Plasticity of the cortical representation of finger extensors induced by paired associative stimulation

This dissertation first explored associative plasticity of the human motor cortical representation with the use of noninvasive transcranial magnetic stimulation (TMS) paired with peripheral electrical stimulation. Paired Associative Stimulation (PAS) has grown in popularity because of its potential clinical applications. PAS techniques are used in combination with electromyography (EMG) measurements to study cortical excitability and features of hand movement. This work focuses on a cohesive approach to answer central questions about: the ideal mechanism to facilitate cortical plasticity via PAS, the interaction between the behavior performed and type of stimulation delivered to the targeted cortical network and the effects of PAS, the interaction between interstimulus timing, stimulus timing during movement and the translation of these effects into measurable changes starting from neurophysiological changes and ending up with the behavioral modulation of hand movement. First the role of interstimulus timing and intracortical facilitation on modulation of cortical excitability is explored in the extrinsic hand muscles by showing that PAS can be conditioned by these facilitatory intracortical networks. Using standard indirect approaches utilizing peripheral EMG measures and novel virtual reality (VR) environments, a graded excitability response is shown for the PAS technique and illustrates that interactions of PAS with voluntary movements impacts the degree as well as the state of cortical excitability. Rules governing the interactions of brain stimulation techniques and motor learning are important because brain stimulation techniques can be used to modify and improve neuro motor adaptation and skill learning with great potential for clinical applications such as facilitation of recovery after stroke. PAS provides us with a unique opportunity to study the rules of plasticity at a systems level, which is a combination of synaptic and non-synaptic (metaplastic) changes. Finally, it is shown that changes in cortical excitability may help modulate certain neurophysiological and clinical features of hand function in a pair of patients with chronic stroke in a pilot study. As expected, stroke patients exhibited a smaller degree of excitability increase. It is demonstrated that sessions of intense training with PAS in a VR environment induces significant neuroplastic changes in the sensorimotor cortex. Explicitly, VR based PAS facilitates corticospinal excitability in the ipsilesional sensorimotor cortex. As a result, this dissertation provides a new methodological and technical framework to condition the standard PAS paradigm to engage other intracortical networks. It also shows how PAS can be used to affect motor learning and the role of state of cortical excitation in induction of homeostatic or non-homeostatic plasticity for patients with neurological and neuromuscular impairments for example stroke plus the potential behavioral consequences of PAS in human motor cortex to facilitate functional recovery of hand function