Subcortical atrophy correlates with the perturbational complexity index in patients with disorders of consciousness

Background: The complexity of neurophysiological brain responses to direct cortical stimulation, referred to as the perturbational complexity index (PCI), has been shown able to discriminate between consciousness and unconsciousness in patients surviving severe brain injury as well as several other conditions (e.g., wake, dreamless sleep, sleep and ketamine dreaming, anesthesia). Objective: This study asks whether, in patients with a disorder of consciousness (DOC), the complexity of the neurophysiological response to cortical stimulation is preferentially associated with atrophy within specific brain structures. Methods: We perform a retrospective analysis of 40 DOC patients and correlate their maximal PCI to MR-based measurements of cortical thinning and subcortical atrophy. Results: PCI was systematically and inversely associated with the degree of local atrophy within the globus pallidus, a region previously linked to electrocortical and behavioral arousal. Conversely, we fail to detect any association between variance in cortical ribbon thickness and PCI. Conclusion: These findings corroborate the previously reported association between pallidal atrophy and low behavioral arousal and suggest that this region's role in maintaining the overall balance of excitation and inhibition may critically affect the emergence of complex cortical interactions in chronic disorders of consciousness. This finding thus also suggests a target for potential neuromodulatory intervention in DOC patients.