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

Department of Psychiatry, University of Cambridge, Cambridge, England, United Kingdom
American Journal of Psychiatry (Impact Factor: 12.3). 04/2005; 162(3):485-94. DOI: 10.1176/appi.ajp.162.3.485
Source: PubMed


Impaired prefrontal cortical function is regarded as a central feature of schizophrenia. Although many neuroimaging studies have found evidence of abnormal prefrontal activation when patients with schizophrenia perform cognitive tasks, the extent to which this abnormality depends on the presence of active psychotic symptoms and on the demands of the task is unclear. The authors tested the hypothesis that prefrontal functional abnormalities in schizophrenia would be more evident in patients with active psychosis than in patients who were in remission and would become more apparent in the face of increasing task demands.
The authors used functional magnetic resonance imaging (fMRI) to examine prefrontal cortical activity during a paced letter verbal fluency task in three groups of subjects: acutely psychotic patients with schizophrenia, schizophrenia patients in remission, and healthy volunteers. Online subject performance was measured by utilizing a clustered fMRI acquisition sequence that allowed overt verbal responses to be made in the relative absence of scanner noise.
Patients with schizophrenia showed less activation than the healthy comparison subjects in the anterior cingulate and the inferior frontal and right middle frontal cortices, independent of psychotic state and task demand. Acutely psychotic patients showed less activation than the healthy comparison subjects, but these differences were less marked than the differences between the patients in remission and the healthy comparison subjects. Acutely psychotic patients had less activation than the comparison subjects in the anterior cingulate but no significant difference in lateral prefrontal activation. Increasing task demand led to greater anterior cingulate and middle frontal activation in patients with active psychosis than in patients in remission.
Schizophrenia is associated with impaired prefrontal function, but its manifestation depends on the severity of psychotic symptoms and the level of task difficulty.

