Slow-Wave Activity Saturation and Thalamocortical Isolation During Propofol Anesthesia in Humans

Abstract

The altered state of consciousness produced by general anesthetics is associated with a variety of changes in the brain's electrical activity. Under hyperpolarizing influences such as anesthetic drugs, cortical neurons oscillate at ~1 Hz, which is measurable as slow waves in the electroencephalogram (EEG). We have administered propofol anesthesia to 16 subjects and found that, after they had lost behavioral responsiveness (response to standard sensory stimuli), each individual's EEG slow-wave activity (SWA) rose to saturation and then remained constant despite increasing drug concentrations. We then simultaneously collected functional magnetic resonance imaging and EEG data in 12 of these subjects during propofol administration and sensory stimulation. During the transition to SWA saturation, the thalamocortical system became isolated from sensory stimuli, whereas internal thalamocortical exchange persisted. Rather, an alternative and more fundamental cortical network (which includes the precuneus) responded to all sensory stimulation. We conclude that SWA saturation is a potential individualized indicator of perception loss that could prove useful for monitoring depth of anesthesia and studying altered states of consciousness.

Thalamocortical synchronization during induction and emergence from propofol-induced unconsciousness

“…Previous studies in humans have observed significant increases in slow oscillation power during loss of consciousness (7,12) and have established that these oscillations correspond to ON and OFF states where neurons are periodically silenced (11). Notably, unlike propofol-induced α waves, these slow oscillations are spatially incoherent (7,11), implying a state of "fragmentation" of cortical activity (11).…”

“…Electroencephalogram (EEG) recordings in humans during gradual induction of unconsciousness with propofol show the appearance of frontal β oscillations (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) at the onset of sedation, followed by the appearance of coherent frontal α (8-12 Hz) oscillations (7)(8)(9)(10) and widespread slow (0.1-1 Hz) and δ (1-4 Hz) oscillations (7,11,12) when subjects no longer respond to sensory stimuli. Biophysical models of neuronal dynamics have shown that whereas α and β oscillations can be generated by propofol's actions in cortex alone (13), coherent α oscillations require the participation of both thalamus and cortex (14).…”

Monitoring (un)consciousness: the implications of a new definition of ‘anaesthesia’

“…electrophysiology or brain imaging technologies [17,18]. However, if as discussed above, several different brain states are compatible with 'anaesthesia' (including some that involve degrees of awareness), then it follows that all anaesthetic drugs do not necessarily produce the same pattern of neuronal activity, but potentially induce their own, distinct patterns.…”

“…Other methodologies indicate that brain responses are highly agent-specific [33,34]. Recent work using functional magnetic resonance imaging (fMRI) has suggested that with very slow propofol induction, a state is reached where the thalamocortical region of the brain becomes an 'island' of activity, apparently separated from sensory input, and that this is associated with loss of this region's response to auditory and nociceptive inputs [18]. However, other parts of the brain retained their response to these stimuli.…”

“…In other words, the drugs used to achieve the distinct brain states compatible with anaesthesia must be acting by different fundamental mechanisms. [18]. Or, at higher doses, propofol interacts with nACh receptors in the brain, where at conventional doses it is only weakly active (Table 1), and hence at high dose produces a wider loss of function of those activities mediated by these receptors (e.g.…”