Transcranial magnetic stimulation (IMS), a noninvasive form of brain stimulation, is being developed as an investigative and clinical tool for a number of neuropsychiatric disorders. Recently, studies have begun using IMS to probe the effective connectivity among brain areas- how directly perturbing the activity of a given brain area affects the activity of other areas. Such studies hold great promise for developing novel diagnostic and ultimately therapeutic approaches to disorders associated with defective cortico-cortical interactions, such as schizophrenia and Alzheimer's disease. Fully exploiting this potential requires understanding how IMS activates a cortical target and how that activation propagates to distant, anatomically connected sites. The proposed research will focus on two novel, complementary strategies that should expand our understanding of how IMS induced activity propagates through cortical circuits. The first approach is based on developing a comprehensive analysis of TMS action on cortical circuits through large-scale computer modeling. The second approach uses hd-EEG to experimentally measure propagation of cortical responses to TMS and how they vary as a function of wakefulness and sleep. ? ? ?
