The implication of functional connectivity strength in predicting treatment response of major depressive disorder: a resting EEG study.
ABSTRACT Predicting treatment response in major depressive disorder (MDD) has been an important clinical issue given that the initial intent-to-treat response rate is only 50 to 60%. This study was designed to examine whether functional connectivity strengths of resting EEG could be potential biomarkers in predicting treatment response at 8 weeks of treatment. Resting state 3-min eyes-closed EEG activity was recorded at baseline and compared in 108 depressed patients. All patients were being treated with selective serotonin-reuptake inhibitors. Baseline coherence and power series correlation were compared between responders and non-responders evaluated at the 8th week by Hamilton Depression Rating Scale. Pearson correlation and receiver operating characteristic (ROC) analyses were applied to evaluate the performance of connectivity strengths in predicting/classifying treatment responses. The connectivity strengths of right fronto-temporal network at delta/theta frequencies differentiated responders and non-responders at the 8th week of treatment, such that the stronger the connectivity strengths, the poorer the treatment response. ROC analyses supported the value of these measures in classifying responders/non-responders. Our results suggest that fronto-temporal connectivity strengths could be potential biomarkers to differentiate responders and slow responders or non-responders in MDD.
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ABSTRACT: Temporal and spectral perspectives are two fundamental facets in deciphering fluctuating signals. In resting state, the dynamics of blood oxygen level-dependent (BOLD) signals recorded by functional magnetic resonance imaging (fMRI) has been proven to be strikingly informative (0.01-0.1 Hz). The distinction between slow-4 (0.027-0.073 Hz) and slow-5 (0.01-0.027 Hz) has been described, but the pertinent data have never been systematically investigated. This study used fMRI to measure spontaneous brain activity and to explore systemically the different spectral characteristics of slow-4 and slow-5 at regional, inter-regional, and network levels, respectively assessed by regional homogeneity (ReHo) and mean amplitude of low-frequency fluctuation (mALFF), functional connectivity patterns, and graph theory. Results of paired t-tests supported/replicated recent research dividing low-frequency BOLD fluctuation into slow-4 and slow-5 for ReHo and mALFF. Inter-regional analyses showed that for brain regions reaching statistical significance, functional connectivity strengths at slow-4 were always weaker than those at slow-5. Community detection algorithm was applied to functional connectivity data and unveiled two modules sensitive to frequency effects: one comprised sensorimotor structure, and the other encompassed limbic/paralimbic system. Graph theoretical analysis verified that slow-4 and slow-5 differed in local segregation measures. Although the manifestation of frequency differences seemed complicated, the associated brain regions can be grossly categorized into limbic/paralimbic, midline, and sensorimotor systems. Our results suggest that future resting fMRI research addressing the three above systems either from neuropsychiatric or psychological perspectives may consider using spectrum-specific analytical strategies.Brain connectivity. 01/2014;
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ABSTRACT: Structural and metabolic alterations in prefrontal brain areas, including the subgenual (SGPFC), medial (MPFC) and dorsolateral prefrontal cortex (DLPFC), have been shown in major depressive disorder (MDD). Still it remains largely unknown how brain connectivity within these regions is altered at the level of neuronal oscillations. Therefore, the goal was to analyze prefrontal electroencephalographic phase synchronization in MDD and its changes after antidepressant treatment. In 60 unmedicated patients and 60 healthy controls (HC), a 15-min resting electroencephalogram (EEG) was recorded in subjects at baseline and in a subgroup of patients after 2 weeks of antidepressant medication. EEG functional connectivity between the SGPFC and the MPFC/DLPFC was assessed with eLORETA (low resolution brain electromagnetic tomography) by means of lagged phase synchronization. At baseline, patients revealed increased prefrontal connectivity at the alpha frequency between the SGPFC and the left DLPFC/MPFC. After treatment, an increased connectivity between the SGPFC and the right DLPFC/MPFC at the beta frequency was found for MDD. A positive correlation was found for baseline beta connectivity and reduction in scores on the Hamilton Depression Rating Scale. MDD is characterized by increased EEG functional connectivity within frontal brain areas. These EEG markers of disturbed neuronal communication might have potential value as biomarkers.Psychiatry Research Neuroimaging 03/2014; · 2.83 Impact Factor
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ABSTRACT: Recently, Deep Brain Stimulation (DBS) has been evaluated as an experimental therapy for treatment-resistant depression (TRD). While there have been encouraging results in open-label trials, about half of the patients fail to achieve meaningful benefit. Although progress has been made in understanding the neurobiology of MDD, the ability to characterize differences in brain dynamics between those who do and do not benefit from DBS is lacking. In this study we investigated EEG resting state data recorded from 12 patients that have undergone DBS surgery. Of those, six patients were classified as responders to DBS, defined as an improvement of 50% or more on the 17-item Hamilton Rating Scale for Depression (HAMD-17). We compared hemispheric frontal theta and parietal alpha power asymmetry and synchronization asymmetry between responders and non responders. Hemispheric power asymmetry showed statistically significant differences between responders and non-responders with healthy controls showing an asymmetry similar to responders but opposite to non-responders. This asymmetry was characterized by an increase in frontal theta in the right hemisphere relative to the left combined with an increase in parietal alpha in the left hemisphere relative to the right in non-responders compared to responders. Hemispheric mean synchronization asymmetry showed a statistically significant difference between responders and non-responders in the theta band, with healthy controls showing an asymmetry similar to responders but opposite to non-responders. This asymmetry resulted from an increase in frontal synchronization in the right hemisphere relative to the left combined with an increase in parietal synchronization in the left hemisphere relative to the right in non-responders compared to responders. Connectivity diagrams revealed long range differences in frontal/central-parietal connectivity between the two groups in the theta band. This pattern was observed irrespective of whether EEG data were collected with active DBS or with the DBS stimulation turned off, suggesting stable functional and possibly structural modifications that may be attributed to plasticity.Neuropsychopharmacology accepted article preview online, 28 November 2013. doi:10.1038/npp.2013.330.Neuropsychopharmacology 11/2013; · 7.83 Impact Factor