Hyperconnectivity and altered dynamic interactions of a nucleus accumbens network in post-stroke depression (original) (raw)
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Psychological Medicine, 2013
BackgroundMajor depressive disorder (MDD) is characterized by alterations in brain function that are identifiable also during the brain's ‘resting state’. One functional network that is disrupted in this disorder is the default mode network (DMN), a set of large-scale connected brain regions that oscillate with low-frequency fluctuations and are more active during rest relative to a goal-directed task. Recent studies support the idea that the DMN is not a unitary system, but rather is composed of smaller and distinct functional subsystems that interact with each other. The functional relevance of these subsystems in depression, however, is unclear.MethodHere, we investigated the functional connectivity of distinct DMN subsystems and their interplay in depression using resting-state functional magnetic resonance imaging.ResultsWe show that patients with MDD exhibit increased within-network connectivity in posterior, ventral and core DMN subsystems along with reduced interplay fro...
Journal of Affective Disorders, 2018
Background: Previous studies have demonstrated altered resting state functional connectivity (rsFC) in patients with post-stroke depression (PSD). It remains unclear whether rsFC is changed at the network level as was shown for major depressive disorder (MDD). To address this question, we investigated rsFC of resting sate networks (RSNs) in PSD. Methods: Eleven subjects with PSD underwent fMRI scanning at rest before and after treatment. The severity of depression was assessed using the aphasic depression rating scale (ADRS). We performed functional network connectivity (FNC) analysis for RSNs, region of interest-FC analysis (ROI-FC) and calculation of brain matter volumes in ROIs overlapping with RSNs and in other brain regions associated with mood maintenance. Results: We found positive correlation of FNC between anterior default mode network (aDMN) and salience network (SAL) with depression severity before treatment, the latter accompanied by the increase of white matter in the middle frontal and left angular gyri. FNC of aDMN and left frontoparietal network (LFP) decreased after treatment. ROI-FC and the brain matter volumes of several regions of DMN, LFP and SAL also showed a correlation with ADRS or significant change after treatment. Limitations: Limitations include small sample size and methodological issues concerning altered hemodynamics in stroke. However, we took complex preprocessing steps to overcome these issues. Conclusion: Present results of altered rsFC in PSD are consistent with previous findings in MDD. The convergence of results obtained in PSD and MDD supports the validity of rsFC approach for investigation of brain network dysfunctions underling these psychiatric symptoms.
The British Journal of Psychiatry
Background: Patients in remission/recovery following episodes of Major Depressive Disorder (MDD) remain highly vulnerable to future relapse/recurrence. Whilst psychological determinants of this risk are well established, little is known about associated biological mechanisms. Recent work has implicated the Default Mode Network (DMN) in this vulnerability but specific hypotheses remain untested within the high-risk, recovered-state of MDD. Aims: 1) To test the hypothesis that there is excessive Default Mode Network (DMN) functional connectivity (FC) during task performance within recovered-state MDD; 2) To test for connected DMN cortical gyrification abnormalities. Method: A multimodal fMRI/MRI study, including task-based FC and cortical folding analysis, comparing 20 recovered-state MDD patients with 20 matched healthy controls. Results: Recovered-state MDD patients showed significant task-based DMN hyperconnectivity, associated with hypogyrification of key DMN regions (bilateral precuneus). Conclusions: This is the first evidence of connected structural and functional DMN abnormalities in recovered-state MDD, supporting recent hypotheses on biological-level vulnerability.
Psychiatry and Clinical Neurosciences, 2009
Aim: Reports on resting brain activity in healthy controls have described a default-mode network (DMN) and important differences in DMN connectivity have emerged for several psychiatric conditions. No study to date, however, has investigated resting-state DMN in relatively early depression before years of medication treatment. The objective of the present study was, therefore, to investigate the DMN in patients seeking help from specialized mental health services for the first time for symptoms of depression.Methods: Fourteen depressed subjects and 15 matched controls were scanned using 4-T functional magnetic resonance imaging while resting with eyes closed. All but one subject was medication free. A precuneus/posterior cingulate cortex (P/PCC) seed-region connectivity analysis was used to identify the DMN and compare study groups in regions of relevance to depression.Results: The P/PCC analysis identified the DMN well in both study groups, consistent with prior literature. Direct comparison showed significantly reduced correlation between the P/PCC and the bilateral caudate in depression compared with controls and no areas of increased connectivity in the depressed group.Conclusions: The present study is the first to investigate resting-state DMN in the early stages of treatment-seeking for depression. Depressed subjects had decreased connectivity between the P/PCC and the bilateral caudate, regions known to be involved in motivation and reward processing. Deficits in DMN connectivity with the caudate may be an early manifestation of major depressive disorder.
