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Background. The D-Amino acid oxidase activator (G72 or DAOA) is believed to play a key role in the regulation of central glutamatergic transmission which is seen to be altered in psychosis. It is thought to regulate D-amino acid oxidase (DAO), which metabolizes D-serine, a co-agonist of NMDA-type glutamate receptors and to be involved in dendritic arborization. Linkage, genetic association and expression studies have implicated the G72 gene in both schizophrenia and bipolar disorder. Aims. To examine the influence of G72 variation on brain function in the healthy population. Method. Fifty healthy volunteers were assessed using functional magnetic resonance imaging while performing a verbal fluency task. Regional brain activation and task-dependent functional connectivity during word generation was compared between different rs746187 genotypes. Results. G72 rs746187 genotype had a significant effect on activation in the left postcentral and supramarginal gyri (FWE P < 0.05), and on the task-dependent functional coupling of this region with the retrosplenial cingulate gyrus (FWE P < 0.05). Conclusions. Our results may reflect an effect of G72 on glutamatergic transmission, mediated by an influence on D-amino acid oxidase activity, on brain areas particularly relevant to the hypoglutamatergic model of psychosis. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: Superior temporal lobe dysfunction is a robust finding in functional neuroimaging studies of schizophrenia and is thought to be related to a disruption of fronto-temporal functional connectivity. However, the stage of the disorder at which these functional alterations occur is unclear. We addressed this issue by using functional MRI (fMRI) to study subjects in the prodromal and first episode phases of schizophrenia. Methods: Subjects with an at risk mental state (ARMS) for psychosis, a first psychotic episode (FEP), and controls were studied using fMRI while performing a working memory task. Activation in the superior temporal gyrus (STG) was assessed using statistical parametric mapping, and its relationship to frontal activation was examined using dynamic causal modeling. Results: The STG was differentially engaged across the three groups. There was deactivation of this region during the task in controls, whereas subjects with FEP showed activation and the response in subjects with ARMS was intermediately relative to the two other groups. There were corresponding differences in the effective connectivity between the STG and the middle frontal gyrus across the three groups, with a negative coupling between these areas in controls, a positive coupling in the FEP group, and an intermediate value in the ARMS group. Conclusions: A failure to deactivate the superior temporal lobe during tasks that engage prefrontal cortex is evident at the onset of schizophrenia and may reflect a disruption of fronto-temporal connectivity. Qualitatively similar alterations are evident in people with prodromal symptoms of the disorder. Hum Brain Mapp, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The majority of psychopathology is rooted early in life and first emerges during childhood and adolescence. However, little is known about how risk genes affect brain function to increase biological vulnerability to psychopathology in childhood, because most imaging genetic studies published so far have been conducted on adult participants. We examined the impact of neuregulin1 (NRG1), a probable susceptibility gene for schizophrenia and bipolar disorder, on brain function in a sample of 102 ten- to twelve-year-old children. Each participant performed a Go/Nogo task, whereas brain responses were measured using functional magnetic resonance imaging. Statistical parametric mapping was used to estimate the impact of genetic variation in NRG1 on brain activation. Response accuracy and reaction times did not differ as a function of NRG1 genotype. However, individuals with the high-risk variant expressed greater brain activation for both Go and Nogo stimuli in the right posterior orbital gyrus, where NRG1 genotype accounted for 11% of interindividual variance. There were no regions showing a significant interaction between NRG1 genotype and stimulus type even at trend level, suggesting that the impact of NRG1 on brain activation was not specific to either response inhibition or motor execution. These results suggest that that genetic variation in NRG1 is associated with different levels of prefrontal engagement in children as young as 10-12 years of age. Our investigation provides support to the idea that genetic factors may affect brain function to moderate vulnerability to psychopathology from childhood. Hum Brain Mapp, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Children and adolescents born before 33 weeks of gestation, that is very preterm, may experience problems with the inhibitory control of behaviour and the allocation of attention. Previous functional magnetic resonance imaging (fMRI) studies have found preterm-born adolescents to display altered brain activation in tasks measuring inhibitory control. However, adolescence is a period during which dynamic changes are occurring in the brain, and it is not yet known whether these functional alterations will persist into adulthood, or instead reflect developmental delay. This study used an event-related fMRI Go/No-Go motor response inhibition paradigm, which included an oddball task measuring attention allocation to infrequent stimuli, to compare blood-oxygen-level-dependent (BOLD) signal between 26 preterm-born adults and 21 controls. Group differences in brain activation were observed in inhibition and attention networks during both conditions. During motor response inhibition, preterm-born participants compared to controls showed increased BOLD signal in medial and right lateral posterior brain regions, including middle temporal/occipital gyrus, posterior cingulate gyrus and precuneus. During oddball trials, preterm-born young adults displayed attenuated brain activation in a fronto-parietal-cerebellar network which is involved in mediating attention allocation. This pattern of reduced brain activation in task-relevant regions of attention allocation, and increased activation in posterior brain regions during inhibitory control, suggests adult alteration of inhibition and attention processing following very preterm birth, which may reflect a developmental delay. Hum Brain Mapp, 2009. