Strengthening functionally specific neural pathways with transcranial brain stimulation.

Cortico-cortical paired associative stimulation (ccPAS) is a recently established offline dual-coil transcranial magnetic stimulation (TMS) protocol [1-3] based on the Hebbian principle of associative plasticity and designed to transiently enhance synaptic efficiency in neural pathways linking two interconnected (targeted) brain regions [4,5]. Here, we present a new 'function-tuning ccPAS' paradigm in which, by pairing ccPAS with the presentation of a specific visual feature, for example a specific motion direction, we can selectively target and enhance the synaptic efficiency of functionally specific, but spatially overlapping, pathways. We report that ccPAS applied in a state-dependent manner and at a low intensity selectively enhanced detection of the specific motion direction primed during the combined visual-TMS manipulations. This paradigm significantly enhances the specificity of TMS-induced plasticity, by allowing the targeting of cortico-cortical pathways associated with specific functions.