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Improvement of cognitive flexibility and cingulate blood flow correlates after atypical antipsychotic treatment in drug-naive patients with first-episode schizophrenia

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Abstract

The aim of this study was to examine the changes in cognitive flexibility and associated cerebral blood flow in the anterior cingulate lobe of drug-naive patients with first-episode schizophrenia who were treated with atypical antipsychotics for 6 weeks. Single photon emission computed tomography (SPECT) images were obtained from 8 healthy subjects both at rest and while performing the flexibility subtest of the TAP (Test for Attentional Performance). SPECT images were obtained in parallel from 8 first-episode drug-naive schizophrenic patients while they were performing the same task both before and after 6 weeks of neuroleptic treatment. In the control group, an increase in the perfusion indices of the dorsal section of the anterior cingulate gyrus was observed in the activation condition. Task performance was altered and the level of perfusion of the brain region related to the task execution was significantly decreased in the patients at baseline. After treatment, there was a significant improvement in both task performance and the level of perfusion of the dorsal section of the anterior cingulate. We conclude that treatment with second-generation neuroleptics improves cognitive flexibility, and there was a relationship between such improvements and normalization of perfusion indices of the involved brain areas.

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... The Word Fluency Test in the cognitive assessment battery was used to assess the richness of thinking; however, performance on this test did not differ between remitters and non-remitters in a post hoc analysis. Thus, impairment in the ability to comprehend and abstract and in thinking flexibility rather than other thinking impairments (e.g., richness) might predict a lower likelihood of PR. Abstract thinking impairment is an established deficit in schizophrenia (31), and impairment in cognitive flexibility has been found in FES patients (32). This subgroup of negative symptoms has a high degree of overlap with cognitive symptoms. ...
... Comparelli et al., further demonstrated that difficulty in abstract thinking was correlated with social cognition and did not differ between early schizophrenia and late schizophrenia (35). However, there has been little research exploring the significance of these impairments in the prognosis of schizophrenia, though there has been some research exploring the underlying neural basis (32,36). Our findings call for further studies with stricter designs to examine the predictive power of negative symptoms for PR, especially thinking symptoms and volition impairment rather than affective symptoms. ...
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Objective: To investigate the persistent remission rate (PRR) and its predictors within the first year of antipsychotic treatment in first-episode schizophrenia (FES) patients. Methods: In a sample of 301 FES patients who remained in antipsychotic treatment for 1 year, we assessed symptoms with the Positive and Negative Syndrome Scale (PANSS), cognition in six domains and functioning with the Personal and Social Performance Scale (PSP). Results: In total, 75.4% (227/301) of FES patients remaining in antipsychotic treatment reached persistent remission (PR) in one year. The PSP score was higher in remitters than non-remitters at the endpoint of the 1-year follow-up (P <0.0001). The PANSS negative score-but not the PANSS total score, positive score or general psychopathological score; PSP score; or cognitive performance at baseline-was negatively associated with PR. Lower scores for "abstract thinking" and "stereotyped thinking" were independent predictors of PR. Conclusions: In FES, nearly 3/4 patients could achieve PR with 1 year of antipsychotic treatment, and having fewer negative symptoms, especially thinking and volition symptoms, can predict PR. Clinical trial registration: www.ClinicalTrials.gov, identifier NCT01057849.
... cognitive performance improvement in drug naïve patients with schizophrenia (Pardo et al., 2011). It would be interesting, however, to extend these initial observations to longitudinal studies in patients with FEP to ascertain motor network connectivity changes in these patients and the effects of antipsychotic treatment. ...
Article
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... In these studies, schizophrenia patients showed increased ReHo in right superior frontal gyrus and right superior temporal gyrus (STG), and decreased ReHo in left fusiform gyrus, left STG, left postcentral gyrus, and right precentral gyrus, which suggest that altered spontaneous brain activity in the resting state may be related to the pathophysiology of schizophrenia (Malaspina et al. 2004). However, the results can be challenged due to lack of control for confounding factors such as illness duration, long-term exposure to antipsychotic medication, and possible progressive brain atrophy (Lui et al. 2010;Pardo et al. 2011;Hu et al. 2016). ...
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... In this study, we used ReHo analysis of resting-state fMRI to explore the effects of PAL on spontaneous brain activity in patients with schizophrenia. It is known that antipsychotics have been reported to reverse the abnormal BOLD signal (Pardo et al., 2011) in schizophrenia. We find that paliperidone can partially alleviate the abnormal spontaneous brain activity as well specifically in the anterior cingulate cortex and lingual gyrus. ...
Article
This study aimed to explore the effects of the long-acting antipsychotic drug palmitate paliperidone in resting-state brain activity of schizophrenia patients. Seventeen schizophrenia outpatients were included and received palmitate paliperidone injection (PAL) treatment for 13 weeks. These patients were compared to seventeen matched healthy controls. All subjects underwent two scan sessions of resting-state magnetic resonance imaging (baseline and the 13th week) and regional homogeneity (ReHo) at resting-state where compared. After 13 weeks of treatment, PAL increased ReHo of the prefrontal cortex, anterior cingulate gyrus and orbital frontal gyrus, while PAL decreased ReHo of the thalamus, parahippocampal gyrus and superior temporal gyrus. Furthermore, improvement of psychiatric symptoms correlated with changing amplitude of ReHo: positively correlated with postcentral gyrus and negatively correlated with the occipital cortex. Baseline ReHo values of the middle occipital gyrus were positively correlated with the rate of reduction of psychiatric symptoms and improvement of social function. These results suggested that PAL might achieve its clinical effect in schizophrenia by influencing the resting-state function of the occipital cortex, lateral prefrontal cortex and temporal lobe. Baseline function of the inferior occipital gyrus might potentially predict the short-term effect of PAL in schizophrenia.
... Shorter treatment programmes (five sessions) though have also been found to be effective in improving executive function after a TBI using a task shifting exercise (Stablum, Umiltà, Mazzoldi, Pastore, &amp; Magon, 2007). A review of treatments to address impairments in cognitive flexibility in other clinical populations (schizophrenia, pathological gambling, anorexia nervosa) indicates that both pharmacological interventions (Grant, Chamberlain, Odlaug, Potenza, &amp; Kim, 2010;Pardo et al., 2011) and cognitive remediation (Delahunty, Morice, &amp; Frost, 1993;Tchanturia, Davies, &amp; Campbell, 2007;Wykes et al., 2007) can be effective. In summary, there is evidence that cognitive remediation may be effective for impairments in executive functions (Cicerone et al., 2011). ...
