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

Christine C Guo,Vinh T Nguyen,Gordon B Parker,Michael J Breakspear,Matthew P Hyett

doi:10.1038/srep11605

Abstract

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.

Highlights

We observed a range of context-specific changes in sensory cortices, including fusiform gyrus (FUS), parahippocampal gyrus (PPA), medial occipital gyrus (mOG) and superior temporal gyrus (STG), as well as higher order brain regions such as ventromedial prefrontal cortex (vmPFC), anterior insula and intraparietal sulcus (IPS) – key regions in emotion processing and salience detection[35,37]
We observed a striking correlation between the reduction in vmPFC dynamics during negative film viewing and depression severity in our melancholic participants
These findings are in accordance with previous reports that subgenual anterior cingulate cortex (ACC) and vmPFC show lower gray matter volume and cell counts, as well as abnormal glucose metabolism and cerebral blood flow in major depression[4], and that these regions represent key neural substrates in emotion-modulating networks, and arguably encode sadness[12,13,38]

Summary

Introduction

We first validated the specific emotional valence (positive and negative, respectively) of each of these films in a second group of healthy participants who rated these films dynamically during an independent viewing (sFig. 2; see Methods for details). Free viewing of these films evoked robust and consistent neural activity, as quantified by the inter-subject correlation (ISC) of voxel-wise BOLD signals (Fig 1a, left). The consistency of neural responses was substantially diminished in the data from our patients with melancholic-MDD during free viewing of emotionally salient films (Fig. 1b, sFig. 3; p < 0 .05, FDR corrected).

Results

Conclusion