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Tesi etd-05072014-113214

Thesis type
Tesi di dottorato di ricerca
Wake-like activities and electrical silences in the human sleeping brain: functional roles and spatio-temporal dynamics in the thalamo-cortical network
Settore scientifico disciplinare
Corso di studi
tutor Dott. Gemignani, Angelo
Parole chiave
  • signal processing
  • K-complex
  • dynamics
  • brain
  • bistability
  • sleep
  • Slow Oscillation
Data inizio appello
Riassunto analitico
As pointed out by several papers, the less than one hertz oscillations or Sleep<br>Slow Oscillations (SSOs) are the electrophysiological stigmata of the mammalian<br>sleep. This cellular behavior, mainly involving thalamus and cortex, consisted of<br>hyperpolarized phases (lasting 500 msec, down states) followed by depolarized<br>ones (lasting 500 msec, up states). The electrical silence during down states, on<br>the one hand, prevents any synaptic and network activity and on the other hand,<br>creates the ionic conditions for a rebound of neural discharge (huge synaptic and<br>network activity during up state). The presence of down states clearly marks the<br>phenomenon of cortical bistability, which in turn reflects a deep hyperpolarization<br>sustained by the opening of different K+-channels. According to the Integrated<br>Information Theory of Giulio Tononi, down states prevent the emergence of largescale<br>neural integrations and thus induce the break down of functional connectivity.<br>This allows a functional segregation of independent cortical modules, which<br>represents the condicio sine qua non for sleep unconsciousness. Other functional<br>roles endowed in the SSO are memory consolidation and synaptic downscaling.<br>The aim of this thesis is to investigate, via EEG, in human spontaneous and evoked<br>SSOs: (i) the relationships between wake-like activities and electrical silence; (ii)<br>the role of the thalamus; (iii) the quenching of sensory processing and thus of<br>consciousness. Regarding point (i) we have found a positive bump preceding<br>the down state characterized by an increase of high frequency activities. The<br>presence of this high frequency activity before down state suggests a cortical<br>ignition mechanism for the spontaneous SSO. As far as point (ii) is concerned, we<br>have investigated how the thalamus influences the cortical expression of the SSOs.<br>To this aim, we have studied SSO features in a case of Fatal Familial Insomnia (FFI)<br>with a selective thalamic neurodegeneration of nuclei mainly involved in spindle<br>generation. In the FFI patient, we have found a reduction of SSO event rate, some<br>morphological alterations of SSO structure, and a significant reduction in grouping<br>high frequency activity during up state. As for point (iii), we studied K-Complexes<br>(KCs), namely SSOs evoked by sensory stimulations. The main results of this<br>study are: a positive wave (P200) precedes the down state (N550); the topology of<br>P200 latency depends on the sensory modality of stimulation (acoustic, tactile and<br>visual) with earliest waves in the related primary sensory areas; the P200 travels as<br>a cortical excitation inducing N550 and P900 (up state) in associative fronto-central<br>areas; when KCs are not evoked the P200-like excitations have lower amplitude<br>compared to evoked KC P200; the down state latency topology is affected by the<br>proneness to bistability, i.e. the amount of K+-channel that favor a synchronized<br>falling into down state. As a whole the results of the thesis indicate that Slow<br>Wave Sleep (SWS) is not a mere quiescent state but rather an active state in which<br>changes of neural dynamics allow a well orchestrated interplay of unconscious<br>behavior and memory consolidation. The final consequence is the maintenance of<br>homeostasis. The SSO is the cellular phenomenon capable to coalesce wake-like<br>activities and electrical silences, synthesizing at microscopic level the macroscopic<br>complexity of SWS. This thesis allowed exploring thalamo-cortical dynamics by<br>studying spontaneous and evoked SSOs. In synthesis the human-environment<br>interaction (including visceral stimuli) during sleep overlaps that of wakefulness,<br>since thalamus and cortical areas devoted to the first step of sensory processing<br>are identical. The difference between wake and sleep is only sustained by the<br>down state. In conclusion the study of SSO clarifies many issues linked to sleep<br>and in particular to the real efficacy of a good sleep. This opens the door to the<br>application of SSO study in different preclinical or clinical conditions.