Trait anhedonia is associated with reduced reactivity and connectivity of mesolimbic and paralimbic reward pathways

Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Journal of Psychiatric Research (Impact Factor: 3.96). 06/2013; 47(10). DOI: 10.1016/j.jpsychires.2013.05.015
Source: PubMed


Anhedonia is the inability to experience pleasure from normally pleasant stimuli. Although anhedonia is a prominent feature of many psychiatric disorders, trait anhedonia is also observed dimensionally in healthy individuals. Currently, the neurobiological basis of anhedonia is poorly understood because it has been mainly investigated in patients with psychiatric disorders. Thus, previous studies have not been able to adequately disentangle the neural correlates of anhedonia from other clinical symptoms. In this study, trait anhedonia was assessed in well-characterized healthy participants with no history of Axis I psychiatric illness. Functional magnetic resonance imaging with musical stimuli was used to examine brain responses and effective connectivity in relation to individual differences in anhedonia. We found that trait anhedonia was negatively correlated with pleasantness ratings of music stimuli and with activation of key brain structures involved in reward processing, including nucleus accumbens (NAc), basal forebrain and hypothalamus which are linked by the medial forebrain bundle to the ventral tegmental area (VTA). Brain regions important for processing salient emotional stimuli, including anterior insula and orbitofrontal cortex were also negatively correlated with trait anhedonia. Furthermore, effective connectivity between NAc, VTA and paralimbic areas, that regulate emotional reactivity to hedonic stimuli, was negatively correlated with trait anhedonia. Our results indicate that trait anhedonia is associated with reduced reactivity and connectivity of mesolimbic and related limbic and paralimbic systems involved in reward processing. Critically, this association can be detected even in individuals without psychiatric illness. Our findings have important implications both for understanding the neurobiological basis of anhedonia and for the treatment of anhedonia in psychiatric disorders.

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    • "rewardingstimuliisstilleffectedinpatientswithdepressioneven whenthefeelingsassociatedwiththerewardingstimuliarenot. Arelatedstudyfoundthatwhenlisteningtopleasantmusical stimuli,activityintheOFC,aswellasthenucleusaccumbens, insula,ACC,ventromedialprefrontalcortex(VMPFC),andthe lateralhypothalamus,wasnegativelycorrelatedwithmeasuresof anhedonia(Kelleretal.,2013). "
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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
    • "Diminished responsiveness to commonly rewarding stimuli has already been observed in both disorders, and appears to be mainly driven by the mesolimbic dopamine system including the ventral tegmental area (VTA), a central structure in the reward-processing circuitry (Keller et al, 2013). "
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    ABSTRACT: Differentiating bipolar disorders (BD) from unipolar depression (UD) remains a major clinical challenge. The identification of neurobiological markers may help to differentiate these disorders, particularly during depressive episodes. This cross-sectional study, including 33 patients with UD, 33 patients with BD and 34 healthy controls, is one of the first to directly compare UD and BD with respect to reward processing. A card-guessing paradigm was employed and brain activity associated with reward processing was investigated by means of fMRI. A 3 (group) × 2 (condition: reward>control, loss>control) ANOVA was conducted using the nucleus accumbens (NAcc) as ROI. Furthermore, a whole-brain approach was applied. A functional connectivity analysis was performed to characterize diagnosis-related alterations in the functional coupling between the NAcc and other brain areas. The ANOVA revealed higher activity for HC than for BD and UD in the NAcc during reward processing. Moreover, UD showed a higher functional connectivity between the NAcc and the VTA than HC. The patients groups could be differentiated in that BD showed a decreased activation, in the reward condition, of the NAcc, caudate nucleus, thalamus, putamen, insula, and prefrontal areas compared to UD. These results may help to refine the understanding of neural correlates of reward processing in both disorders, and to understand the neural underpinnings of anhedonia, a core symptom of depressive episodes.Neuropsychopharmacology accepted article preview online, 16 April 2015. doi:10.1038/npp.2015.110.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 04/2015; 40(11). DOI:10.1038/npp.2015.110 · 7.05 Impact Factor
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    • "These findings suggest that the interaction between reward regions may be accountable for the increased reward salience/motivation in substance abusing individuals. Inversely, in a study that looked at the opposing process of hypo-responsivity to reward, namely, anhedonia or the inability to experience pleasure, it was found that attenuated functional connectivity within reward areas (NAc, paralimbic areas) was associated with trait anhedonia (Keller et al., 2013). In summary, sensitivity to rewards appears to be associated with greater functional coherence or integration of the reward network. "
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    ABSTRACT: Background Emergent studies show that similar to other substances of abuse, cue-reactivity to cannabis is also associated with neural response in the brain's reward pathway (Filbey et al., 2009). However, the inter-relatedness of brain regions during cue-reactivity in cannabis users remains unknown Methods In this study, we conducted a series of investigations to determine functional connectivity during cue-reactivity in 71 cannabis users. First, we used psychophysiological interaction (PPI) analysis to examine coherent neural response to cannabis cues. Second, we evaluated whether these patterns of network functional connectivity differentiated dependent and non-dependent users. Finally, as an exploratory analysis, we determined the directionality of these connections via Granger connectivity analyses Results PPI analyses showed reward network functional connectivity with the nucleus accumbens (NAc) seed region during cue exposure. Between-group contrasts found differential effects of dependence status. Dependent users (N = 31) had greater functional connectivity with amygdala and anterior cingulate gyrus (ACG) seeds while the non-dependent users (N = 24) had greater functional connectivity with the NAc, orbitofrontal cortex (OFC) and hippocampus seeds. Granger analyses showed that hippocampal and ACG activation preceded neural response in reward areas Conclusions Both PPI and Granger analyses demonstrated strong functional coherence in reward regions during exposure to cannabis cues in current cannabis users. Functional connectivity (but not regional activation) in the reward network differentiated dependent from non-dependent cannabis users. Our findings suggest that repeated cannabis exposure causes observable changes in functional connectivity in the reward network and should be considered in intervention strategies.
    Drug and Alcohol Dependence 07/2014; 140. DOI:10.1016/j.drugalcdep.2014.04.002 · 3.42 Impact Factor
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