Dynamic Neural Interactions Supporting the Cognitive Reappraisal of Emotion.

The cognitive reappraisal of emotion is hypothesized to involve frontal regions modulating the activity of subcortical regions such as the amygdala. However, the pathways by which structurally disparate frontal regions interact with the amygdala remains unclear. In this study, 104 healthy young people completed a cognitive reappraisal task. Dynamic causal modeling (DCM) was used to map functional interactions within a frontoamygdalar network engaged during emotion regulation. Five regions were identified to form the network: the amygdala, the presupplementary motor area (preSMA), the ventrolateral prefrontal cortex (vlPFC), dorsolateral prefrontal cortex (dlPFC), and ventromedial prefrontal cortex (vmPFC). Bayesian Model Selection was used to compare 256 candidate models, with our winning model featuring modulations of vmPFC-to-amygdala and amygdala-to-preSMA pathways during reappraisal. Moreover, the strength of amygdala-to-preSMA modulation was associated with the habitual use of cognitive reappraisal. Our findings support the vmPFC serving as the primary conduit through which prefrontal regions directly modulate amygdala activity, with amygdala-to-preSMA connectivity potentially acting to shape ongoing affective motor responses. We propose that these two frontoamygdalar pathways constitute a recursive feedback loop, which computes the effectiveness of emotion-regulatory actions and drives model-based behavior.

Brain functional correlates of emotion regulation across adolescence and young adulthood.

Few studies have examined the neural correlates of emotion regulation across adolescence and young adulthood. Existing studies of cognitive reappraisal indicate that improvements in regulatory efficiency may develop linearly across this period, in accordance with maturation of prefrontal cortical systems. However, there is also evidence for adolescent differences in reappraisal specific to the activation of "social-information processing network" regions, including the amygdala and temporal-occipital cortices. Here, we use fMRI to examine the neural correlates of emotional reactivity and reappraisal in response to aversive social imagery in a group of 78 adolescents and young adults aged 15-25 years. Within the group, younger participants exhibited greater activation of temporal-occipital brain regions during reappraisal in combination with weaker suppression of amygdala reactivity-the latter being a general correlate of successful reappraisal. Further analyses demonstrated that these age-related influences on amygdala reactivity were specifically mediated by activation of the fusiform face area. Overall, these findings suggest that enhanced processing of salient social cues (i.e., faces) increases reactivity of the amygdala during reappraisal and that this relationship is stronger in younger adolescents. How these relationships contribute to well-known vulnerabilities of emotion regulation during this developmental period will be an important topic for ongoing research.

Hard to look on the bright side: neural correlates of impaired emotion regulation in depressed youth.

The cognitive regulation of emotion is impaired in major depressive disorder and has been linked to an imbalance of pre-frontal-subcortical brain activity. Despite suggestions that this relationship represents a neurodevelopmental marker of depression, few studies have examined the neural correlates of emotion regulation in depressed youth. We combined a 'cognitive reappraisal' paradigm with functional magnetic resonance imaging to study the neural correlates of emotional regulation in a large sample of non-medicated depressed adolescents and young adults (n = 53) and healthy controls (n = 64). As compared with healthy controls, young people with depression were less able to reduce negative affect during reappraisal, which corresponded to blunted modulation of amygdala activity. While in healthy individuals amygdala activation was modulated by age, no such relationship was observed in depressed individuals. Heightened activation of the ventromedial pre-frontal cortex (vmPFC) and reduced activation of the dorsal midline cortex was also found for the depressed group. Overall, these findings suggest that brain systems that support cognitive reappraisal are functionally altered in youth depression. We argue that excessive engagement of the vmPFC in particular, may be central to understanding how the process of putting a 'positive spin' on negative emotional material may be altered in depressed youth.

Specific functional connectivity alterations of the dorsal striatum in young people with depression.

BACKGROUND: Altered basal ganglia function has been implicated in the pathophysiology of youth Major Depressive Disorder (MDD). Studies have generally focused on characterizing abnormalities in ventral "affective" corticostriatal loops supporting emotional processes. Recent evidence however, has implicated alterations in functional connectivity of dorsal "cognitive" corticostriatal loops in youth MDD. The contribution of dorsal versus ventral corticostriatal alterations to the pathophysiology of youth MDD remains unclear. METHODS: Twenty-one medication-free patients with moderate-to-severe MDD between the ages of 15 and 24 years old were matched with 21 healthy control participants. Using resting-state functional connectivity magnetic resonance imaging we systematically investigated connectivity of eight dorsal and ventral subdivisions of the striatum. Voxelwise statistical maps of each subregion's connectivity with other brain areas were compared between the depressed and control groups. RESULTS: Depressed youths showed alterations in functional connectivity that were confined to the dorsal corticostriatal circuit. Compared to controls, depressed patients showed increased connectivity between the dorsal caudate nucleus and ventrolateral prefrontal cortex bilaterally. Increased depression severity correlated with the magnitude of dorsal caudate connectivity with the right dorsolateral prefrontal cortex. There were no significant between-group differences in connectivity of ventral striatal regions. CONCLUSIONS: The results provide evidence that alterations in corticostriatal connectivity are evident at the early stages of the illness and are not a result of antidepressant treatment. Increased connectivity between the dorsal caudate, which is usually associated with cognitive processes, and the more affectively related ventrolateral prefrontal cortex may reflect a compensatory mechanism for dysfunctional cognitive-emotional processing in youth depression.

Functional brain imaging studies of youth depression: a systematic review.

BACKGROUND: There is growing interest in understanding the neurobiology of major depressive disorder (MDD) in youth, particularly in the context of neuroimaging studies. This systematic review provides a timely comprehensive account of the available functional magnetic resonance imaging (fMRI) literature in youth MDD. METHODS: A literature search was conducted using PubMED, PsycINFO and Science Direct databases, to identify fMRI studies in younger and older youth with MDD, spanning 13-18 and 19-25 years of age, respectively. RESULTS: Twenty-eight studies focusing on 5 functional imaging domains were identified, namely emotion processing, cognitive control, affective cognition, reward processing and resting-state functional connectivity. Elevated activity in "extended medial network" regions including the anterior cingulate, ventromedial and orbitofrontal cortices, as well as the amygdala was most consistently implicated across these five domains. For the most part, findings in younger adolescents did not differ from those in older youth; however a general comparison of findings in both groups compared to adults indicated differences in the domains of cognitive control and affective cognition. CONCLUSIONS: Youth MDD is characterized by abnormal activations in ventromedial frontal regions, the anterior cingulate and amygdala, which are broadly consistent with the implicated role of medial network regions in the pathophysiology of depression. Future longitudinal studies examining the effects of neurodevelopmental changes and pubertal maturation on brain systems implicated in youth MDD will provide a more comprehensive neurobiological model of youth depression.