fMRI in Resting State as a Radiological Tool in Pharmaceutic Research: An Experimental Clinical Trial with Alprazolam

PURPOSE: The aim of the study was to highlight the presence of modifications in the Default Mode Network (DMN) detected by means of fMRI in Resting State after the administration of a neurotropic drug, the Alprazolam, and therefore to suggest fMRI as an alternative and non invasive tool for future pharmacological experimentations in vivo. METHOD AND MATERIALS: 11 healthy subjects (5 males; mean age: 32 years) were enrolled in a double-blind randomized study. They received Alprazolam or placebo and underwent two fMRI scans each. Data were acquired at 1.5 T (Magnetom Symphony, Siemens, Enlargen, Germany). Functional connectivity and activation maps were obtained by means of independent component analysis using FSL (FMRIB software Library 4.1, Oxford, UK). A F-test (p<0.05) was applied in order to detect statistical differences between groups and Dual-Regression (p<0.05) permitted to obtain spatial maps defining the between-subject group-consistency. RESULTS: The reproducibility of fMRI in Resting State was demonstrated with a consistent detection of DMN in all subjects and all conditions, furthermore a statistically non-significant difference between baselines was found (p<0,11242). The Dual-Regression analysis showed a diffuse significant higher functional connectivity in the brain after the administration of Alprazolam, mainly in the precuneus/posterior cingulate cortex within the DMN, and also between the DMN and other cerebral areas, in particular the basal ganglia. No significant differences in DMN were detected after placebo administration. CONCLUSION: fMRI in Resting State reproducibility was demonstrated and connectivity modifications in DMN and other cerebral areas occur after Alprazolam administration. CLINICAL RELEVANCE/APPLICATION: fMRI should be considered an applicable model in humans during future clinical trials.