Altered directed functional connectivity of the right amygdala in depression: high-density EEG study

Sylvie Fedorová,Jana Hořínková,Eliška Honzírková,Christoph M. Michel,Alena Damborská,Šimon Ondruš,Richard Barteček,Maria Rubega

doi:10.1038/s41598-020-61264-z

Abstract

The cortico-striatal-pallidal-thalamic and limbic circuits are suggested to play a crucial role in the pathophysiology of depression. Stimulation of deep brain targets might improve symptoms in treatment-resistant depression. However, a better understanding of connectivity properties of deep brain structures potentially implicated in deep brain stimulation (DBS) treatment is needed. Using high-density EEG, we explored the directed functional connectivity at rest in 25 healthy subjects and 26 patients with moderate to severe depression within the bipolar affective disorder, depressive episode, and recurrent depressive disorder. We computed the Partial Directed Coherence on the source EEG signals focusing on the amygdala, anterior cingulate, putamen, pallidum, caudate, and thalamus. The global efficiency for the whole brain and the local efficiency, clustering coefficient, outflow, and strength for the selected structures were calculated. In the right amygdala, all the network metrics were significantly higher (p < 0.001) in patients than in controls. The global efficiency was significantly higher (p < 0.05) in patients than in controls, showed no correlation with status of depression, but decreased with increasing medication intake ({{bf{R}}}^{{bf{2}}}{boldsymbol{=}}{bf{0.59}},{bf{and}},{bf{p}}{boldsymbol{=}}{bf{1.52}}{bf{e}}{boldsymbol{ mbox{-} }}{bf{05}}). The amygdala seems to play an important role in neurobiology of depression. Practical treatment studies would be necessary to assess the amygdala as a potential future DBS target for treating depression.

Highlights

Affective disorders belong to the most common and most serious psychiatric disorders[1]
Causal link between a functional inhibition of the lateral habenula and reduction of the default mode network hyperconnectivity was shown on a rat model of depression[30], which might explain the therapeutic effect of the lateral habenula deep brain stimulation (DBS) in treatment-resistant depression (TRD) patients[49]
In line with the aim of the study we focused on resting-state electrophysiological activity of twelve regions of interest (ROIs) of selected deep brain structures

Summary

Introduction

Affective disorders belong to the most common and most serious psychiatric disorders[1]. Better understanding of the connectivity properties of deep brain structures potentially implicated in DBS treatment could have an important value Neuroimaging techniques, such as fMRI and EEG, allow to investigate the integration of functionally specialized brain regions in a network. The functional inhibition of a deep brain structure via DBS might cure depression through reduction of the hyperconnectivity in the large-scale brain network Another example of a particular role of the stimulated structure in the large-scale neural communication is the ACC, whose possible integrative role in cognitive processing[50,51] might explain the most recently reported high efficacy of DBS to subgenual ACC in treating depression[52]. A signal x is said to Granger-cause another signal y if the history of x contains information that helps to predict y above and beyond the information contained in the history of y alone[55]

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