Sviluppo di un sistema per la misura della connettività cortico-corticale nei disturbi della coscienza
Progetto How do we evaluate the potential of a brain to sustain conscious experience if the subject is unable to respond and does not manifest spontaneous intentional behaviors? What should we measure to objectively assess the direct impact on the brain of a particular neurorehabilitation strategy? Medical advances are saving an increasing number of brain-injured people from immediate death. Many survivors face long-term cognitive impairment, fall into a minimally conscious state or into a persistent vegetative state. This ¿silent epidemic¿ of chronic disorders of consciousness exposes a scientific chasm. We know that awareness and cognitive functions do not necessarily correlate with observable behavior. On the other hand, we know that they depend critically on the intrinsic ability of distributed regions of the thalamocortical system to interact causally with each other (effective connectivity). Yet, we don¿t have a practical way to measure, directly and reliably, effective connectivity in the human brain. Using a combination of transcranial magnetic stimulation (TMS) and high-density electroencephalography (hd-EEG) we plan to develop a bedside ¿perturb-and-measure¿ approach to directly probe the internal dialogue of the thalamocortical system. Our proposal is articulated in two steps: (1) From theory to measurement: to identify and apply ideal measures of excitability, effective connectivity and plasticity to the human brain in a controlled experimental set-up using a portable TMS/hd-EEG system. During this first stage, measurements will be carried out in the lab. Normative data will be collected in a large set of control subjects in order to define the normal patterns of activation after TMS on different cortical areas, their specificity and reproducibility within and across subjects. A subset of patients with focal brain lesions (thalamic and cortical) will be invited to the lab to adjust the experimental parameters to the pathologic brain and to identify the changes in cortical excitability and effective connectivity that are associated with the impairment of specific modules of the thalamocortical system. (2) From the laboratory to the bedside: to develop reliable and fast TMS/hd-EEG protocols to measure cortical excitability and effective connectivity at the bedside of brain-injured patients and to guide/promote neurorehabilitation. During this phase TMS/hd-EEG protocols will be carried out at the University Hospital in Milan as well as in selected stroke-units and neurorehabilitation centers in Europe. Directly probing the internal dialogue of the thalamocortical system, independently on the subject¿s behavior, may provide invaluable information in patients with disorders of consciousness. An objective measure of thalamocortical excitability and connectivity will foster evidence-based neurorehabilitation in a vast population of brain-injured subjects.