Executive and mnemonic impairments have been well documented in the high-risk states for development of psychosis and have been pinpointed as a possible core neuropsychological dysfunction. However, their neurofunctional correlates are still not clear.

fMRI was used in 17 patients at risk for developing psychosis (ARMS, “at risk mental state”), 10 patients with a first episode of psychosis (FEP) and 15 age-matched healthy comparison subjects to examine neural responses to increasing difficulty of mnemonic engagement in an object–location paired associate memory task. Groups were matched in terms of age, IQ, gender, and psychopathology ratings. Accuracy and reaction time were recorded during the scan.

As the mnemonic load increased, response latency increased and response accuracy decreased in an approximately linear fashion. No main effect for group was observed. However, a trend towards decreased accuracy in FEP subjects, as compared with controls, was evident. As the task difficulty increased, increased brain activity was observed in the medial frontal cortex and in the medial posterior parietal cortex. Between-groups differences in activation were observed in a cluster spanning the MFG, SFG and SMA and in the right precuneus. However, these neurofunctional abnormalities were more evident in the most demanding level of the task than in the easy level, with the ARMS groups showing less activation than controls and higher activation than FEP.

Abnormal neural activity in medial frontal cortex and posterior parietal cortex during paired associate learning task may represent a neurofunctional substrates of vulnerability to psychosis.