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

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.

Functional connectivity between the amygdala and prefrontal cortex in medication-naive individuals with major depressive disorder

“…Consistent with the previous behavioural, electroencephalogram and functional activation findings of dysfunctional negative emotional processing in individuals with MDD, 7,8,50,51 our finding of decreased amygdala-PFC functional connectivity during fearful face processing and not during happy or neutral face processing supports the involvement of abnormalities in amygdala-PFC functional connectivity in negative emotional processing in individuals with MDD, and it further implicates abnormal negative emotional processing in the neuropathophysiology of MDD. Taken together with the findings of our recent report of decreased amygdala-PFC functional connectivity during a resting -state fMRI in individuals with MDD, 19 our current findings suggest that altered amygdala-PFC functional connectivity may be a key feature of the disorder.…”

“…5 Other groups have demonstrated excessive responses of the amygdala to negative emotion, especially fearful facial expressions, in medicated individuals with MDD. 7,8 Studies of the role of the PFC suggest that functional imbalance between the left and right PFC in emotion processing may also be involved in the neuropathophysiology of MDD. 9 Consistent with this idea, lesions in the left PFC and left PFC dysfunction, which lead to deficits in the capacity to experience positive affect, a key feature of depression, have been reported in association with depression, 10,11 particularly during negative emotion processing, 12 possibly indicating greater dysfunction in the left than the right PFC in individuals with MDD.…”

10.3 Altered Intrinsic Functional Brain Architecture in Children at Familial Risk of Major Depression

“…These results support the possibility that DMN-sgACC hyperconnectivity might underlie depressive rumination (20). Second, several studies reported decreased resting-state connectivity within the cognitive control network in adult patients with MDD (21)(22)(23). In line with this evidence, MDD has been conceptualized as an imbalance between the DMN and the cognitive control network (24)(25)(26).…”

Three‐dimensional echo planar imaging with controlled aliasing: A sequence for high temporal resolution functional MRI

“…Additional components were identified after visual inspection. Names for each RSN were assigned by means of visual comparison to published data (22,(51)(52)(53)(54) …”