EEG power asymmetry and functional connectivity as a marker of treatment effectiveness in DBS surgery for depression

Abstract

Recently, deep brain stimulation (DBS) has been evaluated as an experimental therapy for treatment-resistant depression. Although 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 with 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 with 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.

Figures

Figure 1

Anatomical location of the subgenual cingulate gyrus.

Figure 2

(a) Hemispheric asymmetry (see Equation 2 in the Appendix 1) computed as the weighted sum of frontal θ hemispheric power difference and parietal α hemispheric power difference. (b) The same as the OFF condition in a with data from 15 healthy controls (HC) added to the plot. Asterisks indicate p<0.05 on a Kruskal–Wallis test.

Figure 3

Top: correlation between frontal θ left–right power asymmetry and HAMD-17 scores for the OFF (left) and ON (right) conditions. Bottom: correlation between parietal α left–right power asymmetry and HAMD-17 scores.

Figure 4

(a) Group-averaged hemispheric synchronization asymmetry in the θ band with the DBS electrodes OFF (left) and ON (right) for the R (response) and NR (no-response) groups as labeled on the plots. (b) Same as panel a, where DBS stimulation is turned off in the patient group with healthy controls (HC) added to the plot. Asterisks indicates p<0.05 on a Kruskal–Wallis test. (c) EEG channel configuration used to calculate synchronization asymmetry for frontal and parietal regions. LF, left frontal; LP, left parietal; RF, right frontal; RP, right parietal.

Figure 5

Top: correlation between frontal θ left–right synchronization asymmetry and HAMD-17 scores for the OFF (left) and ON (right) conditions. Bottom: correlation between parietal θ left–right synchronization asymmetry and HAMD-17 scores for the OFF (left) and ON (right) conditions.

Figure 6

(a) Group-averaged connectivity matrices in the θ band for R>NR (top row) and NR>R (bottom row) for the OFF (left) and ON (right) condition. The connectivity values are thresholded at p<0.05 using a Kruskal–Wallis test. (b) Network diagrams corresponding to the connectivity matrices in panel a.