Monitoring brain activity has been a core component of neuroscience since the capability first emerged. The human brain is less understood than the universe and oceans. As such, there’s a massive effort to unravel the mysteries that lie within your mind. Now, researchers can delve deeper into mental activity in real time using a revolutionary two-photon fluorescence microscope method. Here’s what you need to know.
Understanding brain activity is crucial for many industries, including treating neurological diseases like Alzheimer’s. Scientists have spent considerable effort unraveling how neurons communicate and interact during thought. The goal of this research is to fully understand complex neural interactions down to cellular resolution.
Researchers hope to use this data to shed light on fundamental brain functions which could one day lead to improved learning, memory, decision-making, and health care. To accomplish this task they created an advanced two-photon imaging tool capable of tracking dynamic neural processes in real-time, enabling a deeper insight into the brain during learning, activities, and disease states.
Current Methods of Registering Brain Activity
There are several methods of registering brain activity in use today. These approaches have helped the industry develop to this date. However, they do have some significant drawbacks including that they take more time to monitor activity, can be harmful to the patient, and are cost-prohibitive. The two most common methods in use today include Functional Magnetic Resonance Imaging (fMRI) and Electroencephalography (EEG).
Functional Magnetic Resonance Imaging (fMRI)
Functional Magnetic Resonance Imaging is one of the most advanced methods used to monitor brain waves today. This non-invasive procedure integrates magnetic fields and radio waves to create a 3D image of your brain’s electromagnetic pulses. This strategy marked a major improvement over previous options as it allowed researchers to zoom in on a particular set of neurons, improving their overall understanding of brain activity greatly.
Electroencephalography (EEG)
Another method that you may have seen in movies is Electroencephalography. This approach measures your brain’s electrical activity. Patients need to place special sensors on their scalp that are sensitive to electrical currents. This method of tracking brain waves has been used since 1975 when Richard Caton first used it to track the electrical pulses found in rabbits’ and monkeys’ brains with success.
Since then, this method of registering brain activity has improved significantly. In the 1950s, the first modern iteration of the EEG was introduced. It served faithfully as the primary method of tracking brain waves into the 1980s. In 1988, it was used to enable a person, to control a robot and is still used by many researchers.
Study
The study “High-speed two-photon microscopy with adaptive line-excitation” was published in Optica revealing how two-photon microscopy can provide unmatched high-speed images of neural activity. These photos were made at a cellular resolution using a purpose-built two-photon fluorescence microscope.
Two-Photon Fluorescence Microscope
The Two-Photon fluorescence microscope is capable of providing vibrant images deep into brain tissue. To accomplish this task, the mechanism introduces an adaptive sampling structure. This structure would be repeated throughout the experiment to create dynamic 3d images and maps of brain activity.
Adaptive Sampling Strategy
At the core of the study is the introduction of the adaptive sampling strategy. This method replaces traditional point illumination techniques. Instead, a more effective line illumination strategy is employed alongside an updated point scanning method that provides far more detail and monitoring capabilities compared to past methods.
Point Scanning
Point scanning in old methods left much to be desired. For one, it was extremely specific which would often lead to the inability to track an entire neuron sequence across the brain. The new point scanning method uses an altered line illumination strategy to imitate high-resolution point scanning methods. This strategy is crucial in identifying what areas of the brain need to move on to the next step of the process, line scanning.
Line Illumination
Line illumination is a breakthrough for neurology engineers. The method projects a small line of light across a sampled area. This approach excites fluorescence, which makes it easier to track neurological signals across the brain from start to finish. Additionally, this approach allows a much larger area of the brain to be excited, scanned, and mapped in real-time.
Two-Photon Microscope Testing
The testing phase of the two-photon fluorescence microscope involved two lab mice, in which researchers were able to track neuronal activity in a mouse cortex in real time. Notably, the unit can capture image signals up to 198 Hz currently. In this test, the engineers tracked calcium signals which can signal recent neural activity.
Digital Micromirror Device (DMD)
To accomplish this task, a specially configured laser beam pattern is formed using a digital micromirror device (DMD). This unit contains thousands of microscopic mirrors. Each of these mirrors has individual controls that allow them to shape and target light at precise parts of the brain. Additionally, the mirrors can be set up to activate and deactivate based on neural activity, enabling better imaging across all brain states.
source – Molly M Bechtel, University of California, Davis
Two-Photon Fluorescent Microscope Test Results
The test results have yielded some unexpected data that has the potential to improve the current methods and upend the industry. For one, the study revealed how the two-photon fluorescence microscope offers unmatched insight into the brain’s inner workings. The ability to create high-speed images using short-line excitation and the adaptive sampling scheme unlocks the door for many potential future uses.
