fMRI signals from a rat's brain are viewed on the top of an anatomical image of the animal. Despite the fact that the two parts are at the same time, contralateral areas are activated at the same time. Credit: Joana Cabral
Neuroimaging studies – using functional magnetic resonance imaging (fMRI), a widely-used technology to capture live brain activity – have discovered brain-wide complex patterns of correlated brain activity that appear disturbed in a broad spectrum of neurological and psychiatric disorders. These patterns have been discovered not only in humans but also across mammals, including monkeys and rodents.
Noam Shemesh, the principal investigator of the Champalimaud Foundation's Preclinical MRI Lab in Lisbon, and senior author of a study published on February 6th, 2023, in the journal Nature Communications.
"We wanted to understand what lies beneath those correlations and investigate the mechanisms," says Shemesh.
Because of the poor temporal resolution of fMRI, which produces only one image per second, several theoretical studies suggested that standing waves (whose peaks and troughs do not move in space) may support the resonance hypothesis.
The video below illustrates how fMRI-captured brain activity may be reconstructed as the superposition of a small number of macroscopic stationary waves, or resonant modes, oscillating in time. Credit: Joana Cabral
The goal of the project was to speed up image acquisition, and they discovered that distant brain regions actually oscillate together in time. "These oscillatory patterns appear to be equivalent to reverberations or echoes within the brain," says Cabral.
Shemesh: "Our findings show that complex spatial patterns are a result of transiently and independently oscillating underlying modes, just as individual instruments participate in creating a more complex piece in an orchestra," he says. "These are the first times that brain activity captured with fMRI is reconstructed as the superposition of standing waves."
The authors believe these resonant phenomena are at the core of coherent, coordinated brain activity that is required for normal brain functioning as a whole.
The researchers detected the resonant modes in rats in the resting state, which means that they were not exposed to any particular external stimuli, since as already mentioned, our brains continue to generate spontaneous activity patterns that may be captured by fMRI.
Researchers used a powerful ultrahigh-field experimental MRI scanner in Shemesh's lab to visualize oscillations, and performed ultrafast experiments done some time ago by the same lab for other purposes.
"Noam and I met in 2019, and we decided to obtain brain activity recordings at the highest temporal resolution we could achieve with the 9.4 Tesla scanner at his lab," says Cabral. "Noam managed to obtain 16,000 images per 10-minute scan, compared to 600 images at the typical resolution of one image per second."
"We saw clear waves of activity, like waves in the ocean," says Cabral, as they travelled through the brain's cortex and the striatum [a subcortical area of the forebrain] in parallel."
Researchers studied rats in three different conditions: sedated, mildly anesthetized, and deeply anesthetized. (In fact, the animals were lightly sedated in the resting state to avoid any discomfort to them), according to Cabral.
Shemesh concludes: "We found that resonance phenomena drive brain functional networks." This explanation for slow imaging indicates that long-range brain interactions are governed by a "flow" of information that is oscillatory and repetitive.
Cabral claims that increasing the amount of anesthesia reduces the frequency, and duration of resonant stationary waves.
'Functional networks' appear to be harmed in several neurological and psychiatric disorders, according to the author. If confirmed in humans, their findings may also lead to the use of resonant modes as biomarkers for disease.
Shemesh adds, "Our study provides a new "lead" in looking at illness." "We know that long-range brain activity is highly influenced by disease, but we do not understand why or how." Understanding the mechanisms of long-range interactions might lead to a completely new way of characterizing disease and suggesting the type of treatment that might be appropriate, for example, if a patient's specific resonant mode is absent, we may want to enhance that particular mode."
All these findings will require further investigation, according to the researchers, and whether they are bioavailable in humans. However, "once we understand better the nature of functional networks, we can devise informed strategies to modify these network patterns," according to Cabral.
The researchers' new project, "BRAINSTIM: Predicting stimulation strategies to modulate interactions between brain areas," is funded by the "la Caixa" Foundation and the Portuguese bank BPI, with 300,000 euros, and aims to better understand the interactions between pharmacological and electromagnetic brain stimulations in macroscale oscillations.
Joana Cabral, Francisca F. Fernandes, and Noam Shemesh, 6 February 2023, Nature Communications. DOI: 10.1038/s41467-023-36025-x
