Brainstem morphometric differences in children with autism spectrum disorder, developmental coordination disorder, and those typically developing

Bosco, Paolo and Harrison, Laura and Retico, Alessandra and Butera, Christiana and Calderoni, Sara and Muratori, Filippo and Aziz-Zadeh, Lisa and Delafield-Butt, Jonathan (2021) Brainstem morphometric differences in children with autism spectrum disorder, developmental coordination disorder, and those typically developing. In: International Society for Autism Research Virtual Annual Meeting 2021, 2021-05-03 - 2021-05-07, Online.

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Background: The brainstem is a neglected topic in autism research, despite major lines of evidence indicating its active involvement in sensory, motor, affect, arousal, and social regulation (Dadalko & Travers, 2018). It is the substrate of what affective neuroscience identifies as the ‘Core Self’ (Alcaro, Carta, & Panksepp, 2017), and disruption to its growth and function appears to disturb core conscious experience in autism (Delafield-Butt & Trevarthen, 2017; Trevarthen & Delafield-Butt, 2013). Yet, although evidence indicates brainstem growth is disrupted in early childhood (Bosco et al., 2018), how these growth differences compare to closely related neurodevelopmental disorders, such a Developmental Coordination Disorder (DCD), is not yet understood. Objectives: To determine brainstem morphometric differences between children with ASD, DCD, and those typically developing (TD). Methods: Study participants were 87 youths ages 8 to 17 assigned to the ASD (n = 30, 7 female), DCD (n =24, 12 female) or TD (n = 33, 12 female) group. Exclusion criteria for all groups included IQ <80. TD were excluded if they had any neuropsychological or psychopathological disorder. DCD eligibility additionally included performance 16th percentile on the MABC-2 and no concern about an ASD diagnosis. ASD participants had a previous clinical diagnosis confirmed by ADOS-2 and ADI-R. Individuals were excluded if they had another neuropsychological disorder, except attention deficit or anxiety disorder. T1-weighted MPRAGE (1mm isotropic resolution) MRI data were acquired on a 3T MAGNETOM Prisma (Siemens). Brainstem morphology was analysed using SPHARM-MAT (, a 3D Fourier surface representation method¬¬¬. A typical surface was calculated for the TD group, and distances from this norm computed for each vertex. Mean distances at each vertex were computed for each group (ASD, DCD, TD) and compared, taking into account age, gender and supratentorial volume as covariates. Results: Significant brainstem morphological differences were identified between all three (TD, ASD and DCD; Figure 1). Significant differences between TD and ASD (p<0.01) were identified in a large region of the anterior-most surface, extending caudally along the right posterior surface. Differences between TD and DCD groups were similar with reduced significance (p0.01), and the pattern diverged with more inclusion of the anterior ventricular surface and less pronouncement at the right anterior border. Finally, significant differences were found between ASD and DCD groups (p<0.01), specifically at the anterior midline either side of the ventricular surface, and especially in two long anteroposterior columns on the left side adjacent and parallel to the fourth ventricle. Conclusions: Surface morphology differences indicate alterations in local nuclei and/or tract growth within the brainstem, especially approaching the anterior surface in ASD and DCD children, and differentially between them at the ventricular surface. The former may relate to specific nerve growth of the pons, and the latter to cerebellar peduncle connectivity differences, superficial nuclei growth such as the hypoglossal, intercalatus, or vagus and associated tracts, or deeper nuclei such as the inferior olivary nucleus. Brainstem structural differences likely disturbs the integrative function of the Core Self. Higher resolution 7T MRI is required to resolve the underlying differential composition.