Executive Function In Schizophrenia Research Articles

Frontal brain volume correlates of impaired executive function in schizophrenia

Cognitive impairments affect functional capacity in individuals with schizophrenia (SZH), but their neural basis remains unclear. The Wisconsin Card Sorting Test (WCST), and the Stroop Task (SCWT), are paradigmatic tests which have been used extensively for examining executive function in SZH. However, few studies have explored how deficits on these tasks link to brain volume differences commonly seen in SZH. Here, for the first time, we tested associations between FreeSurfer-derived frontal brain volumes and performance on both WCST and SCWT, in a well-matched sample of 57 SZH and 32 control subjects. We also explored whether these associations were dissociable from links to symptom severity in SZH. Results revealed correlations between volumes and task performance which were unique to SZH. In SZH only, volumes of right middle frontal regions correlated with both WCST and Stroop performance: correlation coefficients were significantly different to those present in the control group, highlighting their specificity to the patient group. In the Stroop task, superior frontal regions also showed associations with Stroop interference scores which were unique to SZH. These findings provide important detail around how deficits on these two paradigmatic executive function tasks link to brain structural differences in SZH. Results align with converging evidence suggesting that neuropathology within right middle frontal regions (BA9 and BA46) might be of particular import in SZH. No volumetric associations with symptom severity were found, supporting the notion that the structural abnormalities underpinning cognitive deficits in SZH differ from those associated with symptomatology.

Assessing Executive Functioning in Schizophrenia: Concurrent and Discriminative Validity of a Novel Virtual Cooking Task.

Deficits in executive functions (EF) are strongly related to real-life functioning and negative symptoms (NS) in schizophrenia. Recently, virtual reality has enabled more ecologically valid approaches to assess EF in simulated "real-life" scenarios among which the virtual cooking task (VCT) has gained attention. However, the clinical implications of the VCT in schizophrenia have not been investigated exhaustively. In this study, clinically stable individuals with schizophrenia (n = 38) and healthy controls (n = 42) completed a novel VCT and a set of computerized standard EF tools (CST) to primarily investigate concurrent and discriminant validity. In addition, the study explored links between EF assessments, functioning, and NS while controlling for antipsychotic intake, clinical stability, and age. This VCT consisted of four tasks with increasing difficulty and time constraints. The most relevant findings indicate that (1) the VCT showed moderate to strong correlations with CST, (2) the VCT discriminated EF performance between both the groups, (3) the VCT predicted interpersonal functioning, and (4) the VCT predicted NS in greater extent than CST. Accordingly, the findings give support to the concurrent and discriminant validity of the VCT to assess EF and indicate its value to deepen the study of collateral functional deficits and NS in schizophrenia.

Executive function in schizophrenia and autism in adults shares common components separating high and low performance groups.

The profile of executive function (EF) in adults with Schizophrenia (SCZ) and autism spectrum disorder (ASD) remains unclear. This study aims to ascertain if distinct EF patterns can be identified between each clinical condition by comparing the neuropsychological profile of adults with SCZ and ASD, for whom the differential diagnosis is still highly challenging. Forty-five individuals (15 SCZ, 15 ASD, 15 controls) matched for age, sex, education level, and handedness underwent intelligence evaluation and neuropsychological testing for working memory, inhibition, planning and set-shifting, and verbal fluency subdomains. Principal component analysis (2D-PCA) using variables representing 4 domains was employed to identify patterns in neuropsychological profiles. The ASD group had lower scores on the Digits Forward subtest compared to the SCZ group (7.2 ± 2.1 vs. 9.3 ± 1.9, p = 0.003; Cohen's d: 1.05). ASD also performed significantly worse on the Stroop Word Test compared to the control group (77.7± 17.9 vs. 98.0 ± 12.7, p = 0.009; Cohen's d: 1.31). No significant differences were observed between ASD and SCZ on other EF measures. The larger contributors for the dimensions in 2D-PCA were the Digits Forward subtest and Stroop Word Test. Still, there was substantial overlap between the clinical groups. This study suggests a high degree of similarity of EF between SCZ and ASD. Through four EF measures, the discrimination of low and high-functioning EF groups spanning both diagnostic categories may help to identify the individuals who could better benefit from cognitive rehabilitation strategies.

Neuroimaging features of cognitive impairments in schizophrenia and major depressive disorder.

