Reduced subgenual cingulate-dorsolateral prefrontal connectivity as an electrophysiological marker for depression.

Major Depressive Disorder (MDD) is a widespread mental illness that causes considerable suffering, and neuroimaging studies are trying to reduce this burden by developing biomarkers that can facilitate detection. Prior fMRI- and neurostimulation studies suggest that aberrant subgenual Anterior Cingulate (sgACC)-dorsolateral Prefrontal Cortex (DLPFC) functional connectivity is consistently present within MDD. Combining the need for reliable depression markers with the electroencephalogram's (EEG) high clinical utility, we investigated whether aberrant EEG sgACC-DLPFC functional connectivity could serve as a marker for depression. Source-space Amplitude Envelope Correlations (AEC) of 20 MDD patients and 20 matched controls were contrasted using non-parametric permutation tests. In addition, extracted AEC values were used to (a) correlate with characteristics of depression and (b) train a Support Vector Machine (SVM) to determine sgACC-DLPFC connectivity's discriminative power. FDR-thresholded statistical maps showed reduced sgACC-DLPFC AEC connectivity in MDD patients relative to controls. This diminished AEC connectivity is located in the beta-1 (13-17 Hz) band and is associated with patients' lifetime number of depressive episodes. Using extracted sgACC-DLPFC AEC values, the SVM achieved a classification accuracy of 84.6% (80% sensitivity and 89.5% specificity) indicating that EEG sgACC-DLPFC connectivity has promise as a biomarker for MDD.

Auricular transcutaneous vagus nerve stimulation modulates the heart-evoked potential.

BACKGROUND: There is active interest in biomarker discovery for transcutaneous auricular vagus nerve stimulation (taVNS). However, greater understanding of the neurobiological mechanisms is needed to identify candidate markers. Accumulating evidence suggests that taVNS influences activity in solitary and parabrachial nuclei, the primary brainstem relays for the transmission of visceral sensory afferents to the insula. The insula mediates interoception, which concerns the representation and regulation of homeostatic bodily states. Consequently, interoceptive pathways may be relevant to taVNS mechanisms of action. HYPOTHESES: We hypothesized that taVNS would modulate an EEG-derived marker of interoceptive processing known as the heart-evoked potential (HEP). We also hypothesized that taVNS-induced HEP effects would be localizable to the insula. METHODS: Using a within-subject, sham-controlled design, we recorded EEG and ECG concurrent to taVNS in 43 healthy adults. Using ECG and EEG data, we extracted HEPs. Estimation of the cortical sources of the taVNS-dependent HEP responses observed at the scalp were computed using the Boundary Element Method and weighted Minimum Norm Estimation. Statistics were calculated using cluster-based permutation methods. RESULTS: taVNS altered HEP amplitudes at frontocentral and centroparietal electrode sites at various latencies. The taVNS-dependent HEP effect was localized to the insula, operculum, somatosensory cortex, and orbital and ventromedial prefrontal regions. CONCLUSION: The results support the hypothesis that taVNS can access the insula as well as functionally and anatomically connected brain regions. HEPs may serve as an objective, non-invasive outcome parameter for the cortical effects of taVNS.

An EEG signature of suicidal behavior in female patients with major depressive disorder? A non-replication.

INTRODUCTION: A recent study showed hypoactivity in the beta/gamma band in female suicide ideators and suicide attempters diagnosed with depression, relative to a low-risk group. The current study aimed to conceptually replicate these results. METHODS: In the iSPOT-D sub-sample (n = 402), suicide ideators and low-risk individuals were identified. Confining analyses to females only, differences between low-risk individuals and suicide ideators were tested for using the electroencephalogram (EEG) frequency bands SMR (Sensori-Motor-Rhythm; 12-15 Hz), beta (14.5-30 Hz), beta I (14.5-20 Hz), beta II (20-25 Hz), beta III (25-30 Hz), gamma I (31-49 Hz) using LORETA-software. RESULTS: None of the tested frequency bands showed to be significantly different between suicide ideators and low-risk individuals. CONCLUSIONS: The current study could not conceptually replicate the earlier published results. Several reasons could explain this non-replication, among which possible electromyographic (EMG) contamination in the beta/gamma band in the original study. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00693849. URL: http://clinicaltrials.gov/ct2/show/NCT00693849.

