Functional brain imaging of negative symptoms in schizophrenia: further evidence of prefrontal dysfunction

• Paola Fuentes-Claramonte ^[2] ; Ana Aquino-Servín ^[2] ; María Ángeles Garcia-León ^[1] ; Jordi Ortiz-Gil ^[3] ; Pilar Salgado-Pineda ^[2] ; Amalia Guerrero-Pedraza ^[4] ; Salvador Sarró ^[2] ; Emilio J. Inarejos-Clemente ^[5] ; Raymond Salvador ^[2] ; Peter J. McKenna ^[2] ; Edith Pomarol-Clotet ^[2]
  1. [1] Universidad de Sevilla

     Universidad de Sevilla

     Sevilla, España

     
  2. [2] FIDMAG Germanes Hospitalaries Research Foundation, Barcelona, Spain. CIBERSAM, Barcelona, Spain
  3. [3] CIBERSAM, Barcelona, Spain Psychology Service, Hospital General de Granollers, Granollers, Spain Psychology Department, University of Vic - Central University of Catalonia, Vic, Spain
  4. [4] FIDMAG Germanes Hospitalaries Research Foundation, Barcelona, Spain Fundació Hospitalàries Sant Boi, Sant Boi de Llobregat, Spain
  5. [5] Hospital de Sant Joan de Déu, Esplugues de Llobregat, Spain

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• Localización: European journal of psychiatry, ISSN 0213-6163, Vol. 39, Nº 4, 2025
• Idioma: inglés
• DOI: 10.1016/j.ejpsy.2025.100322
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  • Abstract Background and objectives An influential theory of negative symptoms in schizophrenia is that they are due to frontal lobe dysfunction, although this has not been consistently supported by functional imaging studies to date. Recently, our group found evidence of an association between negative symptoms and prefrontal hypoactivation during a novel executive task sensitive to goal neglect. The present study sought to extend this finding using a different functional imaging paradigm, the n-back working memory task.

    Methods Ninety-six medicated patients with schizophrenia were divided according to the Positive and Negative Symptoms Scale (PANSS) scores into groups with high negative symptom scores (HNS, N=70, negative symptom score range 15-34), and with low negative symptom scores (LNS, N=26, negative symptom score range 6-14). Along with 50 matched healthy controls, they underwent fMRI while performing the 2-back and 1-back versions of the n-back task.

    Results In the 2-back vs 1-back comparison, working memory-related activation was observed in lateral prefrontal and inferior parietal areas in all groups. The HNS patients, but not the LNS patients showed reduced activation in these task-related regions compared to the healthy controls. The HNS patients also showed hypoactivation in the right dorsolateral prefrontal cortex relative to the LNS patients, although this finding was no longer statistically significant when disorganization scores were added as a covariate.

    Conclusion Our results provide further evidence supporting the prefrontal hypothesis of negative symptoms, but also highlight the potential role of disorganization in modulating prefrontal activity.