Modifications of Functional Human Brain Networks by Transcutaneous Auricular Vagus Nerve Stimulation: Impact of Time of Day

Figure 1. Examination schedule to probe for short and longer-lasting taVNS-induced changes in evolving functional brain networks. The schedule consisted of two 1 h stimulation phases (morning: stim 1 and afternoon: stim 2; yellow-shaded blocks) each phase was preceded and followed by a pre- and post-stimulation phase, each lasting one hour (green-shaded blocks). During each of the 3 h blocks, subjects continued laid-back activities (no other activation methods applied, no eating) and they continued performing daily activities during the break (no other activation methods applied). The whole examination schedule (including the break) was embedded into a continuous video-EEG-recording. In our analyses, we neglected data from the first and last 15 min of each phase (darker colours) in order to remove possible transient effects (e.g., due to movements or expectation effects).

Figure 2. (a) Exemplary time courses (grey lines) of average clustering coefficient C, average shortest path length L, assortativity A, and synchronisability S of two subjects. Smoothed time courses (moving average over 17 min) are shown as black lines. Yellow-shaded areas mark the two 1 h stimulation phases. (b) Power spectral density estimates P of the respective time courses.

Figure 3. Relative changes of global network characteristics (average clustering coefficient C, average shortest path length L, assortativity A, and synchronisability S) of all responders (colour-coded). Group medians are shown in black, and all lines are for eye-guidance only. Data normalized to the respective values from the morning pre-stimulation phase (left; white-shaded area) and from the afternoon pre-stimulation phase (right; white-shaded area). Light-grey shaded area marks the break between the two 3 h examination phases. The different scaling of the y-axis for assortativity is due to the fact that this characteristic only rarely deviated from −0.02 which resulted in anomalous large relative deviations. We note that we obtained for the vast majority of investigated networks, indications for a random topology (their assortativity values were confined to the range of A values derived from 1000 random networks with the same number of vertices and edge densities as the evolving functional brain networks).

Figure 4. Bubble chart of taVNS-induced immediate, enduring, prolonged, and longer-lasting relative changes Δ of global network characteristics of all responders (average clustering coefficient C, average shortest path length L, assortativity A, and synchronisability S; Δ = (Ml − Mk)/Mk, where Mk and Ml denote placeholders for the temporal average of the respective characteristics from phase k and phase l; cf. Figure 1). Responders are assigned to subgroups according to their direction of change (positive/negative changes are shown in orange/blue). A disk is centred at a subgroup’s mean relative change, and the diameter of a disk encodes the number of subjects per subgroup. Mean relative changes from both groups are shown as green squares.

Figure 5. Schematic of spatial networks prior to and after taVNS stimulation in the morning (left) and in the afternoon (right), with different rhythmic activities (longer period lengths: top, shorter period lengths: bottom; indicated by greenish waves in the background) that interfere with the stimulation-mediated network modification. The network is separated into different areas based on network properties: (average clustering coefficient C and average shortest path length L): boundary (gray outermost ring), periphery (purple and pink rings in the middle), and core (black innermost ring/circle). The larger the radius of a ring, the higher the L and the smaller the C of vertices in this area. The closer two rings, the more clustered the vertices are in the two areas relative to each other. Local importance hierarchies H (assessed with different centrality concepts) of vertices and edges are not affected by the stimulation.