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. 2009 Dec;30(12):4129-37.
doi: 10.1002/hbm.20834.

Superior temporal lobe dysfunction and frontotemporal dysconnectivity in subjects at risk of psychosis and in first-episode psychosis

Nicolas A Crossley  1 , Andrea Mechelli, Paolo Fusar-Poli, Matthew R Broome, Pall Matthiasson, Louise C Johns, Elvira Bramon, Lucia Valmaggia, Steven C R Williams, Philip K McGuire
Affiliations

Superior temporal lobe dysfunction and frontotemporal dysconnectivity in subjects at risk of psychosis and in first-episode psychosis

Nicolas A Crossley et al. Hum Brain Mapp. 2009 Dec.

Abstract

Background: Superior temporal lobe dysfunction is a robust finding in functional neuroimaging studies of schizophrenia and is thought to be related to a disruption of fronto-temporal functional connectivity. However, the stage of the disorder at which these functional alterations occur is unclear. We addressed this issue by using functional MRI (fMRI) to study subjects in the prodromal and first episode phases of schizophrenia.

Methods: Subjects with an at risk mental state (ARMS) for psychosis, a first psychotic episode (FEP), and controls were studied using fMRI while performing a working memory task. Activation in the superior temporal gyrus (STG) was assessed using statistical parametric mapping, and its relationship to frontal activation was examined using dynamic causal modeling.

Results: The STG was differentially engaged across the three groups. There was deactivation of this region during the task in controls, whereas subjects with FEP showed activation and the response in subjects with ARMS was intermediately relative to the two other groups. There were corresponding differences in the effective connectivity between the STG and the middle frontal gyrus across the three groups, with a negative coupling between these areas in controls, a positive coupling in the FEP group, and an intermediate value in the ARMS group.

Conclusions: A failure to deactivate the superior temporal lobe during tasks that engage prefrontal cortex is evident at the onset of schizophrenia and may reflect a disruption of fronto-temporal connectivity. Qualitatively similar alterations are evident in people with prodromal symptoms of the disorder.

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Figures

Figure 1
Figure 1
Areas activated when subjects from the three groups were performing the working memory tasks. Regions showed correspond to the combined 1‐ and 2‐back conditions against 0‐back condition, with a threshold of P < 0.05, corrected with FWE with clusters >10 and masked with contrasts of activated regions for each independent group at P < 0.001. Coordinates and Z‐scores are reported in Table I. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]
Figure 2
Figure 2
Comparison of FEP and controls when performing the working memory task. Only areas significant at P < 0.001 uncorrected and with cluster size >10 are shown. Bold signal from the highlighted area in the STG is shown in the lower graph. The two columns in each group represent the 1‐ and 2‐back conditions. Notice that in both conditions the FEP group showed activation of the STG, in contrast to the deactivation evident in controls. The ARMS group showed an intermediate pattern of activation in this region. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]
Figure 3
Figure 3
Model connecting selected regions to superior temporal gyrus (STG). Note that the directions of the connections are unidirectional to STG. SMA = supplementary motor area; MFG = middle frontal gyrus; INS = insula; PAR = posterior parietal.
Figure 4
Figure 4
Scatter plot of coupling parameters (rate of change in activation per unit of time) for each subject in the three groups. Coupling between prefrontal and superior temporal cortex was positive in the FEP group, negative in controls, and around neutral in the ARMS group. Highlighted with black diamonds are the two subjects in the ARMS group who later made the transition to psychosis (see text).
See this image and copyright information in PMC

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