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This paper provides a selective review of cognitive and psychological flexibility in the context of treatment for psychological distress after traumatic brain injury, with a focus on acceptance-based therapies. Cognitive flexibility is a component of executive function that is referred to mostly in the context of neuropsychological research and practice. Psychological flexibility, from a clinical psychology perspective, is linked to health and well-being and is an identified treatment outcome for therapies such as acceptance and commitment therapy (ACT). There are a number of overlaps between the constructs. They both manifest in the ability to change behaviour (either a thought or an action) in response to environmental change, with similarities in neural substrate and mental processes. Impairments in both show a strong association with psychopathology. People with a traumatic brain injury (TBI) often suffer impairments in their cognitive flexibility as a result of damage to areas controlling executive processes but have a positive response to therapies that promote psychological flexibility. Overall, psychological flexibility appears a more overarching construct and cognitive flexibility may be a subcomponent of it but not necessarily a pre-requisite. Further research into therapies which claim to improve psychological flexibility, such as ACT, needs to be undertaken in TBI populations in order to clarify its utility in this group.
... Schizophrenia is a severe psychiatric condition characterized by hallucination, delusion and impaired perception and cognition, 1,2 which have been attributed to structural and functional alterations of the brain, including the cingulate cortex. [3][4][5] Schizophrenia patients have exhibited abnormalities in cortical thickness, 6 gray matter volume (GMV), 7 metabolism, 8 cerebral blood flow, 9 taskevoked activation, 10 spontaneous activity, 11 anatomical connection 12 and resting-state functional connectivity (rsFC) 13 in the cingulate cortex. However, the cingulate cortex is a structurally 14 and functionally 15 heterogeneous region. ...
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Schizophrenia patients have shown altered resting-state functional connectivity (rsFC) of the cingulate cortex; however, it is unknown whether rsFCs of the cingulate subregions are differentially affected in this disorder. We aimed to clarify the issue by comparing rsFCs of each cingulate subregion between healthy controls and schizophrenia patients. A total of 102 healthy controls and 94 schizophrenia patients underwent resting-state functional magnetic resonance imaging with a sensitivity-encoded spiral-in imaging sequence to reduce susceptibility-induced signal loss and distortion. The cingulate cortex was divided into nine subregions, including the subgenual anterior cingulate cortex (ACC), areas 24 and 32 of the pregenual ACC, areas 24 and 32 of the anterior mid-cingulate cortex (aMCC), posterior MCC (pMCC), dorsal (dPCC) and ventral (vPCC) posterior cingulate cortex (PCC) and retrosplenial cortex (RSC). The rsFCs of each cingulate subregion were compared between the two groups and the atrophy effect was considered. Results with and without global signal regression were reported. Most cingulate subregions exhibited decreased rsFCs in schizophrenia after global signal regression (GSR). Without GSR, only increased rsFC was found in schizophrenia, which primarily restricted to the aMCC, PCC and RSC. Some of these increased rsFCs were also significant after GSR. These findings suggest that GSR can greatly affect between-group differences in rsFCs and the consistently increased rsFCs may challenge the functional disconnection hypothesis of schizophrenia.
... Handley et al. showed frontal hypoperfusion secondary to neuroleptics (haloperidol and aripiprazole) in healthy volunteers, but anterior cingulate perfusion was increased after neuroleptic treatment[43]. The same results were found by Pardo et al.[44]. The relative hypoperfusion found in the ACC is possibly minimized by neuroleptics. ...
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The aim of this study was to investigate the association between visual hallucinations in dementia with Lewy bodies (DLB) and brain perfusion using single-photon emission computed tomography. We retrospectively included 66 patients with DLB, 36 of whom were having visual hallucinations (DLB-hallu) and 30 of whom were not (DLB-c). We assessed visual hallucination severity on a 3-point scale of increasing severity: illusions, simple visual hallucinations and complex visual hallucinations. We performed voxel-level comparisons between the two groups and assessed correlations between perfusion and visual hallucinations severity. We found a significant decrease in perfusion in the left anterior cingulate cortex, the left orbitofrontal cortex and the left cuneus in the DLB-hallu group compared with the DLB-c group. We also found a significant correlation between decreased bilateral anterior cingulate cortex, left orbitofrontal cortex, right parahippocampal gyrus, right inferior temporal cortex and left cuneus perfusion with the severity of hallucinations. Visual hallucinations seem to be associated with the impairment of anterior and posterior regions (secondary visual areas, orbitofrontal cortex and anterior cingulate cortex) involved in a top-down and bottom-up mechanism, respectively. Furthermore, involvement of the bilateral anterior cingulate cortex and right parahippocampal gyrus seems to lead to more complex hallucinations.
... However, although opposite changes to neuropil is a compelling hypothesis to describe differential effects of FGA and SGA medications, other hypotheses should be noted. First, SGA-mediated increases in cortical thickness may be related to blood flow changes as SGAs can normalize blood flow deficits associated with first-episode psychosis (Pardo et al. 2011). However, although normalized blood flow may explain increases of thickness relative to FGA-medicated first-episode patients, this does not explain the absolute increase relative to controls. ...
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Background: Whether there are differential effects of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) on the brain is currently debated. Although some studies report that FGAs reduce grey matter more than SGAs, others do not, and research to date is limited by a focus on schizophrenia spectrum disorders. To address this limitation, this study investigated the effects of medication in patients being treated for first-episode schizophrenia or affective psychoses. Method: Cortical thickness was compared between 52 first-episode psychosis patients separated into diagnostic (i.e. schizophrenia or affective psychosis) and medication (i.e. FGA and SGA) subgroups. Patients in each group were also compared to age- and sex-matched healthy controls (n = 28). A whole-brain cortical thickness interaction analysis of medication and diagnosis was then performed. Correlations between cortical thickness with antipsychotic dose and psychotic symptoms were examined. Results: The effects of medication and diagnosis did not interact, suggesting independent effects. Compared with controls, diagnostic differences were found in frontal, parietal and temporal regions. Decreased thickness in FGA-treated versus SGA-treated groups was found in a large frontoparietal region (p < 0.001, corrected). Comparisons with healthy controls revealed decreased cortical thickness in the FGA group whereas the SGA group showed increases in addition to decreases. In FGA-treated patients cortical thinning was associated with higher negative symptoms whereas increased cortical thickness in the SGA-treated group was associated with lower positive symptoms. Conclusions: Our results suggest that FGA and SGA treatments have divergent effects on cortical thickness during the first episode of psychosis that are independent from changes due to illness.
