Of the 17 subjects enrolled in this analysis (rating at least a “3” out of “4”), 12 subjects experienced nausea rated as “4,” severe. The average duration of linear vection stimulus for those 12 subjects whose maximum nausea rating was “4” (and therefore terminated prior to the maximum 20 minutes) was 9.1 ± 4.5 minutes (mean ± s.d.). For other intermediate nausea level transitions for all 17 subjects, the average duration until subjects reached the 0-to-1 transition was 1.9 ± 2.1 minutes, the 1-to-2 transition was 3.8 ± 2.3 min, and the 2-to-3 transition was 6.9 ± 4.3 min. Nine (9) of the 17 subjects monotonically increased their nausea ratings without any decreasing nausea level transitions. Eight (8) subjects exhibited at least one decreasing level transition at some point during the experiment, which is not uncommon in linear vection studies where nausea sensation is known to fluctuate. This “drop-off” may have been due to spontaneous change in gaze focus and/or attention processes.
Of the 12 subjects who reached a global nausea level of 4, nine (9) subjects completed the SSQ. An initial repeated measures ANOVA indicated that there were differences in SSQ nausea factor intensity between the different global (0–4) nausea levels for the nausea specific factor (F(3,24)=119.4, p<0.001), oculomotor factor (F(1.3,10.4)=37.1, p<0.001, using Greenhouse-Geisser correction for Maulchy's W of 0.01 indicating non-sphericity), and disorientation factor (F(3,24)=86.7, p<0.001). Post hoc testing demonstrated that all three symptom factors (nausea, oculomotor and disorientation) increased in severity with increasing global nausea level ratings (p<0.01 for all comparisons).
For the stimulus-based analysis, four 4-minute temporal windows (immediately before and after both the onset and termination of the nauseogenic stimulus: “I,” “II,” “III,” and “IV”) were compared (), revealing increases in SCR, HR, and LF/HF HRV over the course of the experiment. An initial repeated measures ANOVA indicated that there were within-subject differences among stimulus-based windows for average SCR (F(1.3,20.8)=15.7, p<0.001, using Greenhouse-Geisser correction for Maulchy's W of 0.04) (), HR (F(3,45)=16.7, p<0.001) (), and the ratio of LF to HF (F(3,45)=3.5, p=0.02) () but not for respiratory rate (F(3,39)=0.6, p=0.6), normalized HF (F(3,45)=1.9, p=0.1), and normalized LF (F(3,45)=1.9, p=1) (, respectively).
Figure 2 Stimulus-based analysis of physiological indices. (A) Timing of 4-minute windows of interest are shown over a plot of a representative subject's nausea level. (B–G) Average change in skin conductance, HR, respiratory rate, normalized HF, normalized (more ...)
For the post hoc analyses, average SCL significantly increased over baseline for windows II, III and IV (II: Δ = 0.68 ± 0.98 μS (mean±s.d.), p<0.05; III: 1.94 ± 1.65 μS, p<0.001; IV: 2.46 ± 2.11 μS, p<0.001) (, ). SCL also increased over the course of the experiment (II to III: Δ = 1.26 ± 1.71 μS, p<0.05; II to IV: Δ = 1.78 ± 2.25 μS, p<0.05; III to IV: Δ = 0.52 ± 0.65 μS, p<0.05) ().
Skin Conductance Response. Difference from baseline for both stimulus-based and percept-based analyses.
HR increased significantly over baseline for window II (Δ = 7.4±8.2 beats per minute (bpm), p<0.01); III (Δ = 12.0±7.0 bpm, p<0.001) and had a trending increase over baseline for window IV (Δ = 5.4±8.1 bpm, p=0.05) (, ). Average HR increased significantly from II to III (Δ = 4.6±6.1 bpm, p<0.05), but decreased significantly from III to IV (Δ = -6.6±4.6 bpm, p<0.001) after the stimulus terminated ().
Heart Rate. Difference from baseline for both stimulus-based and percept-based analyses.
In regard to HRV, the ratio of LF to HF trended upward (Δ = 0.92±1.52 a.u., p=0.08) between windows II and III (). No other significant differences or trends were found.
For the percept-based analysis approach, we compared 1-minute temporal windows beginning just after state transition with baseline values (). Overall, we found increases in SCR, HR, normalized LF, and LF/HF, and a decrease in normalized HF. An initial repeated measures ANOVA indicated significant differences among percept-based analysis windows for SCR (F(3,48)=13.7, p<0.001) (), HR (F(3,45)=18.4, p<0.001) (), normalized HF (F(3,45)=3.6, p=0.02) (), normalized LF (F(3,45)=4.0, p=0.01) (), and the ratio of LF to HF (F(3,45)=5.7, p<0.01) (), but not respiratory rate (F(3,39)=0.5, p=0.7) ().
Figure 3 Percept-based analysis of physiological indices. (A) Timing of 4-minute baseline and 1-minute post nausea rating transition windows are shown over a plot of a representative subject's nausea level. (B–G) Mean change in SCL, HR, respiratory rate, (more ...)
In the post hoc analyses, SCR increased for 0-to-1 (Δ = 0.99±1.26 μS, p<0.05), for 1-to-2 (Δ = 1.32±1.31 μS, p<0.01), and for 2-to-3 (Δ = 1.76±1.68 μS, p<0.01) (, ). SCR also significantly increased with increasing nausea level (from 0-to-1 to 2-to-3: Δ = 0.77±1.13 μS, p<0.05, and from 1-to-2 to 2-to-3: Δ = 0.44±0.67 μS, p<0.05) ().
HR significantly increased in all windows of interest (0-to-1: Δ = 8.4±7.0 bpm, p<0.001; 1-to-2: Δ = 12.7±10.4 bpm, p<0.001; 2-to-3: Δ = 15.0±11.4 bpm, p<0.001) (, ). HR also significantly increased between 0-to-1 and 2-to-3 (Δ = 6.6±8.9 bpm, p<0.05) ().
In regard to HRV, normalized HF significantly decreased from baseline following the 2-to-3 rating transition window (Δ = −0.11±0.13 a.u., p<0.05) (), while normalized LF significantly increased following the 2-to-3 window (Δ = 0.13±0.16 a.u., p<0.05) (). The LF/HF ratio also significantly increased over baseline following both the 1-to-2 transition (Δ = 1.54±2.11 a.u., p<0.05) and the 2-to-3 transition (Δ = 2.57±3.49 a.u., p<0.05) (, ).
Heart Rate Variability. Difference from baseline for both stimulus-based and percept-based analyses.
Point-process HF HRV data were analyzed for five 90-second temporal windows (START, 0-to-1, 1-to-2, 2-to-3, and END), averaged over all subjects (). For these group data, the “START” window demonstrated increasing HF, peaking 10 to 20 seconds after stimulus onset, with gradual decrease thereafter. Conversely, the “END” window demonstrated gradual increase in HF following stimulus cessation. The 0-to-1, 1-to-2, and 2–3 windows demonstrated gradual decrease in HF by 30 seconds after transition in nausea level, but interestingly, phasic bursts of HF increase were also seen 10 to 20 seconds before subjects rated a change in nausea level.
Figure 4 Average across subjects of normalized point process HF HRV. (A) Schematic representation of the 90-second window placements. (B–F) HF HRV timeseries within windows of interest averaged across subjects demonstrate robust gradual decrease following (more ...)