Skip to content

Cortical Network Engagement Differs During Different States of Un/consciousness in Humans

Key findings

  • This study investigated the electrophysiological response of the human brain to brief electrical stimulation during three states: conscious, arousable unconscious (non-REM sleep), and unarousable unconscious (general anesthesia)
  • In the two unconscious states, compared with the awake state, overall complexity and connectivity decreased when consciousness was lost, responses were fewer and smaller, and variability was larger
  • However, the responses were not identical for the two unconscious states: during sleep, changes were mostly homogeneous across brain regions, while during anesthesia the prefrontal cortex was the most disrupted
  • These results are a step toward a better understanding of the neural correlates of lack of arousability and unconsciousness, and they have substantial therapeutic implications considering the increasing clinical use of deep brain stimulation

Despite decades of research, there are more controversies than agreements about what happens in the human brain during unconsciousness. In particular, there's no consensus on which brain regions are necessary for consciousness and arousability.

Rina Zelmann, PhD, an instructor in the Massachusetts General Hospital Center for Neurotechnology and Neurorecovery, Sydney S. Cash, MD, PhD, co-director of the Center, and colleagues recently compared the intra-individual physiology of the conscious, awake state with two of the most obvious non-pathological unconscious states: natural sleep and general anesthesia.

In Neuron, they provide direct evidence of increased variability in neural responses, reduced information transfer and reduced complexity during unconsciousness compared with the awake state. In addition, there were region-specific differences between arousable unconsciousness (sleep) and non-arousable unconsciousness (anesthesia).


To investigate the sensitivity of brain networks to un/conscious states in a safe, controlled way, the researchers examined responses to very brief electrical stimulation.

The study participants were 20 patients with epilepsy who had electrodes implanted to identify the focus of their seizures. After the epileptogenic network was known and could be avoided, the team recorded intracranial EEGs while they delivered 0.2-millisecond pulses of electricity:

  • In the epilepsy monitoring unit (EMU) while participants were awake (n=17)
  • In the EMU during non-REM sleep at the beginning of the night (n=13)
  • In the operating room (OR) while awake before electrode explantation (n=16)
  • In the OR after propofol-induced general anesthesia (n=14)

Brain responses were compared while awake vs. sleep in the EMU (n=13), awake vs. anesthetized in the OR (n=14) and awake in different environments (n=13). Seven participants received electrical stimulation during all four states.

Key Results

In the two unconscious states, compared with the awake state, overall complexity and connectivity decreased when consciousness was lost, responses were fewer and smaller and variability was larger.

However, the differences were more pronounced during anesthesia than sleep, with a relative increase in response variability and a decrease in information transfer capabilities during anesthesia.

During sleep and anesthesia, relative complexity and connectivity measures were similarly reduced in posterior regions, but during anesthesia, the reduction was significantly more pronounced in the prefrontal cortex (PFC). Correspondingly, variability increased uniformly during sleep, but during anesthesia, variability was higher in the PFC.


Non-invasive and animal studies have suggested unconsciousness under anesthesia might not be a singular phenomenon but rather involve several distinct shifts that disrupt both the neural correlates of consciousness and those of arousability. The findings from this study expand on that differentiation, as propofol prevented the PFC from activating, which appears necessary for arousal.

Recognizing the brain's distinct responses to stimulation during different states also has direct therapeutic implications. Deep brain stimulation is increasingly common for movement disorders, epilepsy and psychiatric disorders, and the electrical current is usually adjusted during the awake state. Future research seems important to examine how neuromodulation changes the brain during sleep, too.

Learn more about research in the Department of Neurosurgery

Learn more about research in the Department of Neurology

Related topics


For the first time, researchers have direct evidence of learning-related replay in the human brain during sleep. A recent study using implanted multi-electrode arrays in two participants found identical neural firing patterns during game-play awake periods and sleep periods.


At Massachusetts General Hospital, Brian Edlow, MD, is exploring the use of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) for the accurate evaluation of 'covert consciousness,' consciousness that cannot be assessed using conventional bedside behavioral examination.