... [33][34][35] Longitudinal studies utilizing structural neuroimaging techniques comparing drug-naïve patients before and after psychotropic treatment have observed positive effects 33,34,36 or no brain structure modification 35 after psychotropic treatment, while functional neuroimaging studies have observed enhancements in neuroplasticity and in brain connectivity. [37][38][39][40] The findings reported herein should be interpreted in the context of a number of limitations. The relatively small number of patients enrolled may preclude wider conclusions. ...
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Objective: Borderline personality disorder (BPD) is a devastating condition that causes intense disruption of patients' lives and relationships. Proper understanding of BPD neurobiology could help provide the basis for earlier and effective interventions. As neuroimaging studies of patients with BPD are still scarce, volumetric and geometric features of the cortical structure were assessed to ascertain whether structural cortical alterations are present in BPD patients. Methods: Twenty-five female outpatients with BPD underwent psychiatric evaluation (SCID-I and II) and a 1.5 T magnetic resonance imaging (MRI) brain scan. The control group comprised 25 healthy age-matched females. Images were processed with the FreeSurfer package, which allows analysis of cortical morphology with more detailed descriptions of volumetric and geometric features of cortical structure. Results: Compared with controls, BPD patients exhibited significant cortical abnormalities in the fronto-limbic and paralimbic regions of both hemispheres. Conclusion: Significant morphologic abnormalities were observed in patients with BPD on comparison with a healthy control group through a multimodal approach. This study highlights the involvement of regions associated with mood regulation, impulsivity, and social behavior in BPD patients and presents a new approach for further investigation through a method of structural analysis based on distinct and simultaneous volumetric and geometric parameters.
... Additionally, the effects of antipsychotic drugs have not been controlled for. Although previous studies have related antipsychotics and cognitive performance (Keefe et al., 1999 ), the influence of different antipsychotics on different cognitive functions is not clear: some studies have found an improvement (Andersen et al., 2011; Pardo et al., 2011 ) whereas others have found no differences (Stip, 2006; Robles et al., 2011). Nevertheless, our study found lower scores on CR in SSD than in HC and the CR measure correctly classified a high percentage of the sample into SSD or HC. ...
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Introduction: The concept of cognitive reserve (CR) has been defined as individual differences in the efficient utilization of brain networks which allow some people to cope better than others with brain pathology. CR has been developed mainly in the field of aging and dementia after it was observed that there appears to be no direct relationship between the degree of brain pathology and the severity of clinical manifestations of this damage. The present study applies the concept of CR to a sample of children and adolescents with a first episode of schizophrenia, aiming to assess the possible influence of CR on neuropsychological performance after two year follow-up, controlling for the influence of clinical psychopathology. Methods: 35 patients meeting DSM-IV criteria for schizophrenia or schizoaffective disorder (SSD) and 98 healthy controls (HC) matched for age and gender were included. CR was assessed at baseline, taking into account premorbid IQ, educational-occupational level and leisure activities. Clinical and neuropsychological assessments were completed by all patients at two year follow-up. Results: The CR proxy was able to predict working memory and attention at two year follow-up. Verbal memory and cognitive flexibility were not predicted by any of the variables included in the regression model. The SSD group obtained lower scores than HC on CR. CR measures correctly classified 79.8% of the sample as being SSD or HC. Conclusions: Lower scores on CR were observed in SSD than in HC and the CR measure correctly classified a high percentage of the sample into the two groups. CR may predict SSD performance on working memory and attention tasks.
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People with schizophrenia have exhibited reduced functional activity in the anterior cingulate cortex during the performance of many types of cognitive tasks and during the commission of errors. According to conflict theory, the anterior cingulate cortex is involved in the monitoring of response conflict, acting as a signal for a need for greater cognitive control. This study examined whether impaired conflict monitoring in people with schizophrenia could underlie reduced anterior cingulate activity during both correct task performance and error-related activity. Functional activity in the anterior cingulate of 13 schizophrenia patients and 13 healthy comparison subjects was investigated by using event-related fMRI and a Stroop task that allowed simultaneous examination of activity during both conflict (incongruent trials) and error (commission of error trials). In the presence of comparable reaction time measures for conflict as well as comparable error rates, the schizophrenia subjects showed both decreased conflict- and error-related activity in the same region of the anterior cingulate cortex. Moreover, those with schizophrenia did not exhibit significant post-conflict or post-error behavioral adjustments. Concurrently reduced conflict- and error-related activity in the anterior cingulate cortex along with reduced trial-to-trial adjustments in performance has not previously been reported in schizophrenia. The current results suggest that impaired conflict monitoring by the anterior cingulate cortex might play an important role in contributing to cognitive control deficits in patients with schizophrenia.
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Cliff (1993) has proposed the use of a measure of effect size alternative to traditionalmean differences: {? = Pr(xi1 > xj2) - Pr(xi1 j2)}which, taken a pair of values, xi1 and xj2, from the first and second populations respectively, gives the probability that the value from the first populationis higher than the one from the second, minus the probability of the inverse, which is,in fact, an alternative measure of effect size. In this paper we test, using computersimulation techniques, the robustness and power of Wilcoxon-Mann-Whitney''s U,and Cliff''s d statistics with samples of equal and unequal sizes under homoscedasticityand heteroscedasticity. We conclude that d test looks like a good alternative to traditionalmean tests, not only because it is not so much restricted by the parametric assumptions, but because it tests an effect size indicator which is nearer to researchers'' real interests.
