The management of patients with disorders of consciousness (DoC) represents a topic of great importance and topicality in the medical-scientific field because of the complexity and extent of associated disabilities and the difficulty in identifying effective therapeutic approaches. Despite significant advances in neuroscience, much remains to be elucidated about the mechanisms that regulate consciousness, and which of these to act on to stimulate plasticity and thus promote responsiveness and functional recovery in patients. Evidence on treatments that promote arousal and communication skills in individuals with DoC is still limited.

Among the possible interventions proposed in the literature, sensory stimulation would act by stimulating synaptic plasticity, counteracting the sensory deprivation to which these patients are exposed.

Published studies on the topic have produced results that are not unique and difficult to compare across different stimulation protocols (content, intensity, frequency, modality), settings and patient populations.

Smell is a primitive and complex sense related to emotions, memory and language. When we smell an odor, its molecules reach the nasal cavity and bind to the receptors of olfactory neurons, which transform the chemical information into an electrical signal that reaches the olfactory bulb and is then transmitted to the brain areas (piriform cortex, amygdala, thalamus, hypothalamus, insula, anterior cingulate cortex, orbitofrontal cortex) deputed to the emotional perception of smell and its storage. Studies in the literature have demonstrated the ability of the olfactory stimulus to influence emotional and cognitive processes (attention, memory, language), motor gesture, and autonomic nervous system response in healthy subjects. The use of stimuli with emotional and familiar content for the subject has also been shown to increase the likelihood of observing a behavioral response in patients with DoC.

In DoC patients, the use of the olfactory stimulus (intensity, modality, timing, measurement tools) in the recovery process is still limited, and it has not yet been clarified what effect it has on awakening and neurovegetative nervous system response.

This study aims to investigate, in both healthy subjects and patients with obsessive compulsive disorder (DoC) resulting from severe Acquired Brain Injury (sABI), the effects that odors of various types produce at the level of the autonomic nervous system (ANS) and brain connectivity.

More specifically, this study aims to evaluate, in healthy subjects and in patients with DoC, the effects of neutral, pleasant, and unpleasant olfactory stimuli on ANS, brain connectivity, reactivity, and the possible onset of habituation following repeated administration of the same olfactory stimulus.

Inclusion Criteria:

• Age between 18 and 90 years;
• Glasgow Come Scale (GCS) score between 8 and 13;
• Level of Cognitive Function (LCF) score between 2 and 3;
• Latency from the acute event of not more than 2 months;
• Spontaneous eye opening.

Exclusion Criteria:

• Documented history of brain injury prior to the one that resulted in hospitalization;
• Documented history of uncorrected visual or hearing impairment;
• Documented history of chronic rhinosinusitis with or without the presence of naso-sinus polyps;
• Previous history of psychiatric and/or neurological disorders that resulted in significant disability prior to the acute event;
• Acute pathology at the time of recruitment, head injury, or ischemic or expansive injury with suspected peripheral olfactory tract involvement.