Electroencephalography Source Functional Connectivity Reveals Abnormal High-Frequency Communication Among Large-Scale Functional Networks in Depression

Whitton, Alexis E.; Deccy, Stephanie; Ironside, Manon L.; Kumar, Poornima; Beltzer, Miranda; Pizzagalli, Diego A.

doi:10.1016/j.bpsc.2017.07.001

Cited by 65 publications

(78 citation statements)

References 70 publications

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“…The solution space consists of 6239 cortical gray matter voxels with a spatial resolution of 5 x 5 x 5 mm in a realistic head model. eLORETA is a suitable tool to investigate network activity and connectivity (Neuner et al, 2014;Thatcher et al, 2014;Liu et al, 2017;Samogin et al, 2019) and has provided important network insights into psychiatric disorders (Whitton et al, 2018;Imperatori et al, 2019;Samogin et al, 2019).…”

Section: Exact Low-resolution Electromagnetic Tomography (Eloreta)mentioning

confidence: 99%

Posttraumatic Stress Disorder Is Associated with α Dysrhythmia across the Visual Cortex and the Default Mode Network

Clancy

Andrzejewski

Simon

et al. 2020

eNeuro

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Visual-cortex-DMN alpha dysrhythmia in PTSD p. 3 3 Posttraumatic stress disorder is associated with alpha dysrhythmia across the visual cortex and the default mode network ABSTRACT Anomalies in default mode network (DMN) activity and alpha (8-12 Hz) oscillations have been independently observed in posttraumatic stress disorder (PTSD). Recent spatiotemporal analyses suggest that alpha oscillations support DMN functioning via interregional synchronization and sensory cortical inhibition. Therefore, we examined a unifying pathology of alpha deficits in the visual-cortex-DMN system in PTSD. Human patients with PTSD (N = 25) and two control groups-patients with Generalized Anxiety Disorder (GAD; N = 24) and healthy controls (HC; N = 20)-underwent a standard eyes-open resting state (S-RS) and a modified resting state (M-RS) of passively viewing salient images (known to deactivate the DMN). High-density electroencephalogram (hdEEG) were recorded, from which intracortical alpha activity (power and connectivity/Granger causality) was extracted using the exact low-resolution electromagnetic tomography (eLORETA). Patients with PTSD (vs. GAD/HC) demonstrated attenuated alpha power in the visual cortex and key hubs of the DMN (posterior cingulate cortex/PCC and medial prefrontal cortex/mPFC) at both states, the severity of which further correlated with hypervigilance symptoms. With increased visual input (at M-RS vs. S-RS), patients with PTSD further demonstrated reduced alpha-frequency directed connectivity within the DMN (PCC mPFC) and, importantly, from the visual cortex (VC) to both DMN hubs (VC PCC and VC mPFC), linking alpha deficits in the two systems. These interrelated alpha deficits align with DMN hypoactivity/hypoconnectivity, sensory disinhibition, and hypervigilance in PTSD, representing a unifying neural underpinning of these anomalies. The Visual-cortex-DMN alpha dysrhythmia in PTSD p. 4 4 identification of visual-cortex-DMN alpha dysrhythmia in PTSD further presents a novel therapeutic target, promoting network-based intervention of neural oscillations. SIGNIFICANCE STATEMENT Alpha (8-12 Hz) oscillations and the default mode network (DMN) both dominate the restingstate brain activity and are found to be closely related. In addition, aberrant alpha and DMN activities are both implicated in the pathophysiology of posttraumatic stress disorder (PTSD). Linking alpha and DMN aberrations in PTSD, our high-density EEG source analysis reveals that PTSD is associated with alpha power deficits across the DMN and visual cortex (VC) and deficient alpha-frequency connectivity from the VC to the DMN. That this visual-cortex-DMN alpha dysrhythmia further underpins hypervigilance symptoms in PTSD highlights a temporalspatial network pathology, promoting network-based neural oscillatory interventions.

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Section: Exact Low-resolution Electromagnetic Tomography (Eloreta)mentioning

confidence: 99%

Posttraumatic Stress Disorder Is Associated with α Dysrhythmia across the Visual Cortex and the Default Mode Network

Clancy

Andrzejewski

Simon

et al. 2020

eNeuro

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“…Our human brain is considered as an integrated network, which consists of anatomically separated but functionally linked brain regions (van den Heuvel and Hulshoff Pol, 2010 ). Many studies using the fMRI technique reveal that the pathophysiology of MDD involves a large-scale dysfunction in functional brain networks (Kaiser et al, 2015 ; Lv et al, 2016 ; Williams, 2017 ; Whitton et al, 2018 ). The functional connectivity (FC) is used as a most common measure for exploring the functional brain networks.…”

Section: Introductionmentioning

confidence: 99%

Multivariate Classification of Major Depressive Disorder Using the Effective Connectivity and Functional Connectivity

Geng

Liu

et al. 2018

Front. Neurosci.

