Neural correlates of impaired cognitive control over working memory in schizophrenia.
BACKGROUND
One of the most common deficits in patients with schizophrenia (SZ) is in working memory (WM), which has wide-reaching impacts across cognition. However, previous approaches to studying WM in SZ have used tasks that require multiple cognitive-control processes, making it difficult to determine which specific cognitive and neural processes underlie the WM impairment.


METHODS
We used functional magnetic resonance imaging to investigate component processes of WM in SZ. Eighteen healthy controls (HCs) and 18 patients with SZ performed an item-recognition task that permitted separate neural assessments of 1) WM maintenance, 2) inhibition, and 3) interference control in response to recognition probes.


RESULTS
Before inhibitory demands, posterior ventrolateral prefrontal cortex (VLPFC), an area involved in WM maintenance, was activated to a similar degree in both HCs and patients, indicating preserved maintenance operations in SZ. When cued to inhibit items from WM, HCs showed reduced activation in posterior VLPFC, commensurate with appropriately inhibiting items from WM. However, these inhibition-related reductions were absent in patients. When later probed with items that should have been inhibited, patients showed reduced behavioral performance and increased activation in mid-VLPFC, an area implicated in interference control. A mediation analysis indicated that impaired inhibition led to increased reliance on interference control and reduced behavioral performance.


CONCLUSIONS
In SZ, impaired control over memory, manifested through proactive inhibitory deficits, leads to increased reliance on reactive interference-control processes. The strain on interference-control processes results in reduced behavioral performance. Thus, inhibitory deficits in SZ may underlie widespread impairments in WM and cognition.
Department of Psychology (TSE, CI, EES), Columbia University, New York, New York. Electronic address: Tse4@columbia.edu.
Teal S
TS
Eich
Helen Wills Neuroscience Institute (DEN), University of California, Berkeley, California.
Derek Evan
DE
Nee
Department of Psychology (TSE, CI, EES), Columbia University, New York, New York.
Catherine
C
Insel
Division of Cognitive Neuroscience (CM), New York State Psychiatric Institute; Department of Psychiatry (CM, EES), Columbia University, New York, New York.
Chara
C
Malapani
Department of Psychology (TSE, CI, EES), Columbia University, New York, New York; Department of Psychiatry (CM, EES), Columbia University, New York, New York.
Edward E
EE
Smith
D000328:Adult; D001931:Brain Mapping; D003072:Cognition Disorders / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000150:complications / Q000503:physiopathology*; D008570:Memory, Short-Term / Q000502:physiology*; D017397:Prefrontal Cortex / Q000503:physiopathology*; D012559:Schizophrenia / Q000150:complications / Q000503:physiopathology*; D012565:Schizophrenic Psychology
Executive function; fMRI; inhibition; interference control; prefrontal cortex; retrieval; schizophrenia