Visually induced nausea causes characteristic changes in cerebral, autonomic and endocrine function in humans

Abstract

An integrated understanding of the physiological mechanisms involved in the genesis of nausea remains lacking. We aimed to describe the psychophysiological changes accompanying visually induced motion sickness, using a motion video, hypothesizing that differences would be evident between subjects who developed nausea in comparison to those who did not. A motion, or a control, stimulus was presented to 98 healthy subjects in a randomized crossover design. Validated questionnaires and a visual analogue scale (VAS) were used for the assessment of anxiety and nausea. Autonomic and electrogastrographic activity were measured at baseline and continuously thereafter. Plasma vasopressin and ghrelin were measured in response to the motion video. Subjects were stratified into quartiles based on VAS nausea scores, with the upper and lower quartiles considered to be nausea sensitive and resistant, respectively. Twenty-eight subjects were exposed to the motion video during functional neuroimaging. During the motion video, nausea-sensitive subjects had lower normogastria/tachygastria ratio and cardiac vagal tone but higher cardiac sympathetic index in comparison to the control video. Furthermore, nausea-sensitive subjects had decreased plasma ghrelin and demonstrated increased activity of the left anterior cingulate cortex. Nausea VAS scores correlated positively with plasma vasopressin and left inferior frontal and middle occipital gyri activity and correlated negatively with plasma ghrelin and brain activity in the right cerebellar tonsil, declive, culmen, lingual gyrus and cuneus. This study demonstrates that the subjective sensation of nausea is associated with objective changes in autonomic, endocrine and brain networks, and thus identifies potential objective biomarkers and targets for therapeutic interventions.

Figure 1

Flowchart of the overall experimental design in which psychophysiological responses to the motion and control video were measured Nausea ratings derived from the motion video in Study 1 were used to stratify subjects into quartiles with the upper quartile being considered as nausea-susceptible and the lower quartile being nausea-resistant. Central responses to the motion video from subjects from these two groups were then measured using fMRI. Of the 20 ‘dropouts’, 12 subjects did not want to participate in the fMRI study, 6 subjects could not attend at a convenient time and 2 subjects did not attend their scanning appointment.

Figure 2

Effects of the motion and control videos The effect of the motion video (•) and the control video (▪) nausea ratings (A), anxiety ratings (B), EGG normogastria/tachygastria ratio (C), mean blood pressure (D), cardiac sympathetic index (E) and cardiac vagal tone (F) in nausea-sensitive subjects. Data shown are group mean ± SEM. ***P < 0.001, **P < 0.01, *P < 0.05.

Figure 3

Differential activation of the left anterior cingulate cortex from a two-way interaction analysis group × time (cluster P = 0.041)

Figure 4

Plot of the mean BOLD response in the right anterior cingulate cortex showing differential activations between the groups and the time bins NS, nausea-sensitive; NR, nausea-resistant.

Figure 5

Positive correlation of nausea VAS scores with brain activity in the left inferior frontal and middle occipital gyri in nausea-susceptible subjects