| Background:Cognitive control deficits among schizophrenia patients are related to impairments in their daily functioning.Understanding the nature of these deficits is critical to develop effective therapies for this aspect of the illness.Functional magnetic resonance imaging(fMRI),a method that can measure the activation and synchronization of brain regions,has been used to examine the pathophysiological mechanisms associated with these deficits.As shown in fMRI studies,abnormal functional connectivity within the fronto-parietal network(FPN)is associated with cognitive control impairments in schizophrenia.Moreover,evidence suggests that cognitive control deficits in schizophrenia may also be associated with abnormal connectivity between networks.Specifically,study suggested that the functional segregation between the task "negative" default mode network(DMN)and task-positive networks such as the cingulo-opercular network(CON)and FPN is a key factor underlying cognitive control deficit among patients.Moreover,connectivity between FPN and CON may also contribute to cognitive control impairments in schizophrenia,and a meta-analysis has found that the connectivity between FPN and CON is atypical in schizophrenia patients.Finally,cortical-thalamo-cerebellar disturbances have been observed in schizophrenia patients,1with work showing that decreased resting-state connectivity between FPN and cerebellar network(CER)was associated with decreased cognitive controlThe literature reviewed above indicates that it is still not clear how deficits in functional connectivity might relate to cognitive control in schizophrenia.Further,it is not yet clear which aspects of cognitive control relate to which functional connectivity deficits.Diamond proposed that the core sub-components of cognitive control are working memory,inhibitory control and cognitive flexibility Fluid intelligence(e.g.,reasoning and problem solving),which is a key higher-order aspect of cognition,was built from core sub-components of cognitive control.Although working memory,inhibitory control,cognitive flexibility and fluid intelligence are dissociable,they are all aspects of cognitive control.Thus,the psychological and neurological mechanisms contributing to different aspects of cognitive control might have unique relationships,but may also have relationships shared across subcomponents.In schizophrenia patients,whether the connectivity mechanisms contributing to different aspects of cognitive control deficits are shared or unique across sub-constructs is still unclear.Method:Participants(50 healthy individuals and 49 patients)with rest fMRI data were included in the current study.A series of tasks were used to measure different components of cognitive control Specifically,average accuracy of verbal and spatial n-back tasks was used to measure working memory Inhibitory control was assessed using scores on the Stroop task(e.g.,average accuracy of incongruent trials)and stop-signal task(e.g.,stop signal reaction time).Cognitive flexibility was assessed using the scores on task-switching task(e.g.,average reaction time of switch cost)and D-KEFS verbal fluency task(e.g.,the number of correct words in a minute).Fluid intelligence(high-order aspect of cognitive control)was assessed using scores on the matrix reasoning subtest from the WAIS-III Dosenbach parcellation was used to define regions falling into the DMN,FPN,CON and CER.The mean time series for each of these ROIs were extracted.Then,the ROI-ROI connectivity matrix(Fisher-z values)was calculated for all ROIs for each participant.Within and between connectivity were examined for the DMN,FPN,CON and CER.Hierarchical regressions and follow-up correlation analysis with demographic variables(e.g.,age,gender and education)as covariates were used to determine the relationship between connectivity measures and cognitive controlResults:At the network level,hierarchical regressions showed that:1)increased connectivity within FPN was associated with decreased working memory,inhibitory control,and high-order aspects of cognitive control in schizophrenia patients;2)Increased connectivity between FPN and CON and decreased separation between DMN and FPN were both associated with decreased inhibitory control and high-order aspects of cognitive control in patients;and 3)Decreased separation between DMN and CON was associated with decreased high-order aspects of cognitive control in patients.At the region level,results showed that 1)the relationship of working memory to connectivity of right dlPFC to the whole FPN network was associated with working memory in patients,2)the connectivity between several FPN regions to FPN,DMN and CON related to inhibitory control in patients.Further,connectivity of several DMN regions to the FPN,and one CON region(right precuneus)in their connectivity to the FPN were associated with inhibitory control,3)FPN regions accounts for the largest proportion(68.42%)of associated regions that predict high-order cognitive control,with the connectivity of nine FPN regions to their own FPN network or to DMN and CON associated with fluid intelligence in patients,and the connectivity of three DMN regions(e.g.,right vmPFC,left IPS and mPFC)to FPN and CON predicted fluid intelligence in patientsDiscussion:The current study examined the relationship between network connectivity and cognitive control deficits in schizophrenia patients,and the results revealed increased connectivity within or between neuro-cognitive networks(e.g.,DMN,FPN and CON)was associated with decreased cognitive control.Specifically,working memory deficits in schizophrenia patients were associated with increased FPN connectivity.Inhibitory control deficits in patients were associated with increased FPN connectivity,DMN-FPN connectivity,and FPN-CON connectivity.Moreover,fluid intelligence deficits were associated with increased FPN connectivity,DMN-FPN connectivity,DMN-CON connectivity,and FPN-CON connectivity.Previous studies examined the network connectivity disruptions associated with specific aspect of cognitive control deficits in schizophrenia patients However,since different studies used different participants that may vary in clinical characteristics,it is hard to compare results across studies to understand shared versus unique connectivity correlates of impairments in different components of cognitive control.Further,although some studies examined a battery of cognitive control tasks,these studies have typically not examined specific subcomponents of cognitive control(e.g.,inhibitory control).The current study measured a variety of cognitive control facets in the same group of individuals,and calculated the relationship between each cognitive control component and each network parameter separately.By comparing the results of different cognitive control components,we found both shared and specific network connectivity associations to the sub-constructs of cognitive control among patients.Finally,the relationship between reduced separation between DMN and task-positive networks and cognitive control dysfunction may reflect an impaired ability to resist interference from self-reflective or introspective processes,and increased rest FPN-CON connectivity was associated with decreased inhibitory control and fluid intelligence might indicate patients' cognitive control deficits might be associated decreased network separation and organization. |
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