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A revolutionary peek into the noradrenaline system

A revolutionary peek into the noradrenaline system

summary: Researchers have delved into the brain’s noradrenaline system, uncovering insights that could help understand disorders such as ADHD, anxiety, and depression.

The study is notable for its innovative methodology: recording chemical activity in real time using routine clinical electrodes for epilepsy. This approach, the result of 11 years of refinement, now allows scientists to monitor brain activity that was previously hidden from view.

This research represents a major leap forward in understanding the workings of the NA system and broader brain chemistry dynamics.

Key facts:

  1. The team has developed a pioneering method to record real-time chemical activity from standard clinical electrodes, a major breakthrough after more than 11 years of development.
  2. Using this technique, researchers have gained new insights into the noradrenaline system, especially its association with emotional intensity and its importance in conditions such as ADHD.
  3. This methodology can now be applied without the need for exclusive electrodes, relying instead on those already in clinical use.

source: Virginia Tech University

An international team of researchers has provided valuable insights into the brain’s noradrenaline (NA) system, which has been a long-time target of medications to treat attention-deficit/hyperactivity disorder, depression, and anxiety.

Equally important behind the findings is the pioneering methodology developed by the researchers to record real-time chemical activity from standard clinical electrodes that are routinely implanted to monitor epilepsy.

Published online in the magazine Current biology Out Monday (October 23), the research not only provides new insights into brain chemistry, which could have implications for a wide range of medical conditions, but also highlights a remarkable new ability to obtain data from the living human brain.

The electrodes were located in the amygdala, an area of ​​the brain that is deeply intertwined with emotional processing and is strongly influenced by NA signals. Credit: Neuroscience News

“Our group describes the first ‘fast’ neurochemistry recorded by voltammetry from conscious humans,” said Reed Montagu, co-author and lead author of the study, the VTC Vernon Mountcastle Research Professor at Virginia Tech, and director of the Center for the Humanities. Neuroscience Research and Human Neuroimaging Laboratory of the Fralin Biomedical Research Institute at VTC.

“This is a huge step forward, and the systematic approach has been fully applied to humans – after more than 11 years of intensive development.”

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About the method

Potentiometer techniques to obtain real-time electrochemical readouts in rodents and other laboratory models have yielded profound insights into brain function for nearly 30 years, but there has been no clear path to using these techniques in humans, because they require inserting electrodes into the brain. .

“Instead, we focused on what is already being used on patients in medical procedures,” said Montagu, who is also a professor in the Department of Physics in Virginia Tech’s College of Science and in the Department of Psychiatry and Behavioral Medicine at Virginia Tech. Carillion School of Medicine. “When do surgeons actually put a wire into someone’s brain? And can we design a way to take advantage of that?”

The team’s initial methods required inserting exclusive carbon fiber electrodes designed at the Fralin Biomedical Research Institute into awake patients receiving deep brain stimulation surgery to treat Parkinson’s disease or other disorders.

The research team has now demonstrated that electrochemistry can be performed using electrodes that already exist and are in standard clinical use, opening a window into brain activity that has never been seen before.

About the noradrenaline system

The electrodes were located in the amygdala, an area of ​​the brain that is deeply intertwined with emotional processing and is strongly influenced by NA signals.

The NA system originates in a small nucleus in the midbrain known as the locus coeruleus (LC), and has long been a focal point for the development of drugs aimed at treating conditions such as ADHD, depression, and anxiety.

“The LC-NA system is thought to regulate arousal and attention, and is a drug target in multiple clinical conditions, but our understanding of its role in health and disease has been hampered by a lack of direct recordings in humans.” Lead author Dan Pang, associate professor of clinical medicine and Lundbeck Foundation Fellow at Aarhus University, Denmark, and adjunct associate professor at the Fralin Institute for Biomedical Research. “We have addressed this problem.”

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In the study, three patients viewed neutral checkerboard images mixed with emotionally charged images from the International Emotional Imagery Database, shedding light on how the NA system responds to different emotional states.

As expected, NA levels were associated with emotional intensity, especially during encounters with unexpected images, underscoring the importance of the NA system in conditions such as ADHD.

“This is pioneering work that represents a major technical advance in our ability to understand human brain activity,” said Wael Asaad, director of functional neurosurgery and epilepsy at Rhode Island Hospital and vice chair of research in the Department of Neurosurgery at Brown University. He did not participate in the research.

“While it has been possible to record electrical brain activity in humans in a variety of settings for many years, this only gives us half the picture,” Asaad said. “How these neurons communicate with neurotransmitters in real time, over short timescales,” Asaad said. “It was generally more difficult to study.”

“In addition to the scientific value of this study, the techniques it demonstrates will be of tremendous value to a wide range of studies. It represents a major milestone in our efforts to understand the functions of human brain circuits.”

About the team

In previous studies, the group was the first to observe sub-second differences in brain chemicals in awake humans in a pioneering 2011 study.

Scientists later explored how dopamine and serotonin together support human decision-making and sensory processing in a series of publications in 2016, 2018 and 2020 using specially designed electrodes inserted during deep brain stimulation surgery.

About neuroscience research news

author: John Pasteur
source: Virginia Tech University
communication: John Pastor – Virginia Tech
picture: Image credited to Neuroscience News

Original search: Open access.
Noradrenaline tracks emotional modulation of attention in the human amygdala“By Reed Montague et al. Current biology


a summary

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Noradrenaline tracks emotional modulation of attention in the human amygdala

Highlights

  • Sub-second neuromodulation dynamics can be measured using clinical depth electrodes
  • Noradrenaline dynamics in the human amygdala reflect attention and arousal
  • The coupling between noradrenaline and pupil dilation depends on the cognitive state

summary

The noradrenaline (NA) system is one of the major nervous systems in the brain; It originates in a small nucleus in the midbrain, the locus coeruleus (LC), and is widely distributed throughout the brain.

The LC-NA system is thought to regulate arousal and attention and is a drug target in multiple clinical situations. However, our understanding of its role in health and disease is hampered by a lack of direct recordings in humans.

Here, we address this issue by showing that electrochemical estimates of subsecond NA dynamics can be obtained using clinical depth electrodes implanted for epilepsy monitoring.

We made these recordings in the amygdala, a developmentally ancient structure that supports emotional processing and receives dense LC-NA projections, while patients (n = 3) performed an emotional visual oddball task.

The task was designed to induce different cognitive states, with the oddball stimuli comprising emotionally arousing images, which varied in terms of arousal (low vs. high) and valence (negative vs. positive). Consistent with theory, NA estimates tracked affective modulation of attention, with stronger oddball responding in the high arousal condition.

Parallel estimates of pupil dilation, a common behavioral proxy for LC-NA activity, supported the hypothesis that pupil-NA coupling changes with cognitive state, with pupil and NA estimates being positively related to strange stimuli in a high but not low arousal state. -State of excitement.

Our study provides proof of concept that neuromodulator monitoring is now possible using depth electrodes in standard clinical use.