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Deficits in working memory (WM) are a core symptom of schizophrenia patients and have been linked to dysfunctional prefrontal activation, which might be caused by a mesocortical hypodopaminergic state. Aripiprazole--a partial dopamine antagonist--is a novel antipsychotic, which increases frontal dopamine concentrations in preclinical studies. However, little is known about specific medication effects on the modulation of frontal activation during WM performance. We measured BOLD-response during a WM task in a longitudinal fMRI-study in eleven schizophrenia patients first when they received conventional antipsychotics (T1) and a second time after they had been switched to aripiprazole (T2). A healthy control group matched for age, handedness and gender was investigated at two corresponding time points. Data was analyzed with SPM5 in a 2 x 2 x 2 design (groupxsessionxtask). Schizophrenia patients showed fewer correct responses compared to healthy controls at T1 and a trend-wise normalization at T2. The task activated the fronto-parietal network during the contrast 2-back>0-back in all participants. At T1 patients revealed a hypoactivation in the dorsal anterior cingulate cortex (ACC), which normalized after switch to aripiprazole and correlated with improved task performance. This was due to a significant increase in the patients group while the control group did not change, as corroborated by a significant groupxtime interaction in this region. This study showed for the first time that the partial dopamine antagonist aripiprazole increases BOLD-signal during a WM task in the cognitive part of the ACC in schizophrenia patients, which may reflect its beneficial effect on cognitive deficits.
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Deficits in attention are a stable feature of schizophrenia and likely to interfere with social function. In this study, we explored whether 2 types of attentional dysfunction, increasingly variable and declining reaction times over the course of a continuous performance task, were linked to psychosocial deficits. Participants were 102 adults with schizophrenia spectrum disorders in ongoing outpatient treatment. Concurrent assessments included the Conners' Continuous Performance Test II, the Inventory of Interpersonal Problems, and the Ways of Coping Questionnaire. Analysis of covariance controlling for global performance on the Continuous Performance test suggested that participants with a pattern of increasingly variable performance on the task (n = 14) reported being more domineering and taken advantage of socially, than those whose performance was less variable (n = 88). No differences were found between groups for assessments of coping or between participants who showed a declining vs non-declining reaction time.
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Paradigms exploring cognitive inhibition involve motor responses, which may confound the results. We compare cognitive inhibition activation obtained without motor involvement, to motor inhibition alone, in a group of young right-handed volunteers, utilizing a classical color Stroop task (CST), and a Stop Task. Comparison of fMRI activation was performed contrasting lateralization indexes of different Regions of Interest (ROI). Cognitive inhibition showed left brain lateralization, while motor inhibition showed right brain lateralization. Homologue brain areas involved the inferior frontal gyrus, inferior parietal lobule, middle temporal gyrus, and anterior cingulate gyrus. These circuitries appear to support that inhibition is a complicated function involving working memory, attention, semantic decision, and motivation modules.
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Schizophrenia is characterized by a lack of integration between thought, emotion, and behavior. A disruption in the connectivity between brain processes may underlie this schism. Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) were used to evaluate functional and anatomical brain connectivity in schizophrenia. In all, 29 chronic schizophrenia patients (11 females, age: mean=41.3, SD=9.28) and 29 controls (11 females, age: mean=41.1, SD=10.6) were recruited. Schizophrenia patients were assessed for severity of negative and positive symptoms and general cognitive abilities of attention/concentration and memory. Participants underwent a resting-fMRI scan and a DTI scan. For fMRI data, a hybrid independent components analysis was used to extract the group default mode network (DMN) and accompanying time-courses. Voxel-wise whole-brain multiple regressions with corresponding DMN time-courses was conducted for each subject. A t-test was conducted on resulting DMN correlation maps to look between-group differences. For DTI data, voxel-wise statistical analysis of the fractional anisotropy data was carried out to look for between-group differences. Voxel-wise correlations were conducted to investigate the relationship between brain connectivity and behavioral measures. Results revealed altered functional and anatomical connectivity in medial frontal and anterior cingulate gyri of schizophrenia patients. In addition, frontal connectivity in schizophrenia patients was positively associated with symptoms as well as with general cognitive ability measures. The present study shows convergent fMRI and DTI findings that are consistent with the disconnection hypothesis in schizophrenia, particularly in medial frontal regions, while adding some insight of the relationship between brain disconnectivity and behavior.
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The study's goal was to characterize the typology of patient outcomes based on social and occupational functioning and psychiatric symptoms following antipsychotic drug treatment, and to explore predictors of group membership representing the best/worst outcomes. A hierarchical cluster analysis was used to define groups of patients (n=1449) based on endpoint values for psychiatric symptoms, social functioning, and useful work measured up to 30 weeks of treatment. Stepwise logistic regression was used to construct predictive models of cluster membership for baseline predictors, and with 2/4/8 weeks of treatment. Five distinct clusters of patients were identified at endpoint (Clusters A-E). Patients in Cluster A (25.6%, best outcome) had minimal psychiatric symptoms and mild functional impairment, while patients in Cluster D (14.3%) and E (14.8%) (worst outcome) had moderate-to-severe symptoms and severe functional impairment. Occupational functioning, disorganized thinking, and positive symptoms were sufficient to describe the clusters. Membership in the best/worst clusters was predicted by baseline scores for functioning and symptom severity, and by early changes in symptoms with treatment. Psychiatric symptoms and functioning provided complementary information to describe treatment outcomes. Early symptom response significantly improved the prediction of outcome, suggesting that early monitoring of treatment response may be useful in clinical practice.
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To analyze the prevalence of negative symptoms in antipsychotic-treated outpatients with schizophrenia spectrum disorders. A cross-sectional, retrospective multicenter study was carried out between May 2004 and April 2005 in 1,704 adult psychiatric outpatients meeting DSM-IV criteria for schizophrenia, schizophreniform, or schizoaffective disorder. We used 5 items of the Positive and Negative Syndrome Scale (PANSS) negative symptoms subscale to individually determine the presence of a negative symptom when the score on the item was > 3. Primary negative symptoms were considered present when patients fulfilled all of the following: > 3 score on the corresponding item; < 3 score on any positive item; no extrapyramidal symptoms; <or= 3 score on anxiety and depression items; dose of haloperidol, when applicable, <or= 15 mg/d; and no antiparkinsonian treatment. A total of 1,452 evaluable patients (863 men, 60.9%), 40.7 +/- 12.2 (mean +/- SD) years of age, were included. One or more negative symptoms were present in 57.6% of patients, with primary negative symptoms in 12.9% of subjects. The most frequent negative symptom items were social withdrawal (45.8%), emotional withdrawal (39.1%), poor rapport (35.8%), and blunted affect (33.1%). Negative symptoms (1-blunted affect, 2-emotional withdrawal, 3-poor rapport, 4-social withdrawal, 5-verbal fluency) were most associated with maleness (symptom 4); age > 40/45 years (men/women; symptoms 1,2,4); single/unmarried status (symptoms 2-4); unemployment (symptoms 3,4); higher score on the Clinical Global Impressions (CGI) scale and PANSS total score (symptoms 1-5); lower score on the PANSS positive symptoms subscale (symptoms 1,3); more than 52 weeks of treatment (symptoms 1-3,5); and high antipsychotic dose (symptom 2). The prevalence of negative symptoms in patients with schizophrenia spectrum disorders treated with antipsychotics in routine clinical practice not only is still considerably high but also seems to be related to poorer functioning, unemployment, greater severity, and less positive symptomatology and higher antipsychotic dose.
