Cortical Sensorimotor Mechanisms for Neural Control of Skilled Manipulation

abstract: The human hand is a complex biological system. Humans have evolved a unique ability to use the hand for a wide range of tasks, including activities of daily living such as successfully grasping and manipulating objects, i.e., lifting a cup of coffee without spilling. Despite the ubiquitous nature of hand use in everyday activities involving object manipulations, there is currently an incomplete understanding of the cortical sensorimotor mechanisms underlying this important behavior. One critical aspect of natural object grasping is the coordination of where the fingers make contact with an object and how much force is applied following contact. Such force-to-position modulation is critical for successful manipulation. However, the neural mechanisms underlying these motor processes remain less understood, as previous experiments have utilized protocols with fixed contact points which likely rely on different neural mechanisms from those involved in grasping at unconstrained contacts. To address this gap in the motor neuroscience field, transcranial magnetic stimulation (TMS) and electroencephalography (EEG) were used to investigate the role of primary motor cortex (M1), as well as other important cortical regions in the grasping network, during the planning and execution of object grasping and manipulation. The results of virtual lesions induced by TMS and EEG revealed grasp context-specific cortical mechanisms underlying digit force-to-position coordination, as well as the spatial and temporal dynamics of cortical activity during planning and execution. Together, the present findings provide the foundation for a novel framework accounting for how the central nervous system controls dexterous manipulation. This new knowledge can potentially benefit research in neuroprosthetics and improve the efficacy of neurorehabilitation techniques for patients affected by sensorimotor impairments.Dissertation/ThesisDoctoral Dissertation Neuroscience 201

Inducing and detecting neuroplasticity: insights from TMS-EEG and RS-EEG

Damage to the brain, such as stroke, can lead to severe cognitive and motor disabilities in the affected individuals. Neuroplasticity refers to the intrinsic capacities of the brain to reorganize cortical networks at different spatial and temporal scales, potentially resulting in spontaneous recovery of function after such damage. A better understanding about the measurement and the support of those neuroplastic processes is an important prerequisite to improve therapeutic interventions and ultimately the outcome of the recovery process. This thesis comprises the results of two studies that investigated the ability to induce neuroplasticity using repetitive transcranial magnetic stimulation (TMS) and the ability to measure neuroplasticity using a combination of TMS and electroencephalography (EEG) or resting state (RS)-EEG measurements in cohorts of young and healthy individuals. The first study utilized continuous theta burst stimulation (cTBS) to induce neuroplasticity targeting the primary motor cortex. After-effects on cortical and corticospinal excitability were quantified in terms of TMS-evoked potentials (TEP) and motor-evoked potentials. The study demonstrated that cTBS-induced neuroplasticity leads to significant local and remote changes in cortical excitability that were measurable with TMS-EEG. The modulation of the N45 peak of the TEP suggests that the neuroplastic effects of cTBS are mediated by changes in gamma-aminobutyric acid (GABA)A-mediated cortical inhibition. The second study investigated the suitability of RS-EEG for individualized longitudinal tracking of neuroplastic processes. In this scenario, it is important to distinguish whether observed changes in activity between measurements are attributable to incidental variations in cognitive state or truly related to processes of neuroplastic reorganization. A classification algorithm was adopted to extract individual-specific signatures from EEG oscillations at rest. These signatures were very robust across multiple days and detectable across different cognitive states, indicating a close relationship to the underlying neurophysiology. Using these individual activity pattern, it was possible to distinguish inter-day variations in cognitive state from simulated changes in the neurophysiological organization of the brain with very high accuracy. The current thesis therefore provides important support for the usability of TMS-EEG and RS-EEG as methodological approaches to measure neuroplasticity within healthy and young individuals. Furthermore, cTBS may be used as a strategy to interact with abnormally elevated or reduced levels of GABAA-mediated cortical inhibition. Further studies are required to validate the significance of the current findings and to test whether they can be translated into clinical practice, especially into the realms of stroke recovery

INFLUENCE OF ELECTROMAGNETIC STIMULATION ON NEOCORTICAL NEURONS AND NETWORK : A SIMULATION BASED STUDY

Ph.DDOCTOR OF PHILOSOPH