Are we in the science fiction era of brain imaging? A point of view on advances and challenges in brain investigation

The researcher’s side: Development of on-scalp magnetoencephalography

In 2018, new magnetic sensors – optically pumped magnetometers (OPMs) – emerged, which allow the recording of brain activity directly on the scalp without the need for cryogenic cooling. This alleviates the need for thermal insulation space to protect the scalp from the extreme cold of liquid helium, which is necessary for superconducting quantum interference devices.¹ Many developments followed, both in cognitive neuroscience and in clinical epilepsy. In particular, my colleagues and I demonstrated that on-scalp magnetoencephalography based on OPMs is able to successfully detect and localize interictal epileptic activity.² In a 2022 editorial for Radiology, Dr. Elysa Widjaja wondered whether on-scalp magnetoencephalography was reality or science fiction³ because the development of a new wearable imaging tool usable at the patient’s bedside sounded like a dream.

While that particular dream is not yet realized, we decided to further investigate this new technique in the context of clinical epilepsy. We studied clinical populations beyond adult patients – for example, infants with epilepsy who are unable to remain still without sedation and those who have a low head circumference, which limits the use of other neuroimaging techniques, including cryogenic magnetoencephalography.⁴ We assessed whether OPMs can probe deep brain interictal activity, such as that localized in the medial temporal lobe, and took advantage of the flexibility of OPMs to design a custom setup targeting this brain region.⁵ We established the localization accuracy of the technique in realistic clinical settings using the first simultaneous recordings of OPMs with stereoelectroencephalography (SEEG) – the most precise intracranial electrode-based recording technique.⁶ We also examined ictal activity, (i.e., activity occurring during seizures), despite challenges posed by spontaneous, ictal, and hyperventilation-induced movements.⁷ All in all, this body of work suggests that on-scalp magnetoencephalography using OPMs is close to replacing cryogenic magnetoencephalography.⁸ But does this mean that it is no longer science fiction? Current research shows that this is no longer science fiction – it is science at work.

This new brain imaging era brings a whole set of questions and challenges. Which type of sensors should be used to perform optimal investigation (e.g., helium-based versus rubidium-based OPMs⁹)? Is it still necessary to combine magnetoencephalography with scalp electroencephalography?¹⁰ The first questions we tried to answer with on-scalp magnetoencephalography are mostly informed by previous clinical applications and research using cryogenic magnetoencephalography. However, this emergent technique could also open the door to new areas of investigation such as fetal magnetoencephalography,¹¹ medullar magnetoneurography,¹² peripheral nerve magnetoneurography,¹³ and magnetomyography.¹⁴ Would we be able to study cerebral activity from the periphery?¹⁵ Would we be able to predict the neurodevelopmental functioning at the individual level? Could we imagine practical relocation of an on-scalp magnetoencephalography system, either at another institution with its own magnetically shielded room¹⁶ or at the subject’s location thanks to a movable miniaturized magnetic shielding system?¹⁷ Might greater accessibility to this technology launch the use of on-scalp magnetoencephalography for the screening of neurological pathologies (e.g., epilepsy and Alzheimer’s disease, with already known biomarkers¹⁸)? Are there biomarkers of other neurological diseases that could be discovered thanks to specific positioning of sensors around the nervous system? Could we learn more about the development of cognitive functions? I have no doubt that the coming years will provide exciting answers to these and many other questions.

The clinician’s side: Focus on refractory focal epilepsy

Our understanding of neurological disorders has rapidly evolved since the advent of neuroimaging techniques. Through intracranial and extracranial recordings, the epileptic brain is now better understood than in Hippocrates’ time. We know more and more about epileptogenic networks,¹⁹ and yet, we remain stuck at a frustrating one-third failure rate for epilepsy surgery.²⁰ To put things into context, around 10% of the global population will experience at least one epileptic seizure in the course of a lifetime and 1% will be diagnosed with epilepsy, a disease of the brain with multiple epileptic seizures. Despite an increasing number of anti-seizure medications, one third of patients with epilepsy are still disabled by seizures and could be potential candidates for epilepsy surgery – to date, the only curative treatment for the disease. However, one third of patients who undergo surgery still experience seizures despite appropriate assessment and surgery, making the outcome unsatisfactory, especially when considering potential side effects of the surgery. Will on-scalp magnetoencephalography bring a long-sought revolution in the field and drastically change the landscape of epilepsy surgery? Probably not – at least not until a reliable biomarker of the epileptogenic zone is identified.²¹

Despite the advances achieved by bringing magnetometer sensors closer to the scalp; despite the increase in signal quality and improvements in signal-to-noise ratio, extracranial measurements will be hopelessly restricted by the laws of physics and the infamous inverse problem. This, in a nutshell, reflects the fact that fine-grained information about neural activity is irremediably lost when propagating out of the brain.²² While most brain researchers are usually limited by the anatomical boundaries of scalp and skull, the clinical management of epilepsy extends beyond the limits of the skull thanks to SEEG, which allows the recording of intracranial brain activity and is a standard part of presurgical assessment.²³ This offers a unique opportunity to take a direct look into the brain,²⁴ to electrically stimulate the brain,²⁵ and induce seizures²⁶ or reduce seizures.²⁷ It also allows the detection of subtle intracranial changes to which extracranial recordings are blind,²⁸ including in subcortical brain areas²⁹ and non-implanted brain areas, thanks to intracranial source localization.³⁰ Microelectrodes go one step further, allowing one to see the activity of a single neuron. But which technique will eventually be the most useful for discovering this putative perfect biomarker and circumscribe the epileptogenic zone with a 100% success rate in epilepsy surgery? Are current neuroimaging methods efficient enough but misused? Should we combine together all available brain imaging techniques?³¹ Should we study the neuronal single-cell activity³² or the whole-brain connectome?³³ All options are considered. From a therapeutic approach, new techniques have also emerged, such as laser interstitial thermal therapy or focused ultrasound – stereotactic minimally invasive therapeutic methods that use heat to ablate small brain areas. Are they any better than resective surgery?³⁴ While these techniques are not science fiction anymore, should we ask for George Lucas’ help to find the best way to cure refractory focal epilepsy?

Funding Sources

The author has no funding sources to declare.

Conflicts of Interest

The author has no conflicts of interest to declare.