We have discovered that the the fast repetitive presentation of a visual checkerboard (a photic """"""""tetanus"""""""") leads to a persistent enhancement of early components of the visual evoked potential in normal humans. This lasting enhancement of the visual evoked potential is thought to be a form of human long-term potentiation (LTP) - the neuronal process underlying learning and memory. The potentiated response is largest in the hemisphere contralateral to the tetanized visual hemifield, and is limited to one component of the visual evoked response. Exposure to a photic tetanus also results in improved performance in a behavioral task. This study will be the first to investigate non-invasively the parameters and possible mechanisms of a form of LTP in humans. The goal of this proposal is to: 1) determine the optimal stimulus parameters of this potentiation, and 2) determine if this potentiated response obeys the established rules and cellular mechanisms of LTP and long-term depression (LTD) and 3) study its behavioral relevance. The study involves three research sites. The overall design, coordination, and animal studies will be by Dr. Teyler, at the University of Idaho, the co-discoverer of """"""""human LTP"""""""". The optimal stimulus parameters and """"""""rules testing"""""""" will be by Drs. Kirk and Hamm at the University of Auckland, New Zealand. The Yale site, led by Drs. Cavus and Krystal, will test whether the potentiation of this visual evoked response in humans is dependent on NMDA receptor activity. This study will provide us for the first time with tools to assess cortical plasticity noninvasively in humans. Such ability could have future applications in better understanding LTP and in the assessment of disorders that are thought to involve impairment in the cortical plasticity, such as Alzheimer's disease, Depression and Schizophrenia.