Cognitive dysfunctions are one of the key symptoms of schizophrenia (SZ) and major depressive disorder (MDD), which exist not only during the onset of diseases but also before the onset, even after the remission of psychiatric symptoms. With the development of neuroimaging techniques, these non-invasive approaches provide valuable insights into the underlying pathogenesis of psychiatric disorders and information of cognitive remediation interventions. This review synthesizes existing neuroimaging studies to examine domains of cognitive impairment, particularly processing speed, memory, attention, and executive function in SZ and MDD patients. First, white matter (WM) abnormalities are observed in processing speed deficits in both SZ and MDD, with distinct neuroimaging findings highlighting WM connectivity abnormalities in SZ and WM hyperintensity caused by small vessel disease in MDD. Additionally, the abnormal functions of prefrontal cortex and medial temporal lobe are found in both SZ and MDD patients during various memory tasks, while aberrant amygdala activity potentially contributes to a preference to negative memories in MDD. Furthermore, impaired large-scale networks including frontoparietal network, dorsal attention network, and ventral attention network are related to attention deficits, both in SZ and MDD patients. Finally, abnormal activity and volume of the dorsolateral prefrontal cortex (DLPFC) and abnormal functional connections between the DLPFC and the cerebellum are associated with executive dysfunction in both SZ and MDD. Despite these insights, longitudinal neuroimaging studies are lacking, impeding a comprehensive understanding of cognitive changes and the development of early intervention strategies for SZ and MDD. Addressing this gap is critical for advancing our knowledge and improving patient prognosis.

Comparing the functional neuroanatomy of proactive and reactive control between patients with schizophrenia and healthy controls.

Cognitive control deficits are associated with impaired executive functioning in schizophrenia. The Dual Mechanisms of Control framework suggests that proactive control requires sustained dorsolateral prefrontal activity, whereas reactive control marshals a larger network. However, primate studies suggest these processes are maintained by dual-encoding regions. To distinguish between these theories, we compared the distinctiveness of proactive and reactive control functional neuroanatomy. In a reanalysis of data from a previous study, 47 adults with schizophrenia and 56 controls completed the Dot Pattern Expectancy task during an fMRI scan examining proactive and reactive control in frontoparietal and medial temporal regions. Areas suggesting specialized control or between-group differences were tested for association with symptoms and task performance. Elastic net models additionally explored these areas' predictive abilities regarding performance. Most regions were active in both reactive and proactive control. However, evidence of specialized proactive control was found in the left middle and superior frontal gyri. Control participants showed greater proactive control in the left middle and right inferior frontal gyri. Elastic net models moderately predicted task performance and implicated various frontal gyri regions in control participants, with additional involvement of anterior cingulate and posterior parietal regions for reactive control. Elastic nets for patient participants implicated the inferior and superior frontal gyri, and posterior parietal lobe. Specialized cognitive control was unassociated with either performance or schizophrenia symptomatology. Future work is needed to clarify the distinctiveness of proactive and reactive control, and its role in executive deficits in severe psychopathology.

Frontal lobe functions in schizophrenia: Interest of the Stuss approach

ObjectiveThe term Executive Functions (EFs) refers to the higher-level skills we use every day to control and coordinate our cognitive abilities and behaviours. EFs are mainly supported by the frontal lobes and its connections. EFs are frequently impaired in schizophrenia, but the profiles of executive deficits accompanying schizophrenia remains unclear. The use of specific EFs models might help to shed new light on this issue. Stuss (Stuss & Alexander, 2007; Stuss, 2008, 2011, 2017) proposed an integrative and operant model of EFs which has never been used to explore and characterize deficits in schizophrenia.The aim of this study is to further examine EFs in schizophrenia in the light of the frontal lobe functional approach developed by Stuss (2008, 2011, 2017) in order to question EFs impairment homogeneity and heterogeneity in schizophrenia. MethodsForty-five patients with schizophrenia and fifty-five healthy controls were recruited. They all completed a series of neuropsychological tests selected and adapted to measure the five majors' functions of the frontal lobe described by Stuss (2017). ResultsPatients showed deficits in almost all the frontal functions. Inside each frontal lobe function, correlations were observed between all the corresponding measures. The study of profiles highlighted a heterogeneous functioning in schizophrenia. ConclusionsThe model of Stuss (Stuss & Alexander, 2007; Stuss, 2008, 2011, 2017) allows accurate and specific measures of the frontal functions and observation. Beyond “cold” or “hot” EFs division, this integrative approach is helpful to understand links within neurocognition.

