Brain high-order interactions of the high brain

The timeless mystery of consciousness and its modern exploration
Consciousness has long been one of the most profound mysteries of human existence. From philosophers to neuroscientists, the quest to understand what it means to experience existence has captivated minds for centuries. Today, this ancient enigma is being tackled through the lens of modern neuroscience, thanks to synergistic interactions between theoretical and technical advancements. These interactions offer us unprecedented insights into the brain’s complex workings, shedding light on how consciousness emerges, how it can be altered, and how to turn it off.
The challenge of tracking consciousness: an open question in neuroscience
Despite these unprecedented advances, the challenge of accurately tracking consciousness remains. Neuroscientists have made significant strides, but understanding the link between conscious experience and brain activity still needs to be resolved. One promising avenue of research points to the complexity of brain activity as a marker for changes in consciousness. But what exactly does “complexity” mean in this context, and why is it so important?
Complexity and high-order interactions: the symphony of the brain
In neuroscience, complexity refers to the brain’s ability to coordinate multiple processes while maintaining distinct functionalities. Imagine an orchestra where each musician plays a different part, yet together they create a harmonious piece of music. This is analogous to how various regions of the brain work together. Sometimes, groups of neurons (like strings in an orchestra) play similar roles, which can be considered redundancy. At other times or even simultaneously, distinct groups (like strings and percussion) work together to create something new, a process known as synergy. These high-order interactions—where more than just pairs of elements are involved—are crucial for understanding the brain’s complex behavior, as the brain comprises billions of neurons and trillions of connections. When listening to this substantial neuronal symphony, focusing only on the activity of pairs of neurons or brain regions seems to be an unfair reduction. New theories and methods are currently being developed to honor and embrace the vast complexity of our brain. In particular, recent advancements in information theory have enabled researchers to measure these high-order interactions in the brain, providing a window into the relationship between the brain orchestra and the enormous repertoire of conscious experiences. 
Ketamine and altered consciousness: a new frontier in mental health
Ketamine, a drug initially used as an anesthetic, is now recognized for its potent and fast-acting effects in treating depression. It doesn’t just change mood—it also profoundly affects consciousness, making it a valuable tool for both mental health treatment and investigating consciousness. To better understand and make the most of ketamine’s potential, we need reliable ways to track how it changes brain activity. By studying these changes, especially those related to the brain’s high-order interactions, we can learn more about how ketamine works and what it reveals about the nature of consciousness and mental health.
Portable EEG and accessibility
Traditionally, studying changes in consciousness due to drugs like ketamine required patients to visit specialized centers where their brain activity could be monitored in a controlled environment. But what if we could track these changes in real time, even as patients go about their daily lives? Portable EEG technology holds the promise to make this a reality, offering a noninvasive, accessible way to monitor brain activity outside of the lab.
This technology has the potential to revolutionize how we study and treat psychiatric disorders. For patients with reduced mobility or those living far from treatment centers, portable EEG could provide unprecedented access to care, enabling continuous monitoring of their mental health from the comfort of their homes.
High-order interaction in the high brain: tracking consciousness alterations with portable EEG

Overview of experimental design and data analysis.A. Subjects participated in a double-blind crossover design using portable EEG, capturing both resting states and task-based recordings (namely, a gamified oddball paradigm inducing a typical mismatch negativity). In randomized sessions, participants received both ketamine and saline infusions.B. Analysis of high-order interactions (HOI) entailed measurements of total correlation (TC) and dual total correlation (DTC), O-information and S-information (see Methods). C. Feature selection across the two designs (rest and task) was employed to pinpoint the primary differences between the ketamine and saline conditions.

Our study explored how ketamine affects brain high-order interactions both at rest and during a simple cognitive task using portable EEG. We found that ketamine induced an increase in the redundancy of brain activity. These changes could serve as markers for shifts in consciousness and specific altered experiences, like feelings of derealization (a sense of detachment from reality), as reported in psychometric tests. Interestingly, the effects were more pronounced when participants were at rest rather than engaged in a task, possibly because performing a cognitive task during the ketamine experience helps ground their experience, reducing the impact of the drug.
The future of consciousness research and treatment
Our study underscores the potential of using high-order interactions to track changes in consciousness, particularly in the context of psychoactive drugs like ketamine. As portable EEG technology continues to advance, we foresee a future where monitoring mental health becomes more accessible and personalized, allowing for real-time tracking of psychiatric treatments in everyday settings.
As we continue to explore the mysteries of consciousness, tools like these will be crucial in bridging the gap between the laboratory and the real world. They will lead to a better understanding of consciousness in ecological settings and, ultimately, to better outcomes for patients.