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Several studies report that patients with schizophrenia who experience auditory verbal hallucinations (AVH) tend to misidentify their own speech as that of somebody else. We tested the hypothesis that this tendency is associated with poor functional integration within the network of regions that mediate the evaluation of speech. Using functional magnetic resonance imaging, we measured brain responses from 11 schizophrenics with AVH, 10 schizophrenics without AVH, and 10 healthy controls. Stimuli comprised prerecorded words, which varied for their source (self, alien) and acoustic quality (undistorted, distorted). Participants had to indicate whether each word was spoken in their own or another person's voice via a button press. Using dynamic causal modeling, we estimated the impact of one region over another ('effective connectivity') and how this was modulated by source and distortion. In controls and in patients without AVH, the connectivity between left superior temporal and anterior cingulate cortex was significantly greater for alien- than for self-generated speech; in contrast, the reverse trend was found in schizophrenic patients with AVH. In conclusion, when patients with AVH appraise their own speech we find impaired functional integration between left superior temporal and anterior cingulate cortex. Although this finding is based on external rather than internal speech, the same mechanism may contribute to the faulty appraisal of inner speech that putatively underlies AVH. Hum Brain Mapp 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Studies of spoken and written language suggest that the perception of sentences engages the left anterior and posterior temporal cortex and the left inferior frontal gyrus to a greater extent than nonsententially structured material, such as word lists. This study sought to determine whether the same is true when the language is gestural and perceived visually. Regional neural activity was measured using functional MRI while Deaf and hearing native signers of British Sign Language (BSL) detected semantic anomalies in well-formed BSL sentences and when they detected nonsense signs in lists of unconnected BSL signs. Processing BSL sentences, when contrasted with signed lists, was reliably associated with greater activation in the posterior portions of the left middle and superior temporal gyri and in the left inferior frontal cortex, but not in the anterior temporal cortex, which was activated to a similar extent whether lists or sentences were processed. Further support for the specificity of these areas for processing the linguistic-rather than visuospatial-features of signed sentences came from a contrast of hearing native signers and hearing sign-naïve participants. Hearing signers recruited the left posterior temporal and inferior frontal regions during BSL sentence processing to a greater extent than hearing nonsigners. These data suggest that these left perisylvian regions are differentially associated with sentence processing, whatever the modality of the linguistic input. Hum Brain Mapp, 2005. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Auditory hallucinations are thought to arise through the misidentification of self-generated verbal material as alien. The neural mechanisms that normally mediate the differentiation of self-generated from nonself speech are unclear. We investigated this in healthy volunteers using functional MRI. Eleven healthy volunteers were scanned whilst listening to a series of prerecorded words. The source (self/nonself) and acoustic quality (undistorted/distorted) of the speech was varied across trials. Participants indicated whether the words were spoken in their own or another person's voice via a button press. Listening to self-generated words was associated with more activation in the left inferior frontal and right anterior cingulate cortex than words in another person's voice, which was associated with greater engagement of the lateral temporal cortex bilaterally. Listening to distorted speech was associated with activation in the inferior frontal and anterior cingulate cortex. There was an interaction between the effects of source of speech and distortion on activation in the left temporal cortex. In the presence of distortion participants were more likely to misidentify their voice as that of another. This misattribution of self-generated speech was associated with reduced engagement of the cingulate and prefrontal cortices. The evaluation of auditory speech involves a network including the inferior frontal, anterior cingulate, and lateral temporal cortex. The degree to which different areas within this network are engaged varies with the source and acoustic quality of the speech. Accurate identification of one's own speech appears to depend on cingulate and prefrontal activity. Hum Brain Mapp, 2005. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

During verbal-fluency tasks, impairments in performance and functional abnormalities in the inferior frontal cortex have been observed in both schizophrenia patients and their unaffected relatives. We sought to examine whether such functional abnormalities are a specific marker of genetic vulnerability to schizophrenia. We studied a sample of 132 subjects, comprising 39 patients with schizophrenia, 10 unaffected monozygotic (MZ) cotwins of schizophrenia probands, 28 patients with bipolar disorder, 7 unaffected MZ cotwins of bipolar disorder probands and 48 healthy controls. Blood oxygen level-dependent response was measured using functional magnetic resonance imaging during the performance of an overt verbal-fluency task with two levels of task difficulty, in a cytoarchitectonic region of interest encompassing Brodmann areas 44 and 45 bilaterally. Patients with schizophrenia and the unaffected MZ cotwins of schizophrenia probands showed increased activation in the inferior frontal cortex relative to healthy controls and bipolar patients. Increased engagement of the inferior frontal cortex during verbal-fluency may thus be a marker of genetic vulnerability to schizophrenia. Hum Brain Mapp, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]