Neural correlates of impaired cognitive control over working memory in schizophrenia

Teal S Eich; Derek Evan Nee; Catherine Insel; Chara Malapani; Edward E Smith

doi:10.1016/j.biopsych.2013.09.032

Neural correlates of impaired cognitive control over working memory in schizophrenia

Biol Psychiatry. 2014 Jul 15;76(2):146-53. doi: 10.1016/j.biopsych.2013.09.032. Epub 2013 Oct 10.

Authors

Teal S Eich¹, Derek Evan Nee², Catherine Insel³, Chara Malapani⁴, Edward E Smith⁵

Affiliations

¹ Department of Psychology (TSE, CI, EES), Columbia University, New York, New York. Electronic address: Tse4@columbia.edu.
² Helen Wills Neuroscience Institute (DEN), University of California, Berkeley, California.
³ Department of Psychology (TSE, CI, EES), Columbia University, New York, New York.
⁴ Division of Cognitive Neuroscience (CM), New York State Psychiatric Institute; Department of Psychiatry (CM, EES), Columbia University, New York, New York.
⁵ Department of Psychology (TSE, CI, EES), Columbia University, New York, New York; Department of Psychiatry (CM, EES), Columbia University, New York, New York.

Abstract

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.

Keywords: Executive function; fMRI; inhibition; interference control; prefrontal cortex; retrieval; schizophrenia.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Adult
Brain Mapping
Cognition Disorders / physiopathology*
Female
Humans
Magnetic Resonance Imaging
Male
Memory Disorders / complications
Memory Disorders / physiopathology*
Memory, Short-Term / physiology*
Prefrontal Cortex / physiopathology*
Schizophrenia / complications
Schizophrenia / physiopathology*
Schizophrenic Psychology

Abstract

Publication types

MeSH terms

Grants and funding