The Key to a Balanced Brain


In a world where external and internal stimuli can throw our entire body system off balance, how does our brain prevent itself from becoming overly stimulated? The answer lies in our brain’s ability to maintain the balance of neural excitation (E) and inhibition (I), known as the E/I ratio. By regulating the E/I ratio, the brain prevents over-stimulation and under-stimulation.

E/I ratio is an aspect that is continually changing and developing throughout childhood and adolescence. With the aim of drawing meaningful connections between E/I ratio and brain maturation, researchers from the Centre for Sleep and Cognition at the Yong Loo Lin School of Medicine (NUS Medicine) looked at how E/I ratio changes in youths, by studying the MRI brain scans of children, adolescents and young adults. Their research was published in Proceedings of the National Academy of Sciences of the United States of America.

The Importance of Balance

Described as the Yin and Yang of the brain, researchers have found that too much excitation or excessive inhibition can be harmful, leading to a higher risk of developing brain disorders, such as autism, Alzheimer’s disease and schizophrenia. In less severe situations, someone with too much excitation might overthink in social situations, resulting in anxiety.

Indeed, a common drug for reducing anxiety symptoms is Xanax, which increases neural inhibition, thus reducing neural excitation. In more severe scenarios, over-excitation can cause an epileptic seizure. On the opposite end of the spectrum, too much inhibition indicates an absence of brain activity, effectively putting the person in a vegetative state. Therefore, inhibition is needed to balance excitation. Overall, a balanced E/I ratio is important for a well-functioning brain.

Despite E/I’s importance for brain health, it is hard to measure its ratio in the human brain without using invasive techniques. Therefore, the team developed a technique, combining artificial intelligence and biophysical modeling to infer E/I ratios from non-invasive, non-radioactive MRI scans. The team demonstrated the validity of their estimated E/I ratios through an experiment, during which participants ingested anti-anxiety medication (Xanax) or a placebo.

The researchers hypothesized that once Xanax is ingested, inhibition will increase, so the overall E/I ratio will decrease. To test this hypothesis, they scanned healthy individuals on two separate occasions after administering Xanax or a placebo. For some participants, Xanax might be administered in the first session, while for others it might be administered in the second session. All parties involved in this experiment were unaware of whether an MRI session involved the placebo or the anti-anxiety drug. The researchers found that estimated E/I ratio markers were indeed lower after participants had ingested Xanax, compared with the placebo, and thus validating their technique.

E/I Ratio and Healthy Development

The researchers then proceeded to use MRI brain scans to study brain development in a large sample of more than 1000 children, adolescents and young adults. 

 They discovered that E/I ratios decrease with healthy development. To establish the link between E/I ratios and cognitive function, they divided participants, ranging from age 7 to 23, into high and low-performance groups based on their scores on certain cognitive tests such as memory and intelligence. They found that the high performing groups had lower E/I ratios than their peers of the same age, suggesting that cognitive abilities improve as the E/I ratio matures during development.

“Our findings enhance our understanding of brain development and highlight potential avenues for understanding the emergence of psychopathology in youth," said Associated Professor Thomas Yeo, from the NUS College of Design and Engineering and Principal Investigator of this study. "Hopefully, these findings will lead us to figure out which brain circuits get over-excited or over-inhibited easily, or pinpoint certain abnormal brain regions specific to an individual patient. This could shed more light on how medication or brain stimulation can be customized according to individuals, that would shape the course of treatment of brain disorders in the long run.” 

StepUp Note

This research reminds us how our brains are always balancing excitation (increasing stimulation) and inhibition (decreasing stimulation).  It shows that our most effective performance occurs when we have the most balance (the smallest amount of difference) between brain excitation and brain inhibition when we are actively involved in learning.  StepUp exercises help children create active movement without becoming overactive or too excited. 

Note by Nancy W Rowe, MS, CCC/A

Reposted from National University of Singapore



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