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“Cognitive dysmetria” theory of schizophrenia (SZ) has highlighted that the cerebellum plays a critical role in understanding the pathogenesis and cognitive impairment in SZ. Despite some studies have reported the structural disruption of the cerebellum in SZ using whole brain approach, specific focus on the voxel-wise changes of cerebellar WM microstructure and its associations with cognition impairments in SZ were less investigated. To further explore the voxel-wise structural disruption of the cerebellum in SZ, the present study comprehensively examined volume and diffusion features of cerebellar white matter in SZ at the voxel level (42 SZ vs. 52 controls) and correlated the observed alterations with the cognitive impairments measured by MATRICS Consensus Cognitive Battery. Combing voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) methods, we found, compared to healthy controls (HCs), SZ patients did not show significant alteration in voxel-level cerebellar white matter (WM) volume and tract-wise and skeletonized DTI features. In voxel-wise DTI features of cerebellar peduncles, compared to HCs, SZ patients showed decreased fractional anisotropy and increased radial diffusivity mainly located in left middle cerebellar peduncles (MCP) and inferior cerebellar peduncles (ICP). Interestingly, these alterations were correlated with overall composite and different cognitive domain (including processing speed, working memory, and attention vigilance) in HCs but not in SZ patients. The present findings suggested that the voxel-wise WM integrity analysis might be a more sensitive way to investigate the cerebellar structural abnormalities in SZ patients. Correlation results suggested that inferior and MCP may be a crucial neurobiological substrate of cognition impairments in SZ, thus adding the evidence for taking the cerebellum as a novel therapeutic target for cognitive impairments in SZ patients.

Purpose: The purpose of this study was to comprehensively evaluate alterations of resting-state spontaneous brain activity in patients with idiopathic generalized epilepsy (IGE) and its subgroups [juvenile myoclonic epilepsy (JME) and generalized tonic-clonic seizures (GTCS)].Methods: Resting state functional magnetic resonance imaging (fMRI) data were acquired from 60 patients with IGE and 60 healthy controls (HCs). Amplitude of low frequency fluctuation (ALFF), global functional connectivity density (gFCD), local FCD (lFCD), and long range FCD (lrFCD) were used to evaluate spontaneous brain activity in the whole brain. Moreover, the coupling between ALFF and FCDs (gFCD, lFCD, and lrFCD) was analyzed on both voxel-wise and subject-wise levels. Two-sample t-tests were used to analyze the difference in ALFF, FCDs and coupling on a subject-wise level between the two groups. Nonparametric permutation tests were used to evaluate differences in coupling on a voxel-wise level.Key findings: Patients with IGE and its subgroups showed reduced ALFF, gFCD and lrFCD in posterior regions of the default mode network (DMN). In addition, decreased ALFF and increased coupling with FCD were found in the cerebellum, while decreased coupling was observed in the bilateral pre- and postcentral gyrus in IGE compared with the coupling in HCs. Similar findings were found in the analysis between each of the two subgroups of IGE (JME and GTCS) and HCs, and JME patients had increased coupling in the cerebellum and bilateral middle occipital gyrus compared with coupling in the GTCS patients.Significance: This study demonstrated a multifactor abnormality of the DMN in IGE and emphasized that the abnormality in the cerebellum was associated with dysfunctional motor symptoms during seizures and might participate in the regulation of GSWDs in IGE.

