ReviewEmotional valence modulates brain functional abnormalities in depression: Evidence from a meta-analysis of fMRI studies
Highlights
► Activation of emotion identification and regulation areas is altered in depression. ► Limbic areas show mirroring effects for negative and positive emotion. ► Prefrontal areas show valence-specific activation abnormalities. ► Emotional valence modulates neural abnormalities in depression.
Introduction
Major depressive disorder is characterized by maladaptive and persistent emotional responses to stressors (Hammen, 2005). Such an emotional response has the potential to interfere with functioning in all aspects of daily life. Therefore, depression is likely to be associated with fundamental abnormalities in emotional processing, which continuously influence the processing of incoming sensory information (Harmer et al., 2009). Research has indeed demonstrated preferential processing of negative compared to positive information in depressed patients for multiple cognitive domains, such as perception, attention and memory (Disner et al., 2011, Roiser et al., 2012). Neuroimaging research provides a tool to visualize the core of the emotional dysfunction that occurs in the brain of depressed patients.
Several models of emotion processing in the depressed brain have been proposed, in which several brain regions are hypothesized to play a key role, with models differing in their emphases regarding the functions involved (for instance compare (Drevets et al., 2008, Krishnan and Nestler, 2008, Leppanen, 2006, Mayberg, 1997, Phillips et al., 2003). Emotion identification is generally attributed to subcortical structures such as the ventral striatum and amygdala, integration of somatic responses is subserved by the insula and anterior cingulate cortex (ACC) and affective state monitoring is related to medial and dorsolateral prefrontal cortex (DLPFC) function. However, the predictions arising from these models have not been systematically evaluated in the light of recent literature. Moreover, the models do not make clear predictions regarding interactions between activation abnormalities and emotional valence.
Emotional processing could be abnormal in depressed patients at different levels of processing. The initial appraisal of incoming information may be biased, leading to preferential processing of negative information and an amplified emotional response. In particular, it has been suggested that the amygdala may be highly sensitive to negative information (Murray et al., 2011), whereas the ventral striatum, an area predominantly involved in processing positive information, has been hypothesized to be less sensitive in depressed patients (Diekhof et al., 2008). Monitoring of the affective state may also be compromised by reduced cognitive control from the DLPFC and ACC, leading to insufficient capacity to downregulate the response of the amygdala (Beck, 2008, Pizzagalli, 2011). Although these general models of emotional dysfunction in depression lead to specific predictions, empirical studies investigating the neural correlates of emotional dysfunction in depressed patients have produced inconsistent results. It is still insufficiently known which levels are affected during the basic processing of emotional stimuli in emotion perception tasks and whether activation abnormalities are modulated by emotional valence at different levels of processing.
Meta-analysis of functional magnetic resonance imaging (fMRI) studies in depressed patients is critical to validate and advance models of emotional dysfunction in depression. To date, two such meta-analyses have been performed (Diekhof et al., 2008, Fitzgerald et al., 2008). Their findings however were not fully consistent. In particular, while Fitzgerald and colleagues found that processing negative stimuli resulted in hypoactivation in depressed patients in pregenual anterior cingulate, Diekhoff and colleagues found that negative stimuli resulted in hyperactivation of the same area. Similarly, the amygdala is identified as hyperactive during negative emotional processing in one of the meta-analyses (Fitzgerald et al., 2008), but not the other one. This variation in results is probably due to methodological limitations, as these previous meta-analyses included a limited sample of studies (6 in Fitzgerald et al., 2008; 10 in Diekhof et al., 2008), and employed a potentially biased fixed-effects meta-analytical approach that does not adequately incorporate between-study variance, and as a consequence has since been superseded (Eickhoff et al., 2009). Furthermore, these studies did not take into account negative findings or region-of-interest studies, and thereby introduced bias in their selection of study samples.
In the present work, the brain activation patterns of depressed patients were compared to healthy subjects in a meta-analysis on the processing of negative and positive emotion. An up-to-date systematic literature search was conducted to identify a larger number of studies relative to previous meta-analyses. In addition, an innovative analytical procedure for the pooling of results was employed. This approach employs not only the locations of significant effects, but also their effect size. Because statistical thresholds are taken into account during this analysis, this method allows for the combination of results from studies investigating the whole brain and specific regions of interest. It was hypothesized that depressed patients would show greater activation in amygdala and anterior cingulate cortex and less activation in ventral striatum and prefrontal areas. Furthermore, the consistency of results across emotional valence and stimulus type was explored.
Section snippets
Literature search
A literature search was performed to identify relevant fMRI studies investigating processing of emotional information in depressed patients. The search was conducted using standardized search strings capturing the key elements “(f)MRI AND depression OR MDD AND emotion(*) OR affect(*) OR reward”. Articles were retrieved from the electronic databases PubMed, EMBASE and Web of Science until September 1, 2011. The search string was constructed to comprise the following Medical Subject Headings
Study selection
The initial database search elicited 2896 results (search strategy depicted in Fig. 1). In the title-abstract review 197 articles were selected that fulfilled the inclusion criteria. The inter-rater reliability of the two independent observers was good (Cohens κ = 0.90). In total, 44 studies met our inclusion criteria (described in Table 1), including data from a total of 795 depressed patients and 792 healthy controls (HC). A variety of emotional tasks were represented in every contrast. The
Discussion
A meta-analysis of neuroimaging studies on emotion processing in major depression was conducted to test predictions from models about the brain areas involved in dysfunctional emotion processing and to examine whether emotional valence modulates activation abnormalities. We were able to include 44 studies that contrasted MDD patients to healthy controls performing tasks with emotional stimuli during fMRI measurements. For the processing of negative emotion, depressed patients showed more
Acknowledgement
Dr. Costafreda is supported by a Academic Clinical Lectureship from the National Institute for Health Research (UK).
