UC San Diego

Rationale: Working memory deficits are a core feature of psychotic disorders, readily evident in the first episode and persistent throughout the illness. Whereas impaired performance on visual working memory tasks has been observed in individuals at clinical high-risk (CHR) for psychosis, the nature and underlying neural mechanisms of this impairment remain largely unknown. There is some evidence that failure to modulate brain oscillatory activities in the alpha/beta frequency bands may constrain visual working memory capacity in schizophrenia, but it is unclear whether these potential neural processes are already implicated in the CHR stage. Design: Using electroencephalogram (EEG), this study examined neural oscillations in the alpha (9-13 Hz) and beta (15-30 Hz) frequency bands in 48 individuals between 15-30 years of age meeting the Criteria of Prodromal Syndromes (CHR) and 47 demographically matched healthy control (HC) participants during a change localization visual working memory paradigm. Aim 1 compared behavioral visual working memory capacity between the two groups. Aim 2 examined suppression of alpha and beta neural activities during the maintenance and retrieval of visual working memory and correlated these metrics of oscillatory modulation with behaviorally measured visual working memory capacity. Aim 3 explored the associations among working memory capacity, broader measures of neurocognition, and global functioning. Results: Working memory capacity was significantly reduced in individuals at CHR (M=3.02, SD=0.37) compared to HC (M=3.23, SD=0.40; t(93)=-5.67, p=.009). The CHR group also showed attenuated alpha and beta suppression during both retention and retrieval stages of the task (F(1,93)=4.45, p=.038), which significantly predicted working memory capacity in this group (r=-0.41, p=0.004). Further, visual working memory capacity was correlated with a range of clinical and cognitive measures in CHR (r’s > 0.30, p’s < 0.05). Conclusions: This was the first study to date to directly quantify visual working memory capacity among individuals at CHR and provided evidence for a notable capacity reduction in this core cognitive ability in the at-risk state. Importantly, the EEG findings highlighted a key neural mechanism underlying such impairments and suggested that the neural architecture required for effective modulation of oscillatory activities may be critically disrupted in emerging psychosis.