The researchers found that the new method enabled them to monitor individual neurons on a level never before possible. This new data will go toward creating advanced computational algorithms which will one day help neurologists isolate and better understand the use of individual neurons.
Benefits
This study brings a long list of benefits to the market. For one, this style of brain imaging allows researchers to understand the functional architecture of the brain in ways that were previously unimaginable. They can now see how certain brain cells interact and communicate during specific processes.
Treating Neurological Diseases
This understanding may prove paramount in fighting the rise of neurological diseases like Alzheimer’s and Parkinson’s. Both of these ailments take the lives of hundreds of thousands of people yearly. In the US, approximately +120K people die from Alzheimers alone. Sadly, this number is set to rise to 13.8M globally by 2060.
Understanding how the brain operates in these states versus when it’s healthy can allow engineers to bridge this gap and return the brain to its original operations. For now, the data holds immense value in unlocking the many secrets needed to make this type of treatment a reality.
Learning
Another major reason why monitoring brain activity is crucial to a nation’s future is that it could be used to enhance learning. Understanding what makes a memory stick or how to recall items faster are just a few areas of interest that this style of brain monitoring could improve. In the future, school curricula could be based on neural retention rather than today’s many standards.
Images Faster
Using the old methods to measure neurological activity was effective but time-consuming. They also didn’t provide fast enough images to give researchers the details needed for a complex understanding of mental actions. This new method is 10x faster than traditional two-photon microscopy, enabling researchers to monitor and track mental phenomena that older systems couldn’t register.
Less Harm
The faster performance equals less exposure to the patients. Additionally, the system requires less powerful lasers. By reducing the laser’s power and shortening exposure, patients enjoy far less energy radiation deposited on their brain tissue. The new system only illuminates the neurons in question, lowering the risk of damage to sensitive tissue.
Less Costs
Cost reduction is another benefit that the new approach has on its side. According to the study, the two-photon fluorescence microscope requires 10x less laser power compared to the traditional two-photon methods. This reduction in power equals more sustainability and less environmental impact.
Expandable
One of the biggest advantages of the new technique is that it can be combined with other effective methods seamlessly. Already, the researchers have stated plans to couple the device with other procedures like beam multiplexing and remote focusing. These techniques increase imaging speed and allow for the creation of volumetric 3D images in real-time.
Researchers
This study was conducted at the University of California, Davis, with Yunyang Li as the lead author. The research team included Ben Mattison, Junjie Hu, Kwun Nok Mimi Man, Shu Guo, and Weijian Yang. Funding for the project came from various sources, including the Burroughs Wellcome Fund, the National Science Foundation, the National Institute of Neurological Disorders and Stroke, and the National Eye Institute.
Two Companies That can Prosper from this Research
Many manufacturers could integrate this technology into their offerings to provide a higher level of service to the market. From companies seeking to alleviate dementia to robotics firms, there are endless reasons why tapping into the brain’s activity and understanding makes sense. Here are two firms that are positioned to adopt this tech in the coming months.
1. BrainChip Holdings Ltd 
BrainChip Holdings Ltd is a popular brain network software simulator. The company entered the market in 2004 and is based out of Australia. Its founder, Peter Van Der Made has been instrumental in keeping the pioneering efforts of the firm focused on integrating advanced artificial intelligence (AI) and machine learning (ML) to improve their results.
Today, the firm offers a variety of products, including an IoT infrastructure modeled after the brain’s neural network. Another popular product that has helped BrainChip gain notoriety is the Akita Development Environment, which allows developers to create, train, and test experimental neural networks.
BrainChip Holdings has seen some drawbacks since 2023. However, the company’s latest software and ventures into the AI and ML sectors have rekindled investor interest. As such, BrainChip Holdings Ltd is seen as having strong upside potential.
2. Biogen
Biogen is a pharmaceutical research firm that has made waves in the market recently. The Massachusetts-based manufacturer specializes in neurological disease treatment and care. Currently, it has products that help treat neurological, neurodegenerative, and autoimmune diseases.
Biogen has seen some criticism for fast-tracking some of its treatments, but that hasn’t slowed the company’s rise to prominence in the market. Their latest release, Leqembi, was approved by the FDA fast-track and is designed to treat Alzheimer’s disease. The company has seen the use of its latest drug nearly triple over the last year, which has helped the firm secure stronger market positioning. As such, Biogen’s early exposure to the Alzheimer’s treatment market and its combination of offerings makes it a potential strong buy for traders.
Two-Photon Microscope Provides a Glimpse Into the Future
The Two-Photon fluorescence microscope takes humanity one step closer to being able to interact with its surroundings using only thought. This innovative research team has pushed the boundaries of neurological research and has emerged with never-before-seen insight into human brain activity. This research is sure to spawn additional studies that could one day lead to less neurological disease and many other advancements.
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