Neural correlates of relational and item-specific encoding during working and long-term memory in schizophrenia

John D. Ragland, Robert S. Blumenfeld, Ian S. Ramsay, Andrew Yonelinas, Jong Yoon, Marjorie Solomon, Cameron S. Carter, Charan Ranganath

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


Successful long-term memory (LTM) depends upon effective control of information in working memory (WM), and there is evidence that both WM and LTM are impaired by schizophrenia. This study tests the hypothesis that LTM deficits in schizophrenia may result from impaired control of relational processing in WM due to dorsolateral prefrontal cortex (DLPFC) dysfunction. fMRI was performed on 19 healthy controls and 20 patients with schizophrenia during WM tasks emphasizing relational (reorder trials) versus item-specific (rehearse trials) processing. WM activity was also examined with respect to LTM recognition on a task administered outside the scanner. Receiver operator characteristic analysis assessed familiarity and recollection components of LTM. Patients showed a disproportionate familiarity deficit for reorder versus rehearse trials against a background of generalized LTM impairments. Relational processing during WM led to DLPFC activation in both groups. However, this activation was less focal in patients than in controls, and patients with more severe negative symptoms showed less of a DLPFC increase. fMRI analysis of subsequent recognition performance revealed a group by condition interaction. High LTM for reorder versus rehearse trials was associated with bilateral DLPFC activation in controls, but not in patients who activated the left middle temporal and inferior occipital gyrus. Results indicate that although patients can activate the DLPFC on a structured relational WM task, this activation is less focal and does not translate to high retrieval success, suggesting a disruption in the interaction between WM and LTM processes in schizophrenia.

Original languageEnglish (US)
Pages (from-to)1719-1726
Number of pages8
Issue number2
StatePublished - Jan 16 2012
Externally publishedYes

Bibliographical note

Funding Information:
Research was supported by National Institute of Mental Health grants R01MH084895 , R01MH059883 , and R01MH083734 . We thank the participants for their time and effort and Joshua Phillips for assistance with manuscript preparation.


  • Episodic memory
  • Familiarity
  • Functional imaging
  • Neurocognition
  • Recollection


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