Key pointsr Nausea is a highly individual and variable experience. The reasons for this variability are incompletely understood although psychophysiological factors have been proposed.r Herein we describe objective psychophysiological changes induced by the subjective sensation of motion sickness.r In comparison to subjects who did not develop nausea, nausea-sensitive subjects demonstrated electrogastrographic and autonomic changes, which included an increase in sympathetic nervous system activity with a concomitant reduction in parasympathetic activity. Furthermore, differences were also evident in plasma ghrelin, and subcortical and cortical activity.r These data have a number of important implications for future research examining the physiological mechanisms that underlie nausea:• The physiological, hormonal and cortical patterns identified herein represent potential biomarkers of the physiological mechanisms of nausea.• Reverse translation of the physiological factors identified may facilitate refinement of animal models used to investigate novel anti-emetic agents and emetic liability of candidate drugs, increasing their validity and translation of finding to 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.(

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