Cognitive Control Deficits in Schizophrenia: Mechanisms and Meaning

Department of Psychiatry, UC Davis Imaging Research Center, Davis School of Medicine, University of California, Sacramento, CA 95817, USA.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology (Impact Factor: 7.05). 01/2011; 36(1):316-38. DOI: 10.1038/npp.2010.156
Source: PubMed


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.

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    • "cognitive disorganisation). While many aspects of cognition are impaired (Green, 1996; Lesh et al., 2011), it has been purported that memory processes in particular are severely affected (e.g. verbal memory: Toulopoulou and Murray, 2004; working memory: Manoach et al., 2000; see Aleman et al. (1999), for a meta- analysis). "
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    • "Combined with the orderly relationships between cost and purchasing decisions observed (Figure 1), this potentially suggests engagement in more deliberative, goal-directed decisions rather than habit-based responding. Use of higher-level cognitive processes is further supported by the bilateral dlPFC activation observed, given the central role of dlPFC in supporting cognitive control (Lesh et al, 2011), including during decision-making (Hare et al, 2009). "
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    • "In contrast, we could not replicate the finding of decreased prefrontal-thalamic connectivity. As this finding may be a highly relevant one, given the vast number of evidence reporting deficits of top-down functional control of prefrontal areas in schizophrenia, this issue might be worth highlighting (Lesh et al., 2011; Tu et al., 2013). The discrepancy might be based on the fact that disruption of functional connections in patients with schizophrenia is influenced by a number of endogenous disease-specific and treatment-associated molecular changes, whereas the present study included solely the modulation of the glutamatergic system . "
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