Translational Challenge Models in Support of Efficacy Studies: Neurobehavioral and Cognitive Changes Induced by Transcranial Magnetic Stimulation in Healthy Volunteers

Transcranial Magnetic Stimulation (TMS) was proposed as a neurophysiological tool almost three decades ago. It now encompasses a very wide range of applications including clinical research and the treatment of psychiatric, neurologic and medical conditions such as depression, schizophrenia, addictions, post-traumatic stress disorders, pain, migraine, stroke, Alzheimer's disease, autism, multiple sclerosis and Parkinson's disease. By inducing electrical brain responses through the administration of magnetic pulses, TMS is in a unique position to painlessly modulate cortical regions and offers good spatial resolution and excellent temporal resolution, particularly when applied using single pulses. However, despite the impressive number of papers describing the use of TMS to modulate cognitive functions, the mechanisms underlying the behavioral changes observed after stimulation have not been fully identified. Here we present a review of the ability of TMS to transiently compromise brain function in humans. The primary aim was to investigate its capacity for use as a 'cognitive challenge model' in human pharmacological studies. The data reviewed include findings on executive function, attention and episodic memory. For each cognitive process, the convergent and divergent results are discussed in terms of paradigm differences and in order to define the optimal methodology for obtaining the desired effects.