Schizophrenia Research Forum - A Catalyst for Creative Thinking

Mansouri FA, Buckley MJ, Tanaka K. Mnemonic function of the dorsolateral prefrontal cortex in conflict-induced behavioral adjustment. Science. 2007 Nov 9 ; 318(5852):987-90. Pubmed Abstract

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Comment by:  Nicolas RüschGianfranco Spalletta
Submitted 6 November 2007
Posted 6 November 2007

This very interesting paper by Mansouri and colleagues demonstrates that executive functioning in monkeys as measured by a variant of the Wisconsin Card Sorting Test is primarily related to lesions in the dorsolateral prefrontal cortex. The finding is consistent with magnetic resonance imaging findings on structural correlates of executive dysfunction in persons with schizophrenia, one of the more prominent cognitive deficits in this disorder.

Manual morphometry studies found a link between dorsolateral prefrontal volume loss and executive dysfunction in schizophrenia (Antonova et al., 2004). A recent voxel-based morphometry study (Rüsch et al., 2007) compared frontal gray matter volume differences in patients with schizophrenia and high versus low performance in the Wisconsin Card Sorting Test. Consistent with the new study of Mansouri et al., the strongest difference between both groups was found in the dorsolateral prefrontal cortex, with gray matter volume loss in this area being related to executive dysfunction. Gray matter volume loss in the anterior cingulate was also significantly, but less strongly, related to executive functioning.

However, Rüsch and colleagues also found volumetric correlations between this dorsolateral prefrontal area and thalamic and cerebellar regions, which points to extended gray matter networks involved in executive dysfunction. Thus, the frontal cortical areas frequently associated with executive dysfunction, impressively studied by Mansouri and colleagues, could be at the core of an executive circuit that also comprises subcortical areas such as the thalamus.

Finally, executive functions, at least in humans, are a multifaceted concept which is influenced by a number of factors in a highly complex fashion, especially in psychosis. Indeed, it would not only be related to a mere neural substrate, but rather it would reflect the influence of psychological and social factors such as education, intelligence, and social learning which may secondarily affect brain structure (Corrigan and Penn, 2001).

Neurobiological correlates of executive functioning (Barch, 2006) are a stimulating challenge for researchers and clinicians alike, not only for their theoretical interest, but also for their diagnostic, rehabilitative-therapeutic and prognostic implications. Therefore, executive functioning and its relation to functional and structural connectivity across the brain, both in healthy controls and in individuals with schizophrenia, clearly deserves further investigation using electrophysiological methods as well as functional magnetic resonance and diffusion tensor imaging.


Antonova E, Sharma T, Morris R, Kumari V. The relationship between brain structure and neurocognition in schizophrenia: a selective review. Schizophr Res. 2004 Oct 1;70(2-3):117-45. Abstract

Barch DM. What can research on schizophrenia tell us about the cognitive neuroscience of working memory? Neuroscience. 2006 Apr 28;139(1):73-84. Abstract

Corrigan PW, Penn DL (2001). Social cognition and schizophrenia. Washington DC: American Psychological Association.

Rüsch N, Spoletini I, Wilke M, Bria P, Di Paola M, Di Iulio F, Martinotti G, Caltagirone C, Spalletta G. Prefrontal-thalamic-cerebellar gray matter networks and executive functioning in schizophrenia. Schizophr Res. 2007 Jul 1;93(1-3):79-89. Abstract

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