Symptomatic and functional correlates of regional brain physiology during working memory processing in patients with recent onset schizophrenia

Department of Psychology, University of California Los Angeles, Los Angeles, CA 90095, United States.
Psychiatry Research (Impact Factor: 2.47). 09/2009; 173(3):177-82. DOI: 10.1016/j.pscychresns.2009.02.008
Source: PubMed


Patients with schizophrenia show altered patterns of functional activation during working memory processing; specifically, high-performing patients appear to hyper-activate and low-performing patients appear to hypo-activate when compared with controls. It remains unclear how these individual differences in neurophysiological activation relate to the clinical presentation of the syndrome. In this functional magnetic resonance imaging (fMRI) study, the relationship is examined using partial least squares (PLS), a multivariate statistical technique that selects underlying latent variables based on the covariance between two sets of variables, in this case, clinical variables and regional fMRI activations during a verbal working memory task. The PLS analysis extracted two latent variables, and the significance of these associations was confirmed through permutation. Lower levels of activation during task performance across frontal and parietal regions of interest in the left hemisphere were found to covary with poorer role functioning and greater severity of negative and disorganized symptoms, while lower activation in right frontal and subcortical regions of interest was found to covary with better social functioning and fewer positive symptoms. These results suggest that appropriately lateralized patterns of functional activation during working memory processing are related to the severity of negative and disorganized symptoms and to the level of role and social functioning in schizophrenia.

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Available from: Joseph Ventura
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    • "These self-regulatory mechanisms are reliant on cognitive control processes mediated by the lateral prefrontal cortex (LPFC; Heatherton and Wagner, 2011; Ochsner et al., 2012). LPFC dysfunction in cognitive control is a well-established neural impairment in schizophrenia (Barch, 2005; Manoach, 2003; Minzenberg et al., 2009) that is associated with worse symptoms (Goghari et al., 2010; MacDonald et al., 2005; Menon et al., 2001; Nishimura et al., 2011; Perlstein et al., 2001; van Veelen et al., 2010) and global functioning deficits (Sanz et al., 2009; Yoon et al., 2008). However, there is a paucity of research examining how LPFC dysfunction contributes to illness severity. "
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    ABSTRACT: LPFC dysfunction is a well-established neural impairment in schizophrenia and is associated with worse symptoms. However, how LPFC activation influences symptoms is unclear. Previous findings in healthy individuals demonstrate that lateral prefrontal cortex (LPFC) activation during cognitive control of emotional information predicts mood and behavior in response to interpersonal conflict, thus impairments in these processes may contribute to symptom exacerbation in schizophrenia. We investigated whether schizophrenia participants show LPFC deficits during cognitive control of emotional information, and whether these LPFC deficits prospectively predict changes in mood and symptoms following real-world interpersonal conflict. During fMRI, 23 individuals with schizophrenia or schizoaffective disorder and 24 healthy controls completed the Multi-Source Interference Task superimposed on neutral and negative pictures. Afterwards, schizophrenia participants completed a 21-day online daily-diary in which they rated the extent to which they experienced mood and schizophrenia-spectrum symptoms, as well as the occurrence and response to interpersonal conflict. Schizophrenia participants had lower dorsal LPFC activity (BA9) during cognitive control of task-irrelevant negative emotional information. Within schizophrenia participants, DLPFC activity during cognitive control of emotional information predicted changes in positive and negative moods on days following highly distressing interpersonal conflicts. Results have implications for understanding the specific role of LPFC in response to social stress in schizophrenia, and suggest that treatments targeting LPFC-mediated cognitive control of emotion could promote adaptive response to social stress in schizophrenia.
    Full-text · Article · Aug 2014 · Clinical neuroimaging
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    • "Several MRI studies have reported volume reductions in schizophrenia (see review by Shenton et al. [11••]). Involvement of the frontal lobe has been related to negative symptoms and cognitive impairments in schizophrenia, including deficits in executive and problem-solving functions and working memory [12, 13]. Several MRI studies have also examined frontal lobe involvement in SPD, although the findings are more mixed. "
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    ABSTRACT: Individuals with schizotypal personality disorder (SPD) share genetic, phenomenologic, and cognitive abnormalities with people diagnosed with schizophrenia. To date, 15 structural MRI studies of the brain have examined size, and 3 diffusion tensor imaging studies have examined white matter connectivity in SPD. Overall, both types of structural neuroimaging modalities have shown temporal lobe abnormalities similar to those observed in schizophrenia, while frontal lobe regions appear to show more sparing. This intriguing pattern suggests that frontal lobe sparing may suppress psychosis, which is consistent with the idea of a possible neuroprotective factor. In this paper, we review these 18 studies and discuss whether individuals with SPD who both resemble and differ from schizophrenia patients in their phenomenology, share some or all of the structural brain imaging characteristics of schizophrenia. We attempt to group the MRI abnormalities in SPD into three patterns: 1) a spectrum of severity-abnormalities are similar to those observed in schizophrenia but not so severe; 2) a spectrum of region-abnormalities affecting some, but not all, brain regions affected in schizophrenia; and 3) a spectrum of compensation-abnormalities reflecting greater-than-normal white matter volume, possibly serving as a buffer or compensatory mechanism protecting the individual with SPD from the frank psychosis observed in schizophrenia.
    Full-text · Article · Feb 2012 · Current Psychiatry Reports
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    • "Interestingly, the activity in this region returned to normal levels when patients were symptom-free [1]. Lower levels of activation during verbal WM task performance in the left hemisphere across frontal and parietal regions were associated with poorer role functioning and greater severity of negative and disorganised symptoms [59]. A recent study identified disturbed parieto-occipital functional connectivity as related with positive symptoms of SZ [50]. "
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    ABSTRACT: Objective. Despite observations that abnormal parietal lobe (PL) function is associated with psychotic-like experiences, our knowledge about the nature of PL involvement in schizophrenia is modest. The objective of this paper is to investigate the role of the PL in schizophrenia. Method. Medline databases were searched for English language publications using the following key words: parietal lobe, combined with schizophrenia, lesions, epilepsy, cognition, rare genetic disorders, MRI, fMRI, PET, and SPECT, respectively, followed by cross-checking of references. Results. Imaging studies in childhood onset schizophrenia suggest that grey matter abnormalities start in parietal and occipital lobes and proceed to frontal regions. Although, the findings are inconsistent, several studies with patients at risk to develop schizophrenia indicate early changes in the PL. Conclusions. We want to propose that in a proportion of individuals with emerging schizophrenia structural and functional alterations may start in the PL and progress to frontal regions.
    Full-text · Article · Oct 2011
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