Preserved working memory and altered brain activation in persons at risk for psychosis

Siti N Yaakub, Kavitha Dorairaj, Joann S Poh, Christopher L Asplund, Ranga Krishnan, Jimmy Lee, Richard S E Keefe, R Alison Adcock, Stephen J Wood, Michael W L Chee

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


OBJECTIVE: Patients with schizophrenia exhibit impairments in working memory that often appear in attenuated form in persons at high risk for the illness. The authors hypothesized that deviations in task-related brain activation and deactivation would occur in persons with an at-risk mental state performing a working memory task that entailed the maintenance and manipulation of letters.

METHOD: Participants at ultra high risk for developing psychosis (N=60), identified using the Comprehensive Assessment of At-Risk Mental States, and healthy comparison subjects (N=38) 14 to 29 years of age underwent functional MRI while performing a verbal working memory task. Group differences in brain activation were identified using analysis of covariance.

RESULTS: The two groups did not show significant differences in speed or accuracy of performance, even after accounting for differences in education. Irrespective of task condition, at-risk participants exhibited significantly less activation than healthy comparison subjects in the left anterior insula. During letter manipulation, at-risk persons exhibited greater task-related deactivation within the default-mode network than comparison subjects. Region-of-interest analysis in the at-risk group revealed significantly greater right dorsolateral prefrontal cortex activation during manipulation of letters.

CONCLUSIONS: Despite comparable behavioral performance, at-risk participants performing a verbal working memory task exhibited altered brain activation compared with healthy subjects. These findings demonstrate an altered pattern of brain activation in at-risk persons that contains elements of reduced function as well as compensation.

Original languageEnglish
Pages (from-to)1297-307
Number of pages11
JournalAmerican Journal of Psychiatry
Issue number11
Publication statusPublished - Nov 2013


  • Adolescent
  • Adult
  • Brain
  • Case-Control Studies
  • Female
  • Functional Neuroimaging
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Memory, Short-Term
  • Neuropsychological Tests
  • Psychotic Disorders
  • Young Adult


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