Validation of an ecological momentary assessment to measure processing speed and executive function in schizophrenia

Cognitive impairments are a core feature of schizophrenia that have negative impacts on functional outcomes. However, it remains challenging to assess these impairments in clinical settings. Smartphone apps provide the opportunity to measure cognitive impairments in an accessible way; however, more research is needed to validate these cognitive assessments in schizophrenia. We assessed the initial accessibility, validity, and reliability of a smartphone-based cognitive test to measure cognition in schizophrenia. A total of 29 individuals with schizophrenia and 34 controls were included in the analyses. Participants completed the standard pen-and-paper Trail Making Tests (TMT) A and B, and smartphone-based versions, Jewels Trail Tests (JTT) A and B, at the single in-lab visit. Participants were asked to complete the JTT remotely once per week for three months. We also investigated how subjective sleep quality and mood may affect cognitive performance longitudinally. In-lab and remote JTT scores moderately and positively correlated with in-lab TMT scores. Moderate test-retest reliability was observed across the in-lab, first remote, and last remote completion times of the JTT. Additionally, individuals with schizophrenia had significantly lower performance compared to controls on both the in-lab JTT and TMT. Self-reported mood had a significant effect on JTT A performance over time but no other significant relationships were found remotely. Our results support the initial accessibility, validity and reliability of using the JTT to measure cognition in schizophrenia. Future research to develop additional smartphone-based cognitive tests as well as with larger samples and in other psychiatric populations are warranted.

Executive Dysfunctions in Schizophrenia: A Critical Review of Traditional, Ecological, and Virtual Reality Assessments.

In recent years, interest has grown in measuring executive function in schizophrenia with ecological and virtual reality (VR) tools. However, there is a lack of critical analysis comparing those tools with traditional ones. This paper aims to characterize executive dysfunction in schizophrenia by comparing ecological and virtual reality assessments with traditional tools, and to describe the neurobiological and psychopathological correlates. The analysis revealed that ecological and VR tests have higher levels of verisimilitude and similar levels of veridicality compared to traditional tools. Both negative symptoms and disorganization correlate significantly with executive dysfunction as measured by traditional tools, but their relationships with measures based on ecological and VR methods are still unclear. Although there is much research on brain correlates of executive impairments in schizophrenia with traditional tools, it is uncertain if these results will be confirmed with the use of ecological and VR tools. In the diagnosis of executive dysfunction, it is important to use a variety of neuropsychological methods—especially those with confirmed ecological validity—to properly recognize the underlying characteristics of the observed deficits and to implement effective forms of therapy.

Empathic Tendency and Theory of Mind Skills in Young Individuals with Schizophrenia: Its’ Associations with Self-Reported Schizotypy and Executive Function

Objectives Social function deficit is known as a core feature of schizophrenia. This study aimed to investigate differences in empathic tendencies and theory of mind (ToM) skills between healthy controls and young individuals with schizophrenia, and to examine the associations between empathic tendencies, ToM skills and schizotypy, and executive function in schizophrenia. Methods Thirty patients with schizophrenia and 30 healthy controls were enrolled and assessed using the interpersonal relationship index (IRI; perspective taking, fantasy, empathic concern, and personal distress subscales), ToM-Picture Story Task (ToM-PST; sequence and cognitive questionnaire), Wisconsin schizotypy scale (revised physical anhedonia and perceptual aberration), and Stroop tests for empathic tendencies, ToM skills, schizotypy, and executive function. Results In individuals with schizophrenia, the IRI for perspective taking and ToM-PST score for cognitive function were lower, and the IRI for personal distress was higher than those in healthy controls. The IRIs for perspective taking and fantasy were related to revised physical anhedonia, and that for empathic concern was associated with revised physical anhedonia and perceptual aberration. The ToM-PST score for sequence was associated with the Stroop test score for schizophrenia. Conclusion These findings indicate deficits in empathic tendencies and ToM skills, which may be independently and primarily associated with schizotypy and executive function in young individuals with schizophrenia. Key Words: Empathy · Executive function · Schizophrenia · Schizotypy · Social cognition · Theory of mind 중심 단어: 공감 · ë§ˆìŒì´ë¡ Â· 사회인지 · 실행기능 · 조현병 · 조현형차원

