Regional Deficits in Brain Volume in Schizophrenia: A Meta-Analysis of Voxel-Based Morphometry Studies

Department of Experimental Psychology, University of Oxford, Oxford, England, United Kingdom
American Journal of Psychiatry (Impact Factor: 12.3). 01/2006; 162(12):2233-45. DOI: 10.1176/appi.ajp.162.12.2233
Source: PubMed


Voxel-based morphometry is a method for detecting group differences in the density or volume of brain matter. The authors reviewed the literature on use of voxel-based morphometry in schizophrenia imaging research to examine the capabilities of this method for clearly identifying specific structural differences in patients with schizophrenia, compared with healthy subjects. The authors looked for consistently reported results of relative deficits in gray and white matter in schizophrenia and evaluated voxel-based morphometry methods in order to propose a future strategy for using voxel-based morphometry in schizophrenia research.
The authors reviewed all voxel-based morphometry studies of schizophrenia that were published to May 2004 (15 studies). The studies included a total of 390 patients with a diagnosis of schizophrenia and 364 healthy volunteers.
Gray and white matter deficits in patients with schizophrenia, relative to healthy comparison subjects, were reported in a total of 50 brain regions. Deficits were reported in two of the 50 regions in more than 50% of the studies and in nine of the 50 regions in one study only. The most consistent findings were of relative deficits in the left superior temporal gyrus and the left medial temporal lobe. Use of a smaller smoothing kernel (4-8 mm) led to detection of a greater number of regions implicated in schizophrenia.
This review implicates the left superior temporal gyrus and the left medial temporal lobe as key regions of structural difference in patients with schizophrenia, compared to healthy subjects. The diversity of regions reported in voxel-based morphometry studies is in part related to the choice of variables in the automated process, such as smoothing kernel size and linear versus affine transformation, as well as to differences in patient groups. Voxel-based morphometry can be used as an exploratory whole-brain approach to identify abnormal brain regions in schizophrenia, which should then be validated by using region-of-interest analyses.

