Functional connectivity of the human amygdala in health and in depression.

Wujun Lyu,Wei Cheng,Fajin Lyu,Jiang Qiu,Yu Li,Shih-Jen Tsai,Edmund T Rolls,Ching-Po Lin,Albert C Yang,Kaixiang Zhuang,Chu-Chung Huang,Xiongfei Xie,Peng Xie,Jianfeng Feng

doi:10.1093/scan/nsy032

Abstract

To analyse the functioning of the amygdala in depression, we performed the first voxel-level resting state functional-connectivity neuroimaging analysis of depression of voxels in the amygdala with all other voxels in the brain, with 336 patients with major depressive disorder and 350 controls. Amygdala voxels had decreased functional connectivity (FC) with the orbitofrontal cortex, temporal lobe areas, including the temporal pole, inferior temporal gyrus and the parahippocampal gyrus. The reductions in the strengths of the FC of the amygdala voxels with the medial orbitofrontal cortex and temporal lobe voxels were correlated with increases in the Beck Depression Inventory score and in the duration of illness measures of depression. Parcellation analysis in 350 healthy controls based on voxel-level FC showed that the basal division of the amygdala has high FC with medial orbitofrontal cortex areas, and the dorsolateral amygdala has strong FC with the lateral orbitofrontal cortex and related ventral parts of the inferior frontal gyrus. In depression, the basal amygdala division had especially reduced FC with the medial orbitofrontal cortex, which is involved in reward; and the dorsolateral amygdala subdivision had relatively reduced FC with the lateral orbitofrontal cortex, which is involved in non-reward.

Highlights

There is considerable evidence that the amygdala is involved in emotion (Aggleton, 2000; Whalen and Phelps, 2009; LeDoux, 2012; Rolls, 2014, 2018)
The largest clusters of voxels with altered functional connectivity with the amygdala were in the medial orbitofrontal cortex (634 voxels, Table 2). (These voxel numbers are those with altered functional connectivity with amygdala voxels with p < 0.05 FDR corrected.) Additional areas with voxels with reduced functional connectivity with the amygdala in depression included the lateral orbitofrontal cortex, parahippocampal and fusiform gyri; inferior and middle temporal gyri; the temporal pole; the insula; occipital visual areas; the mid-cingulate cortex; the striatum; and the precentral and postcentral gyrus (Table 2, Figs. 1 and 2)
One main finding is that the amygdala has reduced functional connectivity with a major region with altered functional connectivity in depression, the medial orbitofrontal cortex BA 13 (Cheng et al, 2016), which is implicated in reward (Grabenhorst and Rolls, 2011; Rolls, 2014) (Table 2, Figs. 1-4)

Summary

Introduction

There is considerable evidence that the amygdala is involved in emotion (Aggleton, 2000; Whalen and Phelps, 2009; LeDoux, 2012; Rolls, 2014, 2018). In order to perform this voxel-level functional connectivity analysis, we utilised and required a uniquely large sample of 336 patients with major depressive disorder and 350 controls. In a previous study with 70 participants, lower FC between the amygdala and hippocampus and parahippocampus was reported (Cullen et al, 2014) This investigation is very different from a previous analysis of functional connectivity in depression (Cheng et al, 2016), as follows. Part of the reason for these differences is that in the previous investigation we focused on voxel-to-voxel whole brain connectivity, which limits the results that can be established, whereas here we focus on the amygdala, and are able to report significant differences in its FC in depression, and even of its subdivisions

Objectives

Methods

Results

Conclusion