Prefrontal Cortical Changes Following Cognitive Training in Patients with Chronic Schizophrenia: Effects of Practice, Generalization, and Specificity

Translational Research in Cognitive and Affective Mechanisms laboratory, Department of Psychology, University of Minnesota, Minneapolis, MN 55455, USA.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology (Impact Factor: 7.05). 08/2010; 35(9):1850-9. DOI: 10.1038/npp.2010.52
Source: PubMed


Cognitive training is increasingly used in the treatment of schizophrenia, but it remains unknown how this training affects functional neuroanatomy. Practice on specific cognitive tasks generally leads to automaticity and decreased prefrontal cortical activity, yet broad-based cognitive training programs may avoid automaticity and increase prefrontal cortex (PFC) activity. This study used quasi-randomized, placebo-control design and pre/post neuroimaging to examine functional plasticity associated with attention and working memory-focused cognitive training in patients with schizophrenia. Twenty-one participants with schizophrenia or schizoaffective disorder split into two demographically and performance matched groups (nine scanned per group) and nine control participants were tested 6-8 weeks apart. Compared with both patient controls and healthy controls, patients receiving cognitive training increased activation significantly more in attention and working memory networks, including dorsolateral prefrontal cortex, anterior cingulate and frontopolar cortex. The extent to which activity increased in a subset of these regions predicted performance improvements. Although this study was not designed to speak to the efficacy of cognitive training as a treatment, it is the first study to show that such training can increase the ability of patients to activate the PFC regions subserving attention and working memory.

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Available from: Kristen Haut, Jan 21, 2015
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    • "In one study, cognitive training in attention, working memory, logical thinking, and executive functioning domains led to greater activation in the prefrontal cortex on a spatial working memory task compared to a group that did not receive cognitive training[60]. Similarly, another research group showed increased activation in regions of the prefrontal cortex (that is, the dorsolateral prefrontal cortex, anterior cingulated, and frontopolar cortex) along with associated improvements in attention and working memory following a cognitive remediation program targeting attention and working memory in schizophrenia patients[61]. Thus, current research shows promising results for restoring working memory abilities following cognitive remediation in schizophrenia patients; however, given that the training programs examined are typically broadbased , it remains difficult to determine which aspects of training are providing the benefit. "
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    ABSTRACT: In most domains of cognition, individuals with schizophrenia are generally found to be one standard deviation below the mean of the controls. As a result, examining the impact of cognitive remediation in individuals with schizophrenia has been a burgeoning area of research. However, the state of the literature remains unclear as to which domains of cognition should be targeted to produce the most widespread and durable benefits for individuals with schizophrenia. One suggestion is that targeting lower-level cognitive processes that are important for higher-level and more complex aspects of cognition may produce the most widespread benefits in cognition and everyday functioning. Relatively few studies have examined the effects of working memory or processing speed training in schizophrenia, as most studies examine broad-based remediation programs. Thus, a need exists for targeted working memory and processing speed training studies to better understand the mechanisms of cognitive enhancement in patients. This study aims to 1) investigate near-transfer gains (that is, the transfer of learning to related contexts) associated with working memory and processing speed training in schizophrenia patients; 2) investigate far-transfer gains (that is, the transfer of learning to new contexts) associated with working memory and processing speed training (that is, gains in other neurocognitive domains and social cognition); and 3) investigate real-world gains associated with training (that is, gains in daily functioning). A double-blind randomized controlled trial with a three parallel group design will be conducted. A random sample of 81 patients with schizophrenia or schizoaffective disorder will be recruited through outpatient clinics at Foothills Hospital and community support programs in Calgary, Alberta. Participants will be randomly assigned using a computer-generated program in a 1:1:1 ratio to a working memory-training group, a processing speed-training group, or a no-training control group. Training will be completed at home for 30 minutes per day, 5 days per week, for a total of 10 weeks. Neurocognitive, social cognitive, and daily functioning measures will be administered both pre- and post-training to detect training-related gains. The primary outcome measures will include working memory and processing speed (near-transfer measures), as well as fluid intelligence (far-transfer measure). Trial registration Current controlled trials NCT02478827 (, registered on 15 June 2015).
    Full-text · Article · Dec 2016 · Trials
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    • "To date, only a few studies have exclusively targeted WM training (particularly auditory WM) in psychosis. Results have been promising, with WM training being associated with improvements in both verbal WM and general cognitive ability (Fisher et al., 2009; Hubacher et al., 2013; Subramaniam et al., 2014; Wexler et al., 2000; Haut et al., 2010). Whether a targeted approach such as this is more beneficial , either in terms of size or cost effectiveness of effect, however, remains uncertain (Wykes et al., 2011). "
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    ABSTRACT: Background: Cognitive deficits are a core feature of schizophrenia and related psychotic disorders and are associated with decreased levels of functioning. Behavioural interventions have shown success in remediating these deficits; determining how best to maximise this benefit while minimising the cost is an important next step in optimising this intervention for clinical use. Aims: To examine the effects of a novel working-memory focused cognitive remediation (CR) training on cognitive difficulties based on internet delivery of training and weekly telephone support. Method: Participants with a diagnosis of psychosis (n=56) underwent either 8weeks of CR (approximately 20h) or 8weeks of treatment as usual (TAU). General cognitive ability, working memory and episodic memory were measured both pre and post intervention for all participants. Results: In addition to improvements on trained working memory tasks, CR training was associated with significant improvements in two tests of verbal episodic memory. No association between CR and changes in general cognitive ability was observed. Effect sizes for statistically significant changes in memory were comparable to those reported in the literature based primarily on 1:1 training. Conclusions: The cognitive benefits observed in this non-randomised preliminary study indicate that internet-based working memory training can be an effective cognitive remediation therapy. The successes and challenges of an internet-based treatment are discussed.
    Full-text · Article · Sep 2015 · Schizophrenia Research
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    • "Cingulate activation, especially of the anterior regions, is often abnormal in schizophrenia, where one meta-analysis concluded that patients had lower activity in the right anterior cingulate, and higher activity in the left anterior cingulate (9). This was partly replicated in the reviewed studies, where Haut et al. (57) reported increased right activity and Bor et al. (58) reported an increase in left cingulate activity. The anterior cingulate cortex is associated with performance monitoring and prefrontal task engagement (9). "
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    ABSTRACT: Cognitive impairment is an important aspect of schizophrenia, where cognitive remediation therapy (CRT) is a promising treatment for improving cognitive functioning. While neurobiological dysfunction in schizophrenia has been the target of much research, the neural substrate of cognitive remediation and recovery has not been thoroughly examined. The aim of the present article is to systematically review the evidence for neural changes after CRT for schizophrenia. The reviewed studies indicate that CRT affects several brain regions and circuits, including prefrontal, parietal, and limbic areas, both in terms of activity and structure. Changes in prefrontal areas are the most reported finding, fitting to previous evidence of dysfunction in this region. Two limitations of the current research are the few studies and the lack of knowledge on the mechanisms underlying neural and cognitive changes after treatment. Despite these limitations, the current evidence suggests that CRT is associated with both neurobiological and cognitive improvement. The evidence from these findings may shed light on both the neural substrate of cognitive impairment in schizophrenia, and how better treatment can be developed and applied.
    Full-text · Article · Aug 2014 · Frontiers in Psychiatry
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