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Neurological Soft Signs Are Associated With Altered Cerebellar-Cerebral Functional Connectivity in Schizophrenia.

ABSTRACT: Cerebellar dysfunction is associated with neurological soft signs (NSS), which is a promising endophenotype for schizophrenia spectrum disorders. However, the relationship between cerebellar-cerebral resting-state functional connectivity (rsFC) and NSS is largely unexplored. Moreover, both NSS and cerebellar-cerebral rsFC have been found to be correlated with negative symptoms of schizophrenia. Here, we investigated the correlations between NSS and cerebellar-cerebral rsFC, explored their relationship with negative symptoms in a main dataset, and validated the significant findings in a replication dataset. Both datasets comprised schizophrenia patients and healthy controls. In schizophrenia patients, we found positive correlations between NSS and rsFC of the cerebellum with the inferior frontal gyrus and the precuneus, and negative correlations between NSS and rsFC of the cerebellum with the inferior temporal gyrus. In healthy controls, NSS scores were positively correlated with rsFC of the cerebellum with the superior frontal gyrus and negatively correlated with rsFC between the cerebellum and the middle occipital gyrus. Cerebellar-prefrontal rsFC was also positively correlated with negative symptoms in schizophrenia patients. These findings were validated in the replication dataset. Our results suggest that the uncoupling of rsFC between the cerebellum and the cerebral cortex may underlie the expression of NSS in schizophrenia. NSS-related cerebellar-prefrontal rsFC may be a potential neural pathway for possible neural modulation to alleviate negative symptoms.

SUBMITTER: Cai XL

PROVIDER: S-EPMC8379549 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Subtle abnormalities in sensory integration, motor coordination and sequencing of complex motor acts or neurological soft signs (NSS) are characteristic phenomena in patients with schizophrenia at any stage of the illness. Previous MRI studies in schizophrenia found NSS to be associated with cortical, thalamic and cerebellar changes. Since these studies mainly focused on first-episode or recent onset schizophrenia, the cerebral correlates of NSS in chronic schizophrenia remained rather unclear. 49 middle-aged patients with chronic schizophrenia with a mean duration of illness of 20.3 ± 14.0 years and 29 healthy subjects matched for age and sex were included. NSS were examined on the Heidelberg Scale and correlated to grey matter (GM) by using whole brain high resolution magnetic resonance imaging (3 Tesla) with SPM12/CAT12 analyses. As expected, NSS in patients were significantly (p?0.001) elevated in contrast to healthy controls, a finding, which not only applied to NSS total score, but also to the respective subscales "motor coordination", "sensory integration", "complex motor tasks", "right/left and spatial orientation" and "hard signs". Within the patient group NSS total scores were significantly correlated to reduced GM in right lingual gyrus, left parahippocampal gyrus, left superior temporal gyrus, left thalamus (medial dorsal nucleus) and left posterior lobe of the cerebellum (declive). Respective negative associations could also be revealed for the subscales "motor coordination", "complex motor tasks" and "right/left and spatial orientation". These findings remained significant after FWE-correction for multiple comparisons and were confirmed when years of education, chlorpromazine-equivalents or variables indicating the severity of psychopathology were introduced as additional covariates. According to our results lingual, parahippocampal, superior temporal, inferior and middle frontal gyri, thalamus and cerebellum have to be considered as important sites of NSS in chronic schizophrenia. That these findings only applied for patients but not healthy controls may indicate a different pathogenesis of NSS.

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Neurological Soft Signs Are Associated With Altered Cerebellar-Cerebral Functional Connectivity in Schizophrenia.

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