The heart knows best: baseline heart rate variability as guide to transcutaneous auricular vagus nerve stimulation in depression

Figures

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  Fig. 1. Study Design. Left panel: A Sham stimulation at the earlobe. B Verum stimulation at the right cymba conchae. Right panel: Illustration of cross-over, single-blind, randomized, sham-controlled trial. Stimulation was started after the blood sample (−60 min) and ended after the stress task. VAS scales were collected after the baseline (0 min), after stress exposure (5 min) and after recovery (5 min). A final blood sample was collected 40 min after stress exposure. Timescales are approximate and did vary according to time needed for completing experimental procedures such as VAS scales. Image created with Biorender.com.

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  Fig. 2. Consort Flow Diagram of the MODULATE study. Ninety-four percent (61/65) of the randomized participants completed a first test day (T1) with taVNS versus 89 percent (49/55) with a sham stimulation; the difference was not significant (p = 0.543). At the second test day (T2) 84.61 (55/65) of randomized participants received the planned sham stimulation and 83.64% (46/55) received the planned verum stimulation (p > 0.999). In total, 51 controls and 59 participants with MDD were randomized to the intervention and completed the first session (T1) and were thus used for analysis.

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  Fig. 3. Impact of acute stress and taVNS on emotional reactivity. A-C Effects on Stress Perception. All values were transformed with Tukey ladder of power transformation for statistical analyses but are presented as untransformed scores. From left to right: A. Main effect of acute stress, B. Main effect of Group, C. 2-way interaction effect of intervention and RMSSD group. D-F Effects on Negative Emotions (Composite Score). From left to right: D. Main effect of acute stress, E. Main effect of Group, F. 2-way interaction effect of intervention and RMSSD group, G-I Effects on Positive Emotions (Composite Score). From left to right: G. Main effect of acute stress, H. Main effect of Group, I. 2-way interaction effect of intervention and RMSSD group, Significance:***:p < 0.001, ** p < 0.01, *p < 0.05, #p < 0.1, ns:p > 0.1.

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  Fig. 4. Impact of acute stress and taVNS on heart rate variabitlity (RMSSD in ms). Results are presented as raw values (in ms). A Interaction of Stress and RMSSD group; B Interaction of intervention with RMSSD group. C 3-way interaction for Stress, Intervention and RMSSD group. Note that scales differ between (A,B and C), to be able to display all error bars appropriately. Significance:***:p < 0.001, ** p < 0.01, *p < 0.05, #p < 0.1, ns:p > 0.1.

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  Fig. 5. Levels of TNF-α and IL-6 according to intervention. Values are back-transformed and were measured in pg/mL. They represent the averaged effect of RMSSD group*Intervention regardless of condition (BL/STR). A. Intervention*RMSSD(low/high) for TNF-α, B. Intervention*RMSSD(low/high) for IL-6. Significance: ***:p < 0.001, ** p < 0.01, *p < 0.05, #p < 0.1, ns:p > 0.1.