At the molecular and cellular levels, ketamine and dexmedetomidine operate quite differently; however, in surgical settings, both effectively anesthetize patients. A groundbreaking study conducted by neuroscientists at The Picower Institute for Learning and Memory at MIT reveals how these distinct drugs achieve this common outcome, potentially identifying a measurable signature of unconsciousness to enhance anesthesiology practices.
The researchers discovered a shared characteristic: the way these drugs influence brain waves generated by collective neuron activity. When brain waves are synchronized, meaning their peaks and troughs align, it enables local neuron networks in the cortex to communicate effectively, fostering conscious functions like attention and reasoning. Conversely, when these brain waves fall out of sync, communication deteriorates, resulting in unconsciousness. This insight is articulated by Picower Professor Earl K. Miller, senior author of the recent study published in Cell Reports.
Led by graduate student Alexandra Bardon, the study not only deepens the scientific understanding of the consciousness-unconsciousness divide but also offers anesthesiologists a unified measure to maintain patients at the proper level of consciousness during surgical procedures.
“Observing the shifted phase in our recordings makes it challenging to distinguish the drug used,” states Miller, who is also a faculty member in MIT’s Department of Brain and Cognitive Sciences. “This finding is significant for medical practices. Moreover, if unconsciousness has a universal signature, it may unveil the mechanisms underpinning consciousness itself.”
If additional anesthetic drugs are shown to influence phase alignment similarly, anesthesiologists may rely on brain wave phase synchronization as a dependable marker of unconsciousness while adjusting dosages. This knowledge could pave the way for developing closed-loop systems that can assist anesthesiologists by regulating drug doses based on real-time brain wave metrics indicating the patient’s level of unconsciousness.
Miller is collaborating with co-author Emery N. Brown, an esteemed anesthesiologist and professor at the Picower Institute, to advance such systems. In a recent clinical trial conducted with colleagues in Japan, Brown demonstrated that using EEG to monitor brain wave activity allowed anesthesiologists to safely reduce sevoflurane doses during surgery in young children, leading to improved postoperative outcomes.
Phase Findings
Traditionally, the phase aspect of brain waves hasn’t garnered much attention in anesthesia research. However, in this study, Bardon, Brown, and Miller focused on it by anesthetizing two animals. Following the onset of unconsciousness, their measurements revealed a significant increase in “phase locking,” particularly at lower frequencies. This phase locking indicates that the relative phase differences remained more stable. What intrigued the researchers was the misalignment that emerged: within each hemisphere, the brain wave phases between the dorsolateral and ventrolateral regions of the prefrontal cortex became misaligned, regardless of the anesthetic used.
Interestingly, the alignment of brain wave phases across hemispheres improved, indicating a substantial departure from conscious states, where typically, brain hemispheres do not synchronize efficiently. This suggests that distinct phase alignment changes are a correlate of unconsciousness compared to wakefulness.
The Bardon and Miller team wrote in Cell Reports, “The increase in interhemispheric alignment of activity by anesthetics appears to reverse the typical pattern observed in a conscious, cognitively engaged brain.”
Determined by Distance
Distance is a pivotal factor influencing phase alignment adjustments. Even across the mere 2.5 millimeters of a single electrode array, researchers noted low-frequency waves shifted by 20-30 degrees out of alignment. When considering the 20-millimeter gap between electrode arrays in the upper and lower regions of a single hemisphere, this represents an approximate 180-degree phase shift—a complete offset of brain waves.
This distance-dependent phenomenon aligns with the concept of waves traversing the cortex. In a prior 2022 study, Miller and Brown’s labs illustrated that the anesthetic propofol generates a potent low-frequency traveling wave across the cortex, overwhelming other wave frequencies. The new findings open numerous avenues for further research, prompting questions like: Does propofol exhibit this unique phase alignment signature? What implications do traveling waves have in this context? Additionally, given that sleep is characterized by increased power in slow wave frequencies, how might phase alignment distinguish between sleep and anesthesia-induced unconsciousness?
Alongside Bardon, Brown, and Miller, contributors to this study include Jesus Ballesteros, Scott Brincat, Jefferson Roy, Meredith Mahnke, and Yumiko Ishizawa. Support for the research came from the U.S. Department of Energy, the National Institutes of Health, the Simons Center for the Social Brain, the Freedom Together Foundation, and the Picower Institute.
Photo credit & article inspired by: Massachusetts Institute of Technology
