might be explained by disruptions of collicular and brainstem functions. The results of two separate lines of investigation: 1. the cognitive, etiologic, and pathogenic aspects of autism on one hand, and two. the functional anatomy of the colliculus on the other, are considered in order to bridge the gap between basic brain science and clinical studies and to promote future research in this unexplored area.

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Section: Autism Theoriesmentioning

confidence: 99%

The “Primitive Brain Dysfunction” Theory of Autism: The Superior Colliculus Role

Jure

2022

Front. Integr. Neurosci.

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“…Ablation studies have shown that while the cortex allows for discrimination of sensory inputs, the SC is necessary to initiate movements toward these events 13 . Recently, this subcortical area has been implicated in influencing social behaviors and has been purported to lead to neurodevelopmental disorders such as Autism Spectrum Disorder (ASD) [14][15][16][17] . Although many studies have shed light on SC function, its microcircuitry and formation continue to be poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Valproic Acid Affects Neuronal Specification and Differentiation During Early Optic Tectum Development of Zebrafish

Dixon

Calder

Lilya

et al. 2022

Preprint

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The mammalian superior colliculus and its non-mammalian homolog, the optic tectum (OT), are midbrain structures that integrate multimodal sensory inputs and guide non-voluntary movements in response to prevalent stimuli. Recent studies have implicated this structure as a possible site affected in Autism Spectrum Disorder (ASD). Interestingly, fetal exposure to valproic acid (VPA) has also been associated with an increased risk of ASD in humans and animal models. Therefore, we took the approach of determining the effects of VPA treatment on zebrafish OT development as a first step in identifying the mechanisms that allow its formation. We describe the normal OT development during the first 5 days of development and show that in VPA treated embryos, while proliferation of the OT neuroepithelium continued, neuronal specification stalled. This was followed by impairment of neurite extension and complexity, suggesting that in addition to neurogenesis, VPA treatment affects axonogenesis and dendritogenesis. VPA treatment was most detrimental during the first three days of development and did not appear to be linked to oxidative stress. In conclusion, our work provides a foundation for research into mechanisms driving OT development, as well as the relationship between the OT, VPA, and ASD.

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“…BAEP typically manifests as five major peaks; peaks I and II originate from the auditory vestibular nerve, while peaks III‐V reflect responses from deeper structures including the cochlear nucleus (peak III), superior olive (peak IV) and lateral and inferior colliculus (Crest V; Wilkinson & Jiang, 2006). Brainstem auditory pathways are functionally and structurally altered in patients with ASD (Burstein & Geva, 2021). Delayed V waves are associated with an increased risk of diagnosing ASD (Cohen et al, 2013; Miron et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Exploring brainstem auditory evoked potentials and mental development index as early indicators of autism spectrum disorders in high‐risk infants

Wang¹,

Carroll

Zhang³

et al. 2022

Autism Research

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This study of infants from Hubei Province, China examined brainstem auditory evoked potentials (BAEP) and mental development index (MDI) as possible early indicators associated with autism spectrum disorders (ASD). The 34 ASD cases and 102 controls who had recovered from perinatal conditions were matched for age, sex, gestational age, birth weight and maternal age. BAEP absolute latencies (AL) I, III, V and interpeak latencies (IPL) I-III, III-V, I-V were compared in ASD cases and controls at ages 1, 3 and 6 months. MDI scores were compared in these infants from 1 month to 2 years old. Multiple logistic regression analysis was performed to test associations among ASD, BAEP and MDI. Results showed BAEP AL I, V and IPL III-V prolonged in the ASD group (p < 0.001), and MDI scores in ASD cases sharply declining from 12 to 24 months (p < 0.001). Regression analysis revealed odds ratios (OR) indicating that ASD was likely associated with abnormal values of BAEP AL I at 1 and 3 months

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The Brainstem-Informed Autism Framework: Early Life Neurobehavioral Markers

Cited by 18 publications

References 131 publications

The “Primitive Brain Dysfunction” Theory of Autism: The Superior Colliculus Role

The “Primitive Brain Dysfunction” Theory of Autism: The Superior Colliculus Role

Valproic Acid Affects Neuronal Specification and Differentiation During Early Optic Tectum Development of Zebrafish

Exploring brainstem auditory evoked potentials and mental development index as early indicators of autism spectrum disorders in high‐risk infants

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