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Review
, 36 (1), 316-38

Cognitive Control Deficits in Schizophrenia: Mechanisms and Meaning

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Review

Cognitive Control Deficits in Schizophrenia: Mechanisms and Meaning

Tyler A Lesh et al. Neuropsychopharmacology.

Abstract

Although schizophrenia is an illness that has been historically characterized by the presence of positive symptomatology, decades of research highlight the importance of cognitive deficits in this disorder. This review proposes that the theoretical model of cognitive control, which is based on contemporary cognitive neuroscience, provides a unifying theory for the cognitive and neural abnormalities underlying higher cognitive dysfunction in schizophrenia. To support this model, we outline converging evidence from multiple modalities (eg, structural and functional neuroimaging, pharmacological data, and animal models) and samples (eg, clinical high risk, genetic high risk, first episode, and chronic subjects) to emphasize how dysfunction in cognitive control mechanisms supported by the prefrontal cortex contribute to the pathophysiology of higher cognitive deficits in schizophrenia. Our model provides a theoretical link between cellular abnormalities (eg, reductions in dentritic spines, interneuronal dysfunction), functional disturbances in local circuit function (eg, gamma abnormalities), altered inter-regional cortical connectivity, a range of higher cognitive deficits, and symptom presentation (eg, disorganization) in the disorder. Finally, we discuss recent advances in the neuropharmacology of cognition and how they can inform a targeted approach to the development of effective therapies for this disabling aspect of schizophrenia.

Figures

Figure 1
Figure 1
Simplified graphical depiction of the role of the prefrontal cortex (PFC) during the classic Stroop task, in which the stimulus is identical but the engagement of control processes is modulated by the rule. (a) Under low cognitive control demands (ie, word reading), the PFC is minimally engaged and the response is biased towards the prepotent word reading response, which is represented by relatively thicker black vertical arrows. (b) In contrast, under high cognitive control demands (ie, color naming), the PFC is strongly recruited to bias responding away from the prepotent response and toward the appropriate response represented by the large red vertical arrow.
Figure 2
Figure 2
Regions in which patients with schizophrenia showed co-occurring hypoactivation compared with controls across a full set of executive function studies (reprinted with permission from Minzenberg et al, 2009).
Figure 3
Figure 3
From cells to circumstantiality: a unified model outlining (a) γ-aminobutyric acid (GABA)-ergic cellular abnormalities, (b) ‘micro-circuit' gamma oscillatory function, (c) regional recruitment of the prefrontal cortex (PFC) in mediating cognitive control, (d) engagement of the ‘macro-circuit', the coordinated activation of frontal and parietal regions as a neural system, (e) cognitive/behavioral performance on cognitive control tasks (eg, AX-Continuous Performance Task (AX-CPT) and Stroop), and (f) disorganization symptoms.

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