Review
Default-mode brain dysfunction in mental disorders: A systematic review

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Abstract

In this review we are concerned specifically with the putative role of the default-mode network (DMN) in the pathophysiology of mental disorders. First, we define the DMN concept with regard to its neuro-anatomy, its functional organisation through low frequency neuronal oscillations, its relation to other recently discovered low frequency resting state networks, and the cognitive functions it is thought to serve. Second, we introduce methodological and analytical issues and challenges. Third, we describe putative mechanisms proposed to link DMN abnormalities and mental disorders. These include interference by network activity during task performance, altered patterns of antagonism between task specific and non-specific elements, altered connectively and integrity of the DMN, and altered psychological functions served by the network DMN. Fourth, we review the empirical literature systematically. We relate DMN dysfunction to dementia, schizophrenia, epilepsy, anxiety and depression, autism and attention deficit/hyperactivity disorder drawing out common and unique elements of the disorders. Finally, we provide an integrative overview and highlight important challenges and tasks for future research.

Section snippets

The default-mode network

The DMN concept although only first introduced into the published literature in 2001 has rapidly become a central theme in contemporary cognitive and clinical neuroscience. Here we identify five key elements.

Methods and measurement models

In order to understand the findings relating DMN activity to mental disorders reviewed below and so to draw out the relevant and appropriate implications, a survey of key methodological and analytical issues is presented. Resting brain states and the DMN have been principally investigated using fMRI (e.g. Greicius et al., 2003, Greicius et al., 2004, Greicius et al., 2007), although positron emission tomography (PET; e.g. Raichle et al., 2001) and electrophysiology have also been employed (e.g.

Putative mechanisms for default-mode-related dysfunction in mental disorder

DMN abnormalities may take a number of different forms and be implicated in a number of different ways in the pathophysiology of mental disorder. Here we outline some putative mechanisms of potential significance for the study of the causal pathways to mental disorder. All empirical research described in the following section refers to resting state fMRI data unless otherwise stated.

A systematic review of empirical studies of default-mode abnormalities and mental disorders

For this review, computerised searches were conducted using the Nature journals online, PubMed, Proquest 5000, Psycinfo and ScienceDirect databases. The following terms default-mode, resting state, low frequency oscillations, functional connectivity and task-positive network were entered into the databases. Further, the table of contents of journals that often publish articles relevant to this topic were also reviewed including Biological Psychiatry, Human Brain Mapping, Journal of Cognitive

Integration and future directions

In the current paper we have considered the relevance of the DMN in relation to mental disorders. There are a number of important observations that may be drawn from the preceding sections, which have significance for theoretical models of psychopathology and provide directions for future research.

In conclusion

In recent years there has been a surge of scientific interest in resting state brain function and the DMN. This interest has extended to the altered patterns of DMN activity in individuals with mental disorder. In the current paper we have described some putative mechanisms for default-mode related dysfunction in mental disorder and have attempted to draw out the potential significance of these for theoretical models of psychopathology. Future research should now focus on a systematic

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