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Digital archive of theses discussed at the University of Pisa


Thesis etd-05072014-113214

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