Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects one in 66 children in Canada. The contributions of changes in the cortex and cerebellum to autism have been studied for decades. However, our understanding of brainstem contributions has only started to emerge more recently. Disruptions of sensory processing, startle response, sensory filtering, sensorimotor gating, multisensory integration and sleep are all features of ASD and are processes in which the brainstem is involved. In addition, preliminary research into brainstem contribution emphasizes the importance of the developmental timeline rather than just the mature brainstem. Therefore, the purpose of this systematic review is to compile histological, behavioral, neuroimaging, and electrophysiological evidence from human and animal studies about brainstem contributions and their functional implications in autism. Moreover, due to the developmental nature of autism, the review pays attention to the atypical brainstem development and compares findings based on age. Overall, there is evidence of an important role of brainstem disruptions in ASD, but there is still the need to examine the brainstem across the life span, from infancy to adulthood which could lead the way for early diagnosis and possibly treatment of ASD..
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by repetitive behaviors, poor social skills, and difficulties with communication. Beyond these core signs and symptoms, the majority of subjects with ASD have some degree of auditory and vestibular dysfunction. Dysfunction in these sensory modalities is significant as normal cognitive development depends on an accurate representation of our environment. The hearing difficulties in ASD range from deafness to hypersensitivity and subjects with ASD have abnormal sound-evoked brainstem reflexes and brainstem auditory evoked potentials. Vestibular dysfunction in ASD includes postural instability, gait dysfunction, and impaired gaze. Untreated vestibular dysfunction in children can lead to delayed milestones such as sitting and walking and poor motor coordination later in life. Histopathological studies have revealed that subjects with ASD have significantly fewer neurons in the auditory hindbrain and surviving neurons are smaller and dysmorphic. These findings are consistent with auditory dysfunction. Further, the cerebellum was one of the first brain structures implicated in ASD and studies have revealed loss of Purkinje cells and the presence of ectopic neurons. Together, these studies suggest that normal auditory and vestibular function play major roles in the development of language and social abilities, and dysfunction in these systems may contribute to the core symptoms of ASD. Further, auditory and vestibular dysfunction in children may be overlooked or attributed to other neurodevelopmental disorders. Herein we review the literature on auditory and vestibular dysfunction in ASD. Based on these results we developed a brainstem model of central auditory and vestibular dysfunction in ASD and propose that simple, non-invasive but quantitative testing of hearing and vestibular function be added to newborn screening protocols.
The proper formation of axonal and dendritic morphologies is crucial for the precise wiring of the nervous system that ultimately leads to the generation of complex functions in an organism. The Semaphorin3A-Neuropilin1/Plexin-A4 signaling pathway has been shown to have multiple key roles in neurodevelopment, from axon repulsion to dendrite elaboration. This study demonstrates that three specific amino acids, the KRK motif within the Plexin-A4 receptor cytoplasmic domain, are required to coordinate the downstream signaling molecules to promote Sema3A-mediated cortical neuron dendritic elaboration, but not inhibitory axon guidance. Our results unravel a novel Semaphorin3A-Plexin-A4 downstream signaling pathway and shed light on how the disparate functions of axon guidance and dendritic morphogenesis are accomplished by the same extracellular ligand in vivo.
The data from digitized social interactions can take us beyond the limits of the naked eye and help us capture the autistic capacity for social readiness. Using personalized analytics, we can track the person’s dynamics with biosensors that continuously co-register the micro-movements derived from their biorhythms. More important yet, we can track the spontaneously self-emerging cohesiveness of their social rapport and better inform our decisions on whether and when the socio-motor patterns of autistic people unexpectedly match those of neurotypical controls performing the same social task. Our new unifying statistical methods help us bridge the enormous social gap that current diagnostics, missing this information, have created between autistic and neurotypical people.
Understanding the limits and faulty assumptions in the ADOS will help us better understand ASD and will help us better characterize neurodevelopmental trajectories.
Using big data approaches will help us understand and model heterogeneity in the autism population, which is important for precision medicine and personalized support.
Dysregulation in critical developmental networks identified in autism specific neurons derived from induced pluripotent stem cells (iPSCs).
Abnormal RNA editing identified in post-mortem brains samples from individuals with autism.
A complete protocol for analysis of data acquired from RNA and genome sequencing experiments.
Abnormal dendritic spines from iPSCs derived pyramidal neurons from ASD patients.
The ventral tegmental area, a region involved in reward and social behavior, is linked directly to the cerebellum, a structure implicated in autism.
Multiple genetic variants contribute to a more severe autism phenotype.
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We are funded in part by the New Jersey Governor’s Council for the Medical Research and Treatments of Autism and by the NJ DOH.
Younger siblings of children with ASD are known to be at higher risk for developing language delays. The Infancy Studies Lab at Rutgers University-Newark has created an engaging interactive acoustic experience with the aim of helping baby siblings of children with ASD develop better pre-language skills known to be important for optimal and efficient language acquisition. Watch this short video to learn more about how to participate in this exciting, innovative research study.
