Article

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: 2.68). 09/2009; 173(3):177-82. DOI: 10.1016/j.pscychresns.2009.02.008
Source: PubMed

ABSTRACT 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.

Download full-text

Full-text

Available from: Joseph Ventura, Jul 29, 2015
1 Follower
 · 
134 Views
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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.
    08/2014; 6. DOI:10.1016/j.nicl.2014.08.012
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Schizophrenia is associated with changes in the structure and functioning of a number of key brain systems, including prefrontal and medial temporal lobe regions involved in working memory and declarative memory, respectively. Imaging techniques provide an unparalleled window into these changes, allowing repeated assessments across pre- and post-onset stages of the disorder and in relation to critical periods of brain development. Here we review recent directions in structural and functional neuroimaging research on schizophrenia. The view emerging from this work is that schizophrenia is fundamentally a disorder of disrupted neural connectivity, the sources of which appear to be genetic and environmental risk factors influencing brain development both prenatally and during adolescence.
    Current Directions in Psychological Science 08/2010; 19(4-4):226-231. DOI:10.1177/0963721410377601 · 3.93 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Abnormalities in the frontal lobe are considered to be central to the pathology of schizophrenia. Neuroimaging studies indeed report abnormal function of the frontal lobe in schizophrenia patients. However, the nature of these functional abnormalities is unclear, in particular whether they are affected by medication. We therefore investigated whether frontal functioning is already abnormal in first-episode medication-naive schizophrenia, and if so, if this dysfunction is related to symptomatology. Thirty medication-naive male patients with first-episode schizophrenia and 36 matched healthy controls performed a modified working memory task while fMRI data were acquired. During the task, subjects were presented with novel task (NT) and practiced task (PT) memory sets. Compared to controls, patients showed reduced performance during NT and PT. However, both groups performed better during PT, indicating that practice improved performance. Importantly, practice reduced brain activation in both patients and controls, but this effect of practice was significantly smaller in patients compared to controls, specifically in the left dorsolateral prefrontal cortex (DLPFC; p=0.01). The reduced effect of practice on brain activation was related to the severity of negative symptoms and disorganization. These results suggest that DLPFC function is deficient in the early phases of schizophrenia and cannot be attributed to the use of antipsychotics.
    Schizophrenia Research 10/2010; 123(1):22-9. DOI:10.1016/j.schres.2010.07.004 · 4.43 Impact Factor
Show more