MECHANISMS OF ACTION OF TMS-INDUCED PERFORMANCE ENHANCEMENT

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. BACKGROUND AND OBJECTIVE: The long-range purpose of the research program presented here is to study the mechanisms of action by which TMS enhances human performance. It is well-established that, when properly applied, TMS can alter human performance. The mechanisms of action underlying TMS-induced performance enhancements, both acute and chronic, are not well understood. We hypothesize that the transient performance enhancement induced by single-session TMS is mediated by increased neuronal excitability at the stimulated site (Aim 1), but not by increased connectivity or recruitment. For multi-session TMS, we hypothesize that TMS adjuvant treatment will increase rate of learning and maximum performance achieved in comparison to motor practice alone, but that TMS alone will not improve either parameter of motor performance. We also hypothesize that adjuvant TMS to SMA hand will have a greater effect on motor learning than adjuvant TMS to M1 hand. We hypothesize that for both motor practice alone and TMS adjuvant therapy: 1. rate of learning will be correlated with increased connectivity: and 2. increased excitability will not be correlated with either performance variable. RESEARCH PLAN AND METHODS: The proposal will use several non-invasive imaging and electrophysiological techniques. Functional MRI will assess alterations in the volume of cortex recruited during performance. TMS and PET will be used cojointly to detect enhancements in inter-regional connectivity. TMS/PET and electrophysiological measures including motor-evoked potentials (MEP) will be used to detect alterations in neuronal excitability. These proposed experiments will determine the mechanisms of action used by single-session M1-hand TMS enhances motor performance. They will also determine the efficacy of multi-session M1-hand and SMA-hand TMS as adjuvants to practice-induced enhancement of motor performance. Further, this study will compare the mechanisms of action of practice-induced motor learning, TMS-alone and TMS as a adjuvant for enhancement of motor performance. The research program presented here will create a knowledge base which will inform the rationale development of TMS as adjuvant treatment to be used in conjunction with primary therapies in the treatment of neurological, psychiatric and developmental disorders. We predict that the results from the proposed studies will have direct impact on the management of stroke which is the third leading cause of death in the US. Treatment of residual symptoms of stroke is mainly physical and occupational therapy. Applying TMS as an adjunct to physical therapy will reduce morbidity and improve quality of life of stroke patients. The findings from this study will also shed light on the mechanism of action of TMS that is being used as an adjunct therapy in depression.