Alexis E Whitton1, Stephanie Deccy2, Manon L Ironside2, Poornima Kumar1, Miranda Beltzer2, Diego A Pizzagalli3. 1. Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts. 2. Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, Massachusetts. 3. Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts. Electronic address: dap@mclean.harvard.edu.
Abstract
BACKGROUND: Functional magnetic resonance imaging studies of resting-state functional connectivity have shown that major depressive disorder (MDD) is characterized by increased connectivity within the default mode network (DMN) and between the DMN and the frontoparietal network (FPN). However, much remains unknown about abnormalities in higher frequency (>1 Hz) synchronization. Findings of abnormal synchronization in specific frequencies would contribute to a better understanding of the potential neurophysiological origins of disrupted functional connectivity in MDD. METHODS: We used the high temporal resolution of electroencephalography to compare the spectral properties of resting-state functional connectivity in individuals with MDD (n = 65) with healthy control subjects (n = 79) and examined the extent to which connectivity disturbances were evident in a third sample of individuals in remission from depression (n = 30). Exact low resolution electromagnetic tomography was used to compute intracortical activity from regions within the DMN and FPN, and functional connectivity was computed using lagged phase synchronization. RESULTS: Compared to control subjects, the MDD group showed greater within-DMN beta 2 band (18.5-21 Hz) connectivity and greater beta 1 band (12.5-18 Hz) connectivity between the DMN and FPN. This hyperconnectivity was not observed in the remitted MDD group. However, greater beta 1 band DMN-FPN connectivity was associated with more frequent depressive episodes since first depression onset, even after controlling for current symptom severity. CONCLUSIONS: 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.
BACKGROUND: Functional magnetic resonance imaging studies of resting-state functional connectivity have shown that major depressive disorder (MDD) is characterized by increased connectivity within the default mode network (DMN) and between the DMN and the frontoparietal network (FPN). However, much remains unknown about abnormalities in higher frequency (>1 Hz) synchronization. Findings of abnormal synchronization in specific frequencies would contribute to a better understanding of the potential neurophysiological origins of disrupted functional connectivity in MDD. METHODS: We used the high temporal resolution of electroencephalography to compare the spectral properties of resting-state functional connectivity in individuals with MDD (n = 65) with healthy control subjects (n = 79) and examined the extent to which connectivity disturbances were evident in a third sample of individuals in remission from depression (n = 30). Exact low resolution electromagnetic tomography was used to compute intracortical activity from regions within the DMN and FPN, and functional connectivity was computed using lagged phase synchronization. RESULTS: Compared to control subjects, the MDD group showed greater within-DMNbeta 2 band (18.5-21 Hz) connectivity and greater beta 1 band (12.5-18 Hz) connectivity between the DMN and FPN. This hyperconnectivity was not observed in the remitted MDD group. However, greater beta 1 band DMN-FPN connectivity was associated with more frequent depressive episodes since first depression onset, even after controlling for current symptom severity. CONCLUSIONS: 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.
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