Greater preserved baseline functional MRI connectivity in zolpidem responders compared to non-responders in patients with disorders of consciousness.

Introduction
Zolpidem is commonly used as sleep inducer but is one of the few available pharmacological treatments for patients with disorders of consciousness (DOC). Some DOC patients have exhibited paradoxical improvements with zolpidem treatment but the neurological profile of responders remains unclear. No fMRI study has ever been conducted in a group of DOC patients. We investigated the baseline functional brain connectivity in DOC patients responding to zolpidem compared to non-responding patients.
Methods
Eleven patients in minimally conscious state and 5 who emerged received a 10 mg single dose of zolpidem. Patients were considered responders if a new behaviour was observed using the Coma Recovery Scale-Revised after zolpidem administration. All patients underwent resting-state fMRI (without zolpidem). Hypothesis-free and seed-based region (thalamus) analyses were conducted with age and gender covariates regressed out, comparing patients with 36 healthy volunteers.
Results
Seven patients qualified as responders (5 sedated, 2 non-sedated) and 9 as non-responders (6 sedated, 3 non-sedated). Hypothesis-free analyses in the sedated group revealed significantly increased intrinsic connectivity among responders in the occipital, occipito-temporal and parieto-occipital areas compared to non-responders. Seed-based analyses showed significantly more preserved positive connectivity of the fronto-insular network in responders compared to non-responders. No significant differences were found between responders and non-responders in the non-sedated condition, possibly due to smaller sample size.
Conclusion
Our findings suggest a greater preservation of global and local connectivity in zolpidem responders at baseline. Targeting more accurately potential responders to zolpidem can improve the clinical management of DOC patients.