Electrophysiological scarring in remitted depressed patients: Elevated EEG functional connectivity between the posterior cingulate cortex and the subgenual prefrontal cortex as a neural marker for rumination.

INTRODUCTION: Prior resting state fMRI studies have revealed that elevated connectivity between the default mode network (DMN) and subgenual prefrontal cortex (sgPFC) connectivity may underly maladaptive rumination, which is a major risk factor for depression. To further evaluate such relationship, we investigated whether posterior regions of the DMN, showed elevated connectivity with the sgPFC in remitted depressed patients (rMDD) and whether this connectivity was related to maladaptive rumination. METHODS: We examined whether rMDD (N = 20) had elevated EEG posterior DMN - sgPFC functional connectivity when compared to age and sex matched healthy controls (N = 17), and whether this posterior DMN - sgPFC connectivity positively correlated with rumination. Using minimum norm as the source estimation method, we extracted current density maps from six regions of interest (ROIs) within the posterior DMN. EEG source-space functional connectivity was calculated using the Amplitude Envelope Correlation method. RESULTS: Relative to controls, rMDD showed increased posterior cingulate cortex (PCC) - sgPFC connectivity in the beta-3 (25-30 Hz) band. As hypothesized, PCC - sgPFC connectivity was positively associated with rumination for rMDD, even after controlling for depression and anxiety. LIMITATIONS: The absence of an MDD patient group and the relatively small sample size can limit the generalizability of the results. CONCLUSIONS: EEG resting state PCC - sgPFC functional connectivity is significantly elevated in rMDD and is associated with rumination, suggesting that EEG PCC - sgPFC connectivity may be useful as a neural marker to identify individuals at risk for depression.

Electroencephalogram Resting State Frequency Power Characteristics of Suicidal Behavior in Female Patients With Major Depressive Disorder.

BACKGROUND: Difficulties in predicting suicidal behavior hamper effective suicide prevention. Therefore, there is a great need for reliable biomarkers, and neuroimaging may help to identify such markers. METHODS: Electroencephalography (EEG) was used to investigate resting state spatial-frequency power characteristics of female patients with major depressive disorder (MDD); 19 were recent suicide attempters (within the previous 30 days), 36 were suicide ideators, and 23 were nonsuicidal. Patients were enrolled at neuroCare Clinic Nijmegen (Nijmegen, the Netherlands) between May 2007 and November 2016, and the primary diagnosis of nonpsychotic MDD was confirmed using the Mini-International Neuropsychiatric Interview, DSM-IV criteria, and a score of ≥ 14 on the 21-item Beck Depression Inventory. Nonparametric, cluster-based permutation tests were applied to detect robust power differences between the study groups on the EEG broadband signal (2-100 Hz). Furthermore, a nonadaptive distributed source imaging method (eLORETA) was utilized to examine if these suicide-based frequency characteristics are localized in brain areas previously reported in the neuroimaging literature. RESULTS: When compared to nonsuicidal depressed patients, attempters and ideators displayed both decreased beta and low gamma activity in the frontal regions. Moreover, ideators had increased alpha activity over the posterior regions and increased high beta, low gamma activity over the left occipital region when compared to psychiatric controls. Attempters had reduced beta and low gamma activity over the right temporal region when compared to ideators. In addition, eLORETA localized attempter and ideator reduced frontal activity within the orbito-, medial-, middle-, superior-, and inferior-frontal areas and the anterior cingulate cortex. In attempters, reduced right temporal activity was localized within the right inferior-, middle-, and superior-temporal cortices and the fusiform gyrus. CONCLUSIONS: Frequency power characteristics of attempters and ideators are consistent with findings from the neuroimaging literature concerning suicide, implying EEG resting state assessment could become a potential biomarker to predict suicide risk.