BREAKDOWN OF CAUSALITY AND CORTICAL DOWNSTATE WITHIN THE SLEEPING BRAIN
Creators: name: PIGORINI, ANDREA
Publisher: name: Universit� degli Studi di Milano
Year: 2014

description: Theoretically, consciousness depends on the brain?s ability to engage in complex activity patterns that are, at once, distributed among interacting cortical areas (integrated) and differentiated in space and time (information-rich). In a recent series of experiments the electroencephalographic response to a direct cortical stimulation in humans was recorded during wakefulness and non-rapid eyes movement sleep (NREM) by means of a combination of transcranial magnetic stimulation (TMS) and high-density electroencephalogram (hd-EEG). TMS/hd-EEG measurements showed that, while during wakefulness the brain is able to sustain long-range specific patterns of activation, during NREM sleep, when consciousness fades, this ability is lost: the thalamocortical system, despite being active and reactive, either breaks down in causally independent modules (producing a local slow wave), or it bursts into an explosive and non-specific response (producing a global EEG slow wave). We hypothesize that, like spontaneous sleep slow waves, the slow waves triggered by TMS during deep sleep are due to bistability between periods of hyperpolarized down-state in cortical neurons, and periods of activation (up-state). In this condition, the inescapable occurrence of a silent, down-state after an initial activation could impair the ability of thalamocortical circuits to sustain long-range, differentiated patterns of activation, a theoretical requisite for consciousness. According to animal experiments the extracellular signature of the downstate is a transient suppression of high frequency (&lt;20Hz) power in the local field potential (LFP). However, detecting this feature in human EEG recording is challenging because of the resistive properties of the skull, muscular artifacts and the high distance of scalp electrodes from deeper cortical sources making difficult to observe a modulation of gamma activity. These drawbacks can nevertheless be overcome by using a perturbational approach similar to TMS and simultaneous intracranial recordings. To this aim, in the present thesis we employ intracerebral electrical stimulation (ICS) and simultaneous stereotactic electroencephalographic (stereo-EEG) recordings. Specifically, we recorded cortico-cortical evoked potentials (CCEPs) during wakefulness and NREM sleep and analyzed them by means of time-frequency analysis and phase locking measures both within (phase-locking factor, PLF) and across (phase-locking value, PLV) recording sites. We observed that, while during wakefulness ICS triggers a widespread pattern of sustained causal effects (phase-locked activity), during NREM sleep the same initial activation induces a cortical downstate in its cortical targets ? as reflected by a clear-cut suppression of high frequency (&gt;20Hz) oscillations ? that is followed by a loss of both PLF and PLV, in spite of restored levels of neuronal activity. These results point to bistability as the underlying critical mechanism that prevents the emergence of complex interactions in human thalamocortical networks when consciousness is lost during NREM sleep. This finding is particularly relevant because a similar mechanism may play a role in other conditions where loss of consciousness is paralleled by the appearance of spontaneous (or TMS evoked) slow waves such as some kind of anesthesia and in brain injured subjects.