Whole brain resting-state analysis reveals decreased functional connectivity in major depression
2010
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 wholebrain 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:
Human Brain Mapping, 2014
Resting-state studies conducted with stroke patients are scarce. The study of brain activity and connectivity at rest provides a unique opportunity for the investigation of brain rewiring after stroke and plasticity changes. This study sought to identify dynamic changes in the functional organization of the default mode network (DMN) of stroke patients at three months after stroke. Eleven patients (eight male and three female; age range: 48-72) with right cortical and subcortical ischemic infarctions and 17 controls (eleven males and six females; age range: 57-69) were assessed by neurological and neuropsychological examinations and scanned with resting-state functional magnetic ressonance imaging. First, we explored group differences in functional activity within the DMN by means of probabilistic independent component analysis followed by a dual regression approach. Second, we estimated functional connectivity between 11 DMN nodes both locally by means of seed-based connectivity analysis, as well as globally by means of graph-computation analysis. We found that patients Tibor Auer and Maria Matar o shared latest authorship. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. r Human Brain Mapping 00:00-00 (2014) r had greater DMN activity in the left precuneus and the left anterior cingulate gyrus when compared with healthy controls (P < 0.05 family-wise error corrected). Seed-based connectivity analysis showed that stroke patients had significant impairment (P 5 0.014; threshold 5 2.00) in the connectivity between the following five DMN nodes: left superior frontal gyrus (lSFG) and posterior cingulate cortex (t 5 2.01); left parahippocampal gyrus and right superior frontal gyrus (t 5 2.11); left parahippocampal gyrus and lSFG (t 5 2.39); right parietal and lSFG (t 5 2.29). Finally, mean path length obtained from graphcomputation analysis showed positive correlations with semantic fluency test (r s 5 0.454; P 5 0.023), phonetic fluency test (r s 5 0.523; P 5 0.007) and the mini mental state examination (r s 5 0.528; P 5 0.007). In conclusion, the ability to regulate activity of the DMN appears to be a central part of normal brain function in stroke patients. Our study expands the understanding of the changes occurring in the brain after stroke providing a new avenue for investigating lesion-induced network plasticity. Hum Brain Mapp 00:000-000, 2014.
The subgenual anterior cingulate cortex (sgACC) appears to play a central role in the pathophysiology of major depressive disorder (MDD). To wit, its functional interactive profile with the left dorsal lateral prefrontal cortex (DLPFC) has been shown to be related to treatment outcomes with transcranial magnetic stimulation (TMS) treatment outcomes. Nevertheless, previous research on sgACC functional connectivity (FC) in MDD has yielded inconsistent results, partly due to small sample sizes and limited statistical power of prior work. Here, leveraging a large multi-site sample (1660 MDD patients vs. 1341 healthy controls) from Phase II of the Depression Imaging REsearch ConsorTium (DIRECT), we systematically delineated case-control difference maps of sgACC FC and examined their clinical relevance to previously identified TMS targets. We also investigated case-control FC difference maps of left DLPFC sub-fields. In MDD patients we found significantly increased FC between sgACC and th...
Intrinsic connectivity networks in major depressive disorder: A combined fMRI and EEG study
Major depressive disorder (MDD) is one of the most serious psychiatric diseases, but its pathophysiology remains poorly understood. The application of neuroimaging techniques has enhanced our means to understand this illness. The study of intrinsic connectivity networks, i.e., sets of brain regions that show a high degree of interconnectedness even in the absence of a task, showed that MDD patients demonstrate an increased connectivity within the default mode network (DMN), which is active in a resting state and is implicated in self-referential processing, and a decreased connectivity in task-positive networks (TPNs), which increase their activity in attention tasks. This suggests a 'dominance' of the DMN over the TPN in MDD patients, but the cortical localization of this 'dominance' is not fully understood. Besides, this effect has been investigated using fMRI and its electrophysiological underpinning is not known. In this study,
A brain network model for depression: From symptom understanding to disease intervention
CNS neuroscience & therapeutics, 2018
Understanding the neural substrates of depression is crucial for diagnosis and treatment. Here, we review recent studies of functional and effective connectivity in depression, in terms of functional integration in the brain. Findings from these studies, including our own, point to the involvement of at least four networks in patients with depression. Elevated connectivity of a ventral limbic affective network appears to be associated with excessive negative mood (dysphoria) in the patients; decreased connectivity of a frontal-striatal reward network has been suggested to account for loss of interest, motivation, and pleasure (anhedonia); enhanced default mode network connectivity seems to be associated with depressive rumination; and diminished connectivity of a dorsal cognitive control network is thought to underlie cognitive deficits especially ineffective top-down control of negative thoughts and emotions in depressed patients. Moreover, the restoration of connectivity of these ...