Anxiety and executive functions relationships in schizophrenia: A meta-analysis

Poor executive functions (EF) in schizophrenia are prevalent and most frequently explained as neuropathological conditionality. However, a growing number of studies argue that the contribution of psychological factors (e.g. anxiety) to cognitive deficits in schizophrenia is underestimated. The aim of this study was therefore to meta-analytically investigate the correlations between anxiety and EF performance among patients with a schizophrenia diagnosis. The meta-analysis included 10 studies conducted on a group of 518 patients with schizophrenia; the grand effect was not statistically significant. However, the exclusion of outlier results led to a small significant correlation (r = −0.11) between anxiety and EF in schizophrenia. Moreover, extant relations between state anxiety and EF (r = −0.12), anxiety and EF measures based on reaction time (r = −0.17), and anxiety and EF tests operating on verbal material (r = −0.12) were observed. The results interpreted in light of Attentional Control Theory indicate that the heightened level of anxiety observed among persons diagnosed with schizophrenia might be one of the sources of EF deficits.

Examination and Comparison of Cognitive and Executive Functions in Clinically Stable Schizophrenia Disorder, Bipolar Disorder, and Major Depressive Disorder.

Background Schizophrenia (SC), bipolar disorder (BD), and major depressive disorder (MDD) are associated with various cognitive and executive dysfunctions. The aim of the present study was to evaluate and compare cognitive and executive dysfunctions in schizophrenia, bipolar disorder, and major depressive disorder. Materials and Methods Sixty-four schizophrenia patients, 68 bipolar patients, 62 patients with major depressive disorder, and 75 healthy individuals participated in the present study. All participants were assessed with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), Young Mania Rating Scale (YMRS), Positive and Negative Syndrome Scale (PANSS), Beck Depression Inventory (BDI-II), Trial Making Test (TMT), Four-Choice Reaction Time Task, Ruler Drop Method (RDM), Tower of London (TOL) task, and the Wisconsin Card Sorting Task (WCST). Data were analyzed by chi-square, Kolmogorov-Smirnov, and independent t-tests; ANOVA; and MANOVA. Results In the cognitive function, the scores of SC, BD, and MDD patients were lower than those of healthy individuals. Also, the scores of MDD patients were lower than those of other patients, and the scores of BD patients were lower than those of SC patients. In the executive function, the scores of SC, BD, and MDD patients were lower than those of healthy individuals. Moreover, the scores of the MDD group were higher than those of the BD and SC groups, and the scores of the SC group were higher than those of the BD group. Conclusion Patients with SC, BD, and MDD have poorer cognitive and executive functions than healthy individuals, even when these patients are in a stable state. Assessment of cognitive and executive functions in SC, BD, and MDD patients can help in understanding the pathology of these disorders.

Subcortical neural tracks play an important role in executive function in schizophrenia: An experimental study among patients with schizophrenia and healthy comparisons

The literature has long emphasized the involvement of cortical and subcortical networks in executive function impairments among patients with schizophrenia. However, previous studies have not examined the relative involvement of monocular (mostly subcortical) versus binocular (mostly cortical) neural tracks in patients' EF deficits.Patients with schizophrenia and healthy comparisons were administered a dichotic version of the Stroop task, in which eye-of-origin manipulation was employed to isolate the involvement of monocular (mostly subcortical; thalamic regions) versus binocular (mostly cortical; extrastriate cortex) visual pathways. The eye-of-origin manipulation, in which a color patch (e.g., a green patch) was presented to one eye, and a word (e.g., “RED”) to the other eye, enabled a split of the conflicting information between the two monocular channels. This results in the presentation of conflicting information to the higher cortical regions, but not to the lower subcortical structures. In the Stroop color task, when the monocular neural channels were not exposed to the conflicting information, the differences in task performance between the patients and the HCs significantly increased, and only the patients exhibited larger task conflict. When monocular neural channels were not exposed to the conflicting information, a robust dysfunction of the patients' group was observed. This abnormality might result from impairments in cortical regions or reduced computational power available for solving the conflict. However, additional studies that take into account the resolution of monocular and binocular neural channels are needed to enrich our understanding of the interplay between cortical and subcortical mechanisms in patients' EF deficits.

