Functional Brain Imaging in Schizophrenia: Selected Results and Methods

Psychology Service, VA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA.
Current Topics in Behavioral Neurosciences 01/2010; 4(4):181-214. DOI: 10.1007/7854_2010_54
Source: PubMed


Functional brain imaging studies of patients with schizophrenia may be grouped into those that assume that the signs and symptoms of schizophrenia are due to disordered circuitry within a critical brain region and studies that assume that the signs and symptoms are due to disordered connections among brain regions. Studies have investigated the disordered functional brain anatomy of both the positive and negative symptoms of schizophrenia. Studies of spontaneous hallucinations find that although hallucinations are associated with abnormal brain activity in primary and secondary sensory areas, disordered brain activation associated with hallucinations is not limited to sensory systems. Disordered activation in non-sensory regions appear to contribute to the emotional strength and valence of hallucinations, to be a factor underlying an inability to distinguish ongoing mental processing from memories, and to reflect the brain's attempt to modulate the intensity of hallucinations and resolve conflicts with other processing demands. Brain activation studies support the view that auditory/verbal hallucinations are associated with an impaired ability of internal speech plans to modulate neural activation in sensory language areas. In early studies, negative symptoms of schizophrenia were hypothesized to be associated with impaired function in frontal brain areas. In support of this hypothesis meta-analytical studies have found that resting blood flow or metabolism in frontal cortex is reduced in schizophrenia, though the magnitude of the effect is only small to moderate. Brain activation studies of working memory (WM) functioning are typically associated with large effect sizes in the frontal cortex, whereas studies of functions other than WM generally reveal smaller effects. Findings from some functional connectivity studies have supported the hypothesis that schizophrenia patients experience impaired functional connections between frontal and temporal cortex, although the nature of the disordered connectivity is complex. More recent studies have used functional brain imaging to study neural compensation in schizophrenia, to serve as endophenotypes in genetic studies and to provide biomarkers in drug development studies. These emerging trends in functional brain imaging research are likely to help stimulate the development of a general neurobiological theory of the complex symptoms of schizophrenia.

