Out-of-sync: disrupted neural activity in emotional circuitry during film viewing in melancholic depression.

While a rich body of research in controlled experiments has established changes in the neural circuitry of emotion in major depressive disorders, little is known as to how such alterations might translate into complex, naturalistic settings--namely involving dynamic multimodal stimuli with rich contexts, such as those provided by films. Neuroimaging paradigms employing dynamic natural stimuli alleviate the anxiety often associated with complex tasks and eschew the need for laboratory-style abstractions, hence providing an ecologically valid means of elucidating neural underpinnings of neuropsychiatric disorders. To probe the neurobiological signature of refined depression subtypes, we acquired functional neuroimaging data in patients with the melancholic subtype of major depressive disorder during free viewing of emotionally salient films. We found a marked disengagement of ventromedial prefrontal cortex during natural viewing of a film with negative emotional valence in patients with melancholia. This effect significantly correlated with depression severity. Such changes occurred on the background of diminished consistency of neural activity in visual and auditory sensory networks, as well as higher-order networks involved in emotion and attention, including bilateral intraparietal sulcus and right anterior insula. These findings may reflect a failure to re-allocate resources and diminished reactivity to external emotional stimuli in melancholia.