Functional magnetic resonance imaging in schizophrenia

Raquel E Gur, Ruben C Gur, Raquel E Gur, Ruben C Gur

Abstract

The integration of functional magnetic resonance imaging (fMRI) with cognitive and affective neuroscience paradigms enables examination of the brain systems underlying the behavioral deficits manifested in schizophrenia; there have been a remarkable increase in the number of studies that apply fMRI in neurobiological studies of this disease. This article summarizes features of fMRI methodology and highlights its application in neurobehavioral studies in schizophrenia. Such work has helped elucidate potential neural substrates of deficits in cognition and affect by providing measures of activation to neurobehavioral probes and connectivity among brain regions. Studies have demonstrated abnormalities at early stages of sensory processing that may influence downstream abnormalities in more complex evaluative processing. The methodology can help bridge integration with neuropharmacologic and genomic investigations.

Figures

Figure 1.
Figure 1.
This functional connectivity analysis map illustrates the negative interaction between the intensity of the vocal cue of an emotion and the mean time series of inferior frontal gyrus (IFG) seed region (red sphere). This map indicates that functiona connectivity between IFG and auditory processing regions in superior temporal gyrus (STG) is significantly modulated by cue saliency: decreasing cue saliency increases IFG-STG functional coupling, while increasing cue saliency decreases this coupling Reprinted with permission from ref 2: Leitman DI, Wolf DH, Ragland JD, et al. "It's not what you say, but how you say it": a reciprocal temporo-frontal network for affective prosody. Front Hum Neurosci 2010;4:19-31. Copyright © Frontiers Research Foundation 2010
Figure 2.
Figure 2.
Examples of stimuli used in “oddball” studies of attentional processing (top) and contrast images of patients with schizophrenia and comparison subjects for target and novel stimuli. Greater activation in patients is depicted by the blue scale, whereas greater activation in comparison subjects is shown by the red scale. Images are in radiological convention (left hemisphere to viewer's right). Reprinted with permission from ref 13: Gur RE, Turetsky BI, Loughead J, et al. Visual attention circuitry in schizophrenia investigated with oddball event-related functional magnetic resonance imaging. Am J Psychiatry. 2007;164:442-449. Copyright © American Psychiatric Association 2007
Figure 3.
Figure 3.
Group differences in left STG-DLPFC and STG-VLPFC connectivity (Left Column) and in left PHIP-DLPFC and PHIP-VLPFC connectivity (right column). For the left column, panel A: group-averaged STG timeseries correlation maps for control group (left) and schizophrenia group (right), from a representative coronal plane (y = 30). A region of DLPFC shows greater connectivity (measured as average Fisher's Z-transformed correlation coefficients) with STG in controls, while a region in VLPFC shows greater connectivity with STG in patients. Panel B results of voxel-by-voxel t-tests are overlaid on the two prefrontal regions of interest and a standard reference brain (Colin, MNI), in the same coronal plane. The group differences seen within DLPFC and VLPFC are statistically significant. For the right column, Panel A: groupaveraged PHIP timeseries correlation maps reveal a region within DLPFC showing greater connectivity with PHIP in controls, while a region within VLPFC shows greater connectivity with PHIP in patients. Panel B: group differences seen within DLPFC and VLPFC are statistically significant. STG, superior temporal gyrus; DLPFC, dorsolateral prefrontal cortex; VLPFC, ventrolateral prefrontal cortex; PHIP, parahippocampal gyrus; CNT, control; SCH, schizophrenia; ROI, region of interest. Reprinted with permission from ref 1 3: Gur RE, Turetsky BI, Loughead J, et al. Visual attention circuitry in schizophrenia investigated with oddball event-related functional magnetic resonance imaging. Am J Psychiatry. 2007;164:442-449. Copyright © American Psychiatric Association 2007
Figure 4.
Figure 4.
Regions activated for emotion identification task relative to baseline (block analysis) in controls (upper row), patients (middle row), and the controls-patients contrast (bottom row). No patients-controls contrast survived correction. Significance thresholds are based on spatia extent using a height of z>3.1 and a cluster probability of P<.05. Images are displayed over a Talairach-normalized template in radiological convention (left hemisphere to viewer's right). The z-level coordinates are provided. AM, amygdala; IF (47), inferior frontal (Brodmann area 47); HI, hippocampus; IF (45), inferior frontal (Brodmann area 45); TH, thalamus. Reprinted with permission from ref 1 3: Gur RE, Turetsky BI, Loughead J, et al. Visual attention circuitry in schizophrenia investigated with oddball event-related functional magnetic resonance imaging. Am J Psychiatry. 2007;164:442-449. Copyright © American Psychiatric Association 2007
Figure 5.
Figure 5.
Association between brain activity and clinical measures. A, Correlations between event-related activation for the 4 emotional expressions in activated regions and severity of clinical ratings for flat affect. B, Scatterplot of the association between percentage of signal change for the appearance of fear expressions and severity of flat affect. MO, Mid-occipital; FG,=fusiform gyrus AM, amygdala; IF (47), inferior fronta (Brodmann area 47); HI, hippocampus; IF (45), inferior fronta (Brodmann area 45); TH, thalamus. Reprinted with permission from ref 13: Gur RE, Turetsky BI, Loughead J, et al. Visual attention circuitry in schizophrenia investigated with oddball event-related functional magnetic resonance imaging. Am J Psychiatry. 2007;164:442-449. Copyright © American Psychiatric Association 2007

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