This is an application for a Mid-Career Investigator Patient-Oriented Research-Career-Award. A five-year learning, research, and mentorship program focused on the use of transcranial magnetic stimulation (TMS) as a probe for cortical excitatory and inhibitory processes is outlined. A number of pilot projects probing cortical excitability in both health and in psychopathological conditions will be followed by more definitive studies guided by the generated pilot data. The applicant is capitalizing on his extensive clinical training in Neurology, Psychiatry and Clinical Neurophysiology in linking TMS and electroencephalographic (EEG) measures of cortical activity. The five-year career-plan has two overarching goals. The first goal is to allow the time necessary for the applicant to become thoroughly familiar with magnetic theory, limitations and advantages of magnetic brain stimulation, and the methodology of assessing brain excitability. The second goal is to develop EEG based measures of cortical excitability to be examined in conjuntion with TMS measures. This effort should lead to developing methodology capable of defining cortical excitation and inhibition in non-motor cortical regions. A limited research study is included as part of the career award application. This study is a continuation of our initial efforts in examining cortical excitability in cocaine-dependent subjects. Fifteen subjects will be included in three age and gender-matched groups. Two groups will be comprised of cocaine-dependent subjects. One group will have no history of developing frank psychotic symptoms and the other will have a history of developing such symptoms. A normal control group will be included. The TMS measured motor threshold and length of the TMS induced silent periods will be compared between the three groups.
