Effects of Psychotic State and Task Demand on Prefrontal Function in Schizophrenia: An fMRI Study of Overt Verbal Fluency

Abstract

Schizophrenia is associated with impaired prefrontal function, but its manifestation depends on the severity of psychotic symptoms and the level of task difficulty.

Alterations of fronto-temporal connectivity during word encoding in schizophrenia

“…Taken together with the results of other studies that have directly assessed the relationship of fronto-temporal dysfunction to illness severity (Andreasen et al, 1997;Lawrie et al, 2002;Fu et al, 2005), these findings indicate that the degree of left STG overactivation and abnormally positive STG-prefrontal interactions may be state-dependent, correlating with the severity of active illness, and tending to normalize during remission. However, patients in the current study were clinically stable and had mild to moderate symptoms indicating that abnormal fronto-temporal connectivity may be a trait-like variable.…”

Abnormal prefrontal activation directly related to pre-synaptic striatal dopamine dysfunction in people at clinical high risk for psychosis

“…When performing the verbal fluency task, both controls and ARMS subjects activated left prefrontal cortex, including left inferior frontal gyrus, in line with previous studies in controls 28 and patients with schizophrenia. 43 As predicted, activation within this network was significantly different in the two groups, with the ARMS subjects showing greater activation in the left inferior frontal gyrus and in the right middle frontal gyrus. As the differential activation we observed was evident in the context of comparable response accuracy, and the analysis was restricted to images associated with correct responses, it is unlikely to be related to group differences in task performance and may instead reflect a difference at the neurophysiological level.…”

“…Whether prefrontal activation in patients with schizophrenia is reduced or increased relative to controls depends on the task employed and whether there are group differences in behavioural performance. 43 Studies of verbal fluency in which performance in patients was impaired have often reported reduced prefrontal activation in schizophrenia, whereas some of those in which performance was matched have shown either no difference or greater activation relative to controls. 58 A further difference between the two studies is that the correlation we observed was with activation in the inferior frontal cortex, whereas that the previous study was in a more dorsal part of the prefrontal cortex.…”

Epistasis between the DAT 3′ UTR VNTR and the COMT Val158Met SNP on cortical function in healthy subjects and patients with schizophrenia

“…We used 2 well-characterized functional polymorphisms (COMT Val158Met and DAT 3Ј UTR VNTR) and functional MRI to study healthy volunteers and patients with schizophrenia, with genotype subgroups of sufficient size to detect interactive effects of both genes on activation by using an ANOVA. Subjects were scanned while they performed an overt phonological verbal fluency paradigm, which is associated with activation in the frontal, cingulate, and temporal cortex in healthy volunteers (46)(47)(48)(49)(50)(51)(52)(53)(54), and with impaired performance (55,56) and altered activation (51,54,(57)(58)(59)(60) in schizophrenia. On the basis of evidence that variation in DAT (at the 3Ј UTR VNTR) and in COMT (at the Val158Met SNP) separately modulate fronto-temporal activation during verbal fluency, and that these effects are altered in patients with schizophrenia (27, 84), we predicted that there would be an epistatic interaction between their effects on regional activation in the same sample and paradigm.…”