Compressed sensorimotor-to-transmodal hierarchical organization in schizophrenia

Abstract

Background 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. Methods We applied a novel combination of connectome gradient and stepwise connectivity analysis to resting-state fMRI to characterize the sensorimotor-to-transmodal cortical hierarchy organization (96 patients v. 122 controls). Results 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 fronto-parietal and ventral attention regions along the classical sensation-to-cognition continuum (voxel-level corrected, p < 0.05). Conclusions 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 cascading impairments from the disruption of the 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.

Linking cerebellar functional gradients to transdiagnostic behavioral dimensions of psychopathology

“…In the present study, we found that individuals with higher behavioral (general psychopathology) composites in LV1 have diminished differentiation between the sensorimotor and supramodal cognitive systems within cerebellar functional principal gradient organizations across psychiatric diagnoses, which is conceptually consistent with our previous studies ( Dong et al, 2020 , Dong et al, 2021 ) and other researcher ( Elliott et al, 2018 ). In our previous studies, we found schizophrenia patients showed diminished differentiation in intra-cerebellar, cerebellar-cerebral gradient and cerebral-cerebral gradient.…”

Functional Gradients of the Cerebellum: a Review of Practical Applications

“…2000 instead of 4,000,000 datapoints (see Figure 8 and [16] for an example). Other examples of studies using functional gradients to detect differences in patient populations in structures other than the cerebellum include [17][18][19].…”

“…Limitations specific to functional gradients analyses are mostly related to the novelty of this field, and include the lack of standardization for the calculation of functional gradients, the absence of a solidified framework for the interpretation of functional gradient abnormalities in patient populations, and the paucity of experiments analyzing functional gradient anatomy at the singlesubject level. Efforts to address these issues are ongoing, including the development of toolboxes for the generation of functional gradients [11,31], the emergence of a field of functional gradient research that is focused on patient populations [16][17][18][19], and preliminary data supporting that general principles of functional gradient organization in the average cerebellum remain observable in individual subjects [1,16].…”

Magnetic Resonance Imaging throughout the Clinical Course of Schizophrenia: Neurobiological Underpinnings and Clinical Implications

“…Reconstruction of macroscale brain connectome in first-episode schizophrenia patients by combining DWI and fMRI data revealed that connectome rich club structures exhibited significant impairment in medication-naïve patients, which provides further evidence that brain connectivity disruption may play an important role in the early stage of schizophrenia pathophysiology [15]. A recent fMRI study combining connectome gradient and stepwise connectivity analysis demonstrated abnormal compression of sensorimotor-to-transmoda cortical hierarchy organization in schizophrenia, providing new insight into the pathological relationship between early sensory and cognitive impairment [16].…”