Non-invasive ultrasonic modulation of visual evoked response by GABA delivery through the blood brain barrier

GABA is an inhibitory neurotransmitter that is maintained outside the brain by the blood brain barrier in normal condition. In this paper we demonstrate the feasibility of modulating brain activity in the visual cortex of non-human primates by transiently permeabilizing the blood brain barrier (BBB) using focused ultrasound (FUS) coupled with ultrasound contrast agents (UCA), followed by intra-venous injection of GABA. The visual evoked potentials exhibited a significant and GABA-dose-depend decrease in activity. The effect of the sonication only (with and without UCA) was also investigated and was shown to decrease the activity 8.7 times less than the GABA-induced inhibition enabled by BBB permeabilization. Finally, the UCA harmonic response was monitored during sonication to estimate the level of stable cavitation (a signature of the effectiveness of BBB permeabilization) and to avoid damage due to inertial cavitation (the sonication was automatically shut down when this condition was detected). Our results extend the promise of the exploration and treatment of the brain using non-invasive, controllable, repeatable, and reversible neuromodulation.