The “circuit” metaphor of the brain is as indisputable as it is familiar: neurons make direct physical connections to create networks of activity, such as storing memories or forming thoughts. But the metaphor is also incomplete. What makes these circuits and networks come together? New evidence suggests that at least some of this coordination comes from electric fields.
A new open access learn Meninges When animals played working memory games, the electrical field that emerged from the underlying electrical activity of all participating neurons showed that information about what they were remembering was coordinated across two major brain regions. The field, in turn, appeared to drive neural activity, or fluctuations in voltage expressed across cell membranes.
If neurons are musicians in an orchestra and brain regions are their sections, memory is the music they produce, the study’s authors say, and the electric field is the conductor.
The physical mechanism by which this current electric field influences the membrane voltage of the constituent neurons is called “ephaptic coupling”. Those membrane voltages are fundamental to brain function. When they cross a threshold, neurons “spike,” sending an electrical transmission that signals other neurons across connections called synapses. But any amount of electrical activity can cause an ongoing electric field that influences spiking, says the study’s senior author. Earl K. MillerPickover Professor in the Department of Brain and Cognitive Sciences at MIT.
“Many cortical neurons spend a lot of time teetering on the edge of spiking,” says Miller. “Changes in the electric field around them will push them one way or another. It’s hard to imagine evolution not exploiting it.
Specifically, the new study showed that electric fields guided the electrical activity of networks of neurons to produce a shared representation of information stored in working memory, says the lead author. Dimitris Pinotsis, Associate Professor at City, University of London and Research Affiliate at The Pickover Institute for Learning and Memory. He noted that the findings could improve the ability of scientists and engineers to read information from the brain, which could help design brain-controlled prosthetics for people with paralysis.
“Using complex systems theory and mathematical pen-and-paper calculations, we predicted that the brain’s electrical fields would direct neurons to produce memories,” says Pinotsis. “Our experimental data and statistical analyzes support this prediction. This is an example of how mathematics and physics can shed light on areas of the brain and provide insights for building brain-computer interface (BCI) devices.
Rule the fields
In a 2022 Research, Miller and Pinotsis developed a biophysical model of electrical fields produced by neural electrical activity. They showed that aggregate fields evoked from groups of neurons in a brain region are more reliable and stable representations of the information animals use to play working memory games than the electrical activity of individual neurons. Neurons are somewhat fickle devices, and their fluctuations cause informational inconsistencies called “representational drift.” a Commentary Earlier this year, scientists also noted that in addition to neurons, electric fields affected the brain’s molecular infrastructure and its tuning, so the brain processes information efficiently.
In the new study, Pinotsis and Miller extended their investigation to ask whether ephaptic coupling spreads a controlled electrical field across multiple brain regions to form a memory network, or “engram.”
So they broadened their analyzes to examine two regions of the brain: the frontal eye fields (FEF) and the supplementary eye fields (SEF). Both of these areas, which control voluntary eye movements, are relevant to the memory game the animals play, because in each round the animals see an image on a screen (like the numbers on a clock). After a short delay, they had to look in the same direction from which the object had just come.
As the animals played, the scientists recorded local field potentials (LFPs, a measure of local electrical activity) generated by the number of neurons in each region. The scientists fed this recorded LFP data into mathematical models that predicted individual neural activity and overall electrical fields.
The models allowed Pinotsis and Miller to calculate whether changes in fields predicted changes in membrane voltages, or whether changes in activity predicted changes in fields. To perform this analysis, they used a mathematical method called Granger causality. Clearly, this analysis shows that, within each region, the fields have a strong causal influence on neural activity and not the other way around. Consistent with last year’s study, the analysis showed that measures of affective strength were more consistent for fields than for neural activity, suggesting that fields are more reliable.
The researchers examined causality between the two brain regions and found that electrical fields, but not neural activity, reliably represented the transfer of information between the FEF and SEF. More specifically, they found that transfer typically flows from the FEF to the SEF, which is consistent with previous studies of how the two regions interact. The FEF leads to the initiation of an eye movement.
Finally, Pinotsis and Miller used another mathematical technique called representational similarity analysis to determine whether the two regions process the same memory. Electric fields, but not LFPs or neural activity, represent the same information in both regions, unifying them into an engram memory network.
Further clinical implications
Given the evidence that electrical fields arise from neural electrical activity, Miller speculated that to direct neural activity to represent information, perhaps one function of electrical activity in individual neurons is to produce the fields that then control them.
“It’s a two-way street,” Miller says. “Spiking and synapses are very important. That is the basis. But then the fields reverse and influence the spiking.
That could have important implications for mental health treatments, because whether neurons spike can influence the strength of their connections and thus the activity of the circuits they form, a phenomenon called synaptic plasticity.
Clinical technologies such as transcranial electrical stimulation (TES) alter electrical fields in the brain, Miller notes. If electrical fields not only reflect neural activity but actively shape it, TES technologies can be used to alter circuits. Properly designed electric field manipulations, he says, could one day help patients rewire faulty circuits.
Funding for the study came from UK Research and Innovation, the US Office of Naval Research, The JPB Foundation and the Pickover Institute.