Human Brain Project researchers identify new marker of ALS outcomes

A study by researchers from the Human Brain Project (HBP) has identified a new marker that can predict the clinical course of patients with amyotrophic lateral sclerosis (ALS) using magnetoencephalography. This marker can be measured in the brain during its resting state and highlights the importance of cerebral flexibility for ALS patients. The study was conducted by the Institute of Systems Neurosciences of Marseille, in collaboration with the Consiglio Nazionale delle Ricerche, the Parthenope University of Naples and the Institute of Diagnosis and Care Hermitage Capodimonte of Naples, and the University Melbourne Monash. It was published online on September 30, 2022, in Neurology.

ALS is a neurodegenerative disease of the brain and spinal cord which results in a loss of muscle control. The ability to move, speak and, eventually, breathe is gradually impaired. There is no known cure, but treatments to improve symptoms, including magnetic stimulation, are being tested.

“The behavior of the brain of an ALS patient is often difficult to understand. Deficiencies can be caused by neural dysfunction in a small area of ​​the brain that influences a much larger area, which means you need whole-brain scans to predict clinical outcome,” says Pierpaolo Sorrentino of INS, the study’s final author. “Patients may have difficulty with motor tasks during scans. This new method, instead, can be applied to the resting brain, making it easier for patients and more consistent.”

The researchers collected magnetoencephalography data on 42 ALS patients and 42 healthy controls at the Parthenope University of Naples, whose MEG facilities recently became part of EBRAINS, a digital research infrastructure developed under the HBP. The new study builds on previous work by the same group, which applied the methodology to Parkinson’s disease.

“A healthy brain is flexible, able to reconfigure itself to respond to stimuli, triggering neuronal avalanches in different areas,” adds Sorrentino. “Think of it like a goalkeeper waiting for a penalty. If you’re fast enough, constantly moving rather than staying in one place is a better strategy to be ready for most possible trajectories.”

“Neuronal avalanches spread in patterns that we can monitor with whole-brain scans,” says Arianna Polverino of the Hermitage Capodimonte Institute for Diagnosis and Care, lead author of the study. “We call the collection of all unique patterns the ‘functional repertoire,’ a measure of brain flexibility.”

The researchers focused on quantifying the functional repertoire of ALS brains, even when the patient is unstressed and the brain is in a resting state. “We found that functional repertoire restriction corresponded to more severe functional impairment. The more flexible the brain, the better the clinical outcome: the functional repertoire can be used as a reliable predictor of how the clinical outlook for a patient will likely evolve.”

“It’s often hard to tell how a particular therapy is working – now we might have a strong marker to predict its outcome,” says Sorrentino.

The next step, scientists say, is to use this non-invasive readout in a longitudinal study which follows the progress of the disease in a patient-specific way and adapts the treatment accordingly. “The ultimate goal is to apply the predictive power of the functional repertoire in personalized medicine, perhaps extending the same approach to brain dynamic to other large-scale applications,” concludes Polverino.

Provided by Human Brain Project