Brain networks encoding memory come together via electrical fi

The circuitry metaphor of the brain is as indisputable as it is familiar: neurons forge direct physical connections to create functional networks, for example to store memories or produce thoughts. But the metaphor is also incomplete. What pushes these circuits and networks to come together? New evidence suggests that at least some of this coordination comes from electric fields.

A new free access study inCerebral cortexshows that when animals played working memory games, information about what they remembered was coordinated in two key brain regions by the electric field that emerged from the underlying electrical activity of all participating neurons. The field, in turn, seemed to drive neural activity, or apparent voltage fluctuations across cell membranes.

If neurons are musicians in an orchestra, brain regions are their sections, and memory is the music they produce, the study authors say, then the electric field is the conductor.

The physical mechanism by which this dominant electric field influences the membrane tension of the constituent neurons is called ephaptic coupling. These membrane tensions are fundamental for brain activity. When they cross a threshold, neurons increase, sending an electrical transmission that signals other neurons through connections called synapses. But any amount of electrical activity could contribute to a dominant electric field that also influences the spike, according to the study’s lead author.Earl K.MillerProfessor Picower in the Department of Brain and Cognitive Sciences at MIT.

Many cortical neurons spend a long time dithering about to ramp up, Miller says. Changes in their surrounding electric field can push them one way or another. It is difficult to imagine an evolution without exploiting this.

In particular, the new study showed that electric fields drive the electrical activity of neural networks 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 Fellow at the Picower 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 aid in the design of brain-controlled prostheses for people with paralysis.

Using complex systems theory and mathematical calculations with pen and paper, we predicted that electrical fields in the brain guide neurons to produce memories, Pinotsis says. Our experimental data and statistical analyzes support this prediction. This is an example of how math and physics illuminate brain fields and how they can provide information for building brain-computer interface (BCI) devices.

Fields prevail

In a 2022study, Miller and Pinotsis developed a biophysical model of electric fields produced by neuronal electrical activity. They showed that the global fields that emerged from groups of neurons in a brain region were more reliable and stable representations of the information animals used to play working memory games than the electrical activity of individual neurons. Neurons are somewhat finicky devices whose whims produce information inconsistency called representational drift. In aopinion pieceEarlier this year, scientists also postulated that in addition to neurons, electric fields affect the molecular infrastructure of the brain and its tuning so that the brain processes information efficiently.

In the new study, Pinotsis and Miller extended their investigation to whether ephaptic coupling extends the governing electric field across multiple regions of the brain to form a memory network, or engram.

They therefore broadened their analyzes to focus on two regions of the brain: the frontal eye fields (FEF) and the supplementary eye fields (SEF). These two regions, which govern voluntary eye movement, were relevant to the working memory game the animals were playing because at each turn the animals saw an image on a screen positioned at some angle around the center (like the numbers on a clock). After a brief delay, they must have been looking in the same direction the object had just been.

As the animals played, the scientists recorded the local field potentials (LFPs, a measure of local electrical activity) produced by dozens of neurons in each region. The scientists fed this recorded LFP data into mathematical models that predicted individual neural activity and global electric fields.

The models allowed Pinotsis and Miller to then calculate whether changes in fields predicted changes in membrane voltages, or whether changes in this activity predicted changes in fields. To do this analysis, they used a mathematical method called Granger causality. Unambiguously, this analysis showed that in each region the fields had a strong causal influence on neuronal activity and not the other way around. Consistent with last year’s study, the analysis also showed that measures of influence strength remained much more stable for fields than for neural activity, indicating that fields were more reliable.

The researchers then checked for causality between the two brain regions and found that electric fields, but not neural activity, reliably accounted for the transfer of information between FEF and SEF. Specifically, they found that transfer generally shifted from FEF to SEF, which is consistent with previous studies of how the two regions interact. FEF tends to lead the way by initiating eye movement.

Finally, Pinotsis and Miller used another mathematical technique called representation similarity analysis to determine if the two regions were in fact processing the same memory. They found that electric fields, but not LFPs or neural activity, represented the same information in both regions, unifying them in an engram memory network.

Other clinical implications

Considering evidence that electrical fields emerge from neuronal electrical activity but then come to drive neuronal activity to represent information, Miller hypothesized that perhaps a function of electrical activity in individual neurons is to produce the fields that then govern them.

It’s a two-way street, says Miller. Spikes and synapses are very important. It is the foundation. But then the fields turn around and influence the doping.

This could have important implications for mental health treatments, he says, because if and when neurons spike influence the strength of their connections, and therefore the function 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 electric fields not only reflect neural activity but actively shape it, then TES technologies could be used to modify 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 Picower Institute.