Metabolic Changes Underlying Bold Signal Variations after Administration of Zolpidem

Zolpidem is a non-benzodiazepine drug belonging to the imidazopiridine class, which has selectivity for stimulating the effect of gamma aminobutyric acid [GABA] and is used for the therapy of insomnia. Nonetheless, several reports have been published over recent years about a paradoxical arousing effect of Zolpidem in patients with severe brain damage. We studied a PVS case using 1H-MRS and BOLD signal, before and after Zolpidem administration. Significantly increased BOLD signal was localized in left frontal superior cortex, bilateral cingulated areas, left thalamus and right head of the caudate nucleus. A transient activation was observed in frontal cortex, comprising portions of anterior cingulate, medial, and orbito-frontal cortices. Additionally, significant pharmacological activation in sensory-motor cortex is observed 1 hour after Zolpidem intake. Significant linear correlations of BOLD signal changes were found with primary concentrations of NAA, Glx and Lac in the right frontal cortex. We discussed that when Zolpidem attaches to the modified GABA receptors of the neurodormant cells, dormancy is switched off, inducing brain activation. This might explain the significant correlations of BOLD signal changes and 1H-MRS metabolites in our patient. We concluded that 1H-MRS and BOLD signal assessment might contribute to study neurovascular coupling in PVS cases after Zolpidem administration. Although this is a report of a single case, considering our results we recommend to apply this methodology in series of PVS and MCS patients. (author)