Download full-text


Available from: John Suckling, Oct 03, 2015
42 Reads
  • Source
    • "A maximum of 50% of the subjects examined in the present investigation have been included in seven previous studies that investigated the impact of other candidate genes [Mechelli et al., 2008; Papagni et al., 2011; Prata et al., 2008, 2009a,b,c, 2012] and in 3 previous studies that investigated brain dysfunction in psychosis [Costafreda et al., 2009, 2011; Fu et al., 2005]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The genes for the dopamine transporter (DAT) and the D-Amino acid oxidase activator (DAOA or G72) have been independently implicated in the risk for schizophrenia and in bipolar disorder and/or their related intermediate phenotypes. DAT and G72 respectively modulate central dopamine and glutamate transmission, the two systems most robustly implicated in these disorders. Contemporary studies have demonstrated that elevated dopamine function is associated with glutamatergic dysfunction in psychotic disorders. Using functional magnetic resonance imaging we examined whether there was an interaction between the effects of genes that influence dopamine and glutamate transmission (DAT and G72) on regional brain activation during verbal fluency, which is known to be abnormal in psychosis, in 80 healthy volunteers. Significant interactions between the effects of G72 and DAT polymorphisms on activation were evident in the striatum, parahippocampal gyrus, and supramarginal/angular gyri bilaterally, the right insula, in the right pre-/postcentral and the left posterior cingulate/retrosplenial gyri (P < 0.05, FDR-corrected across the whole brain). This provides evidence that interactions between the dopamine and the glutamate system, thought to be altered in psychosis, have an impact in executive processing which can be modulated by common genetic variation. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
    Human Brain Mapping 09/2013; 34(9). DOI:10.1002/hbm.22061 · 5.97 Impact Factor
  • Source
    • "Diversos estudos têm associado as tarefas de FV a localizações cerebrais específicas, em particular aos lobos frontal e temporal, referindo-se que o desempenho nos testes de FVS se encontra mais dependente do funcionamento do lobo temporal e o desempenho nos testes de FVF está mais associado ao funcionamento do lobo frontal (Baldo, Schwartz, Wilkins, & Dronkers, 2006; Birn e cols., 2010; Davidson, Gao, Mason, Winocur, & Anderson, 2008; Gaillard e cols., 2000; Grogan, Green, Ali, Crinion, & Price, 2009; Henry & Crawford, 2004; Phelps, Hyder, Blamire, & Shulman, 1997; Troyer e cols., 1998). O crescente interesse pelos testes de FV tem também possibilitado o seu estudo em grupos clínicos específicos, nomeadamente na dislexia (Brosnan e cols., 2002; Cohen, Morgan, Vaughn, Riccio, & Hall, 1999; Reiter, Tucha, & Lange, 2005), na PHDA (Hurks e cols., 2004; Marchetta, Hurks, Krabbendam, & Jolles, 2008), na epilepsia (Henkin e cols., 2005; Lopes, Simões, Robalo, Fineza, & Gonçalves, 2010; Riva e cols., 2005), na esquizofrenia (Fu e cols., 2005; Vogel e cols., 2009), nas doenças neurodegenerativas (Haugrud, Lanting, & Crossley, 2010; McDowd e cols., 2011; Radanovic e cols., 2009), entre outros. Análises inferenciais em função do gênero têm sido efetuadas, sendo os resultados inconsistentes. "
    [Show abstract] [Hide abstract]
    ABSTRACT: RESUMO Testes de fluência verbal são medidas sensíveis a diferentes funções neuropsicológicas usadas na avaliação da integridade dos lobos frontal e temporal. Participaram neste estudo 120 crianças (7 a 10 anos) que foram avaliadas por meio da prova de fluência verbal semântica e fonêmica. Os resultados obtidos das análises fatoriais exploratória e confirmatória e da análise de correlação parecem indicar que essas duas provas dependem de diferentes funções neurocognitivas. O número de palavras produzidas nas tarefas fonêmicas foi significativamente inferior ao obtido nas tarefas semânticas, uma vez que as primeiras são cognitivamente mais complexas. Não foram observadas diferenças de gênero, mas foi observado um efeito significativo em função da idade da criança, o que corrobora a sensibilidade desses testes aos processos neurodesenvolvimentais. Na análise do desempenho ao longo dos 60 segundos, observa-se uma maior produção de palavras nos primeiros 15 segundos e uma significativa diminuição ao longo dos restantes 45 segundos. ABSTRACT – Semantic and phonemic verbal fl uency in children: cognitive functions and temporal analysis Verbal fluency tests are sensitive to different neuropsychological functions used in assessing the integrity of the frontal and temporal lobes. In this study, 120 healthy children (aged 7 to 10 years) were examined through a semantic and a phonemic verbal fluency test. The results of exploratory factor analysis, confirmatory factor analysis and correlation analysis seem to indicate that these two verbal fluency tests depend on different neurocognitive functions. The number of words produced in the phonemic task was significantly lower than the semantic task, indicating that is cognitively more complex. No gender differences were found, but a significant effect was observed for children's age, showing the sensitivity of these verbal fluency tests to neurodevelopmental processes. The analyze of performance over the 60 seconds showed a significant production of words in the first 15 seconds and decrease over the remaining 45 seconds. Keywords: semantic and phonemic verbal fluency; children; neuropsychology; BANC. RESUMEN – Fluidez verbal semántica y fonémica en niños: funciones cognitivas y análisis temporal Las pruebas de fluidez verbal son medidas sensibles a las diferentes funciones neuropsicológicas utilizadas en la evaluación de la integridad de los lobos frontal y temporal. Participaron de este estudio 120 niños (7 a 10 años) que fueron evaluados mediante la prueba de fluidez verbal semántica y fonémica. Los resultados obtenidos de los análisis factoriales exploratorio y confirmatorio y del análisis de correlación indicaron que esas dos pruebas dependen de diferentes funciones neurocognitivas. El número de palabras producidas en las tareas fonémicas fue significativamente inferior al obtenido en las tareas semánticas, ya que las primeras son cognitivamente más complejas. No hubo diferencias entre los sexos, pero fue observado un efecto significativo en función de la edad de niños, lo que corrobora la sensibilidad de esos testes a los procesos neurológicos del desarrollo. En el análisis del desempeño a lo largo de los 60 segundos, se observa una mayor producción de palabras en los primeros 15 segundos y una significativa disminución a lo largo de los restantes 45 segundos. Palabras clave: fluencia verbal semántica e fonémica; niños; neuropsicología; BANC.
  • Source
    • "However, some fMRI studies detected task related activation of temporal areas—superior, middle, and inferior temporal cortex [BA 21, 22, 37, 39; (Fu et al., 2002)], or mediotemporal regions (Pihlajamaki et al., 2000). Studies in schizophrenia (irrespective to clinical state) show abnormal VFT performance (Elvevag et al., 2001; Rossell, 2006), decreased activation of lateral prefrontal cortex, insula, and anterior cingulate (Curtis et al., 1998; Fu et al., 2005; Yurgelun-Todd et al., 1996), increased deactivation of medial prefrontal cortex (Curtis et al., 1998), slower dynamics of the prefrontal cortex activity (Takizawa et al., 2008), and abnormal pattern of functional network connectivity (Frith et al., 1995). Based on previous findings we expected abnormal activation of prefrontal and temporal regions, abnormal functional connectivity between task modulated networks and its relationship with clinical features of in schizophrenia patients in remission. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Abnormal task-related activation and connectivity is present in schizophrenia. The aim of this study was the analysis of functional networks in schizophrenia patients in remission after the first episode. Twenty-nine male patients in remission after the first episode of schizophrenia and 22 healthy controls underwent examination by functional magnetic resonance during verbal fluency tasks (VFT). The functional connectivity of brain networks was analyzed using independent component analysis. The patients showed lower activation of the salience network during VFT. They also showed lower deactivation of the default mode network (DMN) during VFT processing. Spectral analysis of the component time courses showed decreased power in slow frequencies of signal fluctuations in the salience and DMNs and increased power in higher frequencies in the left frontoparietal cortex reflecting higher fluctuations of the network activity. Moreover, there was decreased similarity of component time courses in schizophrenia—the patients had smaller negative correlation between VFT activated and deactivated networks, and smaller positive correlations between DMN subcomponents. There is still an abnormal functional connectivity of several brain networks in remission after the first episode of schizophrenia. The effect of different treatment modalities on brain connectivity, together with temporal dynamics of this functional abnormality should be the objective of further studies to assess its potential as a marker of disease stabilization.
    Human Brain Mapping 11/2012; 34(3):726-37. DOI:10.1002/hbm.21469 · 5.97 Impact Factor
Show more