Article
To examine the functional association between brain and autonomic activities accompanying decision-making, we simultaneously recorded regional cerebral blood flow using (15)O-water positron emission tomography and event-related brain potentials (ERPs) time-locked to feedback of reward and punishment, as well as cardiovascular parameters, during a stochastic decision-making task. We manipulated the uncertainty of outcomes in the task; specifically, we compared a condition with high predictability of reward/punishment (contingent-reward condition) and a condition with low predictability of reward/punishment (random-reward condition). The anterior cingulate cortex (ACC) was commonly activated in both conditions. Compared with the contingent-reward condition, the orbitofrontal and right dorsolateral prefrontal cortices and dorsal striatum were activated in the random-reward condition, where subjects had to continue to seek contingency between stimuli and reward/punishment. Activation of these brain regions correlated with a positive component of ERPs locked to feedback signals (feedback-related positivity), which showed an association with behavioral decision-making in the contingent-reward condition. Furthermore, cardiovascular responses were attenuated in the random-reward condition, where continuous attention and contingency monitoring were needed, and such attenuation of cardiovascular responses was mediated by vagal activity that was governed by the rostral ACC. These findings suggest that the prefrontal-striatal network provides a neural basis for decision-making and modulation over the peripheral autonomic activity accompanying decision-making.
Article
It is unclear whether task conflict is reflected in the anterior cingulate cortex (ACC) or in more dorsal regions of the medial frontal cortex (MFC). When participants switch between tasks involving incongruent, congruent, and neutral stimuli, it is possible to examine both response conflict (incongruent vs. congruent) and task conflict (congruent vs. neutral). Here, we report an event-related functional magnetic resonance imaging (fMRI) study that examined which areas in frontal cortex, including MFC, are implicated in response conflict, task conflict, or both. Stimuli were incongruent and congruent arrow-word combinations, or arrows and words only in a neutral condition. Participants responded manually to the arrow or word. The task varied every second trial. The behavioral data revealed response conflict (incongruent>congruent) and task conflict (congruent>neutral) in mean reaction times and ex-Gaussian latency distribution components. The imaging data revealed activity in both the ACC and a more dorsal region in the MFC (the medial superior frontal gyrus) related to response conflict as well as task conflict. These conflict effects were observed independent of the task performed (arrow or word) or the trial type (repeat or switch). In lateral prefrontal cortex (LPFC), response conflict was associated with activity in ventral LPFC, whereas task conflict activated both ventral and dorsal regions. Thus, whereas the type of conflict (response vs. task) was differentiated in LPFC, no such differentiation was found in MFC, including the ACC. Models of ACC functioning may require modification to take account of these findings.
Article
To investigate the neurocognitive effectiveness of haloperidol, risperidone, and olanzapine in first-episode schizophrenia-spectrum disorders. This prospective, randomized, open-label study was conducted from February 2001 to February 2005. Data for the present investigation were obtained from a large epidemiologic and 3-year longitudinal intervention program of first-episode psychosis (DSM-IV criteria) conducted at the outpatient clinic and the inpatient unit at the University Hospital Marques de Valdecilla, Santander, Spain. One hundred four patients randomly assigned to haloperidol (N = 35), olanzapine (N = 30), or risperidone (N = 39) who completed clinical and cognitive evaluations at baseline, 6 months, and 1 year were included in the final analysis. Thirty-seven healthy individuals were also longitudinally assessed. A neuropsychological battery that comprised 9 cognitive domains was used. The contribution of clinical changes, concomitant medications, and the severity of motor side effects to cognitive changes was controlled. The main outcome measure was cognitive changes at 1-year follow-up. The 3 treatment groups showed a significant improvement in cognitive scores after 1 year. The differential cognitive effectiveness between antipsychotics was insignificant. The magnitude of cognitive changes was similar in the 3 treatment groups and controls, although a greater improvement on the Finger Tapping Test, Trail Making Test B, and Rey Complex Figure Test was found in the treatment groups. Clinical changes, use of concomitant medications, and the emergence of motor side effects did not significantly account for cognitive changes over time. Haloperidol, olanzapine, and risperidone were equally effective in treating cognitive deficits of psychosis. The effect of practice clearly contributes to cognitive score improvements after treatment with antipsychotics. Our results provide important information regarding the practical utility of antipsychotic treatments to improve cognition and could have implications for developing novel approaches for cognitive pharmacotherapy in schizophrenia.
Article
Cognitive impairment, manifested as mild to moderate deviations from psychometric norms, is present in many but not all schizophrenia patients. The purpose of the present study was to compare the effect of haloperidol with that of second-generation antipsychotic drugs on the cognitive performance of patients with schizophreniform disorder or first-episode schizophrenia. Subjects were 498 patients with schizophreniform disorder or first-episode schizophrenia who were randomly assigned to open-label haloperidol (1 to 4 mg/day [N=103]), amisulpride (200 to 800 mg/day [N=104]), olanzapine (5 to 20 mg/day [N=105]), quetiapine (200 to 750 mg/day [N=104]), or ziprasidone (40 to 160 mg/day [N=82]). The Rey Auditory Verbal Learning Test, Trail Making Test Part A and Part B, WAIS Digit Symbol Test, and Purdue Pegboard Test were administered at baseline and the 6-month follow-up evaluation. Compared with scores at baseline, composite cognitive test scores improved for all five treatment groups at the 6-month follow-up evaluation. However, there were no overall differences among the treatment groups. In addition, there was a weak correlation between the degree of cognitive improvement and changes in Positive and Negative Syndrome Scale scores. Treatment with antipsychotic medication is associated with moderate improvement in the cognitive test performance of patients who have schizophreniform disorder or who are in their first episode of schizophrenia. The magnitude of improvement does not differ between treatment with haloperidol and treatment with second-generation antipsychotics. Moreover, cognitive improvement is weakly related to symptom change.
