title: Cortical mechanisms of loss of consciousness: insight from TMS/EEG studies.
abstract: In a recent series of experiments we recorded the electroencephalogram (EEG) response to a direct cortical stimulation in humans during wakefulness, NREM sleep, REM sleep and anesthesia by means of a combination of transcranial magnetic stimulation (TMS) and high-density EEG (hd-EEG). TMS/hd-EEG measurements showed that, while during wakefulness and REM sleep the brain is able to sustain long-range specific patterns of activation, during NREM sleep and Midazolam-induced anesthesia, when consciousness fades, this ability is lot: 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 sleep and anaesthesia are due to bistability between upand down-states in thalamocortical circuits. In this condition, the inescapable occurrence of a silent, down state after an initial activation impairs the ability of thalamocortical circuits to sustain long-range, differentiated patterns of activation, a theoretical requisite for consciousness. According to animal experiments and computer simulations, thalamocortical bistability may result from increased K-currents, from alterations of the balance between excitation and inhibition and from partial cortical de-afferentation. We hypothesize that these factor may play an important role in determining loss, and recovery, of consciousness also in brain-injured subjects. If this is the case, some types of brain lesions may impair information transmission, above and beyond the associated anatomical disconnection, by inducing bistability in portions of the thalamocortical system that are otherwise healthy.
authors.affiliation: Department of Biomedical and Clinical Scineces, University of Milan, Italy. marcello.massimini@gmail.com
authors.forename: M
authors.initials: M
authors.lastname: Massimini
authors.forename: F
authors.initials: F
authors.lastname: Ferrarelli
authors.forename: S
authors.initials: S
authors.lastname: Sarasso
authors.forename: G
authors.initials: G
authors.lastname: Tononi
mesh_terms: D058256:Brain Waves / Q000502:physiology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology*; D004569:Electroencephalography; D006801:Humans; D012890:Sleep / Q000502:physiology; D050781:Transcranial Magnetic Stimulation; D014474:Unconsciousness / Q000473:pathology*; D014851:Wakefulness / Q000502:physiology