Cortical paired associative stimulation influences response inhibition: cortico-cortical and cortico-subcortical networks

Background The ability to stop a suboptimal response is integral to decision making and is commonly impaired across psychiatric disorders. Cortical paired associative stimulation (cPAS) is a form of transcranial magnetic stimulation in which paired pulses can induce plasticity at cortical synapses. Here we used cPAS protocols to target cortico-cortical and cortico-subcortical networks by using different intervals between the paired pulses in an attempt to modify response inhibition. Methods Twenty-five healthy volunteers underwent 4 cPAS sessions in random order 1 week apart: right inferior frontal cortex (IFC) stimulation preceding right pre-supplementary motor area (pre-SMA) stimulation by 10 or 4 milliseconds; pre-SMA stimulation preceding IFC stimulation by 10 or 4 milliseconds. Subjects were tested on the stop signal task along with the delay discounting task as control at baseline (randomized across sessions and cPAS protocol), and after each cPAS session. Results The stop signal reaction time showed a main effect of cPAS condition when controlling for age (F(3,57)=4.05, p=0.01). Younger subjects had greater impairments in response inhibition when the pre-SMA pulse preceded the IFC pulse by 10 msec. In older individuals, response inhibition improved when the IFC pulse preceded the pre-SMA pulse by 4 msec. There were no effects on delay discounting. Conclusion cPAS modified response inhibition through age-dependent long-term potentiation and depression-like plasticity mechanisms via putative cortico-cortical and cortico-subcortical networks. We show for the first time the capacity for cPAS to modify a cognitive process highly relevant to psychiatric disorders.