Conditioning of transcranial magnetic stimulation: Evidence of sensory-induced responding and prepulse inhibition

Background Transcranial magnetic stimulation (TMS) is a non-invasive method for stimulating the human cortex. Classical conditioning is a phenomenon of developed associations between stimuli. Our primary objective was to determine whether TMS effects could be conditioned. Prepulse inhibition represents another relationship between two stimuli, and a secondary assessment was performed to explore this relationship. Methods An auditory-visual conditioning stimulus (CS) was paired with the TMS unconditioned stimulus (US) over motor cortex producing a motor-evoked potential (MEP) unconditioned response (UR). Two versions of the CS-US pairing paradigms were tested, one with a short intertrial interval (ITI) and another with a long ITI. The short ITI paradigm had more CS-US pairings and shorter session duration than the long ITI paradigm. Tests for conditioned responses (CRs) were performed following CS-US pairing (CS+/US+), by presenting the CS alone (CS+/US−). Reverse testing was also performed after CS-US pairing (CS+/US+) in separate sessions, by presenting the US alone (CS−/US+). Results Evidence for CRs was found only with the short ITI paradigm. The magnitudes of CRs were smaller than TMS-induced MEPs, and the CRs were found only in a percentage of tests. Prepulse inhibition was robustly evident for the long ITI paradigm, but not for the short ITI paradigm. Conclusions We have found evidence that classical conditioning principles can be applied to brain stimulation in humans. These findings provide a method for exploring brain and behavioral relationships in humans, as well as suggesting approaches to enhance therapeutic uses of TMS or other forms of brain stimulation.