A Double Dissociation of Ventromedial Prefrontal Cortical Responses to Sad and Happy Stimuli in Depressed and Healthy Individuals

Department of Psychological Medicine, Institute of Psychiatry, London, England.
Biological Psychiatry (Impact Factor: 10.26). 10/2005; 58(6):495-503. DOI: 10.1016/j.biopsych.2005.04.035
Source: PubMed


The ventromedial prefrontal cortex (VMPFC) is a region implicated in the assessment of the rewarding potential of stimuli and may be dysfunctional in major depressive disorder (MDD). The few studies examining prefrontal cortical responses to emotive stimuli in MDD have indicated increased VMPFC responses to pleasant images but decreased responses to sad mood provocation when compared with healthy individuals. We wished to corroborate these results by examining neural responses to personally relevant happy and sad stimuli in MDD and healthy individuals within the same paradigm.
Neural responses to happy and sad emotional stimuli (autobiographical memory prompts and congruent facial expressions) were measured using blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) in MDD (n = 12) and healthy (n = 12) individuals.
Increased and decreased responses in VMPFC were observed in MDD and healthy individuals, respectively, to happy stimuli, whereas the pattern was reversed for MDD and healthy individual responses to sad stimuli. These findings were not explained by medication effects in depressed individuals.
These findings indicate a double dissociation of the pattern of VMPFC response to happy and sad stimuli in depressed and healthy individuals and suggest abnormal reward processing in MDD.

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    • "Depressionappearstoinfluencehowoneperceivesand experiencessadness.ParticipantswithMDDshowprolongedor heightenedactivityintheamygdalaandACCwhentheyprocess stimulithatexpressnegativevalence(Siegleetal.,2002)and increasedactivityintheinsulaandACCwhenexperiencinga sadmood(Maybergetal.,1999;Keedwelletal.,2005).Giventhe roleofthesebrainregionsinrewardprocessingandemotional regulation(Langeneckeretal.,2007),itispossiblethatthis patternofactivityreflectstheincreasedintensityandsalienceof negativeaffectthatisoftenassociatedwithdepression. "
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    ABSTRACT: Sadness is generally seen as a negative emotion, a response to distressing and adverse situations. In an aesthetic context, however, sadness is often associated with some degree of pleasure, as suggested by the ubiquity and popularity, throughout history, of music, plays, films and paintings with a sad content. Here, we focus on the fact that music regarded as sad is often experienced as pleasurable. Compared to other art forms, music has an exceptional ability to evoke a wide-range of feelings and is especially beguiling when it deals with grief and sorrow. Why is it, then, that while human survival depends on preventing painful experiences, mental pain often turns out to be explicitly sought through music? In this article we consider why and how sad music can become pleasurable. We offer a framework to account for how listening to sad music can lead to positive feelings, contending that this effect hinges on correcting an ongoing homeostatic imbalance. Sadness evoked by music is found pleasurable: (1) when it is perceived as non-threatening; (2) when it is aesthetically pleasing; and (3) when it produces psychological benefits such as mood regulation, and empathic feelings, caused, for example, by recollection of and reflection on past events. We also review neuroimaging studies related to music and emotion and focus on those that deal with sadness. Further exploration of the neural mechanisms through which stimuli that usually produce sadness can induce a positive affective state could help the development of effective therapies for disorders such as depression, in which the ability to experience pleasure is attenuated.
    Frontiers in Human Neuroscience 08/2015; 9:404. DOI:10.3389/fnhum.2015.00404 · 3.63 Impact Factor
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    • "Furthermore , decreased ventral striatum activity when processing positive words in depressed versus healthy adults correlated with symptoms of anhedonia (Epstein et al. 2006), consistent with abnormalities in the reward processing system in depression. Depressed adults also show an opposite pattern of vmPFC activation following happy and sad mood induction, compared to nondepressed adults (Keedwell et al. 2005a). Finally, adolescents with depression show lower rCBF in the dlPFC at rest compared to controls, as measured by ASL (Ho et al. 2013). "
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    ABSTRACT: Introduction: Little is known about the neural correlates of mood states and the specific physiological changes associated with their valence and duration, especially in young people. Arterial spin labeling (ASL) imaging is particularly well-suited to study sustained cerebral states in young people, due to its robustness to low-frequency drift, excellent interscan reliability, and noninvasiveness. Yet, it has so far been underutilized for understanding the neural mechanisms underlying mood states in youth. Methods: In this exploratory study, 21 healthy adolescents aged 16 to 18 took part in a mood induction experiment. Neutral, sad, and happy mood states were induced using film clips and explicit instructions. An ASL scan was obtained following presentation of each film clip. Results: Mood induction led to robust changes in self-reported mood ratings. Compared to neutral, sad mood was associated with increased regional cerebral blood flow (rCBF) in the left middle frontal gyrus and anterior prefrontal cortex, and decreased rCBF in the right middle frontal gyrus and the inferior parietal lobule. A decrease in self-reported mood from neutral to sad condition was associated with increased rCBF in the precuneus. Happy mood was associated with increased rCBF in medial frontal and cingulate gyri, the subgenual anterior cingulate cortex, and ventral striatum, and decreased rCBF in the inferior parietal lobule. The level of current self-reported depressive symptoms was negatively associated with rCBF change in the cerebellum and lingual gyrus following both sad and happy mood inductions. Conclusions: Arterial spin labeling is sensitive to experimentally induced mood changes in healthy young people. The effects of happy mood on rCBF patterns were generally stronger than the effects of sad mood.
    Brain and Behavior 06/2015; 5(6):e00339. DOI:10.1002/brb3.339 · 2.24 Impact Factor
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    • "Another primary area of functional neuroimaging research in MDD involves responses to rewarding stimuli. While early functional magnetic resonance imaging (fMRI) (and non-imaging) studies frequently operationalized reward in terms of the passive viewing or consumption of positively valenced stimuli (for example [36-38]), more recent work has increasingly emphasized constructs of reward anticipation [39-42], reinforcement learning [43,44] and motivation [45-47], which are psychologically and neurobiologically distinct. This shift has been motivated largely by the enhanced understanding of functional segregation of dopaminergic cortico-striatal systems in reward processing, which have been found to underlie anticipation, learning, and salience of rewards, rather than affective responses to them [48]. "
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    ABSTRACT: The neuroimaging literature of Major Depressive Disorder (MDD) has grown substantially over the last several decades, facilitating great advances in the identification of specific brain regions, neurotransmitter systems and networks associated with depressive illness. Despite this progress, fundamental questions remain about the pathophysiology and etiology of MDD. More importantly, this body of work has yet to directly influence clinical practice. It has long been a goal for the fields of clinical psychology and psychiatry to have a means of making objective diagnoses of mental disorders. Frustratingly little movement has been achieved on this front, however, and the 'gold-standard' of diagnostic validity and reliability remains expert consensus. In light of this challenge, the focus of the current review is to provide a critical summary of key findings from different neuroimaging approaches in MDD research, including structural, functional and neurochemical imaging studies. Following this summary, we discuss some of the current conceptual obstacles to better understanding the pathophysiology of depression, and conclude with recommendations for future neuroimaging research.
    Biology of Mood and Anxiety Disorders 03/2014; 4(1):5. DOI:10.1186/2045-5380-4-5
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