Local Dynamic Spontaneous Brain Activity Changes Are Correlation With Cognitive Function And Molecular Features In Schizophrenia

Objective: Resting-state functional magnetic resonance imaging(rs-f MRI)data were widely used to explore changes in spontaneous brain activity associated with cognitive activity in patients with schizophrenia(SZ).However,a static analysis of rs-f MRI data may ignore the unstable and rapidly changing neural interactions in the brain.Moreover,the molecular basis of the neurotransmitter receptors/transporters underlying these neurodynamic alterations is still unclear.Thus,we performed a dynamic analysis of rsf MRI data to explore the dynamic spontaneous neural activity changes in patients with SZ and combined these changes with cognitive activity and information on the molecular characteristics of neurotransmitter receptors/transporters.Methods: The present study was a case-control study.39 patients with schizophrenia who attended the outpatient and inpatient psychiatric departments of the First Affiliated Hospital of Kunming Medical University and met the DSM-5 diagnosis were recruited,and 35 healthy volunteers were recruited in the same period.All subjects underwent rsf MRI data acquisition and assessed for clinical symptoms using the PANSS and RBANS scales.Because of the problems of excessive head movement,the image quality,and the lack of scales,some subjects were excluded,and 30 patients with schizophrenia and 33 healthy controls were finally included.The rs-f MRI data were preprocessed on the MATALAB 2016 a platform using DPABI and the SPM12 toolbox,and the sliding window method was used to obtain dynamic amplitude of lowfrequency fluctuation(d ALFF)and regional homogeneity(d Re Ho).Two-sample t-test was performed to obtain the d ALFF and d Re Ho differential brain regions between groups using years of education and mean frame shift as covariates,and the values of differential brain regions were extracted for Pearson correlation analysis with PANSS and RBANS scores.Then,a spatial correlation analysis(Spearman correlation)was performed using a derived template of spatial expression of neurotransmitter receptors/transporters in the whole brain provided by the Juspace tool with the Tstatistic maps obtained from the intergroup comparisons to further investigate the molecular basis of dynamic alterations in spontaneous neural activity in schizophrenia patients.Results: 1.Compared to healthy controls,the schizophrenia group had significantly increased variability of d ALFF in the left OFC and anterior cingulate cortex(ACC),meanwhile they had significantly decreased variability of d Re Ho in the right orbitofrontal cortex(OFC)and Insula.2.The increased variability of d ALFF introduced by schizophrenia is positively correlated with scores on attention,and is not significantly correlated with scores on immediate memory,visual breadth,attention and delayed memory,or PANSS scores.The decreased variability of d Re Ho introduced by schizophrenia is negatively correlated with scores on verbal ability,and is not significantly correlated with scores on immediate memory,visual breadth,attention and delayed memory,or PANSS scores.3.The increased variability of d ALFF introduced by schizophrenia is spatially correlated with dopamine systems(D1,D2,DAT,and FDOPA),serotonin sestems(5-HT1 b,5-HT4,and SERT),cannabinoid receptor,γ-aminobutyric acid receptor,mu-opioid receptor,vesicular acetylcholine transporter,norepinephrine transporter,metabotropic glutamate receptor densities.The decreased variability of d Re Ho introduced by schizophrenia is spatially correlated with dopamine systems(D1,D2 and DAT),serotonin sestems(5-HT1 a,SERT),cannabinoid receptor(CB1),mu-opioid receptor(MU),norepinephrine transporter(NAT),vesicular acetylcholine transporter(VACh T),metabotropic glutamate receptor(m Glu R5)densities.Conclusions: 1.Temporal dynamic changes of spontaneous brain activity are present in schizophrenic patients and associated with cognitive impairment.2.A series of neurotransmitters receptors possibly related to variability of d ALFF and d Re Ho alterations in schizophrenia,which facilitates an integrative understanding of the molecular mechanism underlying temporal dynamic changes of spontaneous brain activity abnormalities in schizophrenia and may provide clues for new treatment strategies.