Two papers publishing June 20 in the journal Cell show that Egyptian fruit bats and mice, respectively, can “sync” brainwaves in social situations. The synchronization of neural activity in the brains of human conversation partners has been shown previously, as a result of one person picking up social cues from the other and modulating their own behavior based on those cues. These studies now suggest that something similar occurs when animals engage in natural social interactions and find that some aspects of the animals’ social behavior can be predicted based on neural observations.

“Animal models are really important for being able to study brain phenomena at levels that we can’t normally access in humans,” says Michael Yartsev of the Department of Bioengineering at the University of California, Berkeley, and senior author of one of the papers. “Because bats are extremely social and naturally live in highly complex social environments, they are a great model for tackling important scientific questions about social behavior and the neural mechanisms underlying it.”

“If you think of the brain like a black box that receives input and gives some kind of output in response, studying social interactions is like trying to understand how the output of one box provides input to another, and how those two boxes work together and create a loop,” says Weizhe Hong of the Departments of Biological Chemistry and Neurobiology at the University of California, Los Angeles, and senior author of the other paper. “Our research in mice allows us to peer inside these black boxes and get a better look at the internal machinery.”

Previous studies showing how neural activity in humans becomes synchronized during social interactions have used technologies like fMRI and EEG, which look at brain activity with relatively coarse spatial and temporal resolutions. These studies found that when two people interact, structures in their brain simultaneously decode and respond to signals from the other person.

Because the new studies looked at neural activity at a level of detail that is difficult to obtain in humans, they could explore the detailed neural mechanism underlying this phenomenon.

The Berkeley team monitored the bats for sessions of about 100 minutes each as they engaged in a wide range of natural social interactions, such as grooming, mating, and fighting. The bats were filmed with high-speed cameras, and their specific behaviors and interactions were carefully characterized.

As this was happening, the scientists were using a technology called wireless electrophysiology to simultaneously record the brain activity in the bats’ frontal cortices across a wide range of neural signals, ranging from brain oscillations to individual neurons and local neural populations. They saw that the brains of different bats became highly correlated and that this correlation was most pronounced in the high-frequency range of brain oscillations. Furthermore, the correlation between the brains of individual bats extended across multiple timescales of social interactions, ranging from seconds to hours. Remarkably, by looking at the level of correlation, they could predict whether the bats would initiate social interactions or not.

The UCLA team took a different tack. They used a device called a miniaturized microendoscope to monitor the brain activities of mice during social situations. These tiny devices, which weigh only two grams, are fitted on the mice and allow the researchers to monitor the activity of hundreds of neurons at the same time in both animals. They saw that mice also exhibit interbrain correlations in natural social interactions where animals freely interact with each other. Moreover, the access to thousands of individual neurons gave them an unprecedented view of both animals’ decision-making processes and revealed that interbrain correlation emerges from different sets of neurons that encode one’s own behavior and behavior of the social partner.

Social interactions are often nested within the context of a dominance hierarchy. By imaging two mice in a competitive social interaction, they discovered that behavior of the dominant animal drives synchrony more strongly than behavior of the subordinate animal. Remarkably, they also found that the level of correlation between two brains predicts how mice will respond to each other’s behavior as well as the dominance relationships that develop between them.

“Natural social interactions are complex,” says Wujie Zhang, a postdoctoral researcher in Yartsev’s lab and first author of the fruit bat paper. “It is important to embrace this complexity in order to understand real-life social interactions at the neural level.”

“We know that social interactions are altered in many mental diseases in human, including autism spectrum disorders and schizophrenia,” says Lyle Kingsbury, a graduate student in Hong’s lab and first author of the mouse paper. “Developing a genetically tractable model system opens up the possibility of exploring how interbrain synchrony is disrupted in people with these conditions and may provide novel information about possible interventions.”

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Cell, Zhang and Yartsev: “Correlated Neural Activity Across the Brains of Socially Interacting Bats.” https://www.cell.com/cell/fulltext/S0092-8674(19)30551-3 DOI: 10.1016/j.cell.2019.05.023

This research was supported by the National Institutes of Health, the New York Stem Cell Foundation, the Packard Fellowship, the Klingenstein-Simons Fellowship, the Pew Charitable Trust, and the Dana Foundation.

Cell, Kingsbury et al: “Correlated Neural Activity and Encoding of Behavior Across Brains of Socially Interacting Animals.” https://www.cell.com/cell/fulltext/S0092-8674(19)30550-1 DOI: 10.1016/j.cell.2019.05.022

One of the central questions in neuroscience is clarifying where in the brain consciousness, which is the ability to experience internal and external sensations, arises. On February 12 in the journal Neuron, researchers report that a specific area in the brain, the central lateral thalamus, appears to play a key role. In monkeys under anesthesia, stimulating this area was enough to wake the animals and elicit normal waking behaviors.

