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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    • "By contrast, reactive control reflects more transient reactivation of goal information in a stimulus-driven manner. An older empirical literature suggested that patients with SZ have disturbances in both proactive and reactive control (see reviews in Lesh et al., 2011; Melcher, Falkai, & Gruber, 2008). However, recent work in SZ has suggested a divergence between proactive and reactive control capacities, and related PFC function (Lesh et al., 2013), with evidence that patients with SZ rely excessively on reactive processes (Edwards, Barch, & Braver, 2010). "
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    ABSTRACT: Background: Suicide is prevalent in schizophrenia (SZ), yet the neural system functions that confer suicide risk remain obscure. Circuits operated by the prefrontal cortex (PFC) are altered in SZ, including those that support reactive control, and PFC changes are observed in postmortem studies of heterogeneous suicide victims. Aims: We tested whether history of suicide attempt is associated with altered frontal motor cortex activity during reactive control processes. Method: We evaluated 17 patients with recent onset of DSM-IV-TR-defined SZ using the Columbia Suicide Severity Rating Scale and functional magnetic resonance imaging during Stroop task performance. Group-level regression models relating past suicidal behavior to frontal activation controlled for depression, psychosis, and impulsivity. Results: Past suicidal behavior was associated with relatively higher activation in the left-hemisphere supplementary motor area (SMA), pre-SMA, premotor cortex, and dorsolateral PFC, all ipsilateral to the active primary motor cortex. Conclusion: This study provides unique evidence that suicidal behavior in patients with recent-onset SZ directly relates to frontal motor cortex activity during reactive control, in a pattern reciprocal to the relationship with proactive control found previously. Further work should address how frontal-based control functions change with risk over time, and their potential utility as a biomarker for interventions to mitigate suicide risk in SZ.
    Full-text · Article · Sep 2015 · Crisis The Journal of Crisis Intervention and Suicide Prevention
    • "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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    ABSTRACT: Overconfidence in false memories is often found in patients with schizophrenia and healthy participants with high levels of schizotypy, indicating an impairment of meta-cognition within the memory domain. In general, cognitive control is suggested to be modulated by natural fluctuations in oestrogen. However, whether oestrogen exerts beneficial effects on meta-memory has not yet been investigated. The present study sought to provide evidence that high levels of schizotypy are associated with increased false memory rates and overconfidence in false memories, and that these processes may be modulated by natural differences in estradiol levels. Using the Deese-Roediger-McDermott paradigm, it was found that highly schizotypal participants with high estradiol produced significantly fewer false memories than those with low estradiol. No such difference was found within the low schizotypy participants. Highly schizotypal participants with high estradiol were also less confident in their false memories than those with low estradiol; low schizotypy participants with high estradiol were more confident. However, these differences only approached significance. These findings suggest that the beneficial effect of estradiol on memory and meta-memory observed in healthy participants is specific to highly schizotypal individuals and might be related to individual differences in baseline dopaminergic activity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    No preview · Article · Aug 2015 · Psychiatry Research
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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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    ABSTRACT: Drug dependence may be at its core a pathology of choice, defined by continued decisions to use drugs irrespective of negative consequences. Despite evidence of dysregulated decision-making in addiction, little is known about the neural processes underlying the most clinically-relevant decisions drug users make: decisions to use drugs. Here, we combined functional Magnetic Resonance Imaging (fMRI), machine learning, and human laboratory drug administration to investigate neural activation underlying decisions to smoke cannabis. Non-treatment-seeking daily cannabis smokers completed an fMRI choice task, making repeated decisions to purchase or decline 1-12 placebo or active cannabis 'puffs' ($0.25-$5/puff). One randomly selected decision was implemented. If the selected choice had been bought, the cost was deducted from study earnings and the purchased cannabis smoked in the laboratory; alternatively, the participant remained in the laboratory without cannabis. Machine learning with leave-one-subject-out cross-validation identified distributed neural activation patterns discriminating decisions to buy cannabis from declined offers. Twenty-one participants were included in behavioral analyses; 17 purchased cannabis and were thus included in fMRI analyses. Purchasing varied lawfully with dose and cost. The classifier discriminated with 100% accuracy between fMRI activation patterns for purchased versus declined cannabis at the level of the individual. Dorsal striatum, insula, posterior parietal regions, anterior and posterior cingulate and dorsolateral prefrontal cortex all contributed reliably to this neural signature of decisions to smoke cannabis. These findings provide the basis for a brain-based characterization of drug-related decision-making in drug abuse, including effects of psychological and pharmacological interventions on these processes.Neuropsychopharmacology accepted article preview online, 12 May 2015. doi:10.1038/npp.2015.135.
    Full-text · Article · May 2015 · Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology
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