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    • "Auditory verbal hallucinations (AVH, or ''hearing voices'') are distressing symptoms of schizophrenia that affect the majority of patients and diminish their quality of life (Aleman and Larøi 2008). Recent developments in brain imaging reveal that AVH in schizophrenia are associated with a complicated brain connectivity dysfunction (Jardri et al. 2011; Brown and Thompson 2010) that incorporates both functional and anatomical connections (Allen et al. 2008). Diffusion tensor imaging (DTI) is a relatively novel non-invasive technique to investigate the integrity of anatomical connections in the brain. "
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    ABSTRACT: Auditory verbal hallucinations (AVH) in schizophrenia have previously been associated with functional deficiencies in language networks, specifically with functional disconnectivity in fronto-temporal connections in the left hemisphere and in interhemispheric connections between frontal regions. Here, we investigate whether AVH are accompanied by white matter abnormalities in tracts connecting the frontal, parietal and temporal lobes, also engaged during language tasks. We combined diffusion tensor imaging with tract-based spatial statistics and found white matter abnormalities in patients with schizophrenia as compared with healthy controls. The patients showed reduced fractional anisotropy bilaterally: in the anterior thalamic radiation (ATR), body of the corpus callosum (forceps minor), cingulum, temporal part of the superior longitudinal fasciculus (SLF) and a small area in the inferior fronto-occipital fasciculus (IFOF); and in the right hemisphere: in the visual cortex, forceps major, body of the corpus callosum (posterior parts) and inferior parietal cortex. Compared to patients without current hallucinations, patients with hallucinations revealed decreased fractional anisotropy in the left IFOF, uncinate fasciculus, arcuate fasciculus with SLF, corpus callosum (posterior parts-forceps major), cingulate, corticospinal tract and ATR. The severity of hallucinations correlated negatively with white matter integrity in tracts connecting the left frontal lobe with temporal regions (uncinate fasciculus, IFOF, cingulum, arcuate fasciculus anterior and long part and superior long fasciculus frontal part) and in interhemispheric connections (anterior corona radiata). These findings support the hypothesis that hallucinations in schizophrenia are accompanied by a complex pattern of white matter alterations that negatively affect the language, emotion and attention/perception networks.
    Full-text · Article · Nov 2013 · Brain Structure and Function
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    • "Neuroimaging data support the idea that schizophrenia is a brain disorder with altered brain structure and function (Brown and Thompson, 2010 ; Shenton et al., 2001). The dysconnectivity theory of schizophrenia proposes that schizophrenic symptoms arise from abnormalities in neuronal connectivity (Bullmore et al., 1997), and the existence of a widespread anatomical disconnection is now well established for the condition (Stephan et al., 2006). "
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    ABSTRACT: Neuroimaging data support the idea that schizophrenia is a brain disorder with altered brain structure and function. New resting-state functional connectivity techniques allow us to highlight synchronization of large-scale networks, such as the default-mode network (DMN) and salience network (SN). A large body of work suggests that disruption of these networks could give rise to specific schizophrenia symptoms. We examined the intra-network connectivity strength and gray matter content (GMC) of DMN and SN in 26 schizophrenia patients using resting-state functional magnetic resonance imaging and voxel-based morphometry. Resting-state data were analyzed with independent component analysis and dual-regression techniques. We reported reduced functional connectivity within both DMN and SN in patients with schizophrenia. Concerning the DMN, patients showed weaker connectivity in a cluster located in the right paracingulate cortex. Moreover, patients showed decreased GMC in this cluster. With regard to the SN, patients showed reduced connectivity in the left and right striatum. Decreased connectivity in the paracingulate cortex was correlated with difficulties in abstract thinking. The connectivity decrease in the left striatum was correlated with delusion and depression scores. Correlation between the connectivity of DMN frontal regions and difficulties in abstract thinking emphasizes the link between negative symptoms and the likely alteration of the frontal medial cortex in schizophrenia. Correlation between the connectivity of SN striatal regions and delusions supports the aberrant salience hypothesis. This work provides new insights into dysfunctional brain organization in schizophrenia and its contribution to specific schizophrenia symptoms.
    Full-text · Article · May 2013 · Schizophrenia Research
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    • "Some studies assumed that signs and symptoms of the disease are due to a disordered circuitry within a critical brain region, while other assumed that a disordered connection between brain regions may explain the clinical characteristics of the schizophrenia. Data from functional brain imaging support both the hypotheses [171]. "
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    ABSTRACT: We discuss recent evidences about schizophrenia (frequency, onset, course, risk factors and genetics) and their influences to some epidemiological myths about schizophrenia diffuse between psychiatric and psychopathology clinicians. The scope is to evaluate if the new acquisitions may change the rehabilitation approaches to schizophrenia modifying the balance about the neurodevelopmental hypothesis of schizophrenia accepting that the cognitive deficits are produced by errors during the normal development of the brain (neurodevelopmental hypothesis) that remains stable in the course of illness and the neurodegenerative hypothesis according of which they derived from a degenerative process that goes on inexorably. RESEARCH METHOD/DESIGN: A review of the literature about epidemiology of schizophrenia has been performed and the contributions of some of these evidence to neurodevelopmental hypothesis and to rehabilitation has been described. It cannot be definitively concluded for or against the neurodevelopmental or degenerative hypothesis, but efforts in understanding basis of schizophrenia must go on. Until now, rehabilitation programs are based on the vulnerability-stress model: supposing an early deficit that go on stable during the life under favorable circumstances. So, rehabilitation approaches (as neuro-cognitive approaches, social skill training, cognitive-emotional training) are focused on the individual and micro-group coping skills, aiming to help people with schizophrenia to cope with environmental stress factors. Coping of cognitive deficits in schizophrenia may represents the starting-point for further research on schizophrenia, cohort studies and randomized trials are necessary to defined the range of effectiveness and the outcome of the treatments.
    Full-text · Article · Jul 2012 · Clinical Practice and Epidemiology in Mental Health
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