While viewing a video clip, we experience a wide variety of contents, from low-level features of the images to high-level ideas such as the storyline. Each change in our experience must be supported by some corresponding change in neurophysiological activity. Differentiation analysis, which quantifies the differences in brain activity by measuring the distances between observed brain states, was applied here to continuous high-density electroencephalographic data recorded while participants watched short video clips. These clips were manipulated in various ways to change the degree of meaningfulness of their contents. We found that neurophysiological differentiation mirrored that of phenomenal differentiation, being higher for meaningful clips and lower for phase-scrambled versions or random noise. The distinction between meaningful and meaningless clips was present even at the individual level, and moreover, differentiation values correlated with individual subjective reports of meaningfulness. Spatial and spectral breakdowns of the overall effect showed frontal and posterior ROIs and highlighted specific roles for different spectral bands. Comparing the results with a multivariate decoding approach reveals that the two methods are capturing different aspects of brain activity and highlights a crucial theoretical distinction between the level and pattern of activity. In future applications, differentiation analysis may be used to evaluate the subjective meaningfulness of stimuli when behavioral responses may be inadequate, as with disorders of consciousness.