ReviewMedial prefrontal cortex and the self in major depression
Introduction
According to the cognitive theory of depression, depressed patients display systematic errors in the cognitive appraisal of experience that may promote and sustain an unfavorable view of them (Clark and Beck, 1999). These cognitive biases integrate an increased attention to negative stimuli with an increased attention to the self, namely self-focus. Self-focus in depression is not only quantitatively increased (Mor and Winquist, 2002), but also qualitatively distinct (Teasdale, 1999, Watkins, 2008). More specifically, self-focus in depression is characterized by its abstract, evaluative, analytical style (i.e. ‘thinking about’ experience), rather than being a concrete, intuitive, experiential awareness of experience in the moment. From a philosophical perspective, self-focus in depression is thus more about the ‘extended’ or ‘narrative’ aspects of the self (i.e. the self as a continuous object of knowledge), henceforth referred to as ‘self’, rather than about the so-called ‘minimal self’ (i.e. the self as the subject of immediate experience) (Gallagher, 2000).
There is clinical evidence suggesting that self-focus may influence the course of depression. Rumination, which is a form of self-focused attention on negative aspects of one's self triggered by negative affect, appears to predict the onset of depression and interacts with negative cognitive styles to predict a more chronic evolution of depression (Nolen-Hoeksema et al., 2008). Furthermore, therapeutic interventions targeting self-focus to reduce its analytic components, such as Mindfulness-Based Cognitive Therapy (MBCT), were found to be efficient in preventing depressive relapse (Ma and Teasdale, 2004, Teasdale et al., 2000, Bondolfi et al., 2010). Although self-focus is a core issue in the psychopathology of major depression as well as an efficient target in psychotherapy, little attention have been paid to its neural underpinnings (Northoff, 2007). In contrast with the neural bases of the increased attention to negative stimuli, which have been extensively studied over the last decade (Leppänen, 2006), those of self-focus have been addressed only recently by clinical neuroscience.
Self-focus may be operationalized in social neuroscience as the process by which one engages him or herself in self-referential processing (Lemogne et al., 2009). This definition is particularly heuristic in that self-referential processing (i.e. the appraisal of stimuli as strongly related to one's own person) is common to the distinct concepts of the self (Northoff et al., 2006). Several studies combining functional neuroimaging with self-referential tasks in healthy subjects have consistently demonstrated the role of three main regions within the cortical midline structures (CMS): two anterior regions, dorsal and ventral, within the medial prefrontal cortex (MPFC) and one posterior region encompassing the posterior cingulate cortex (PCC), the precuneus and the retrosplenial cortex (Northoff et al., 2006). For instance, Fossati et al. (2003) presented healthy subjects with personality traits and asked them to judge whether each trait described them (i.e. a self-referential task) or whether it described a generally desirable trait (i.e. a judgment of social desirability). Activation in the MPFC was unique to the self-referential condition. Mostly based on the same paradigm, four functional magnetic resonance imaging (fMRI) studies addressing the neural bases of self-referential processing in major depression were published by four independent teams in the last two years (Grimm et al., 2009b, Lemogne et al., 2009, Yoshimura et al., 2010, Johnson et al., 2009).
The aim of this article is to provide an updated overview of the available data regarding the neural bases of self-referential processing in major depression. Although one may consider these results as conflicting, we will argue that they indeed provide compelling evidence for the role of an increased MPFC activity in the depressive self-focus. First, we will briefly review the role of the cortical midline structures (CMS), including both dorsal and ventral MPFC, in the neural underpinnings of self-referential processing in healthy subjects. Second, we will outline the importance of self-focus in the psychopathology of major depression, making the case for studying its neural bases. Third, we will summarize the main results of the fMRI studies that addressed this issue, focusing especially on those regarding the MPFC. Finally, building on topographical dissociations and functional peculiarities related to the default mode network, we will try to integrate these results in the wider framework of social cognition.
Section snippets
The CMS and the self
Self-referential processing in healthy subjects is associated with more activation or less deactivation within the CMS, whatever the domain of the stimuli that are processed (e.g. words, faces) or their sensory modality (Northoff et al., 2006). From the most anterior regions to the most posterior, these structures include the ventral MPFC, the dorsal MPFC, the anterior cingulate cortex (ACC), the PCC, the precuneus and the retrosplenial cortex. Despite their architectonic heterogeneity, these
Behavioral evidence linking self-focus and depression
Several psychometric studies used self-report measures to address the link between self-focus and depression. Although cross-sectional studies have consistently demonstrated a positive correlation between self-reported ‘trait self-focus’ and depressive mood (Mor and Winquist, 2002), such studies were unable to provide causal evidence. Several experimental studies manipulated either the amount of ‘state self-focus’ (e.g. asking subjects to fill a personality questionnaire) or affective states
The MPFC and self-referential processing in major depression
Due to its pivotal role in the neural networks that are impaired in depressed patients, the MPFC is central to neural models of depression (Mayberg, 2003, Drevets et al., 2008). However, both increased and decreased MPFC activation have been reported in depressed patients (Fitzgerald et al., 2008), warranting further studies to disambiguate the role of the MPFC in major depression. Although the MPFC has been found to be consistently activated during self-referential processing in healthy
A tonic–phasic account of fMRI findings in acute phase
As reviewed above, previous fMRI studies provided evidence for both increased (Lemogne et al., 2009, Yoshimura et al., 2010) and decreased (Grimm et al., 2009b, Johnson et al., 2009) activation of the MPFC during self-referential processing in depressed patients. These opposite results are likely to result from differences in experimental design. For instance, personality traits and pictures may differ in their suitability for self-referential processing. However, Lemogne et al. (in press-a)
Conclusion
Self-focus is associated with acute depressive states as well as with an increased risk of depressive relapse through ruminative processes. Additionally, therapeutic interventions targeting self-focus to reduce its analytic components were found to be efficient in preventing depressive relapse. Therefore, there is evidence suggesting that self-focus may play a key role in the psychopathology of depression, making the case for studying its neural underpinnings. The above-reviewed fMRI studies
Role of funding source
None.
Conflict of interest
None of the authors has any conflict of interest to disclose.
Acknowledgement
None.
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