It's a fact of life that the electrical activity of neurons will vary during the same task, even when the ultimate outcome is the same. A new study shows that a lot of ongoing fluctuations in the brain's activity can be explained by the influence local electric fields exerted on the neurons, a phenomenon called "ephaptic coupling." The finding, published in Cerebral Cortex, adds to evidence that the brain's electric fields act as important control signals for underlying brain function.
"The brain is a rollicking sea of electrical influences," said study co-author Earl K. Miller , Picower Professor of Neuroscience in The Picower Institute for Learning and Memory and MIT's Brain and Cognitive Sciences Department. "But the traditional view of brain function focuses only on the spiking and synaptic connections among individual neurons. Now, there is growing evidence for electric field effects. For instance, in this study we show that neural variability is explained by how ephaptic effects are influencing neural activity."
In in 2022 and 2023, Miller and fellow author Dimitris Pinotsis , Associate Professor at City St George's—University of London, published several studies showing that local electric fields in the brain's cortex not only reflected the information neurons were processing better than any individual neuron did, but also the fields actively helped to organize the underlying neural spiking that executes that processing. Like an orchestra conductor, the electric waves can conduct crowds of neurons so that they are "playing the same tune". They further theorize that fields physically exert influence on the structure of the brain via cytoelectric coupling , in which the fields alter the cytoskeleton of neurons, optimizing them to oscillate in synchrony.
Because electric fields can be manipulated, Miller and Pinotsis argue in the new study that understanding how they influence momentary brain function could open the door to therapeutic interventions designed to improve it when it is faltering in disease. It would be difficult to adjust every neural connection, but ephaptic coupling suggests that intervening at the level of electric fields could accomplish that therapeutic end, the researcher said.
"Properly devised electric field manipulations could help patients rewire faulty circuits," Pinotsis and Miller wrote.
Measures and models
In the duo's prior studies, they analyzed signals averaged over time, documenting that in general, even though local (or "mesoscale") electric fields in the cortex arise from the electrical activity of individual neurons, the field ultimately represents and coordinates their function. Think of it this way: Neurons are like individual citizens and the electric fields are their government. Once the citizens establish a government with their individual votes, they are then subject to and unified by the laws the government creates and enforces.
In the new study, the team asked whether mesoscale electric fields not only provide this ephaptic influence overall during working memory tasks, but also trial by trial. After all, that's closer to the timescale of actual brain operations that matter both for healthy function or in disease.
So the scientists looked anew at the data they recorded as animals played a simple video game. The animals were shown a dot in one of six positions around a screen. After the dot disappeared the animals had to hold its former position in memory because to succeed in the game and earn a reward, they had to glance when cued to indicate the direction where the dot had appeared. Meanwhile, the scientists used electrodes implanted in a region of the cortex to record neural electrical spiking and more collective local field potentials. Using that information, they calculated the local prevailing electric field at each moment.
In their statistical analysis of the data, they made several findings. One, as expected, was that neural activity varied sometimes quite widely trial by trial during the task. Another, using a mathematical technique called Granger Causality, showed that the direction of influence between the electric field and the neural activity was strongly in favor of the field. In other words, in the coupling between the two, the fields were dominant.
"We found that that electric fields that emerge from neural activity, captured with LFPs, turn around and influence this activity in a top-down fashion (ephaptic coupling)," the researchers wrote.
Moreover, the team's modeling and calculations showed that the strength of the ephaptic coupling between the field and the neural activity was proportional to the variations in the LFP power—another sign that the fields influenced the neural activity.
"The larger the variability, the more evident the top-down organizing effects," the researchers wrote. "The emerging picture is that electric fields serve as control parameters."
The UK Medical Council, the Army Research Office, the Office of Naval Research, The Freedom Together Foundation, and the Picower Institute funded the study.
