The brain’s “circuit” metaphor is as reliable as it is familiar. To build functional networks that can store memories or generate thoughts, neurons form direct physical connections. However, the metaphor is incomplete as well. What causes these networks and circuits to connect? Electric fields may be the source of at least some of this coordination, according to new evidence.
According to a new study published in Cerebral Cortex, when animals played working memory games, the underlying electrical activity of all participating neurons created an electric field that coordinated the information about what they were remembering across two important brain regions. The field, on the other hand, appeared to be driving the neural activity, or voltage shifts across the cell membranes.
According to the study’s authors, the electric field is the conductor if the neurons are musicians in an orchestra; the brain regions are their sections; and memory is the music they produce.
“Ephaptic coupling” is the physical mechanism by which the constituent neurons’ membrane voltage is affected by the prevailing electric field. Brain activity is fundamentally dependent on those membrane voltages. Neurons “spike” when they cross a threshold, sending an electrical signal across connections known as synapses to other neurons.
“Many cortical neurons spend a significant amount of time wavering on the verge of spiking. Changes in their surrounding electric field can cause them to move in either direction. It’s difficult to envision evolution not taking advantage of that.”
Senior author Earl K. Miller, Picower Professor in the Department of Brain and Cognitive Sciences at MIT.
According to study senior author Earl K. Miller, Picower Professor in the Department of Brain and Cognitive Sciences at MIT, “any amount of electrical activity could contribute to a prevailing electric field that also influences the spiking.”
Miller stated, “Many cortical neurons spend a lot of time wavering on the verge of spiking.” They can be pushed in either direction by changes in the electric field around them. It’s hard to believe evolution wouldn’t take advantage of that.
According to lead author Dimitris Pinotsis, an Associate Professor at the City University of London and a research affiliate at the Picower Institute, the new study demonstrated, in particular, that the electric fields drove the electrical activity of networks of neurons to produce a shared representation of the information stored in working memory. He mentioned that the findings might make it easier for scientists and engineers to read information from the brain, which could be useful in the creation of brain-controlled prosthetics for paralyzed people.
Pinotsis stated, “We predicted that the brain’s electric fields guide neurons to produce memories using the theory of complex systems and mathematical pen and paper calculations.” This prediction is supported by our experimental data and statistical analyses. This exemplifies how the fields of the brain can be illuminated by mathematics and physics, allowing for the development of brain-computer interface (BCI) devices.”
A biophysical model of the electric fields created by neural electrical activity was developed by Miller and Pinotsis in a study that was conducted in 2022. Fields predominate. They demonstrated that, as opposed to the electrical activity of individual neurons, the overall fields that emerged from groups of neurons in a brain region were more reliable and stable representations of the information animals used in working memory games.
“Representational drift” refers to an information inconsistency caused by neurons’ erratic behavior. In a recent opinion piece, the researchers also suggested that electric fields had an impact not only on neurons but also on the molecular infrastructure of the brain, which is necessary for the brain to efficiently process information.
Pinotsis and Miller asked if ephaptic coupling spreads the governing electric field across multiple brain regions to form a memory network, or “engram,” in the new study.
As a result, they expanded their investigations to include two brain regions: The supplementary eye fields (SEF) in addition to the frontal eye fields (FEF). Because the animals would see an image on a screen that was positioned at some angle around the center, similar to the numbers on a clock, these two regions, which control voluntary eye movement, were relevant to the working memory game they were playing. After a brief delay, they were forced to look in the same direction that the object had just been.
The scientists recorded the scores of neurons’ local field potentials (LFPs), a measure of local electrical activity, as the animals played. These recorded LFP data were fed into mathematical models by the researchers, which predicted individual neural activity and the electric fields as a whole.
After that, Pinotsis and Miller were able to use the models to determine whether changes in the activity or the fields predicted changes in membrane voltages or both. They used a mathematical approach known as Granger Causality to conduct this analysis.
This analysis demonstrated without ambiguity that the neural activity was strongly influenced by the fields rather than the other way around in each region. The analysis also confirmed the findings of the previous year’s study by demonstrating that fields were more reliable than neural activity when it came to measures of influence strength.
After checking for causality between the two brain regions, the researchers discovered that the transfer of information between FEF and SEF could be reliably represented by electric fields but not by neural activity. More specifically, they discovered that the transfer typically occurred from SEF to FEF, which is consistent with previous research on the interactions between the two regions. FEF typically initiates eye movements first.
Last but not least, Pinotsis and Miller investigated whether the two regions were in fact processing the same memory by employing a different mathematical approach known as representation similarity analysis. They discovered that the electric fields, but not the LFPs or neural activity, unified the two regions into an engram-memory network by representing the same information.
Further clinical implications Miller hypothesized that individual neurons might be responsible for producing the fields that then govern them, given the evidence that electric fields originate from electrical activity in the brain and then drive that activity in order to represent information.
Miller said, “It’s a two-way street.” The synapses and spikes are crucial. That is the basis. However, the fields then reverse themselves and influence the spiking.”
He stated that because the phenomenon known as synaptic plasticity influences the strength of the connections between neurons and, as a result, the function of the circuits they form, this could have significant effects on treatments for mental health.
Miller said that clinical technologies like transcranial electrical stimulation (TES) change the electrical fields in the brain. TES technologies could be used to alter circuits if electrical fields not only reflect but actively shape neural activity. He stated that electrical field manipulations that are well-designed may one day assist patients in rewiring damaged circuits.
More information: Dimitris A Pinotsis et al, In vivo ephaptic coupling allows memory network formation, Cerebral Cortex (2023). DOI: 10.1093/cercor/bhad251