Pragmatics, Theory of Mind and executive functions in schizophrenia: Disentangling the puzzle using machine learning.

ObjectiveSchizophrenia is associated with a severe impairment in the communicative-pragmatic domain. Recent research has tried to disentangle the relationship between communicative impairment and other domains usually impaired in schizophrenia, i.e. Theory of Mind (ToM) and cognitive functions. However, the results are inconclusive and this relationship is still unclear. Machine learning (ML) provides novel opportunities for studying complex relationships among phenomena and representing causality among multiple variables. The present research explored the potential of applying ML, specifically Bayesian network (BNs) analysis, to characterize the relationship between cognitive, ToM and pragmatic abilities in individuals with schizophrenia and healthy controls, and to identify the cognitive and pragmatic abilities that are most informative in discriminating between schizophrenia and controls.MethodsWe provided a comprehensive assessment of different aspects of pragmatic performance, i.e. linguistic, extralinguistic, paralinguistic, contextual and conversational, ToM and cognitive functions, i.e. Executive Functions (EF)—selective attention, planning, inhibition, cognitive flexibility, working memory and speed processing—and general intelligence, in a sample of 32 individuals with schizophrenia and 35 controls.ResultsThe results showed that the BNs classifier discriminated well between patients with schizophrenia and healthy controls. The network structure revealed that only pragmatic Linguistic ability directly influenced the classification of patients and controls, while diagnosis determined performance on ToM, Extralinguistic, Paralinguistic, Selective Attention, Planning, Inhibition and Cognitive Flexibility tasks. The model identified pragmatic, ToM and cognitive abilities as three distinct domains independent of one another.ConclusionTaken together, our results confirmed the importance of considering pragmatic linguistic impairment as a core dysfunction in schizophrenia, and demonstrated the potential of applying BNs in investigating the relationship between pragmatic ability and cognition.

Neurocognitive and clinical correlates of insight in schizophrenia.

Background:Schizophrenia is a heterogeneous disorder characterized by various symptom dimensions and neurocognitive deficits. Impairment of insight is a core clinical symptom of the disorder. There has been an increasing focus on neurocognition and insight in schizophrenia; although, many studies fail to control for premorbid cognitive status.Materials and Methods:Schizophrenia patients (n = 60) selected for adequate background education were recruited from outpatient services of a tertiary care hospital and community care homes in Southern India. These patients were comprehensively assessed using a neurocognitive battery. Clinical assessments were done using the Positive and Negative Syndrome Scale (PANSS) and Schedule for the Assessment of Insight-expanded version (SAI-E). Partial correlation was performed to examine the relationship of insight with clinical and neurocognitive measures. Statistical significance was set at P = 0.004 (Bonferroni correction for 12 tests of association). Linear regression analysis was performed to examine the predictors of insight.Results:The mean PANSS positive, negative, general psychopathology, and total scores were 14.2 ± 4.9, 17.4 ± 5.0, 34.3 ± 6.8, and 65.8 ± 13.9, respectively. Mean insight score (SAI-E) was 8.5 ± 2.9. In partial correlation done after controlling for IQ, significant negative correlations were observed between insight score and the Wisconsin Card Sorting Test (WCST) total errors (P = 0.001), WCST perseverative errors (P < 0.001). Insight scores had negative correlations with PANSS negative (P < 0.002) and total scores (P < 0.002). WCST perseverative errors were the primary predictor of insight in the regression analysis.Conclusion:Insight has a strong relationship with executive functioning in schizophrenia. This could indicate shared neurobiological substrates for insight and executive functioning.