Article
The aim of this study was to investigate everyday executive functioning abilities in patients with focal cerebellar lesions using an executive battery sensitive for the detection of damage to the prefrontal cortex, including a "real life" situation task. Eleven patients with focal cerebellar infarcts were studied prospectively after their injury. All subjects underwent a complete neurological, neuropsychiatric, and neuropsychological examination, as well as a specific computerized battery (Test of Attentional Performance), and an "ecological" test: the Multiple Errands Task-hospital version (MET-hv, adapted version). Significant differences were found between patients and normal controls in language and executive functions tasks. Significant differences were observed in the flexibility subscale of the Test of Attentional Performance and several subscales of the MET-hv (total amount of failures, interpretation failures, task completion score, and inefficiencies subscale). This study supports previous reports showing a pattern of cognitive abnormalities following focal cerebellar damage that includes impairments of executive function. Moreover, it suggests that the ecological test used in this investigation might be useful for the detection of deficits in real-life executive functioning among this patient population.
Article
While much is known about receptor affinity profiles of antipsychotic medications, less is known about their impact on functional brain systems in patients with schizophrenia. We conducted functional magnetic resonance imaging (fMRI) studies with first-episode schizophrenia patients as they made saccades to unpredictable visual targets before and after 4-6 weeks of antipsychotic treatment. Matched healthy individuals were scanned at similar time intervals. Pretreatment, patients had less activation in frontal and parietal eye fields and cerebellum. After treatment these disturbances were not present, suggesting improved function in attentional and sensorimotor systems. Other pretreatment abnormalities were noted in sensory and ventromedial prefrontal cortex, but after treatment these abnormalities were absent or less prominent, in line with improved function in attentional systems. In addition, although not abnormal at baseline, there was reduced activity after treatment in dorsal prefrontal cortex, dorsal striatum, and dorsomedial thalamus, suggesting a potential adverse effect of treatment on frontostriatal systems, perhaps related to dopamine blockade in the caudate. These findings provide evidence for a complex impact of antipsychotic medication on functional brain systems in schizophrenia and illustrate the potential of neuroimaging biomarkers for both adverse and beneficial drug effects on functional brain systems.
Article
The purpose of this study was to examine the relative contributions of antipsychotic medication, negative symptoms and executive functions to impairment in social functioning in a sample of outpatients with stable schizophrenia. One-hundred and sixty-eight consecutive outpatients with stable schizophrenia were enrolled in a cross-sectional study. We performed a path analysis using multiple regression technique in order to assess the specific effect of antipsychotic type (first-generation antipsychotics versus second-generation antipsychotics) on social functioning and the possible mediating role of executive functions and negative symptoms. Our findings suggested that (i) second generation antipsychotics (SGAs) use predicted better social functioning (Beta=.24, p=.003) and better executive functions (Beta=.25, p=.003); conversely SGAs use was not associated with lesser negative symptoms (Beta=.00, p=.981); (ii) impaired executive functions and severity of negative symptoms were associated with worse social functioning (Beta=.19, p=.016; Beta=.28, p=.001); (iii) when we inserted in the model Positive and Negative Syndrome Scale - Negative Symptom subscale (PANSS-N) and Wisconsin Card Sorting Test - number of achieved sorting categories (WCST-cat), the former failed to show a mediation effect, while the latter seemed to mediate partially the effect of SGAs on social functioning. Taken together, the present results suggest that it is critical to examine individually executive functions and negative symptoms because they seem to relate to social functioning in different and independent ways and thus might represent separable treatment targets. Furthermore, social functioning appears a complex outcome multiply determined with no single predictor variable explaining a sufficient amount of variance.
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Mental processes related to visceral activity have gained growing interest during the last few years. The following study is the first to investigate possible interactions between interoceptive awareness and measures of attentional performance. We tested the hypothesis whether interoceptive awareness is positively related to indices of selective and divided attentional performances. Using a heartbeat perception task, 29 healthy female participants were separated into two groups scoring either high or low in an interoceptive awareness task. Attentional performance was assessed by several tests including the 'd2 test of attention' and subtests from the 'TAP: Test Battery for Attentional Performance'. We observed a significantly better performance in selective and divided attention for participants with high interoceptive awareness. Our data suggests that interoceptive awareness is related to a better performance especially in tasks assessing selective and divided attention. We conclude 1) that perception of bodily states might be a crucial determinant for the processing of external, visual stimuli, 2) that the ability to perceive internal signals might be an indicator of self-focused attention, and 3) that bodily signals may use, at least in part, similar processing resources as signals from the attention system.
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Aberrant brain activation during facial emotion discrimination has been described in chronic schizophrenia, while little is known about early stages of the illness. The aim of the current study was to investigate valence-specific brain activation of emotion discrimination in first-episode schizophrenia. These patients provide the advantage of lacking the effects of long-term medication and chronic illness course and can hence further enhance the understanding of underlying psychopathological mechanisms. Using event-related fMRI, we investigated 18 first-episode schizophrenia patients and 18 matched healthy subjects during an explicit emotion discrimination task presenting happy, sad and neutral monochromatic facial expressions. A repeated measure analysis of variance (ANOVA) with the factors Group (patients, healthy subjects), Gender and Emotion (happy, sad, neutral) was performed on behavioural and functional data. Behavioural performance did not differ between groups. Valence-independent hypoactivations in patients were observed for the anterior cingulate and orbitofrontal cortex while hyperactivations emerged in the posterior cingulate and the precuneus. Emotion-specific group differences were revealed in inferior parietal and orbitofrontal brain areas and the hippocampus. First-episode schizophrenia already affects areas involved in processing of both, emotions and primary facial information. Our study underlines the role of dysfunctional neural networks as the basis of disturbed social interactions in early schizophrenia.
Article
Despite progress in antipsychotic medication, psychosocial functioning limitations remain a major source of disability in schizophrenia. For this purpose, rehabilitation programs, aimed at enhancing community functioning, are currently developed. An important question raised by rehabilitation programs is to identify clinical predictors of psychosocial functioning which could in turn be targets of intervention. It has been suggested that a greater part of the variance in community functioning may be explained by cognitive functioning rather than by symptoms. Moreover, cognitive factors predict community functioning improvement over time. However, community functioning is a multidimensional construct and little is known about the specificity of associations between community functioning dimensions and cognitive factors. Recent studies suggest that functions like memory and executive processes are particularly associated with instrumental and social dimensions of community functioning. Memory processes are associated with both dimensions, whereas executive processes are more related to instrumental aspects of functioning. They could be specifically targeted in interventions aimed at enhancing functioning in those particular dimensions. However, these associations need to be further explored. A lot of methodological and theoretical difficulties limit the possibility to compare studies and to draw clinically useful information. Theoretical models of disability could help in better defining particular community abilities, their level of complexity and the way they could be related to specific cognitive factors. Future results will provide relevant information for enhancing the usefulness of cognitive evaluation, as well as improving the efficiency of rehabilitation programs.
