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

Research output: Contribution to journalArticlepeer-review


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

Colleges, School and Institutes


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