Atypical Temporal Dynamics of Resting State Shapes Stimulus-Evoked Activity in Depression-An EEG Study on Rest-Stimulus Interaction

Abstract

Major depressive disorder (MDD) is a complex psychiatric disorder characterized by changes in both resting state and stimulus-evoked activity. Whether resting state changes are carried over to stimulus-evoked activity, however, is unclear. We conducted a combined rest (3 min) and task (three-stimulus auditory oddball paradigm) EEG study in n=28 acute depressed MDD patients, comparing them with n=25 healthy participants. Our focus was on the temporal dynamics of both resting state and stimulus-evoked activity for which reason we measured peak frequency (PF), coefficient of variation (CV), Lempel-Ziv complexity (LZC), and trial-to-trial variability (TTV). Our main findings are: i) atypical temporal dynamics in resting state, specifically in the alpha and theta bands as measured by peak frequency (PF), coefficient of variation (CV) and power; ii) decreased reactivity to external deviant stimuli as measured by decreased changes in stimulus-evoked variance and complexity-TTV, LZC, and power and frequency sliding (FS and PS); iii) correlation of stimulus related measures (TTV, LZC, PS, and FS) with resting state measures. Together, our findings show that resting state dynamics alone are atypical in MDD and, even more important, strongly shapes the dynamics of subsequent stimulus-evoked activity. We thus conclude that MDD can be characterized by an atypical temporal dynamic of its rest-stimulus interaction; that, in turn, makes it difficult for depressed patients to react to relevant stimuli such as the deviant tone in our paradigm.

Keywords: Depression; EEG; Peak frequency; alpha oscillations; resting state; theta oscillations.

Figure 1

Resting state activity showed differences in theta and alpha between the MDD group and healthy controls. (A) The peak frequency (PF), coefficient of variation (CV), and power measures showed higher PF, lower CV, and lower power in the MDD participants than the controls. (B) In the alpha band, the MDD group had lower PF, higher CV, and lower power. All p-values are FDR corrected for multiple comparisons. **: < 0.01, ***: <0.001.

Figure 2

Trial-to-trial variability (TTV) showed significantly less change in variability in the MDD group for deviant stimuli. (A) TTV curves (80 trials) in both groups for deviant and standard stimuli. (B) Area under the curve (AUC) was measured between 0-500ms for both groups and stimuli. The AUC in the MDD group was significantly lower in the deviant stimuli compared to the healthy controls. All p-values are FDR corrected for multiple comparisons. **: < 0.01.

Figure 3

Lempel-Ziv Complexity (LZC) changes after stimulus onset were significantly lower in the MDD group for deviant stimuli. LZC was measured in 300ms time windows before and after stimulus onset. When the difference was calculated (poststim minus prestim), for deviant stimuli the MDD group showed less of a decrease when compared to healthy controls. All p-values are FDR corrected for multiple comparisons. *: < 0.05.

Figure 4

Frequency Sliding (FS) and Power Sliding (PS) found greater changes to deviant stimuli in the MDD group for theta and alpha frequency bands. (A) In the deviant stimuli, Theta PS was higher in the MDD group and lower (B) for standard stimuli. (C) In the alpha band, both FS and PS were significantly higher for the deviant stimuli in the MDD group. (D) Only the PS was higher in the MDD group for standard stimuli in the alpha band. Area under the curve for 100ms time intervals were measured. Time intervals are shown with grey shading. All p-values are FDR corrected for multiple comparisons. *: < 0.05, **: < 0.01, ***: <0.001.

Figure 5

Spearman correlations found significant relationships between area under the curve (AUC) in TTV and FS, PS and reaction times. (A) For deviant stimuli, AUC in TTV had significant correlations across all participants with FS and PS in the theta band. (B) For standard stimuli, AUC in TTV had significant correlations with PS in theta and alpha. (C) AUC in TTV for deviant stimuli correlated significantly with the mean reaction time. All p-values are FDR corrected for multiple comparisons. *: < 0.05.

Figure 6

Spearman correlations found significant relationships between resting state measures in the theta band and LZC in both stimuli and PS and TTV AUC in deviant stimuli. (A) Resting state theta PF had a negative correlation with prestim LZC in standard stimuli. (B) The CV in the theta band had significant correlations with PS and TTV AUC for deviant stimuli. (C) Resting state theta power had significant negative correlations with both pre- and poststim LZC in both bands. All p-values are FDR corrected for multiple comparisons. *: < 0.05.

Figure 7

Hypothesis: atypical resting state activity leads to increased internal activity and decreased response to external stimuli. (A) In healthy participants, normal resting state activity allows for the quenching of ongoing variability (TTV, LZC) and an optimal signal-to-noise ratio (SNR) to respond to task-relevant stimuli. (B) In MDD participants, atypical resting state activity leads to higher levels of noise in the SNR, overshadowing the task-relevant stimulus. Recent studies support this hypothesis; however, it must be tested directly in future studies.