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    • "The development of structural neuroimaging has allowed the in vivo investigation of the human brain. Over the past two decades, hundreds of studies have shed light on the neuroanatomical correlates of psychiatric (Honea et al., 2005;Fusar-Poli et al., 2011;Selvaraj et al., 2012) and neurological (Whitwell and Jack, 2005;Ferreira et al., 2011;Li et al., 2012) disorders. The vast majority of these studies were performed using Voxel Based Morphometry (VBM), a whole brain technique for characterizing regional volume and tissue concentration differences from structural magnetic resonance imaging (MRI) scans (Ashburner andFriston, 2000, 2001;Good et al., 2001;Mechelli et al., 2005). "
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    ABSTRACT: In recent years, an increasing number of studies have used Voxel Based Morphometry (VBM) to compare a single patient with a psychiatric or neurological condition of interest against a group of healthy controls. However, the validity of this approach critically relies on the assumption that the single patient is drawn from a hypothetical population with a normal distribution and variance equal to that of the control group. In a previous investigation, we demonstrated that family-wise false positive error rate (i.e. the proportion of statistical comparisons yielding at least one false positive) in single case VBM are much higher than expected (Scarpazza et al. 2013). Here we examine whether the use of non-parametric statistics, which does not rely on the assumptions of normal distribution and equal variance, would enable the investigation of single subjects with good control of false positive risk. We empirically estimated false positive rates in single case non-parametric VBM, by performing 400 statistical comparisons between a single disease-free individual and a group of 100 disease-free controls. The impact of smoothing (4, 8 and 12 mm) and type of pre-processing (Modulated, Unmodulated) was also examined, as these factors have been found to influence false positive rates in previous investigations using parametric statistics. The 400 statistical comparisons were repeated using two independent, freely available data sets in order to maximize the generalizability of the results. We found that the family-wise error rate was 5% for increases and 3.6% for decreases in one data set; and 5.6% for increases and 6.3% for decreases in the other data set (5% nominal). Further, these results were not dependent on the level of smoothing and modulation. Therefore, the present study provides empirical evidence that single case VBM studies with non-parametric statistics are not susceptible to high false positive rates. The critical implication of this finding is that VBM can be used to characterize neuroanatomical alterations in individual subjects as long as non-parametric statistics are employed.
    Full-text · Article · Jan 2016 · Frontiers in Neuroscience
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    • "This is in part due to different methodological approaches between studies that vary stimuli, duration, trial design, and response formats across both standardized and non-standardized assessments (Holt et al., 2006; Li et al., 2010; Taylor et al., 2012). Additionally, cross-study comparisons are limited by the inter-individual variability in the neuroanatomy of the core face perception system (Fox et al., 2009), which may be more pronounced in schizophrenia patients (Honea et al., 2005). Subject level functional localizers allow researchers to control for neuroanatomical differences by using perceptual tasks to identify regions of the cortex based on function, rather than relying on anatomical boundaries. "
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    ABSTRACT: Schizophrenia is associated with deficits in face perception and emotion recognition. Despite consistent behavioural results, the neural mechanisms underlying these cognitive abilities have been difficult to isolate, in part due to differences in neuroimaging methods used between studies for identifying regions in the face processing system. Given this problem, we aimed to validate a recently developed fMRI-based dynamic functional localizer task for use in studies of psychiatric populations and specifically schizophrenia. Previously, this functional localizer successfully identified each of the core face processing regions (i.e. fusiform face area, occipital face area, superior temporal sulcus), and regions within an extended system (e.g. amygdala) in healthy individuals. In this study, we tested the functional localizer success rate in 27 schizophrenia patients and in 24 community controls. Overall, the core face processing regions were localized equally between both the schizophrenia and control group. Additionally, the amygdala, a candidate brain region from the extended system, was identified in nearly half the participants from both groups. These results indicate the effectiveness of a dynamic functional localizer at identifying regions of interest associated with face perception and emotion recognition in schizophrenia. The use of dynamic functional localizers may help standardize the investigation of the facial and emotion processing system in this and other clinical populations.
    Full-text · Article · Jan 2016 · Psychiatry Research: Neuroimaging
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    • "Results from the exploratory hippocampal volume analysis are not in line with the previously reported positive relationship between this region and VM (Gur et al., 2000;Ehrlich et al., 2012). In addition, we only observed a trend between-group effect (p = 0.10), and did not replicate hippocampal volume differences between patients and healthy controls that were previously obtained (Honea et al., 2005;Wright et al., 2000). Nonetheless, some previous studies also failed to showany structural hippocampal differences in schizophrenia patients (Niemann et al., 2000;Sanfilipo et al., 2000;Walker et al., 2002). "
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    ABSTRACT: Verbal memory (VM) represents one of the most affected cognitive domains in schizophrenia. Multiple studies have shown that schizophrenia is associated with cortical abnormalities, but it remains unclear whether these are related to VM impairments. Considering the vast literature demonstrating the role of the frontal cortex, the parahippocampal cortex, and the hippocampus in VM, we examined the cortical thickness/volume of these regions. We used a categorical approach whereby 27 schizophrenia patients with 'moderate to severe' VM impairments were compared to 23 patients with 'low to mild' VM impairments and 23 healthy controls. A series of between-group vertex-wise GLM on cortical thickness were performed for specific regions of interest defining the parahippocampal gyrus and the frontal cortex. When compared to healthy controls, patients with 'moderate to severe' VM impairments revealed significantly thinner cortex in the left frontal lobe, and the parahippocampal gyri. When compared to patients with 'low to mild' VM impairments, patients with 'moderate to severe' VM impairments showed a trend of thinner cortex in similar regions. Virtually no differences were observed in the frontal area of patients with 'low to mild' VM impairments relative to controls. No significant group differences were observed in the hippocampus. Our results indicate that patients with greater VM impairments demonstrate significant cortical thinning in regions known to be important in VM performance. Treating VM deficits in schizophrenia could have a positive effect on the brain; thus, subgroups of patients with more severe VM deficits should be a prioritized target in the development of new cognitive treatments.
    Full-text · Article · Dec 2015 · Clinical neuroimaging
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