Article
The aim of this review was to discuss data from double-blind, randomized controlled trials (RCTs) that have investigated the effects of oral and long-acting injectable risperidone on cognitive and psychomotor functioning in patients with schizophrenia or schizoaffective disorder. PubMed/MEDLINE and the Institute of Scientific Information Web of Science database were searched for relevant English-language double-blind RCTs published between March 2000 and July 2008, using the terms schizophrenia, schizoaffective disorder, cognition, risperidone, psychomotor, processing speed, attention, vigilance, working memory, verbal learning, visual learning, reasoning, problem solving, social cognition, MATRICS, and long-acting. Relevant studies included patients with schizophrenia or schizoaffective disorder. Cognitive domains were delineated at the Consensus Conferences of the National Institute of Mental Health-Measurement And Treatment Research to Improve Cognition in Schizophrenia (NIMH-MATRICS). The tests employed to assess each domain and psychomotor functioning, and the within-group and between-group comparisons of risperidone with haloperidol and other atypical antipsychotics, are presented. The results of individual tests were included when they were individually presented and interpretable for either drug; outcomes that were presented as cluster scores or factor structures were excluded. A total of 12 articles were included in this review. Results suggested that the use of oral risperidone appeared to be associated with within-group improvements on the cognitive domains of processing speed, attention/vigilance, verbal and visual learning and memory, and reasoning and problem solving in patients with schizophrenia or schizoaffective disorder. Risperidone and haloperidol seemed to generate similar beneficial effects (on the domains of processing speed, attention/vigilance, [verbal and nonverbal] working memory, and visual learning and memory, as well as psychomotor functioning), although the results for verbal fluency, verbal learning and memory, and reasoning and problem solving were not unanimous, and no comparative data on social cognition were available. Similar cognitive effects were found with risperidone, olanzapine, and quetiapine on the domains of verbal working memory and reasoning and problem solving, as well as verbal fluency. More research is needed on the domains in which study results were contradictory. For olanzapine versus risperidone, these were verbal and visual learning and memory and psychomotor functioning. No comparative data for olanzapine and risperidone were available for the social cognition domain. For quetiapine versus risperidone, the domains in which no unanimity was found were processing speed, attention/vigilance, nonverbal working memory, and verbal learning and memory. The limited available reports on risperidone versus clozapine suggest that: risperidone was associated with improved, and clozapine with worsened, performance on the nonverbal working memory domain; risperidone improved and clozapine did not improve reasoning and problem-solving performance; clozapine improved, and risperidone did not improve, social cognition performance. Use of long-acting injectable risperidone seemed to be associated with improved performance in the domains of attention/vigilance, verbal learning and memory, and reasoning and problem solving, as well as psychomotor functioning. The results for the nonverbal working memory domain were indeterminate, and no clear improvement was seen in the social cognition domain. The domains of processing speed, verbal working memory, and visual learning and memory, as well as verbal fluency, were not assessed. The results of this review of within-group comparisons of oral risperidone suggest that the agent appeared to be associated with improved functioning in the cognitive domains of processing speed, attention/vigilance, verbal and visual learning and memory, and reasoning and problem solving in patients with schizophrenia or schizoaffective disorder. Long-acting injectable risperidone seemed to be associated with improved functioning in the domains of attention/vigilance, verbal learning and memory, and reasoning and problem solving, as well as psychomotor functioning, in patients with schizophrenia or schizoaffective disorder.
Article
Two methods for 3D realignment of activation brain single-photon emission tomographic (SPET) studies are analyzed. The first is based on principal axes transformation (PAT). The second uses the results of the first method as initial values to start a least-squares iterative process (LS) to search for the maximum value of the correlation function. Both methods were tested with simulated and real studies. The results of the PAT method showed a maximum translation error of 0.3 +/- 0.1 pixels and a rotational error of 1.2 +/- 0.7 degrees in a total of 100 runs. For the LS method these errors were 0.2 +/- 0.1 and 0.6 +/- 0.3. The realignment for 34 real studies was assessed by three expert observers. The alignment was found to be satisfactory in all cases for the LS method, and in 18 cases (53%) for the PAT method. From the results we conclude that a combination of both methods allows the accurate realignment of SPET neuroactivation studies.
Article
The main experimental works about neuropsychological impairments of schizophrenia are reviewed. The underlying mechanisms of the cognitive deficits are set in a framework of the limited capacity model. In second point, the current status of the modificability of the cognitive deficits and the clinical and psychosocial consequences of this deficits are presented. At least, neuropsychological rehabilitation programs are reviewed from a clinical point of view.
Article
Abnormalities in the anterior cingulate cortex have been reported in patients with schizophrenia, and have been implicated in the pathophysiology of this disorder. In the present study, we have examined antipsychotic-sensitive binding sites in the left anterior cingulate cortex of schizophrenia patients and controls. Using quantitative autoradiography and [(3)H]spiperone as a ligand, both saturation and competition experiments were performed in post-mortem brain tissue obtained from six schizophrenia and six control cases. Saturation experiments revealed that the maximum number of [(3)H]spiperone binding sites was significantly reduced by 31% in the schizophrenia group as compared to the control group (65.3+/-5.6 fmol/mg tissue versus 94.2+/-7.3 fmol/mg tissue). Increased dissociation constant was also observed in the schizophrenia group (2.2+/-0.4 nM versus 1.3+/-0.2 nM), but was not statistically significant (P=0.07). Competition experiments were performed in order to examine the pharmacological profile of [(3)H]spiperone binding, and revealed that: (i) displacement of [(3)H]spiperone binding by clozapine and mianserin was significantly reduced in the schizophrenia group as compared to the control group (-26% and -16% respectively); (ii) the order of displacement potency of the drugs tested was: haloperidol>mianserin>butaclamol approximately risperidone>clozapine>2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene. Our results suggest a reduction of antipsychotic-sensitive binding sites in the anterior cingulate cortex of patients with schizophrenia. Such abnormality could lead to an imbalance in neurotransmitter regulation in the anterior cingulate cortex which may contribute to the emergence of some symptoms of schizophrenia.