Diffusion kurtosis imaging of gray matter in schizophrenia

Prior postmortem studies have shown gray matter (GM) microstructural abnormalities in schizophrenia. However, few studies to date have examined GM microstructural integrity in schizophrenia in vivo. Here, we employed diffusion kurtosis imaging (DKI) to test for differences in GM microstructure in eighteen schizophrenia (SZ) patients versus nineteen healthy controls (HC). GM microstructure was characterized in each participant using DKI-derived metrics of mean kurtosis (MK) and mean diffusivity (MD). Individual T1-weighted images were used to create subject-specific cortically-labelled regions of interest (ROIs) of the four cortical lobes and sixty-eight cortical GM regions delineated by the Desikan-Killiany atlas, and to derive the associated cortical thickness and area measures. The derived ROIs were also registered to the diffusion space of each subject and used to generate region-specific mean MK and MD values. We additionally administered the Wisconsin Card Sorting Test (WCST), Stroop test, and Trail Making Test part B (Trails-B) to test the relationship between GM metrics and executive function in SZ. We found significantly increased MK and MD in SZ compared to HC participants in the temporal lobe, sub-lobar temporal cortical regions (fusiform, inferior temporal, middle temporal and temporal pole), and posterior cingulate cortex after correcting for multiple comparisons. Correlational analyses revealed significant associations of MK and MD with executive function scores derived from the WCST, Stroop, and Trails-B tests, along with an inverse relationship between MK and MD and cortical thickness and area. A hierarchical multiple linear regression analysis showed that up to 85% of the inter-subject variability in cognitive function in schizophrenia measured by the WCST could be explained by MK in combination with either GM thickness or area. MK and MD appear to be sensitive to GM microstructural pathology in schizophrenia and may provide useful biomarkers of abnormal cortical microstructure in this disorder.

Component mechanisms of executive function in schizophrenia and their contribution to functional outcomes.

Objective:In schizophrenia, scores reflecting deficits in different cognitive processes are strongly correlated, making it difficult to establish a solid relationship between different cognitive mechanisms and other features of this disorder. The objective of this study was to explore whether three frequently postulated executive functions (updating, shifting, and inhibition) could be compared between groups and considered independently in terms of their respective roles in functional outcome.Methods:This study relied on confirmatory factor analysis of schizophrenia patients (n=141) and healthy controls (n=119). The main analyses examined the degree to which three executive functions (updating, set-shifting, and inhibition) could be separated in schizophrenia and compared this model among groups. Structural equation modeling analysis was also performed to examine the extent to which executive function components contribute to functional outcome in schizophrenia.Results:Multiple-group confirmatory factor analysis with unconstrained model parameters indicated that the full three-factor model may fit the data in both groups (χ2 = 61.48, degrees of freedom = 34, p < 0.001, comparative fit index = 0.95; standardized root mean square residual = 0.037; root mean square error of approximation = 0.04; Akaike’s information criteria = 169.49; normed fit index = 0.90), although there was also a good data fit for the patient group with a two-factor model. In the patient group, structural equation modeling suggested that shifting and (principally) updating were associated with the general measure of functional outcome (regression path coefficients: 0.34, p < 0.005; 0.39, p < 0.005, respectively), although when combined the mechanisms fail to contribute.Conclusion:This data suggests that the factor structure may be similar but not identical between groups, and both updating and shifting may play an important role in functional outcome in schizophrenia.

Speed and capacity of working memory and executive function in schizophrenia compared to unipolar depression

Schizophrenia is associated with deficits in working memory (WM) and executive functioning (EF) that are present from prodrome to chronic stages of the disease and are related to social and occupational functioning. Recent empirical findings suggest that schizophrenia patients might suffer from a specific speed deficit regarding WM operations that also affects EF. To test this hypothesis, executive functioning (EF) and working memory (WM) performance of 20 schizophrenia (SC) patients, 20 patients suffering from Major Depressive Disorder (MDD) and 40 healthy control (HC) subjects were compared. While schizophrenia patients performed worse in the measure of EF, no difference between the SC and the MDD patients was found regarding WM capacity. However, the SC group was shown to have an impaired speed in encoding, retrieval and manipulation of WM contents compared to the HC group whereas the MDD group showed no such deficit. Furthermore, while in the MDD group only WM capacity was linked to EF performance, in the SC group EF was determined by both WM capacity and WM speed. Hence, increasing the speed of WM operations might be a fruitful target for future therapeutic interventions, and assessing not only the capacity but also the speed of WM might be helpful in identifying candidates for endophenotypic cognitive markers of SC.

