Whole brain resting-state analysis reveals decreased functional connectivity in major depression

Ilya M Veer

doi:10.3389/fnsys.2010.00041

Abstract

Recently, both increases and decreases in resting-state functional connectivity have been found in major depression. However, these studies only assessed functional connectivity within a specific network or between a few regions of interest, while comorbidity and use of medication was not always controlled for. Therefore, the aim of the current study was to investigate whole-brain functional connectivity, unbiased by a priori definition of regions or networks of interest, in medication-free depressive patients without comorbidity. We analyzed resting-state fMRI data of 19 medication-free patients with a recent diagnosis of major depression (within 6 months before inclusion) and no comorbidity, and 19 age- and gender-matched controls. Independent component analysis was employed on the concatenated data sets of all participants. Thirteen functionally relevant networks were identified, describing the entire study sample. Next, individual representations of the networks were created using a dual regression method. Statistical inference was subsequently done on these spatial maps using voxel-wise permutation tests. Abnormal functional connectivity was found within three resting-state networks in depression: (1) decreased bilateral amygdala and left anterior insula connectivity in an affective network, (2) reduced connectivity of the left frontal pole in a network associated with attention and working memory, and (3) decreased bilateral lingual gyrus connectivity within ventromedial visual regions. None of these effects were associated with symptom severity or gray matter density. We found abnormal resting-state functional connectivity not previously associated with major depression, which might relate to abnormal affect regulation and mild cognitive deficits, both associated with the symptomatology of the disorder.

Highlights

Patients suffering from a major depressive episode typically show pervasive depressed mood or anhedonia, accompanied by several cognitive and physical symptoms (American Psychiatric Association, 1994)
The assemblies of brain areas shown in these networks covered the primary [1], lateral [2] and medial visual cortex [3], sensory-motor cortex [4], ventral stream [8] auditory cortex [12], the hippocampus–amygdala complex [9], precuneus [7] together with the default mode network (DMN) [13], a network associated with salience processing (Seeley et al, 2007) [10], and networks encompassing areas associated with higher order cognition such as attention [11] and working memory [5, 6]
The presence of all 13 networks found with probabilistic ICA (PICA) was confirmed in both the healthy control (HC) and major depressive disorder (MDD) group by testing the main effects of group on the subject specific z-maps of these networks

Summary

Introduction

Patients suffering from a major depressive episode typically show pervasive depressed mood or anhedonia, accompanied by several cognitive and physical symptoms (American Psychiatric Association, 1994). It has been proposed that depressive symptoms are associated with dysregulation of a brain network encompassing large parts of the prefrontal cortex (PFC), limbic areas, and subcortical structures (Mayberg, 1997, 2003; Drevets et al, 2008). Based on data from blood flow and glucose metabolism SPECT and PET studies, and more recently task-related functional MRI (fMRI) studies, current models for depression postulate that ventral and dorsal subsystems of this brain network are differentially affected in this disease (Mayberg, 2003; Drevets et al, 2008). Engagement of lateral PFC regions has been linked to efficient top–down regulation of affective responses (Dolcos et al, 2006; Pessoa, 2008), a mechanism that has been shown to fail in patients suffering depression (Johnstone et al, 2007)

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