References (96)
- et al.
Anticipation of aversive stimuli activates extended amygdala in unipolar depression
Journal of Psychiatric Research
(2007) - et al.
Elevated amygdala activity to sad facial expressions: a state marker of bipolar but not unipolar depression
Biological Psychiatry
(2010) - et al.
Reduced left subgenual anterior cingulate cortical activity during withdrawal-related emotions in melancholic depressed female patients
Journal of Affective Disorders
(2010) - et al.
Cortical analysis of visual context
Neuron
(2003) - et al.
Induction of depressed mood disrupts emotion regulation neurocircuitry and enhances pain unpleasantness
Biological Psychiatry
(2010) - et al.
Ventromedial prefrontal cortex processing during emotional evaluation in late-onset depression: a longitudinal fMRI-study
Biological Psychiatry
(2008) - et al.
Predictors of amygdala activation during the processing of emotional stimuli: a meta-analysis of 385 PET and fMRI studies RID C-1315-2011
Brain Research Reviews
(2008) - et al.
A parametric approach to voxel-based meta-analysis RID C-1315-2011
Neuroimage
(2009) - et al.
Functional neuroimaging of reward processing and decision-making: a review of aberrant motivational and affective processing in addiction and mood disorders
Brain Research Reviews
(2008) - et al.
Emotional processing in anterior cingulate and medial prefrontal cortex RID A-5237-2009
Trends in Cognitive Science (Regular Edition)
(2011)
Altered emotional interference processing in affective and cognitive-control brain circuitry in major depression
Biological Psychiatry
Pattern classification of sad facial processing: toward the development of neurobiological markers in depression
Biological Psychiatry
The subcallosal cingulate gyrus in the context of major depression
Biological Psychiatry
Neural substrates of increased memory sensitivity for negative stimuli in major depression
Biological Psychiatry
Bidirectional communication between amygdala and fusiform gyrus during facial recognition
Neuroimage
FMRI BOLD responses to negative stimuli in the prefrontal cortex are dependent on levels of recent negative life stress in major depressive disorder
Psychiatry Research: Neuroimaging
Amygdalar interhemispheric functional connectivity differs between the non-depressed and depressed human brain
Neuroimage
The neural correlates of anhedonia in major depressive disorder
Biological Psychiatry
Neural responses to monetary incentives in major depression
Biological Psychiatry
Neural abnormalities during cognitive generation of affect in treatment-resistant depression
Biological Psychiatry
The neural substrates of affective processing toward positive and negative affective pictures in patients with major depressive disorder
Progress in Neuro-Psychopharmacology and Biological Psychiatry
Neural correlates of affective processing in response to sad and angry facial stimuli in patients with major depressive disorder
Progress in Neuro-Psychopharmacology and Biological Psychiatry
Decreased functional coupling of the amygdala and supragenual cingulate is related to increased depression in unmedicated individuals with current major depressive disorder
Journal of Affective Disorders
The amygdala, reward and emotion
Trends in Cognitive Science (Regular Edition)
Machine learning classification with confidence: application of transductive conformal predictors to MRI-based diagnostic and prognostic markers in depression
Neuroimage
Amygdala hyperactivation in untreated depressed individuals
Psychiatry Research: Neuroimaging
Emotion and cognition and the amygdala. From what is it? To what's to be done?
Neuropsychologia
Neural representations of subjective reward value
Behavioural Brain Research
Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI
Neuroimage
Neurobiology of emotion perception. II. Implications for major psychiatric disorders
Biological Psychiatry
The orbitofrontal cortex and beyond: from affect to decision-making
Progress in Neurobiology
Meta-analysis of neuroimaging data: a comparison of image-based and coordinate-based pooling of studies
Neuroimage
Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study
Biological Psychiatry
fMRI of alterations in reward selection, anticipation, and feedback in major depressive disorder
Journal of Affective Disorders
A differential pattern of neural response toward sad versus happy facial expressions in major depressive disorder
Biological Psychiatry
Depression is associated with increased sensitivity to signals of disgust: a functional magnetic resonance imaging study
Journal of Psychiatric Research
Automatic mood-congruent amygdala responses to masked facial expressions in major depression
Biological Psychiatry
FMRI activation in the amygdala and the orbitofrontal cortex in unmedicated subjects with major depressive disorder
Psychiatry Research: Neuroimaging
Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain RID B-5598-2008 RID B-5569-2008 RID B-6303-2012
Neuroimage
Prefrontal mechanisms for executive control over emotional distraction are altered in major depression
Psychiatry Research: Neuroimaging
Amygdala hyperactivation and prefrontal hypoactivation in subjects with cognitive vulnerability to depression
Biological Psychology
fMRI correlates of white matter hyperintensities in late-life depression
American Journal of Psychiatry
The regulatory function of self-conscious emotion: insights from patients with orbitofrontal damage
Journal of Personality and Social Psychology
The evolution of the cognitive model of depression and its neurobiological correlates
American Journal of Psychiatry
Controlling the false discovery rate – a practical and powerful approach to multiple testing Rid C-4219-2008
Journal of the Royal Statistical Society Series B: Methodological
Using the Talairach atlas with the MNI template RID A-2231-2010
Neuroimage
Brain activation to emotional words in depressed vs healthy subjects
Neuroreport
Parametric coordinate-based meta-analysis: valid effect size meta-analysis of studies with differing statistical thresholds
Journal of Neuroscience Methods
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