Cognitive Control of Episodic Memory in Schizophrenia: Differential Role of Dorsolateral and Ventrolateral Prefrontal Cortex

John D. Ragland, Charan Ranganath, Joshua Phillips, Megan A. Boudewyn, Ann M. Kring, Tyler A. Lesh, Debra L. Long, Steven J. Luck, Tara A. Niendam, Marjorie Solomon, Tamara Y. Swaab, Cameron S. Carter

Background: Dorsal (DLPFC) and ventral (VLPFC) subregions in lateral prefrontal cortex play distinct roles in episodic memory, and both are implicated in schizophrenia. We test the hypothesis that schizophrenia differentially impairs DLPFC versus VLPFC control of episodic encoding. Methods: Cognitive control was manipulated by requiring participants to encode targets and avoid encoding non-targets based upon stimulus properties of test stimuli. The more automatic encoding response (target versus non-target) was predicted to engage VLPFC in both groups. Conversely, having to overcome the prepotent encoding response (non-targets versus targets) was predicted to produce greater DLPFC activation in controls than in patients. Encoding occurred during event-related fMRI in a sample of 21 individuals with schizophrenia and 30 healthy participants. Scanning was followed by recognition testing outside the scanner. Results: Patients were less successful differentially remembering target versus non-target stimuli, and retrieval difficulties correlated with more severe disorganized symptoms. As predicted, the target versus non-target contrast activated the VLPFC and correlated with retrieval success in both groups. Conversely, the non-target versus target contrast produced greater DLPFC activation in controls than in patients, and DLPFC activation correlated with performance only in controls. Conclusion: Individuals with schizophrenia can successfully engage the VLPFC to provide control over semantic encoding of individual items, but are specifically impaired at engaging the DLPFC to main context for task-appropriate encoding and thereby generate improved memory for target versus non-target items. This extends previous cognitive control models based on response selection tasks to the memory domain.