Leo Tomasevic


My thesis focuses on describing novel functional connectivity properties of the sensorimotor system that are of potential interest in the field of brain-machine interface. In particular, I have investigated how the connectivity changes as a consequence of either pathologic conditions or spontaneous fluctuations of the brain's internal state. An ad-hoc electronic device has been developed to implement the appropriate experimental settings. First, the functional communication among sensorimotor primary nodes was investigated in multiple sclerosis patients afflicted by persistent fatigue. I selected this condition, for which there is no effective pharmacological treatment, since existing literature links this type of fatigue to the motor control system. In this study, electroencephalographic (EEG) and electromyographic (EMG) traces were acquired together with the pressure exerted on a bulb during an isometric hand grip. The results showed a higher frequency connection between central and peripheral nervous systems (CMC) and an overcorrection of the exerted movement in fatigued multiple sclerosis patients. In fact, even though any fatigue-dependent brain and muscular oscillatory activity alterations were absent, their connectivity worked at higher frequencies as fatigue increased, explaining 67% of the fatigue scale (MFIS) variance (p=.002). In other terms, the functional communication within the central-peripheral nervous systems, namely involving primary sensorimotor areas, was sensitive to tiny alterations in neural connectivity leading to fatigue, well before the appearance of impairments in single nodes of the network. The second study was about connectivity intended as propagation of information and studied in dependence on spontaneous fluctuations of the sensorimotor system triggered by an external stimulus. Knowledge of the propagation mechanisms and of their changes is essential to extract significant information from single trials. The EEG traces were acquired during transcranial magnetic stimulation (TMS) to yield to a deeper knowledge about the response to an external stimulation while the cortico-spinal system passes through different states. The results showed that spontaneous increases of the excitation of the node originating the transmission within the hand control network gave rise to dynamic recruitment patterns with opposite behaviors, weaker in homotopic and parietal circuits, stronger in frontal ones. As probed by TMS, this behavior indicates that the effective connectivity within bilateral circuits orchestrating hand control are dynamically modulated in time even in resting state. The third investigation assessed the plastic changes in the sensorimotor system after stroke induced by 3 months of robotic rehabilitation in chronic phase. A functional source extraction procedure was applied on the acquired EEG data, enabling the investigation of the functional connectivity between homologous areas in the resting state. The most significant result was that the clinical ameliorations were associated to a ‘normalization’ of the functional connectivity between homologous areas. In fact, the brain connectivity did not necessarily increase or decrease, but it settled within a ‘physiological’ range of connectivity. These studies strengthen our knowledge about the behavioral role of the functional connectivity among neuronal networks’ nodes, which will be essential in future developments of enhanced rehabilitative interventions, including brain-machine interfaces. The presented research also moves the definition of new indices of clinical state evaluation relevant for compensating interventions, a step forward.

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