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Major depressive disorder (MDD) is a mental disorder characterized by at least 2 weeks of low mood, which is present across most situations. Diagnosis of MDD using rest-state functional magnetic resonance imaging (fMRI) data faces many challenges due to the high dimensionality, small samples, noisy and individual variability. To our best knowledge, no studies aim at classification with effective connectivity and functional connectivity measures between MDD patients and healthy controls. In this study, we performed a data-driving classification analysis using the whole brain connectivity measures which included the functional connectivity from two brain templates and effective connectivity measures created by the default mode network (DMN), dorsal attention network (DAN), frontal-parietal network (FPN), and silence network (SN). Effective connectivity measures were extracted using spectral Dynamic Causal Modeling (spDCM) and transformed into a vectorial feature space. Linear Support Vector Machine (linear SVM), non-linear SVM, k-Nearest Neighbor (KNN), and Logistic Regression (LR) were used as the classifiers to identify the differences between MDD patients and healthy controls. Our results showed that the highest accuracy achieved 91.67% (p < 0.0001) when using 19 effective connections and 89.36% when using 6,650 functional connections. The functional connections with high discriminative power were mainly located within or across the whole brain resting-state networks while the discriminative effective connections located in several specific regions, such as posterior cingulate cortex (PCC), ventromedial prefrontal cortex (vmPFC), dorsal cingulate cortex (dACC), and inferior parietal lobes (IPL). To further compare the discriminative power of functional connections and effective connections, a classification analysis only using the functional connections from those four networks was conducted and the highest accuracy achieved 78.33% (p < 0.0001). Our study demonstrated that the effective connectivity measures might play a more important role than functional connectivity in exploring the alterations between patients and health controls and afford a better mechanistic interpretability. Moreover, our results showed a diagnostic potential of the effective connectivity for the diagnosis of MDD patients with high accuracies allowing for earlier prevention or intervention.

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“…Specifically, hyperconnectivity within the DMN could account for the maladaptive depressive rumination and the excessive self‐focus processing (Broyd et al, ; Hamilton et al, ; Holtzheimer & Mayberg, ). Hyperconnectivity between the DMN and the FPN regions may be more associated with impairments in goal‐directed behavior which is biased towards internal self‐referential thoughts (Kaiser, Andrews‐Hanna, Wager, & Pizzagalli, ; Whitton et al, ). Furthermore, Grimm et al (, ) associated increased self‐focus with the cortical midline structures (CMS), and Northoff et al showed an association between increased self‐focus and the CMS when clinically depressed (Northoff, , ; Northoff, Wiebking, Feinberg, & Panksepp, ).…”

Section: Discussionmentioning

confidence: 99%

Baseline functional connectivity may predict placebo responses to accelerated rTMS treatment in major depression

Wang

Baeken

2019

Human Brain Mapping

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Although in theory sham repetitive transcranial magnetic stimulation (rTMS) has no inherent therapeutic value, nonetheless, such placebo stimulations may have relevant therapeutic effects in clinically depressed patients. On the other hand, antidepressant responses to sham rTMS are quite heterogeneous across individuals and its neural underpinnings have not been explored yet. The current brain imaging study aims to detect baseline neural fingerprints resulting in clinically beneficial placebo rTMS treatment responses. We collected resting-state functional magnetic resonance imaging data prior to a registered randomized clinical trial of accelerated placebo stimulation protocol in patients documented with treatment-resistant depression (http:// clinicaltrials.gov/show/NCT01832805). In addition to global brain connectivity and rostral anterior cingulate cortex (rACC) seed-based functional connectivity (FC), elastic-net regression and cross-validation procedures were used to identify baseline intrinsic brain connectivity biomarkers for sham-rTMS responses. Placebo responses to accelerated sham rTMS were correlated with baseline global brain connectivity in the rACC/ventral medial prefrontal cortex (vmPFC). Concerning the rACC seedbased FC analysis, the placebo response was associated positively with the precuneus/posterior cingulate (PCun/PCC) cortex and negatively with the middle frontal gyrus. Our findings provide first brain imaging evidence for placebo responses to sham stimulation being predictable from rACC rsFC profiles, especially in brain areas implicated in (re)appraisal and self-focus processes. K E Y W O R D S depression, functional connectivity, placebo responses, rostral ACC, sham iTBS, sham rTMS

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Electroencephalography Source Functional Connectivity Reveals Abnormal High-Frequency Communication Among Large-Scale Functional Networks in Depression

Abstract: These findings extend our understanding of the neurophysiological basis of abnormal resting-state functional connectivity in MDD and indicate that elevations in high-frequency DMN-FPN connectivity may be a neural marker linked to a more recurrent illness course.

Cited by 65 publications

References 70 publications

Posttraumatic Stress Disorder Is Associated with α Dysrhythmia across the Visual Cortex and the Default Mode Network

Posttraumatic Stress Disorder Is Associated with α Dysrhythmia across the Visual Cortex and the Default Mode Network

Multivariate Classification of Major Depressive Disorder Using the Effective Connectivity and Functional Connectivity

Baseline functional connectivity may predict placebo responses to accelerated rTMS treatment in major depression

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