Approaches to map cortical excitability beyond the primary motor cortex - Perspectives from cognitive neuroscience, multimodal imaging and clinical applications.

Excitability is a neuronal property quantified as the magnitude of neural response to stimuli. It plays a crucial role in information processing and is disrupted in various neuropsychiatric conditions. In humans, non-invasive measurements of brain excitability have been mostly limited to the primary motor cortex. Here, the response to Transcranial Magnetic Stimulation (TMS) is quantified as the magnitude of the muscular contraction. TMS mapping of brain excitability outside the motor cortex, simultaneously across brain areas, and in deep regions is challenging. Indeed, TMS has little depth penetration, and can only probe one cortical point at a time. Furthermore, the measurement of the responses to stimuli outside the motor cortex requires simultaneous neuroimaging, such as electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Possible solutions include the application of stimulation approaches alternative to TMS, and the investigation of resting state properties of electromagnetic and hemodynamic brain activity. We show that, in combination with TMS or alone, neuroimaging will progressively allow non-invasive and accurate mapping of excitability with high spatio-temporal resolution, across the entire brain, and non-invasively. This will mark a critical advancement for stimulation thresholding in basic neuroscience and clinical medicine, as well as diagnostics of deviant excitability patterns in neuropsychiatric conditions. It is the aim of this review to critically discuss the state-of-the-art of whole brain excitability mapping and provide an outlook on neuroscience and clinical implications.