An international team of researchers has made significant strides in understanding the brain’s noradrenaline (NA) system, a critical target for the treatment of conditions such as attention deficit hyperactivity disorder (ADHD), depression, and anxiety. What makes their findings particularly noteworthy is the groundbreaking methodology they developed to record real-time chemical activity within the living human brain.
Published in the journal Current Biology, this research not only enhances our understanding of brain chemistry but also introduces a remarkable new capacity to gather data from conscious individuals. The method devised by this research team represents a monumental step forward in the field of neurochemistry. It allows for the real-time recording of brain chemistry by employing voltammetry techniques and clinical electrodes routinely implanted for epilepsy monitoring.
Dr. Read Montague, co-corresponding and senior author of the study, who holds the VTC Vernon Mountcastle research professorship at Virginia Tech, and serves as the director of the Center for Human Neuroscience Research and the Human Neuroimaging Laboratory of the Fralin Biomedical Research Institute at VTC, emphasized the significance of their achievement.
He stated, “Our group is describing the first ‘fast’ neurochemistry recorded by voltammetry from conscious humans. This is a big step forward, and the methodological approach was implemented completely in humans—after more than 11 years of extensive development.” Voltammetry techniques have been instrumental in shedding light on brain function in rodents and other laboratory models for approximately 30 years.
However, the transition to applying these techniques to humans posed a significant challenge because they require the insertion of electrodes into the brain. To overcome this hurdle, the researchers sought to leverage existing medical procedures. Dr. Montague explained, “Instead, we focused on what’s already being used by patients for medical procedures.
When are surgeons already putting a wire in someone’s brain? And could we design a method to piggyback on that?” The team initially experimented with the insertion of custom carbon-fiber electrodes developed at the Fralin Biomedical Research Institute into patients undergoing deep brain stimulation surgery for conditions such as Parkinson’s disease.
Through this process, they demonstrated that electrochemistry could be conducted with electrodes already in place and in standard clinical use. This breakthrough opened a window to observe previously unrecorded brain activity in living humans. The electrodes were strategically placed in the amygdala, a region of the brain closely associated with emotional processing and profoundly influenced by noradrenaline (NA) signals.
The NA system originates in a small midbrain nucleus known as the locus coeruleus (LC) and has long been a target for medications aimed at addressing conditions like ADHD, depression, and anxiety. However, our understanding of the system’s role in health and disease has been limited by the lack of direct recordings in humans. Co-corresponding and lead author of the study, Dan Bang, an associate professor of clinical medicine and Lundbeck Foundation Fellow at Aarhus University in Denmark, emphasized the significance of their work.
He said, “The LC-NA system is believed to regulate arousal and attention and is a pharmacological target in multiple clinical conditions, but our understanding of its role in health and disease has been impeded by a lack of direct recordings in humans. We addressed this problem.” In their study, three patients were presented with a combination of neutral checkerboard images and emotionally charged images from the International Affective Pictures Database. T
he research shed light on how the NA system responds to different emotional states, revealing a correlation between NA levels and emotional intensity, particularly when confronted with unexpected images. These findings underscore the NA system’s significance in conditions like ADHD.Â
Dr. Wael Asaad, director of Functional and Epilepsy Neurosurgery at Rhode Island Hospital and vice chair for research in the Department of Neurosurgery at Brown University, who was not involved in the research, praised the work, stating, “This is groundbreaking work that represents a significant technical advance in our ability to understand human brain activity.
While it has been possible to record electrical brain activity in humans in a variety of settings for many years, this gives us only half the picture. How those neurons communicate with neurotransmitters in real-time, at short timescales, has generally been much more difficult to study.
In addition to the scientific value of this study, the techniques it demonstrates will be of tremendous value for a broad range of studies. It represents a milestone in our efforts to understand the functions of human brain circuits.” The research team’s breakthrough method for recording real-time brain chemistry in conscious humans opens new avenues for understanding the brain’s chemistry and its implications for various medical conditions.
This groundbreaking approach leverages clinical electrodes already implanted for epilepsy monitoring, providing unprecedented insights into brain activity and the functioning of the noradrenaline system. The significance of this research extends beyond the specific findings, as it represents a pivotal step toward advancing our comprehension of human brain circuits and neurotransmitter interactions.Â
Reference Â
Noradrenaline tracks emotional modulation of attention in human amygdala, Current Biology (2023). DOI: 10.1016/j.cub.2023.09.074. www.cell.com/current-biology/f … 0960-9822(23)01355-6. Â
