Reduced neurite density index in the prefrontal cortex of adults with autism assessed using neurite orientation dispersion and density imaging

Abstract

BackgroundCore symptoms of autism-spectrum disorder (ASD) have been associated with prefrontal cortex abnormalities. However, the mechanisms behind the observation remain incomplete, partially due to the challenges of modeling complex gray matter (GM) structures. This study aimed to identify GM microstructural alterations in adults with ASD using neurite orientation dispersion and density imaging (NODDI) and voxel-wise GM-based spatial statistics (GBSS) to reduce the partial volume effects from the white matter and cerebrospinal fluid.Materials and methodsA total of 48 right-handed participants were included, of which 22 had ASD (17 men; mean age, 34.42 ± 8.27 years) and 26 were typically developing (TD) individuals (14 men; mean age, 32.57 ± 9.62 years). The metrics of NODDI (neurite density index [NDI], orientation dispersion index [ODI], and isotropic volume fraction [ISOVF]) were compared between groups using GBSS. Diffusion tensor imaging (DTI) metrics and surface-based cortical thickness were also compared. The associations between magnetic resonance imaging-based measures and ASD-related scores, including ASD-spectrum quotient, empathizing quotient, and systemizing quotient were also assessed in the region of interest (ROI) analysis.ResultsAfter controlling for age, sex, and intracranial volume, GBSS demonstrated significantly lower NDI in the ASD group than in the TD group in the left prefrontal cortex (caudal middle frontal, lateral orbitofrontal, pars orbitalis, pars triangularis, rostral middle frontal, and superior frontal region). In the ROI analysis of individuals with ASD, a significantly positive correlation was observed between the NDI in the left rostral middle frontal, superior frontal, and left frontal pole and empathizing quotient score. No significant between-group differences were observed in all DTI metrics, other NODDI (i.e., ODI and ISOVF) metrics, and cortical thickness.ConclusionGBSS analysis was used to demonstrate the ability of NODDI metrics to detect GM microstructural alterations in adults with ASD, while no changes were detected using DTI and cortical thickness evaluation. Specifically, we observed a reduced neurite density index in the left prefrontal cortices associated with reduced empathic abilities.

Polygenic scores for autism are associated with neurite density in adults and children from the general population

“…Although Mendelian Randomisation did not identify a causal relationship, this could be due to the reduced statistical power of the instruments used. This association between autism and reduced neurite density is supported by previous case-control imaging studies [63][64][65] and mice studies focusing on autism-associated genes [66,67]. These findings are paralleled by early postmortem brain studies in autism, which have identified cortical disorganisation [68] and reduced mini-columns in autism [69].…”

The prenatal use of agmatine prevents social behavior deficits in VPA‐exposed mice by activating the ERK/CREB/BDNF signaling pathway

“…In our research, we have only explored the potential protective role of the prefrontal cortex in ASD. Although the core symptoms of ASD are highly associated with abnormalities in the prefrontal cortex (Arai et al, 2023), there might be other protective mechanisms in different brain areas that require further exploration in the future. Therefore, further research is required in later stages.…”

Arousal dysregulation and executive dysfunction in attention deficit hyperactivity disorder (ADHD)

“…Brain imaging techniques have been largely applied to the study of ADHD, where magnetic resonance imaging studies have revealed smaller global brain volumes in ADHD subjects, particularly children ( 48 , 49 ). Moreover, neuroimaging literature on ADHD is inconclusive with small effect sizes unable to inform clinical practice ( 50 ) as these differences are not specific to ADHD, where neuroimaging studies on other developmental disorders, such as autism, have also shown similar differences in brain volume ( 51 , 52 ) when compared to controls.…”