Schizophrenia is a complex mental disorder with disorganized communication among large-scale brain networks, as demonstrated by impaired resting-state functional connectivity (rsFC). Individual rsFC studies, however, vary greatly in their methods and findings. We searched for consistent patterns of network dysfunction in schizophrenia by using a coordinate-based meta-analysis. Fifty-six seed-based voxel-wise rsFC datasets from 52 publications (2115 patients and 2297 healthy controls) were included in this meta-analysis. Then, coordinates of seed regions of interest (ROI) and between-group effects were extracted and coded. Seed ROIs were categorized into seed networks by their location within an a priori template. Multilevel kernel density analysis was used to identify brain networks in which schizophrenia was linked to hyper-connectivity or hypo-connectivity with each a priori network. Our results showed that schizophrenia was characterized by hypoconnectivity within the default network (DN, self-related thought), affective network (AN, emotion processing), ventral attention network (VAN, processing of salience), thalamus network (TN, gating information) and somatosensory network (SS, involved in sensory and auditory perception). Additionally, hypo-connectivity between the VAN and TN, VAN and DN, VAN and frontoparietal network (FN, external goal-directed regulation), FN and TN, and FN and DN were found in schizophrenia. Finally, the only instance of hyper-connectivity in schizophrenia was observed between the AN and VAN. Our meta-analysis motivates an empirical foundation for a disconnected large-scale brain networks model of schizophrenia in which the salience processing network (VAN) plays the core role, and its imbalanced communication with other functional networks may underlie the core difficulty of patients to differentiate self-representation (inner world) and environmental salience processing (outside world). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: The present study aims to investigate structural and functional connectivity (SC and FC) in cerebello-cerebral circuit in idiopathic generalized epilepsy (IGE).Methods: Diffusion tensor imaging and resting-state imaging data were collected from 57 patients with IGE and 66 controls in the present study. First, we performed bidirectional probabilistic fiber tracking between cerebellum and cerebral cortex, consisting of cerebellar efferent and afferent fibers. Then, strength of structural connectivity (SCS), fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) were extracted and compared between groups. Finally, cerebellar FC with cerebral cortex was evaluated with seeding at dentate nucleus. Between-group comparisons were performed using t tests with a significant level setting at p < 0.05 with threshold-free cluster enhancement correction.Results: The patients with IGE showed decreased SCS in cerebellar efferent fibers to sensorimotor cortex in anterior corona radiate and increased SCS in efferent fibers to occipital cortex in posterior corona radiata. The SCS in cerebellar afferent fibers in corticospinal tract from frontal and in retrolenticular part of the internal capsule from occipital cortices were increased in IGE, and SCS in afferent fibers in posterior limb of internal capsule from parietal cortex was decreased. Decreased FA and increased MD and RD were observed in cerebello-cerebral tracts. Besides, decreased cerebellar FC with putamen and motor cortex was observed in IGE.Conclusion: The patients with IGE demonstrated distinct alterations in efferent and afferent pathways between cerebellum and different cerebral cortices, which might be the pathological anatomical basis for cerebellar modulation effect on epileptic activities and contribute to motor deficits.Key Points: • IGE showed decreased SCS in cerebellar efferent fibers to the sensorimotor cortex and increased SCS in efferent fibers to the occipital cortex. • Patients demonstrated increased SCS in cerebellar afferent fibers from the frontal and the occipital cortex and decreased SCS in afferent fibers from parietal cortex. • Decreased FC between motor-related regions and dentate nucleus was observed in IGE. [ABSTRACT FROM AUTHOR]

Intra-cortical myelin is a myelinated part of the cerebral cortex that is responsible for the spread and synchronization of neuronal activity in the cortex. Recent animal studies have established a link between obesity and impaired oligodendrocyte maturation vis-à-vis cells that produce and maintain myelin; however, the association between obesity and intra-cortical myelination remains to be established. To investigate the effects of obesity on intra-cortical myelin in living humans, we employed a large, demographically well-characterized sample of healthy young adults drawn from the Human Connectome Project (n = 1066). Intra-cortical myelin was assessed using a novel T1-w/T2-w ratio method. Linear regression analysis was used to investigate the association between body mass index (BMI), an indicator of obesity, and intra-cortical myelination, adjusting for covariates of no interest. We observed BMI was related to lower intra-cortical myelination in regions previously identified to be involved in reward processing (i.e., medial orbitofrontal cortex, rostral anterior cingulate cortex), attention (i.e., visual cortex, inferior/middle temporal gyrus), and salience detection (i.e., insula, supramarginal gyrus) in response to viewing food cues (corrected p < 0.05). In addition, higher BMIs were associated with more intra-cortical myelination in regions associated with somatosensory processing (i.e., the somatosensory network) and inhibitory control (i.e., lateral inferior frontal gyrus, frontal pole). These findings were also replicated after controlling for key potential confounding factors including total intracranial volume, substance use, and fluid intelligence. Findings suggested that altered intra-cortical myelination may represent a novel microstructure-level substrate underlying prior abnormal obesity-related brain neural activity, and lays a foundation for future investigations designed to evaluate how living habits, such as dietary habit and physical activity, affect intra-cortical myelination. [ABSTRACT FROM AUTHOR]