Sensory Prediction Under Anesthesia May Offer Clues About Conscious Cognition

A new study has examined how the brain constantly works to make predictions about what's happening in our surroundings during consciousness, and how this process breaks down under general anesthesia.

The study, which examined these effects in monkeys, was published in PNAS.

Brain rhythms and conscious thought

Brain regions involved in cognition are generally found near the front of the brain, whereas sensory regions are found toward the back. These regions use relatively low frequency brain rhythms – called alpha and beta rhythms – to suppress processing of stimuli that have become familiar and mundane in the environment, such as an office radio.

But when we hear a surprising sound, like a fire alarm, these sensory regions instead use faster frequency gamma rhythms to communicate with the higher brain regions. These higher regions process the gamma frequencies to decide what to do – like exiting the building after hearing the fire alarm.

This means the brain is constantly making predictions about what's going on around us to ensure that we can react to the unexpected. A new study from Massachusetts Institute of Technology (MIT) researchers has looked deeper into how this conscious cognition works, as well as how unconsciousness under general anesthesia affects it.

The brain’s responses to “oddballs”

To investigate sensory predictions and conscious cognition, the researchers placed macaque monkeys under general anesthesia using the widely used anesthetic drug propofol.

They measured the “spiking” of electrical signals from hundreds of individual neurons and the coordinated rhythms of their aggregated activity (at alpha/beta and gamma frequencies).

They recorded activity in two areas in the cortex of two animals as they listened to sequences of audible tones. Some sequences would all be the same note, such as AAAAA. But other sequences had some surprises thrown in. The researchers called these surprises either a “local oddball”, such as AAAAB, or a “global oddball”, such as a series of AAAAB sequences followed by a surprise AAAAA.

Prior research has suggested that local oddballs can be spotted by a sensory region in the brain called the temporoparietal area (Tpt); but detecting more complicated global oddballs requires a more complex, higher-order region called the Frontal Eye Fields (FEF).

In the new study, the tone sequences were played to the animals both while awake and under general anesthesia. When awake, the top-down alpha/beta rhythms from FEF carried predictions to the Tpt. The Tpt increased gamma rhythms when an oddball occurred, causing gamma activity to increase in the FEF and the prefrontal cortex.

When the monkeys were anesthetized, however, the researchers found that the sensory regions of their brains retained the capacity to detect simple surprises, but communication with the higher-order cognitive region toward the front of the brain was lost. They observed that spiking activity declined overall during unconsciousness, but Tpt spiking still increased when a local oddball came along, though spiking in FEF didn't follow suit as it does in wakefulness.

This meant that this region was unable to engage in "top-down" sensory regulation, keeping it oblivious to both simple and complex surprises.

"What we are doing here speaks to the nature of consciousness," said Earl K. Miller, co-senior author of the study and Picower Professor in MIT’s Department of Brain and Cognitive Sciences.

"Propofol general anesthesia deactivates the top-down processes that that underlie cognition,” Miller added. “It essentially disconnects communication between the front and back halves of the brain."

Additionally, when a global oddball was presented during wakefulness, software was able to "decode" a representation of that among neurons in FEF and the prefrontal cortex (another cognition-oriented region). Miller and his team could also decode local oddballs in the Tpt. But while under general anesthesia, the decoder could no longer reliably detect representation of local or global oddballs in FEF or the prefrontal cortex.

Comparing rhythms between wakeful and unconscious states revealed stark differences. While awake, oddballs increased gamma activity in both Tpt and FEF, while alpha/beta rhythms decreased. Regular, non-oddball stimulation increased alpha/beta rhythms. But under general anesthesia, the increase in gamma rhythms from a local oddball was even greater in Tpt than when the animal was awake.

Potential opportunities to unravel “the mechanisms of consciousness”

The findings suggest that conscious thought requires synchronized communication between basic sensory and higher-order cognitive regions of the brain using specific brain rhythm frequencies.

"These results are particularly important given the newfound scientific interest in the mechanisms of consciousness, and how consciousness relates to the ability of the brain to form predictions," explained Andre Bastos, co-senior author and assistant professor at Vanderbilt University.

"The brain's ability to predict is dramatically altered during anesthesia,” Bastos added. “It was interesting that the front of the brain, areas associated with cognition, were more strongly diminished in their predictive abilities than sensory areas. This suggests that prefrontal areas help to spark an 'ignition' event that allows sensory information to become conscious. Sensory cortex activation by itself does not lead to conscious perception. These observations help us narrow down possible models for the mechanisms of consciousness."

"In the awake brain, brain waves give short windows of opportunity for neurons to fire optimally – the 'refresh rate' of the brain, so to speak," said Yihan Sophy Xiong, a graduate student in Bastos’ lab and lead author of the study. "This refresh rate helps organize different brain areas to communicate effectively. Anesthesia both slows down the refresh rate, which narrows these time windows for brain areas to talk to each other and makes the refresh rate less effective, so that neurons become more disorganized about when they can fire. When the refresh rate no longer works as intended, our ability to make predictions is weakened."

Overall, the findings suggest that conscious thought requires coordination across the cortex from front to back, say the authors.

"Our results therefore suggest an important role for prefrontal cortex activation, in addition to sensory cortex activation, for conscious perception," the researchers wrote in the study.

Reference: Xiong Y (Sophy), Donoghue JA, Lundqvist M, et al. Propofol-mediated loss of consciousness disrupts predictive routing and local field phase modulation of neural activity. PNAS. 2024;121(42):e2315160121. doi: 10.1073/pnas.2315160121

This article is a rework of a press release issued by MIT. Material has been edited for length and content.