Review articleMultimodal neuroimaging as a window into the pathological physiology of schizophrenia: Current trends and issues
Introduction
In research settings, a dataset consisting of multiple imaging modalities can be obtained from a single magnetic resonance imaging (MRI) scanning session, including structural, diffusion tensor, and functional MR images. Whereas MRI analysis using a single data processing method can capture a certain pathological aspect of schizophrenia, the combined application of multiple imaging modalities with multiple image processing protocols may elucidate a far more comprehensive understanding of its nature (Sui et al., 2012) (Fig. 1). Representative multi-modal MRI studies on schizophrenia offer an opportunity to reappraise common beliefs of schizophrenia pathology, yet are still limited (Table 1). In this paper, we reexamine some of the major hypotheses and beliefs from the viewpoint of neuroimaging, and discuss the future direction of multimodal MRI studies.
Section snippets
Progressive brain disease hypothesis
Schizophrenia has been considered a progressive brain disease since Emil Kraepelin first established the concept. Despite increasing evidence suggesting that clinical and cognitive outcome does not always deteriorate in individuals with schizophrenia (Bora and Murray, 2013), the concept of schizophrenia as a “progressive disease” lingers.
Evidence of global and regional progressive brain changes is apparent early in the course of schizophrenia (Kasai et al., 2003, Whitford et al., 2006).
Disconnection hypothesis
Eugen Bleuler changed the name of dementia praecox to schizophrenia, and emphasized that an essential feature of schizophrenia is the splitting of psychic functions. Specifically, he used the expressions “extreme separation of thought and affect” or “splitting of association” (Bleuler, 1911). However, because the loci of pathological connectivity have hitherto been underspecified, the idea of a “disconnection hypothesis” has not developed from an abstract concept to a testable scientific
Neural basis of social cognitive impairment
Impaired social cognition is considered one of the core factors contributing to unfavorable psychosocial functioning in schizophrenia (Penn et al., 1997, Lee et al., 2004, Brunet-Gouet and Decety, 2006, Green and Leitman, 2008). To better understand the neural underpinnings of social cognitive impairment in schizophrenia, we investigated associations between social cognitive performance and gray/white matter abnormalities in a series of studies.
As the first step, we investigated the
Gray–white matter pathological associations
Gray and white matter abnormalities of schizophrenia are well-documented in widespread brain areas (Bora et al., 2011). One reasonable understanding of these findings is to hypothesize that schizophrenia is a brain disorder in which gray and white matter pathologies develop in an intertwined manner. However, the number of studies combining structural and diffusion MRI modalities is limited (Spoletini et al., 2009, Koch et al., 2013). Thus, in a series of multimodal MRI studies, we investigated
Conclusions
This review article has discussed previously reported results and findings, mainly from our own multi-modal MRI studies. Rapidly developing MRI technologies and multi-modal combinations of them can provide biological findings that allow us to test various hypotheses that have influenced our concept of schizophrenia. The advantages of MRI are numerous, including its safety, reliability, and capacity to reflect in vivo pathophysiology, although it is still not enough to identify the core
Authors’ contribution
M.I. managed the literature search and wrote the first draft of the manuscript. J.M. also contributed to the literature search and drafting. M.H., H.T., H.F., and M.T. technically supervised interpretation of the data. All authors contributed to and have approved the final manuscript.
Conflict of interest
The authors declare no conflicts of interest.
Acknowledgements
This work was supported by Grant-in-Aid for Scientific Research on Innovative Areas (23118004; Adolescent Mind & Self-Regulation), Grant-in-Aid for Scientific Research A (15H01690), Grant-in-Aid for Scientific Research B (15H04893) and Grant-in-Aid for Scientific Research C (26461767) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. This work was also supported by research grant from Schizophrenia Research Group, sponsored by Astellas Pharma Inc.
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