White matter microstructure predicts cognitive training-induced improvements in attention and executive functioning in schizophrenia

We examined the relationship between white matter microstructure in schizophrenia using diffusion tensor imaging (DTI) and cognitive improvements induced by 70h (~16weeks) of cognitive training. We measured anatomical connectivity in 48 patients with schizophrenia (SZ) and 28 healthy control participants (HC) at baseline, and then examined the relationship between anatomical connectivity at baseline and training-induced cognitive gains in 30 SZ who performed diffusion imaging after completing 70h of training. Compared with healthy control participants, individuals with schizophrenia showed reduced white matter integrity at baseline, as indexed by fractional anisotropy metrics, in bilateral posterior corona radiata, bilateral retrolenticular internal capsules, bilateral posterior thalamic radiation, left anterior corona radiata, left superior longitudinal fasciculus, left sagittal stratum, right cerebral peduncle and the genu and splenium of the corpus callosum. After training, schizophrenia participants showed significant gains in attention/vigilance, speed of processing, verbal learning, visual learning and executive functioning. White matter integrity within the right fronto-occipital fasciculus predicted training-induced improvements in attention/vigilance, while white matter integrity within the right corticospinal tract and bilateral medial lemnisci predicted cognitive training-induced improvements in executive functioning, areas that did not show white matter tract deficits at baseline. These findings suggest that preserved white matter integrity connecting long-range prefrontal-thalamic-sensorimotor areas may be an important determinant for training-induced neurocognitive plasticity.

Reduced Short-Latency Afferent Inhibition in Prefrontal but not Motor Cortex and Its Association With Executive Function in Schizophrenia: A Combined TMS-EEG Study.

Cholinergic dysfunction is increasingly assumed to be involved in the pathophysiology of schizophrenia. Short-latency afferent inhibition (SAI) is a transcranial magnetic stimulation (TMS) paradigm that has been shown to assay central cholinergic activity from the motor cortex (M1). Recently, we established a method to index SAI from the dorsolateral prefrontal cortex (DLPFC), an area implicated in the pathophysiology of schizophrenia. We investigated SAI in M1 and DLPFC in schizophrenia. We hypothesized that modulation of N100 on TMS-evoked potentials (TEPs) from the DLPFC would be attenuated in patients with schizophrenia compared to healthy controls. SAI was examined in 12 patients, whose age was matched to controls, using TMS combined with electroencephalography (EEG). SAI was recorded with TMS applied to left M1 (M1-SAI) and DLPFC (DLPFC-SAI). For group comparison, we used the SAI data of healthy participants in our previous study. In patients, N100 TEP was significantly attenuated with DLPFC-SAI, whereas P180 TEP was significantly increased with M1-SAI. Between patients and controls, there were significant differences in modulation of P180 TEP by M1-SAI (t22 = -2.748, P = .012; patients > controls) and N100 TEP by DLPFC-SAI (t22 = 5.456, P < .0001; patients < controls). Further, modulation of N100 TEP by DLPFC-SAI significantly correlated with executive function (r = -.740, P = .006, N = 12). Our findings suggest that DLPFC-SAI but not M1-SAI were reduced in patients with schizophrenia and this was linked to deficits in cognition. This may reflect prefrontal cholinergic deficits and represent a biomarker for cholinergic and executive dysfunction in patients with schizophrenia.

Increased plasma asymmetric dimethylarginine is associated with cognitive deficits in patients with schizophrenia.

Cognitive deficits are a core feature of schizophrenia. Previous studies have shown that plasma asymmetric dimethylarginine (ADMA), an endogenous inhibitor of the nitric oxide synthase, was increased in patients with schizophrenia. This study aimed to investigate the association of ADMA with cognitive deficits in schizophrenia. Forty-seven patients with schizophrenia and 45 healthy control subjects were recruited in present study. Cognitive function was assessed with a neuropsychological battery including 7 neurocognitive tests. Schizophrenic symptoms were assessed using the Positive and Negative Syndrome Scale and plasma ADMA concentration was measured by HPLC. We found that patients with schizophrenia exhibited poorer performances in nearly all of the cognitive tests except for the visual memory index compared with healthy controls. Plasma ADMA levels were significantly increased in patients with schizophrenia when compared to normal controls, and the mean ADMA concentration in patients with multiple episode schizophrenia was much higher than that of patients with first episode schizophrenia. For the patients, ADMA was negatively associated with attention, working memory and executive function in schizophrenia. These results suggest that ADMA may be involved in the pathophysiology of schizophrenia-associated cognitive impairments, and plasma ADMA could be a peripheral biomarker for evaluation of cognitive function in schizophrenia.