Previous studies, including EEG and fMRI studies in humans, had suggested that certain areas of the brain, including the parietal cortex and the thalamus, appear to be involved in consciousness. “We decided to go beyond the classical approach of recording from one area at a time,” says senior author Yuri Saalmann, an assistant professor at the University of Wisconsin, Madison. “We recorded from multiple areas at the same time to see how the entire network behaves.”

The investigators used macaques as their animal model. By studying awake, sleeping, and anesthetized animals, they were able to narrow down the region of the brain involved in consciousness to a much more specific area than other studies have done. They were also able to rule out some areas that had been proposed in previous neurocorrelative studies of consciousness. They ultimately focused on the central lateral thalamus, which is found deep in the forebrain.

Once the researchers pinpointed this area, they tested what happened when the central lateral thalamus was activated while the animals were under anesthesia, stimulating the region with a frequency of 50 Hz. “We found that when we stimulated this tiny little brain area, we could wake the animals up and reinstate all the neural activity that you’d normally see in the cortex during wakefulness,” Saalmann says. “They acted just as they would if they were awake. When we switched off the stimulation, the animals went straight back to being unconscious.”

One test of wakefulness was their neural responses to oddball auditory stimulation–a series of beeps interspersed with other random sounds. The animals responded in the same way that awake animals would respond.

“Our electrodes have a very different design,” Saalmann says. “They are much more tailored to the shape of the structure in the brain we want to stimulate. They also more closely mimic the electrical activity that’s seen in a healthy, normal system.”

“The overriding motivation of this research is to help people with disorders of consciousness to live better lives,” says first author Michelle Redinbaugh, a graduate student in the Department of Psychology at the University of Wisconsin, Madison. “We have to start by understanding the minimum mechanism that is necessary or sufficient for consciousness, so that the correct part of the brain can be targeted clinically.”

“There are many exciting implications for this work,” she says. “It’s possible we may be able to use these kinds of deep-brain stimulating electrodes to bring people out of comas. Our findings may also be useful for developing new ways to monitor patients under clinical anesthesia, to make sure they are safely unconscious.”

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This study was funded by the National Institutes of Health, a United States-Israel Binational Science Foundation, and a Wisconsin National Primate Research Center pilot grant.

Neuron, Redinbaugh et al.: “Thalamus modulates consciousness via layer-specific control of cortex“

Mapping different parts of the brain and determining how they correspond to thoughts, actions, and other neural functions is a central area of inquiry in neuroscience, but while previous studies using fMRI scans and EEG have allowed researchers to rough out brain areas connected with different types of neural activities, they have not allowed for mapping the activity of individual neurons.

Now in a paper publishing March 26 in the journal Cell, investigators report that they have used microelectrode arrays implanted in the brains of two people to map out motor functions down to the level of the single nerve cell. The study revealed that an area believed to control only one body part actually operates across a wide range of motor functions. It also demonstrated how different neurons coordinate with each other.

“This research shows for the first time that an area of the brain previously thought to be connected only to the arm and hand has information about the entire body,” says first author Frank Willett, a postdoctoral fellow in the Neural Prosthetics Translational Laboratory at Stanford University and the Howard Hughes Medical Institute. “We also found that this area has a shared neural code that links all the body parts together.”

The study, a collaboration between neuroscientists at Stanford and Brown University, is part of BrainGate2, a multisite pilot clinical trial focused on developing and testing medical devices to restore communication and independence in people affected by neurological conditions like paralysis and locked-in syndrome. A major focus of the Stanford team has been developing ways to restore the ability of these people to communicate through brain-computer interfaces (BCIs).

The new study involved two participants who have chronic tetraplegia–partial or total loss of function in all four limbs. One of them has a high-level spinal cord injury and the other has amyotrophic lateral sclerosis. Both have electrodes implanted in the so-called hand knob area of the motor cortex of their brains. This area–named in part for its knoblike shape–was previously thought to control movement in the hands and arms only.

The investigators used the electrodes to measure the action potentials in single neurons when the participants were asked to attempt to do certain tasks–for example, lifting a finger or turning an ankle. The researchers looked at how the microarrays in the brain were activated. They were surprised to find that the hand knob area was activated not only by movements in the hand and arm, but also in the leg, face, and other parts of the body.

