Contemporary brain imaging technologies are sluggish, revealing structures like tumours, or indirectly measuring brain activity through blood flow. Yet to truly understand cognition, scientists need to see real-time communications between neural networks, on a millisecond basis.
Researchers at the Centre for Human Brain Health, University of Birmingham, as part of the efforts of the UK Quantum Technology Hub, are helping develop a new generation of magnetic systems to improve our understanding of everything from basic cognition to dementia and ADHD.
The brain is the most complex natural structure in the known universe; its roughly 86 billion neurons transmitting 1000 impulses per second. We are unpacking more of its mysteries by the day, like how it consolidates memories when we sleep, and re-moulds and rewires after trauma. Today’s advances in artificial intelligence are thanks to researchers’ increasing ability to mimic the brain’s neural networks.
Yet there is much to be learned about this three-pound organ. Our understanding of conditions like autism and schizophrenia, and the interaction between anatomy, emotions and behaviour, is nascent. Therapies for conditions such as Alzheimer’s and Parkinson's Disease come with heavy side effects or are managerial rather than curative. We struggle to even diagnose widely suffered conditions; Alzheimer’s can only be definitively identified on autopsy, as it requires microscopy examination of brain tissue to identify amyloid deposits.
Entering the vault
The brain’s functional complexity is one reason for our nascent knowledge relative to other parts of our biology, but its encasement in the skull is as big an obstacle. Not being able to physically examine and explore the brain safely in a live patient limits our ability to learn about the brain, and non-invasive imaging technologies all have their weaknesses.
Computed tomography (CT) creates an image through differential absorption of X-rays passed through the head, showing structural abnormalities related to tissue density, such as tumours or atrophy, but does not track metabolic activity. Positron emission tomography (PET) utilises radioactive isotope tracers to show biochemical phenomena, valuable in imaging diseases with abnormal rates of cell metabolism, such as cancer and heart disease. However, PET scans are expensive and involve exposure to radioactive isotopes. Electroencephalograms (EEG) record brain activity using electrodes on the scalp and are commonly used to diagnose epilepsy, but they also pick up signals outside the brain, like electrical activity produced by skeletal muscles and the optical system, which can impair image quality.
Magnetic resonance imaging (MRI) delivers high resolution images of the brain’s structures. This has demonstrated reduction in white matter density in people with dementia and enabled profiling of changes in permeability of the blood-brain barrier to identify conditions such as ischaemia, which contributes to vascular dementia. Functional MRI provides a measure of brain activity based on the degree of oxygenation of the blood flowing to activated brain regions. MRI scanners are costly, however, and require subjects to remain still during imaging, which can be challenging for people with some conditions. Scanners are also noisy, which can be frightening for patients.
Magnetoencephalography (MEG) measures magnetic fields generated by electrical flow through the brain’s network of neurons. Because MEG measurements record moment-to-moment changes in magnetic field strength, they provide information about what happens in the brain during certain activities. “MEG is a direct measure of neural activity, whereas functional MRI reflects changes in blood flow and oxygenated blood, which reflects neuronal activity, but it is an indirect measure of it,” says Professor Ole Jensen, an expert in neuronal oscillation at the Centre for Human Brain Health at University of Birmingham. MEG also operates on a millisecond basis, while MRI is far slower, measuring blood flow only over seconds.
MEG systems can diagnose and monitor disorders including epilepsy, traumatic brain injury, chronic pain and dementia, but current models are bulky and expensive, requiring operational temperatures of -268℃. Using liquid helium to achieve superconductivity, sensors are also placed at some distance from the scalp, limiting the penetration depth of the measurements. Again, subjects must remain still to obtain high quality images.
Quantum sensing the real-time brain
Researchers in the UK Quantum Technology Hub are overcoming this impasse by applying quantum sensor innovation. Through Optically Pumped Magnetometers (OPMs), researchers have created the first wearable MEG system, comprising 13 OPMs placed in a 3D-printed head-cast, which permits free movement during scanning. Not requiring cryogenic conditions, it can be placed directly on the scalp, closer to the brain, enhancing the accuracy of signal detection five-fold. A wearable system imposes less restriction on movement by the subject and avoids the high installation and running costs of a conventional MEG system since there is not need for liquid helium.
Dementia is one promising application for these OPMs, since it involves deep-seated brain structures and networks that current MRG system as less good at picking up. For example, the hippocampus plays a vital role in learning, memory and spatial awareness, but is difficult to image with current technologies as it is situated deep in the temporal lobe. Real-time imaging on a millisecond basis also tells us about spatial and temporal activity in different brain regions, in ways that other imaging tools cannot.
Being able to identify the onset of Alzheimer's Disease through locating amyloid deposits would assist in providing individuals with prognosis, enabling them to plan for the future. Although this is currently beyond the realms of medicine, this could become reality. Low rates of diagnosis in the UK means that thousands of people with dementia are unable to access appropriate support. Professor Jensen also sees applications in other brain conditions like Attention Deficit Hyperactivity Disorder. “The ability to modulate brain oscillations in attentional tasks is diminished in ADHD patients, so we think we can use MEG as a tool for better diagnosing ADHD, and investigating effects of pharmaceuticals”.
Mind-healing for the 21st century
Brain imaging will be increasingly vital as the global population ages, and proportional mortality from cancer and cardiovascular disease falls. Neurological disorders overall were the leading cause group of disability-adjusted life years (DALYs) by 2015, comprising 10.2%, and the second leading cause of deaths at 16.8%, or 9.4 million. Dementia prevalence is rising; the number of people living with dementia will double every 30 years, reaching 75 million people by 2025 with a marked increase in developing economies. Cognitive decline will become a significant public health menace.
Aware of the paltry tool-box for treating and curing neurological conditions, public health agencies, governments and academic institutions are investing heavily in brain science. The US BRAIN initiative is investing in next-generation imaging techniques like magnetic corticography (MRCoG) and functional near-infrared spectroscopy (fNIRS). The Bill and Melinda Gates Foundation, historically focused on infectious and tropical diseases, are also allocating funding to areas like Alzheimer’s. China has built an industrial-scale brain imaging factory in the eastern city of Suzhou and maverick entrepreneur Elon Musk formed Neuralink, to explore brain-computer interface technology as part of a vision to fuse human brains with artificial intelligence.
Professor Jensen is hopeful that OPMs can be part of this upsurge in public and commercial interest. “We are really hoping companies will jump on this and commercialise it, and scale up the system and make it more reliable,” he says. Jensen will lead the University of Birmingham’s newly-formed Centre for Human Brain Health, set to include a dedicated OPM lab.
Its research activities will include combining brain stimulation with OPM sensors to directly measure connectivity in the brain. So-called Transcranial Magnetic Stimulation (TMS) is already used to identify neurological diseases like multiple sclerosis, by stimulating the motor cortex and spotting conduction delays in a muscle. “We will try to look at the same thing, but rather than brain to muscle, we will look from brain region to brain region”.
Jensen believes the University of Birmingham’s multidisciplinary environment puts it in a strong position to contribute substiantially to this vital research area. “The university is a unique setting,” he says. “We have cognitive brain scientists, a group working on brain imaging, and a physics team working on quantum sensors. The fact we are here on the same campus and have a joint lab is going to be powerful”.
The main banner image is from the University's own MEG laboratory. This allows for continuous recordings of ongoing brain activity with a millisecond time resolution. By using advanced analysis tools it is possible to identify where in the brain the measured electrophysiology activity is generated. The Centre for Human Brain Health is an interdisciplinary brain research facility established with the mission of understanding what makes a brain healthy, how to maintain it, and how to prevent and reverse damage.
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