Vestibular Functioning in Children with Neurodevelopmental Disorders Using the Functional Head Impulse Test.

Several studies in children with neurodevelopmental disorders (NDDs) including autism spectrum disorders (ASDs), reading impairment, or attention deficit/hyperactive disorder (ADHD) pointed toward a potential dysfunction of the vestibular system, specifically in its complex relationship with the cerebellum. The aim of the present study was to test the functional vestibulo-ocular reflex (VOR) responses in children with NDDs to measure functional performance of the vestibular system. The VOR is specifically involved in this stabilization of the image on the retina during rapid movements of the head. To perform this study, four groups of children with ASD, ADHD, reading impairment, and with neurotypical development (TD) were enrolled (n = 80). We performed the functional head impulse test (fHIT), which measured the percentage of correct responses by asking the child to identify an optotype briefly presented during passive head impulse in each direction of each semicircular canal plane. We observed significantly lower correct answers in children with NDDs compared with those with TD (p < 0.0001). Surprisingly, there was no significant difference between the three groups of children with NDDs. Our study fostered preliminary evidence suggesting altered efficiency of vestibular system in children with NDDs. VOR abnormalities estimated using the fHIT could be used as a proxy of NDD impairments in children, and represent a potential biomarker.

Functional network dynamics in a neurodevelopmental disorder of known genetic origin.

Dynamic connectivity in functional brain networks is a fundamental aspect of cognitive development, but we have little understanding of the mechanisms driving variability in these networks. Genes are likely to influence the emergence of fast network connectivity via their regulation of neuronal processes, but novel methods to capture these rapid dynamics have rarely been used in genetic populations. The current study redressed this by investigating brain network dynamics in a neurodevelopmental disorder of known genetic origin, by comparing individuals with a ZDHHC9-associated intellectual disability to individuals with no known impairment. We characterised transient network dynamics using a Hidden Markov Model (HMM) on magnetoencephalography (MEG) data, at rest and during auditory oddball stimulation. The HMM is a data-driven method that captures rapid patterns of coordinated brain activity recurring over time. Resting-state network dynamics distinguished the groups, with ZDHHC9 participants showing longer state activation and, crucially, ZDHHC9 gene expression levels predicted the group differences in dynamic connectivity across networks. In contrast, network dynamics during auditory oddball stimulation did not show this association. We demonstrate a link between regional gene expression and brain network dynamics, and present the new application of a powerful method for understanding the neural mechanisms linking genetic variation to cognitive difficulties.

Tracing the structural origins of atypical language representation: consequences of prenatal mirror-imaged brain asymmetries in a dizygotic twin couple.

We investigated the predictive value of prenatal superior temporal sulcus (STS) depth asymmetry in a special case of a female dizygotic twin that showed inverted prenatal asymmetry of this structure. For this purpose, we performed a follow-up investigation in this former fetus at the age of seven, where we assessed the functional language lateralization using task-based and resting-state functional magnetic resonance imaging (fMRI). As control group we employed her twin brother, who showed a typical folding pattern prenatally, as well as a complementary set of four age-matched children that had fetal MRI of their brains and typical STS depth asymmetry. We could show that the twin with the atypical fetal asymmetry of the STS also showed significantly differing rightward language lateralization in the frontal and temporal lobes. Additionally, resting-state data suggest a stronger connectivity between inferior frontal gyri in this case. The twin showed normal cognitive development. This result gives a first glimpse into the STS' atypical asymmetry being a very early morphological marker for later language lateralization.

Global and Local Connectivity Differences Converge With Gene Expression in a Neurodevelopmental Disorder of Known Genetic Origin.

Knowledge of genetic cause in neurodevelopmental disorders can highlight molecular and cellular processes critical for typical development. Furthermore, the relative homogeneity of neurodevelopmental disorders of known genetic origin allows the researcher to establish the subsequent neurobiological processes that mediate cognitive and behavioral outcomes. The current study investigated white matter structural connectivity in a group of individuals with intellectual disability due to mutations in ZDHHC9. In addition to shared cause of cognitive impairment, these individuals have a shared cognitive profile, involving oromotor control difficulties and expressive language impairment. Analysis of structural network properties using graph theory measures showed global reductions in mean clustering coefficient and efficiency in the ZDHHC9 group, with maximal differences in frontal and parietal areas. Regional variation in clustering coefficient across cortical regions in ZDHHC9 mutation cases was significantly associated with known pattern of expression of ZDHHC9 in the normal adult human brain. The results demonstrate that a mutation in a single gene impacts upon white matter organization across the whole-brain, but also shows regionally specific effects, according to variation in gene expression. Furthermore, these regionally specific patterns may link to specific developmental mechanisms, and correspond to specific cognitive deficits.