Article
Stroop s paradigm has been used to evaluate the anterior attention system which regulates the inhibitory capacity of automatic responses. Functional neuroimaging techniques have shown a preponderant role for the anterior cingulate cortex in carrying out this paradigm. To evaluate the activity of the anterior cingulate cortex in view of its clinical importance in the study of neurological and psychiatric disorders. Eleven healthy volunteers took part in the study. The functional images were analyzed using the software SPM99 and by second order individual and group analysis. Initial local analysis showed activation in the right anterior cingulated cortex (Brodmann s area 32) and left central (areas 31 and 23); caudate nucleus (right body and left tail) and thalamus (bilateral). Overall there was significant activation of the left hemisphere, in areas 44 (Broca s area), 7, 40 (supra marginal gyrus and insular cortex, and in the right hemisphere in area 19. In spite of this there was great individual variation. The overall results are concordant with complex functional connections for attention and the control of automatic responses. In our study the anterior cingulated cortex was not selectively activated. The activation of the thalamus and caudate nucleus may be explained by their involvement in the frontostriatal circuits. The lack of individual consistency may be due to different personal cognitive styles of resolving conflicts. According to our results, Stroop s paradigm would not be clinically useful for showing good or bad functioning of the anterior cingulated cortex.
Article
Attentional processes play a central role in information selection, which is impaired in schizophrenic patients. In the present study, we attempted to characterize the attentional performance of chronic schizophrenics using a computerized assessment of the multiple components of attentional function. Two comparable samples, consisting, respectively, of out-patients and in-patients, were tested in order to assess the effect of chronic institutionalization. Twenty-four subjects (half in-patients and half out-patients) fulfillling DSM-IV criteria for schizophrenia were examined with a standard computerized battery for the assessment of attention, namely Testbatterie zur Aufmerksamkeitsprufung (TAP). Both groups were impaired on all measures of attentional processing (in terms of both reaction times and number of errors). There were no significant differences in attentional performance between in- and out-patients. In conclusion, the present findings confirm the presence of pervasive attentional dysfunction in chronic schizophrenia; the lack of significant differences in performance between in- and out-patients supports the hypothesis that the cognitive deficits are inherently associated with the illness and cannot be attributed to environmental/social factors.
Article
Prior work indicates that various aspects of task-irrelevant information (e.g. its salience, task-relatedness, emotionality) can increase the involvement of prefrontal cortex (PFC) in top-down attentional control. In light of these findings, we hypothesize that PFC's involvement increases when task-irrelevant information competes for priority in processing. In an event-related fMRI study using an oddball variant of the Stroop task, we examine the generality of this hypothesis using three manipulations designed to increase the ability of task-irrelevant information to compete for priority in processing. First, we investigated how the frequency of occurrence of task-irrelevant information affects PFC activity. Second, we examined whether conflicting color information (i.e. incongruent trials) increases activity in regions of PFC that are similar to or distinct from those sensitive to infrequently occurring task-irrelevant information. Finally, we examined the impact of the number of levels at which conflict could occur (e.g. non-response only, non-response and response). Activity in posterior-dorsolateral and posterior-inferior PFC increased for infrequently occurring task-irrelevant information, being largest when the task-irrelevant information contained conflicting color-information. In contrast, increases in mid-dorsolateral prefrontal cortex's activity were only noted when conflicting color information was present, being largest when conflict occurred at multiple levels. The anterior cingulate was primarily sensitive to the occurrence of conflict at the response level with only a small sub-region exhibiting sensitivity to non-response conflict as well. From these findings we suggest that posterior DLPFC and PIPFC are involved in biasing processing in posterior processing systems, mid-DLPFC is involved in biasing the processing of the contents of working memory, and ACC is primarily involved in response-related processes.
Article
Current concepts of cognitive control suggest that the anterior cingulate cortex (ACC) is involved in performance monitoring. This idea is supported by the finding that increased ACC activity is found in situations in which errors are likely to occur, even if none are actually made. In addition, recent results suggest that increased ACC activity is negatively correlated with reaction time. We have now compared the error rates and the ACC activity of healthy subjects with short (n=19) vs. long reaction times (n=17) in an auditory choice reaction paradigm and analysed the current density differences in the ACC in the time range of the N1 component with low resolution electromagnetic tomography. Subjects with short reaction times showed significantly more ACC activation (Brodmann Area 24) and an increased error rate. This finding suggests that increased ACC activity is associated with a gain in reaction speed at the expense of correctness and is discussed in the context of current concepts about the role of the ACC in cognitive functions.
Article
Quetiapine improves both psychotic symptoms and cognitive function in schizophrenia. The neural basis of these actions is poorly understood. Three subject groups underwent a single functional magnetic resonance imaging (fMRI) session: drug-naive (n = 7) and quetiapine-treated samples of patients with schizophrenia (n = 8) and a healthy control group (n = 8). The fMRI session included an overt verbal fluency task and a passive auditory stimulation task. In the verbal fluency task, there was significantly increased activation in the left inferior frontal cortex in the quetiapine-treated patients and the healthy control sample compared with the drug-naive sample. During auditory stimulation, the healthy control group and stably treated group produced significantly greater activation in the superior temporal gyrus than the drug-naive sample. Quetiapine treatment is associated with altered blood oxygen level-dependent responses in both the prefrontal and temporal cortex that cannot be accounted for by improved task performance subsequent to drug treatment.
Article
Voxel-based morphometry (VBM) allows the output of structural data in a Statistical Parametric Map of the brain in the same way that the SPM can do with functional data. Using functional magnetic resonance (fMR), we studied brain activation in 14 patients with schizophrenia and 14 matched normal controls. We found significant hypoactivation in patients in several regions, especially in the right hemisphere, in the dorsolateral frontal and temporal regions and in the inferior parietal. Subcortically, we found strong hypoactivity in the thalamus. The optimized VBM method revealed gray matter (GM) abnormalities in the bilateral supramarginal gyrus and cingulate cortex, and in the right inferior temporal regions. Three regions involved in attentional processes showed both structural and functional deficits: the thalamus, the anterior cingulate and the inferior parietal. The results suggest that these regions may be involved in the attentional deficit in schizophrenia.