Altered Functional Networks And Pattern Recognition Of Schizophrenia

As a common,choric mental disease,schizophrenia has a severe effect on the individuals' life and society.Schizophrenia is characterized as positive symptoms including hallucinations,delusions and negative symptoms including cognitive impairments and deficient motivation.The fundamental mechanism of schizophrenia is unclear.The absence of stable and reliable biomarkers makes current diagnosis of schizophrenia,which mainly relies on clinical manifestations by experienced clinician,a challenging task.Recent years,functional Magnetic Resonance Image(fMRI)turns out as a powerful tool to explore fundamental mechanism of schizophrenia.Schizophrenia is characterized as a prototypical disorder of integration of brain function involved almost all intrinsic connectivity networks with the findings of fMRI.However,there is no consistent conclusion regarding the most distinguishing brain circuitry in schizophrenia and current study hint altered functional network in schizophrenia is frequency specific.The current study consists of following parts:1.Schizophrenia is characterized as a prototypical disorder and almost all networks are found altered.Although the networks are found differently altered in schizophrenia,there is no consistent conclusion regarding the most distinguishing brain circuitry in schizophrenia.A novel network-based ensemble method was used to explore the most distinguishing resting sate functional brain networks in schizophrenia.The ensemble learner presented better performance than traditional method(84.7% for classification accuracy,91.9% for sensitivity,74.5% for specificity,all p < 0.05 for permuted test).The most distinguishing connections were located in the right paralimbic system and bilateral default mode network.These connections were correlated with both positive and negative symptoms scores.Our results suggested that functional networks could be used to diagnose schizophrenia and ensemble method could be powerful tool to explore the mechanism of schizophrenia.2.To explore whether altered functional network in schizophrenia is frequency specific,empirical mode decomposition,which is a pure data-driven method suitable for nonlinear and nonstationary signals,was used to decompose blood-oxygen-leveldependent(BOLD)signals into different intrinsic frequency bands.The BOLD signals were decomposed into three frequency bands and significant aberrance only exited at high frequency band(the peak spectral density power was 0.06 Hz).In this frequency,functional connection linking bilateral cuneus and right supplementary motor area,functional networks within basal ganglia and functional connection linking the dorsal striatum and left supplementary motor area were decreased in schizophrenia.In addition,these altered connections were correlated significantly with symptoms severity.Our results found altered corticostriatal-thalamo-cortical circuits were frequency specific.3.Altered interactions between the striatum and salience network are considered as etiological and treatment-sensitive marker in schizophrenia.Whether altered functional connections between the striatum and salience network in unmedicated schizophrenia patients could predict effect of antipsychotic treatment remains unknown.We explored altered distinct pathways connecting the striatum and salience network in unmedicated schizophrenia,the possibility whether baseline aberrance could predict effect of antipsychotic treatment and its reaction to antipsychotic treatment.Baseline schizophrenia patients presented decreased distinct pathway connecting the striatum and salience network.The baseline decreased dorsal(or ventral)the striatum-salience network pathways were correlated with the total negative(positive)symptom score improvement.Our results presented that the baseline striatum-salience network pathways could be predictive markers risperidone mono-therapy.4.The significant role of serotonin in the pathomechanism of schizophrenia makes it a promising opportunity for schizophrenia.However,limited studies directly explore the altered serotonin function in schizophrenia.We explored altered functional pathways of serotonin with the raphe nucleus as seed.Schizophrenia patients presented decreased functional connectivity of the raphe nucleus connected to subcortical dopamine regions.Dopamine related regions further presented decreased functional connections connected to salience networks.In addition,functional connections between the raphe nucleus and dopamine related subcortical regions were correlated with negative symptoms severity.Our results emphasized the importance of the serotonin function in the pathophysiology of schizophrenia.