A New Study Contributes to the ‘Silence’ on the Brain Network Finally being Broken

Studying the brain’s complex network of processes not only improves our understanding of how it works, but it also opens up new pathways for potential treatments for brain illnesses. However, connecting the brain network to actual behavior is difficult.

In a new study, researchers discovered that genetically designed medications may be used to target the suppression or “silencing” of specific parts of monkey brains, revealing alterations to their operational network and the behavioral impacts that result.

For years, scientists have studied the human brain, yet they have only scratched the surface of what this intricate organ has to offer.

The advent of functional magnetic resonance imaging (fMRI) transformed the face of neuroscience in 1990. (fMRI). The premise behind functional magnetic resonance imaging (fMRI) is that when a certain part of the brain is activated, it experiences an increase in blood flow.

This method has also been used to investigate neurological activity in the brains of a variety of animals and people, yielding useful information on cognitive and movement-based activities.

The use of functional magnetic resonance imaging (fMRI) has also demonstrated that “stimulating” one section of the brain has an effect on other physically or functionally related regions. One of the most important concerns in neuroscience is figuring out how to address this “network” of functions in the brain.

In a recent study, Toshiyuki Hirabayashi and Takafumi Minamimoto of the National Institutes for Quantum Science and Technology (QST) demonstrated that gene-targeting drugs in macaque monkeys can cause multifaceted behavioral effects via altered operation of relevant brain networks, paving the way for a better understanding of the network of operations that underpins higher functions in primates (monkeys, humans, etc.).

“Our technique will allow us to study how disturbances to the functional brain network lead to certain symptoms. This will help us to work backward to clarify the network mechanisms behind brain disorders with similar symptoms, thus leading to new treatments,” reveals Dr. Toshiyuki Hirabayashi, principal researcher at QST, who led the study.

Electrical stimulation or the injection of a psychoactive chemical called muscimol are two common methods for activating or suppressing parts of the brain, but due to their specificity, recent research has concentrated on genetic targeting techniques. These techniques, known as chemogenetics, rely on artificial medications that are engineered to bind to genetically produced artificial proteins known as “receptors.”

The medications bind to the receptors, affecting physiological and neurological processes in the brain, spinal cord, and other regions of the body where the receptors are expressed genetically. When chemogenetics and fMRI are combined, non-invasive observation of network-level changes caused by local activity modification is possible.

However, unlike the present study, previous chemogenetic fMRI research has focused on a resting state, which may not yield the most relevant data for studying task- or sensory-related activities.

The researchers looked at the impact of fMRI guided chemogenetics on hand-grasping in macaques as part of their research on functional brain networks. To do so, they studied the part of the brain that controls precise finger movement before silencing (suppressing) it for one hand with a “designer receptor exclusively activated by designer drugs” (DREADD).

Our technique will allow us to study how disturbances to the functional brain network lead to certain symptoms. This will help us to work backward to clarify the network mechanisms behind brain disorders with similar symptoms, thus leading to new treatments.

Dr. Toshiyuki Hirabayashi

The monkeys with silent hand-grasping skills were next given a job of picking up food pellets from a board with small slots. They discovered that the monkeys’ non-muted hand, which was on the same side of the body as the silenced brain region, was capable of picking up pellets.

However, they had difficulty utilizing the affected hand, which was on the opposite side of the body. The researchers also discovered that the designer drug lowered fMRI signals from “downstream” parts of the monkey brains, revealing more about the network breakdown that underpins the altered hand-grasping behavior.

Finally, they discovered that silencing the hand sensory region resulted in unexpectedly increased activity in the foot sensory region, as well as enhanced sensitivity in the foot on the opposite side of the body, suggesting that different sections of the network had inhibitory effects on each other.

These findings show that targeted chemogenetic silencing in macaques can generate stimulatory and inhibitory, or bidirectional, alterations in brain activity, which can be detected by functional magnetic resonance imaging (fMRI).

Furthermore, chemogenetics provides a minimally intrusive means to modify the same location on the brain repeatedly without inflicting brain tissue damage, making the method useful for studying the functioning brain network.

According to Dr. Hirabayashi, “Applying chemogenetic fMRI to higher brain functions in macaques like memory or affection will lead to translational understanding of causal network mechanisms for those functions in the human brain.”