PROBING THE BRAIN�S CAPACITY FOR CONSCIOUSNESS THROUGH THE SPATIOTEMPORAL COMPLEXITY OF THE CORTICAL ACTIVITY EVOKED BY TRANSCRANIAL MAGNETIC STIMULATION
Creators: name: GIRARDI CASALI, ADENAUER
Publisher: name: Universit� degli Studi di Milano
Year: 2012

description: Neuroscience faces the challenging task of developing and implementing objective measures of consciousness that can be applied to patients who are unable to interact with their external environment. The standard clinical assessment of these patients relies heavily on the subjective distinction between voluntary and involuntary or reflexive movements and electrophysiological and neuroimaging protocols have been recently developed to improve diagnosis and probe for signs of awareness. However, because the ability to unambiguously infer the capacity for consciousness through these novel techniques is determined ultimately not by consciousness itself but the awareness of a specific stimulus, their use to diagnose consciousness at the single-patient level is challenged by difficulties related to the application and interpretation of results. This thesis addresses the possibility for investigating the brain?s capacity for consciousness, instead of the neural correlates of particular conscious perceptions, following a path that has not yet been explored. General considerations about what constitutes the content of consciousness led us to hypothesize that consciousness depends on the brain?s capacity to sustain complex patterns of causal interactions between different areas of the thalamocortical system. To investigate this hypothesis, we employed the combination of navigated transcranial magnetic stimulation (TMS) and high-density electroencephalography (hd-EEG) and developed a feasible measure of brain complexity, the Perturbational Complexity Index (PCI), that was calculated in healthy subjects during alert wakefulness, sleep and anesthesia; and at the bedside of brain-injured, non-communicating patients, who gradually recovered from coma. PCI is a measure of the spatiotemporal complexity of the cortical activity evoked by TMS and is high only if many regions of the cerebral cortex react to the initial perturbation quickly and in different ways. Remarkably, in a total of 116 TMS sessions collected from 19 healthy subjects and 17 brain-injured patients, we invariably found high PCI values in conditions in which consciousness was clearly present and low PCI values in conditions in which consciousness was unambiguously reduced. This difference was able to reliably discriminate between conscious and unconscious healthy subjects, producing disjoint distributions that were independent of the stimulation parameters, the strength and the extent of the cortical activation. Moreover, PCI was able to detect progressive changes in consciousness, such as those that occur while a subject is falling asleep, and to discriminate between ambiguous consciousness levels (minimally conscious state) in patients suffering from disorders of consciousness from both lower (vegetative state, sleep/anesthesia) and higher (locked-in syndrome, healthy wakefulness) levels of consciousness. The spatiotemporal complexity of the cortical activity evoked by TMS is a single number that can be calculated at the bedside with little a priori information. Because this measure aims at the brain?s capacity for consciousness, instead of behavioral or neural correlations of conscious perception, this technique does not depend on the willingness or ability of the patient to engage in assessment protocols and can be employed bypassing sensory pathways and subcortical structures to directly probe the thalamocortical system. Our results support PCI as an appropriate tool to approximate an objective measure of the neural correlate of consciousness with the potential to assist the diagnosis and prognosis in brain-injured patients and with unique theoretical implications to a science of consciousness.