Brain functional correlates of formal thought disorder in schizophrenia: examining the frontal/dysexecutive hypothesis.

BACKGROUND: One hypothesis proposed to underlie formal thought disorder (FTD), the incoherent speech is seen in some patients with schizophrenia, is that it reflects impairment in frontal/executive function. While this proposal has received support in neuropsychological studies, it has been relatively little tested using functional imaging. This study aimed to examine brain activations associated with FTD, and its two main factor-analytically derived subsyndromes, during the performance of a working memory task. METHODS: Seventy patients with schizophrenia showing a full range of FTD scores and 70 matched healthy controls underwent fMRI during the performance of the 2-back version of the n-back task. Whole-brain corrected, voxel-based correlations with FTD scores were examined in the patient group. RESULTS: During 2-back performance the patients showed clusters of significant inverse correlation with FTD scores in the inferior frontal cortex and dorsolateral prefrontal cortex bilaterally, the left temporal cortex and subcortically in the basal ganglia and thalamus. Further analysis revealed that these correlations reflected an association only with 'alogia' (poverty of speech, poverty of content of speech and perseveration) and not with the 'fluent disorganization' component of FTD. CONCLUSIONS: This study provides functional imaging support for the view that FTD in schizophrenia may involve impaired executive/frontal function. However, the relationship appears to be exclusively with alogia and not with the variables contributing to fluent disorganization.

Association of formal thought disorder in schizophrenia with structural brain abnormalities in language-related cortical regions.

BACKGROUND: Formal thought disorder (FTD) in schizophrenia has been found to be associated with volume reductions in the left superior temporal cortex. However, there have been negative findings and some studies have also found associations in other cortical regions. METHOD: Fifty-one schizophrenic patients were evaluated for presence of FTD with the Thought, Language and Communication (TLC) scale and underwent whole-brain structural MRI using optimized voxel-based morphometry (VBM). Fifty-nine matched healthy controls were also scanned. RESULTS: Compared to 31 patients without FTD (global TLC rating 0 or 1), 20 patients with FTD (global TLC rating 2-5) showed clusters of volume reduction in the medial frontal and orbitofrontal cortex bilaterally, and in two left-sided areas approximating to Broca's and Wernicke's areas. The pattern of FTD-associated volume reductions was largely different from that found in a comparison between the healthy controls and the patients without FTD. Analysis of correlations within regions-of-interest based on the above clusters indicated that the 'fluent disorganization' component of FTD was correlated with volume reductions in both Broca's and Wernicke's areas, whereas poverty of content of speech was correlated with reductions in the medial frontal/orbitofrontal cortex. CONCLUSIONS: The findings point to a relationship between FTD in schizophrenia and structural brain pathology in brain areas involved in language and executive function.

Executive dysfunction and memory impairment in schizoaffective disorder: a comparison with bipolar disorder, schizophrenia and healthy controls.

BACKGROUND: Deficits in memory and executive performance are well-established features of bipolar disorder and schizophrenia. By contrast, data on cognitive impairment in schizoaffective disorder are scarce and the findings are conflicting. METHOD: We used the Wechsler Memory Scale (WMS-III) and the Behavioural Assessment of the Dysexecutive Syndrome (BADS) to test memory and executive function in 45 schizophrenic patients, 26 schizomanic patients and 51 manic bipolar patients in comparison to 65 healthy controls. The patients were tested when acutely ill. RESULTS: All three patient groups performed significantly more poorly than the controls on global measures of memory and executive functioning, but there were no differences among the patient groups. There were few differences in memory and executive function subtest scores within the patient groups. There were no differences in any test scores between manic patients with and without psychotic symptoms. CONCLUSIONS: Schizophrenic, schizomanic and manic patients show a broadly similar degree of executive and memory deficits in the acute phase of illness. Our results do not support a categorical differentiation across different psychotic categories with regard to neuropsychological deficits.

Awareness of cognitive impairment in schizophrenia and its relationship to insight into illness.

BACKGROUND: Patients with schizophrenia have been found to show unawareness of cognitive impairment. However, its frequency and its relationship to lack of insight into illness are uncertain. METHOD: Forty-two patients with chronic schizophrenia were given tests of executive function and memory. Awareness of cognitive impairment was measured by means of discrepancy scores--differences between patient and psychologist ratings of memory and frontal/executive failures in daily life. Insight into illness was assessed using the Scale to Assess Unawareness of Mental Disorder (SUMD). RESULTS: A majority of the patients were found to underestimate their cognitive impairment; however, some overestimated it. Unawareness of cognitive impairment and lack of clinical insight loaded on different factors in a factor analysis, but these two factors were themselves correlated. CONCLUSIONS: The findings suggest that both unawareness and overestimation of cognitive impairment characterise patients with schizophrenia, although the former is more common. Awareness of cognitive impairment occurs independently of insight into illness at the clinical level, although the two phenomena may be linked at a deeper level.

Failure to deactivate in the prefrontal cortex in schizophrenia: dysfunction of the default mode network?

BACKGROUND: Functional imaging studies using working memory tasks have documented both prefrontal cortex (PFC) hypo- and hyperactivation in schizophrenia. However, these studies have often failed to consider the potential role of task-related deactivation. METHOD: Thirty-two patients with chronic schizophrenia and 32 age- and sex-matched normal controls underwent functional magnetic resonance imaging (fMRI) scanning while performing baseline, 1-back and 2-back versions of the n-back task. Linear models were used to obtain maps of activations and deactivations in the groups. RESULTS: The controls showed activation in the expected frontal regions. There were also clusters of deactivation, particularly in the anterior cingulate/ventromedial PFC and the posterior cingulate cortex/precuneus. Compared to the controls, the schizophrenic patients showed reduced activation in the right dorsolateral prefrontal cortex (DLPFC) and other frontal areas. There was also an area in the anterior cingulate/ventromedial PFC where the patients showed apparently greater activation than the controls. This represented a failure of deactivation in the schizophrenic patients. Failure to activate was a function of the patients' impaired performance on the n-back task, whereas the failure to deactivate was less performance dependent. CONCLUSIONS: Patients with schizophrenia show both failure to activate and failure to deactivate during performance of a working memory task. The area of failure of deactivation is in the anterior prefrontal/anterior cingulate cortex and corresponds to one of the two midline components of the 'default mode network' implicated in functions related to maintaining one's sense of self.