Integrating olfactory assessments in consciousness disorders: methodologies and therapeutic potential

Introduction Current clinical assessments for patients with prolonged disorders of consciousness (pDOC) primarily depend on visual and auditory approaches, which often result in misdiagnosis. The olfactory system possesses a distinct anatomical pathway that projects directly to the cortex without thalamic relay, which may retain responsiveness in pDOC patients. Preliminary evidence suggests a link between smelling and consciousness processes, yet there is a gap in applying these findings clinically. Methods This review combines insights from neuroanatomy, behavioral neuroscience, and neuromodulation studies to propose a framework based on olfaction for assessing and encouraging consciousness recovery. Literature searches were conducted across PubMed, and Web of Science, for studies published from January 2010 to January 2026, with earlier key works identified through reference screening. Results Sensory and cognitively driven sniff response test in pDOC olfactory processing serves as a sensitive biomarker for distinguishing between vegetative and minimally conscious states (MCS) in a single study, and may predict early recovery. Protocols for bedside olfactory discrimination provide quick screening methods but lack multicenter validation. Olfactory training is frequently combined with other senses to improve effectiveness, precluding isolation of its specific contribution. Neuromodulation approaches show preliminary effects on brain rhythms in healthy volunteers, while olfactory electrical stimulation and neurofeedback remain at proof-of-concept stage. No dedicated olfactory rehabilitation protocol has been evaluated in pDOC cohorts. Conclusion Olfactory assessment and stimulation represent a promising but nascent frontier in pDOC care. The sniff response test currently has the strongest empirical foundation, yet all approaches require multicenter validation. Future research should prioritize personalized key odor identification, standardized stimulation protocols, and rigorous clinical trials of neuromodulation techniques. Integrating olfactory measures into multimodal strategies may improve diagnostic accuracy and support consciousness recovery.