Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: Coincident with the global trend of urbanization, a possible association between decreased exposure to nature and increased occurrence of mental disorders has increasingly been reported. Beyond spatial and temporal limitations, new 360° VR technology using one’s own smartphone and portable VR glasses allows modern people to deal with mental fatigue in everyday life. Objective: Based on Attention Restoration Theory (ART), the current study investigates whether the amplitude of the MMN/P3a complex can act as a potential ERP biomarker of involuntary attention restoration during exposure to 360° virtual nature in healthy young adults with different levels of restorative VR experience. Methods: A total of 40 healthy adults completed pre-questionnaires on demographics and simulator sickness and post-questionnaires on simulator sickness and perceived restorativeness before and after exposure to virtual nature, respectively. During the VR exposure, their brain activity was measured with EEG (Electroencephalography) by asking participants to conduct a two-tone auditory passive oddball task. Results: Both amplitude and latency of the MMN/P3a complex between the two between-subject groups were compared. While viewing a nature virtual environment (VE), the high restorative group (N = 19) exhibited significantly reduced P3a amplitudes than the low restorative group (N = 20) did, t (38) = 2.57, P = .02, d = .59. Particularly, a moderate, but significantly negative correlation was found between the self-reported perceived restorative scores and the P3a amplitudes at the fronto-central region (FCz; r = - .38, P = .02). The outcome of 360° virtual nature experience seems to be consistent with that of previous ERP studies on the during-effect of meditation practice. However, the latency of the MMN/P3a complex did not significantly differ between the two restorative groups: (1) aMMN: t (38) = - 1.47, P = .15; (2) P3a: t (38) = - .31, P = .76. Conclusions: These findings of this study will extend those of previous ART and ERP studies on meditation, restoration, and the management of mental fatigue in the real world into the virtual world via . Considering individuals’ restorative experience, the amplitude of the fronto-central MMN/P3a complex can be potentially employed as a distinct ERP component of interest in involuntary attention restoration during virtual nature experience in healthy young adults.