Enhanced group-level dorsolateral prefrontal cortex subregion parcellation through functional connectivity-based distance-constrained spectral clustering with application to autism spectrum disorder.

The dorsolateral prefrontal cortex (DLPFC) assumes a central role in cognitive and behavioral control, emerging as a crucial target region for interventions in autism spectrum disorder neuroregulation. Consequently, we endeavor to unravel the functional subregions within the DLPFC to shed light on the intricate functions of the brain. We introduce a distance-constrained spectral clustering (SC-DW) methodology that leverages functional connection to identify distinctive functional subregions within the DLPFC. Furthermore, we verify the relationship between the functional characteristics of these subregions and their clinical implications. Our methodology begins with principal component analysis to extract the salient features. Subsequently, we construct an adjacency matrix, which is constrained by the spatial properties of the brain, by linearly combining the distance matrix and a similarity matrix. The quality of spectral clustering is further optimized through multiple cluster evaluation coefficient. The results from SC-DW revealed four uniform and contiguous subregions within the bilateral DLPFC. Notably, we observe a substantial positive correlation between the functional characteristics of the third and fourth subregions in the left DLPFC with clinical manifestations. These findings underscore the unique insights offered by our proposed methodology in the realms of brain subregion delineation and therapeutic targeting.

Sensory and motor cortices parcellations estimated via distance-weighted sparse representation with application to autism spectrum disorder.

BACKGROUND: Motor impairments and sensory processing abnormalities are prevalent in autism spectrum disorder (ASD), closely related to the core functions of the primary motor cortex (M1) and the primary somatosensory cortex (S1). Currently, there is limited knowledge about potential therapeutic targets in the subregions of M1 and S1 in ASD patients. This study aims to map clinically significant functional subregions of M1 and S1. METHODS: Resting-state functional magnetic resonance imaging data (NTD = 266) from Autism Brain Imaging Data Exchange (ABIDE) were used for subregion modeling. We proposed a distance-weighted sparse representation algorithm to construct brain functional networks. Functional subregions of M1 and S1 were identified through consensus clustering at the group level. Differences in the characteristics of functional subregions were analyzed, along with their correlation with clinical scores. RESULTS: We observed symmetrical and continuous subregion organization from dorsal to ventral aspects in M1 and S1, with M1 subregions conforming to the functional pattern of the motor homunculus. Significant intergroup differences and clinical correlations were found in the dorsal and ventral aspects of M1 (p < 0.05/3, Bonferroni correction) and the ventromedial BA3 of S1 (p < 0.05/5). These functional characteristics were positively correlated with autism severity. All subregions showed significant results in the ROI-to-ROI intergroup differential analysis (p < 0.05/80). LIMITATIONS: The generalizability of the segmentation model requires further evaluation. CONCLUSIONS: This study highlights the significance of M1 and S1 in ASD treatment and may provide new insights into brain parcellation and the identification of therapeutic targets for ASD.

Exploring the correlation between genetic transcription and multi-temporal developmental autism spectrum disorder using resting-state functional magnetic resonance imaging.

Introduction: The present investigation aimed to explore the neurodevelopmental trajectory of autism spectrum disorder (ASD) by identifying the changes in brain function and gene expression associated with the disorder. Previous studies have indicated that ASD is a highly inherited neurodevelopmental disorder of the brain that displays symptom heterogeneity across different developmental periods. However, the transcriptomic changes underlying these developmental differences remain largely unknown. Methods: To address this gap in knowledge, our study employed resting-state functional magnetic resonance imaging (rs-fMRI) data from a large sample of male participants across four representative age groups to stratify the abnormal changes in brain function associated with ASD. Partial least square regression (PLSr) was utilized to identify unique changes in gene expression in brain regions characterized by aberrant functioning in ASD. Results: Our results revealed that ASD exhibits distinctive developmental trajectories in crucial brain regions such as the default mode network (DMN), temporal lobe, and prefrontal lobes during critical periods of neurodevelopment when compared to the control group. These changes were also associated with genes primarily located in synaptic tissues. Discussion: The findings of this study suggest that the neurobiology of ASD is uniquely heterogeneous across different ages and may be accompanied by distinct molecular mechanisms related to gene expression.

Gender effects on autism spectrum disorder: a multi-site resting-state functional magnetic resonance imaging study of transcriptome-neuroimaging.

Introduction: The gender disparity in autism spectrum disorder (ASD) has been one of the salient features of condition. However, its relationship between the pathogenesis and genetic transcription in patients of different genders has yet to reach a reliable conclusion. Methods: To address this gap, this study aimed to establish a reliable potential neuro-marker in gender-specific patients, by employing multi-site functional magnetic resonance imaging (fMRI) data, and to further investigate the role of genetic transcription molecules in neurogenetic abnormalities and gender differences in autism at the neuro-transcriptional level. To this end, age was firstly used as a regression covariate, followed by the use of ComBat to remove the site effect from the fMRI data, and abnormal functional activity was subsequently identified. The resulting abnormal functional activity was then correlated by genetic transcription to explore underlying molecular functions and cellular molecular mechanisms. Results: Abnormal brain functional activities were identified in autism patients of different genders, mainly located in the default model network (DMN) and precuneus-cingulate gyrus-frontal lobe. The correlation analysis of neuroimaging and genetic transcription further found that heterogeneous brain regions were highly correlated with genes involved in signal transmission between neurons' plasma membranes. Additionally, we further identified different weighted gene expression patterns and specific expression tissues of risk genes in ASD of different genders. Discussion: Thus, this work not only identified the mechanism of abnormal brain functional activities caused by gender differences in ASD, but also explored the genetic and molecular characteristics caused by these related changes. Moreover, we further analyzed the genetic basis of sex differences in ASD from a neuro-transcriptional perspective.

Structural and functional integration of human forebrain organoids with the injured adult rat visual system.

Brain organoids created from human pluripotent stem cells represent a promising approach for brain repair. They acquire many structural features of the brain and raise the possibility of patient-matched repair. Whether these entities can integrate with host brain networks in the context of the injured adult mammalian brain is not well established. Here, we provide structural and functional evidence that human brain organoids successfully integrate with the adult rat visual system after transplantation into large injury cavities in the visual cortex. Virus-based trans-synaptic tracing reveals a polysynaptic pathway between organoid neurons and the host retina and reciprocal connectivity between the graft and other regions of the visual system. Visual stimulation of host animals elicits responses in organoid neurons, including orientation selectivity. These results demonstrate the ability of human brain organoids to adopt sophisticated function after insertion into large injury cavities, suggesting a translational strategy to restore function after cortical damage.