A case-control study of visual, auditory and audio-visual sensory interactions in children with autism spectrum disorder.

To assess the relative integrity of early visual and auditory processes in autism spectrum disorder (ASD), we used frequency-tagged visual and auditory stimulation and high-density electroencephalogram recordings of unimodal and dual-modality responses in a case-control design. To test for the specificity of effects on ASD, we recorded from a smaller group of children with attention-deficit hyperactivity disorder (ADHD). Horizontal 3 cycle per degree (cpd) gratings were presented at 5 Hz, and a random stream of /ba/, /da/, /ga/ syllables was presented at 6 Hz. Grating contrast response functions were measured unimodally and in the presence of a 64-dB auditory input. Auditory response functions were measured unimodally and in the presence of a 40% contrast grating. Children with ASD (n = 34) and ADHD (n = 13) showed a common lack of audio-visual interaction compared to typically developing children (n = 40) when measured at the first harmonic of the visual stimulus frequency. Both patient groups also showed depressed first harmonic responses at low contrast, but the ADHD group had consistently higher first-harmonic responses at high contrast. Children with ASD had a preferential loss of second-harmonic (transient) responses. The alteredtransient responses in ASD are likely to arise very early in the visual pathway and could thus have downstream consequences for many other visual mechanisms and processes. The alteration in audio-visual interaction could be a signature of a comorbid phenotype shared by ASD and ADHD, possibly due to alterations in attentional selection systems.

Leptomeningeal Enhancement in Pediatric Anti-Myelin Oligodendrocyte Glycoprotein Antibody Disease, Multiple Sclerosis, and Neuromyelitis Optica Spectrum Disorder.

BACKGROUND: Anti-myelin oligodendrocyte glycoprotein (MOG) antibody disease (MOGAD) is a type of acquired demyelinating disease that is distinct from multiple sclerosis (MS) and aquaporin-4 antibody neuromyelitis optica spectrum disorder (AQP4-NMOSD). Leptomeningeal enhancement (LME) has been reported in children and adults with MOGAD, and in adults with MS and AQP4-NMOSD, but less is known about LME in pediatric-onset MS (POMS) and pediatric AQP4-NMOSD. Here we compare the rates of LME in children with MOGAD, POMS, and AQP4-NMOSD. METHODS: A retrospective chart review was performed in patients with MOGAD, POMS, and AQP4-NMOSD who presented to our institution. Clinical characteristics, imaging features, and relapsing data were included. Descriptive statistics were used, including chi-square or Fischer exact test, to compare proportions. The Benjamini-Hochberg procedure was used to correct for multiple comparisons. RESULTS: A total of 42 children were included: 16 with POMS, six with AQP4-NMOSD, and 20 with MOGAD. Brain LME was only observed in the MOGAD group (six of 20 = 30%) when compared with zero (0%) POMS and AQP4-NMOSD (P = 0.012). Relapsing disease occurred in nine of 20 (45%), but LME did not associate with relapse. CONCLUSIONS: LME is only observed in pediatric MOGAD and not in POMS or pediatric AQP4-NMOSD. LME did not predict relapses in MOGAD. Further work is needed to determine the clinical significance of LME in pediatric MOGAD.

Across Dimensions: Developing 2D and 3D Human iPSC-Based Models of Fragile X Syndrome.

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and autism spectrum disorder. FXS is caused by a cytosine-guanine-guanine (CGG) trinucleotide repeat expansion in the untranslated region of the FMR1 gene leading to the functional loss of the gene's protein product FMRP. Various animal models of FXS have provided substantial knowledge about the disorder. However, critical limitations exist in replicating the pathophysiological mechanisms. Human induced pluripotent stem cells (hiPSCs) provide a unique means of studying the features and processes of both normal and abnormal human neurodevelopment in large sample quantities in a controlled setting. Human iPSC-based models of FXS have offered a better understanding of FXS pathophysiology specific to humans. This review summarizes studies that have used hiPSC-based two-dimensional cellular models of FXS to reproduce the pathology, examine altered gene expression and translation, determine the functions and targets of FMRP, characterize the neurodevelopmental phenotypes and electrophysiological features, and, finally, to reactivate FMR1. We also provide an overview of the most recent studies using three-dimensional human brain organoids of FXS and end with a discussion of current limitations and future directions for FXS research using hiPSCs.

Functional Connectivity of the Brain Across Rodents and Humans.

Resting-state functional magnetic resonance imaging (rs-fMRI), which measures the spontaneous fluctuations in the blood oxygen level-dependent (BOLD) signal, is increasingly utilized for the investigation of the brain's physiological and pathological functional activity. Rodents, as a typical animal model in neuroscience, play an important role in the studies that examine the neuronal processes that underpin the spontaneous fluctuations in the BOLD signal and the functional connectivity that results. Translating this knowledge from rodents to humans requires a basic knowledge of the similarities and differences across species in terms of both the BOLD signal fluctuations and the resulting functional connectivity. This review begins by examining similarities and differences in anatomical features, acquisition parameters, and preprocessing techniques, as factors that contribute to functional connectivity. Homologous functional networks are compared across species, and aspects of the BOLD fluctuations such as the topography of the global signal and the relationship between structural and functional connectivity are examined. Time-varying features of functional connectivity, obtained by sliding windowed approaches, quasi-periodic patterns, and coactivation patterns, are compared across species. Applications demonstrating the use of rs-fMRI as a translational tool for cross-species analysis are discussed, with an emphasis on neurological and psychiatric disorders. Finally, open questions are presented to encapsulate the future direction of the field.