Sepulcre, J. | Search bioRxiv

bioRxiv2020

Altered Sensorimotor-to-Transmodal Hierarchical Organization in Schizophrenia

For decades, schizophrenia has been primarily conceptualized as a disorder of high-order cognitive functions with deficits in executive brain regions. Yet due to the increasing reports of early sensory processing deficit, recent models focus more on the developmental effects of impaired sensory process on high-order functions. The present study examined whether this pathological interaction relates to an overarching system-level imbalance, specifically a disruption in macroscale hierarchy affecting integration and segregation of unimodal and transmodal networks. We applied a novel combination of connectome gradient and stepwise connectivity analysis to resting-state functional magnetic resonance imaging (rsfMRI) to characterize the sensorimotor-to-transmodal cortical hierarchy organization (96 patients vs. 122 controls). Using these techniques, we demonstrated compression of the cortical hierarchy organization in schizophrenia, with a prominent compression from the sensorimotor region and a less prominent compression from the frontal-parietal region, resulting in a diminished separation between sensory and fronto-parietal cognitive systems. Further analyses suggested reduced differentiation related to atypical functional connectome transition from unimodal to transmodal brain areas. Specifically, we found hypo-connectivity within unimodal regions and hyper-connectivity between unimodal regions and frontoparietal and ventral attention regions along the classical sensation-to-cognition continuum established in prior neuroanatomical work. The compression of cortical hierarchy organization represents a novel and integrative system-level substrate underlying the pathological interaction of early sensory and cognitive function in schizophrenia. This abnormal cortical hierarchy organization suggests cascaded impairments stemming from the disrupted somatosensory-motor system and inefficient integration of bottom-up sensory information with attentional demands and executive control processes partially account for high-level cognitive deficits characteristic of schizophrenia.

neuroscience↗

bioRxiv2019

Linking lysosomal enzyme targeting genes and energy metabolism with altered gray matter volume in children with persistent stuttering

Developmental stuttering is a childhood onset neurodevelopmental disorder with an unclear etiology. Subtle changes in brain structure and function are present in both children and adults who stutter. It is a highly heritable disorder, and up to 12-20% of stuttering cases may carry a mutation in one of four genes involved in mannose-6-phosphate mediated protein intracellular trafficking. To better understand the relationship between genetic factors and brain structural changes, we used gene expression data from the Allen Institute for Brain Science (AIBS) and voxel-based morphometry (VBM) to investigate the spatial correspondence between gene expression patterns and differences in gray matter volume (GMV) between children with persistent stuttering (n=26, 87 scans) and their fluent peers (n=44, 139 scans). We found that expression patterns of two stuttering-related genes (GNPTG and NAGPA) in the brain exhibit a strong positive spatial correlation with the magnitude of GMV differences between groups. Further gene set enrichment analyses revealed that genes whose expression was highly correlated with the GMV differences were enriched for glycolysis and oxidative metabolism in mitochondria. Although the results are correlational and cannot inform us about underlying casual mechanisms, our results suggest a possibility that regions with high expression level of genes associated with stuttering may be particularly vulnerable to the effect of alterations in these genes. This effect may be further exacerbated by the relatively high energy utilization in those brain during the period of a sharp increase in brain energy utilization, which coincides with a period of rapid language development and the onset of stuttering during childhood.

neuroscience↗