“Another thing we looked at in this study was matching movements of the arms and legs,” Willett says, “for example, moving your wrist up or moving your ankle up. We would have expected the resulting patterns of neural activity in motor cortex to be different, because they are a completely different set of muscles. We actually found that they were much more similar than we would have expected.” These findings reveal an unexpected link between all four limbs in motor cortex that might help the brain to transfer skills learned with one limb to another one.

Willett says that the new findings have important implications for the development of BCIs to help people who are paralyzed to move again. “We used to think that to control different parts of the body, we would need to put implants in many areas spread out across the brain,” he notes. “It’s exciting, because now we can explore controlling movements throughout the whole body with an implant in only one area.”

One important potential application for BCIs is allowing people who are paralyzed or have locked-in syndrome to communicate by controlling a computer mouse or other device. “It may be that we can connect different body movements to different types of computer clicks,” Willett says. “We hope we can leverage these different signals more accurately to enable someone who can’t talk to use a computer, since neural signals from different body parts are easier for a BCI to tease apart than those from the arm or hand alone.”

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This work was supported by the Office of Research and Development, Rehabilitation R and D Service, Department of Veterans Affairs, the Executive Committee on Research of Massachusetts General Hospital, NIDCD, NINDS, Larry and Pamela Garlick, Samuel and Betsy Reeves, the Wu Tsai Neuroscience Institute at Stanford, the Simons Foundation Collaboration on the Global Brain, the Office of Naval Research, and the Howard Hughes Medical Institute.

Cell, Willett et al. “Hand Knob Area of Premotor Cortex Represents the Whole Body in a Compositional Way” https://www.cell.com/cell/fulltext/S0092-8674(20)30220-8

While we might often take our sense of touch for granted, for researchers developing technologies to restore limb function in people paralyzed due to spinal cord injury or disease, re-establishing the sense of touch is an essential part of the process. And on April 23 in the journal Cell, a team of researchers at Battelle and the Ohio State University Wexner Medical Center report that they have been able to restore sensation to the hand of a research participant with a severe spinal cord injury using a brain-computer interface (BCI) system. The technology harnesses neural signals that are so miniscule they can’t be perceived and enhances them via artificial sensory feedback sent back to the participant, resulting in greatly enriched motor function.

“We’re taking subperceptual touch events and boosting them into conscious perception,” says first author Patrick Ganzer, a principal research scientist at Battelle. “When we did this, we saw several functional improvements. It was a big eureka moment when we first restored the participant’s sense of touch.”

The participant in this study is Ian Burkhart, a 28-year-old man who suffered a spinal cord injury during a diving accident in 2010. Since 2014, Burkhart has been working with investigators on a project called NeuroLife that aims to restore function to his right arm. The device they have developed works through a system of electrodes on his skin and a small computer chip implanted in his motor cortex. This setup, which uses wires to route movement signals from the brain to the muscles, bypassing his spinal cord injury, gives Burkhart enough control over his arm and hand to lift a coffee mug, swipe a credit card, and play Guitar Hero.

“Until now, at times Ian has felt like his hand was foreign due to lack of sensory feedback,” Ganzer says. “He also has trouble with controlling his hand unless he is watching his movements closely. This requires a lot of concentration and makes simple multitasking like drinking a soda while watching TV almost impossible.”

The investigators found that although Burkhart had almost no sensation in his hand, when they stimulated his skin, a neural signal–so small it was his brain was unable to perceive it–was still getting to his brain. Ganzer explains that even in people like Burkhart who have what is considered a “clinically complete” spinal cord injury, there are almost always a few wisps of nerve fiber that remain intact. The Cell paper explains how they were able to boost these signals to the level where the brain would respond.

The subperceptual touch signals were artificially sent back to Burkhart using haptic feedback. Common examples of haptic feedback are the vibration from a mobile phone or game controller that lets the user feel that something is working. The new system allows the subperceptual touch signals coming from Burkhart’s skin to travel back to his brain through artificial haptic feedback that he can perceive.

The advances in the BCI system led to three important improvements. They enable Burkhart to reliably detect something by touch alone: in the future, this may be used to find and pick up an object without being able to see it. The system also is the first BCI that allows for restoration of movement and touch at once, and this ability to experience enhanced touch during movement gives him a greater sense of control and lets him to do things more quickly. Finally, these improvements allow the BCI system to sense how much pressure to use when handling an object or picking something up–for example, using a light touch when picking up a fragile object like a Styrofoam cup but a firmer grip when picking up something heavy.

The investigators’ long-term goal is to develop a BCI system that works as well in the home as it does in the laboratory. They are working on creating a next-generation sleeve containing the required electrodes and sensors that could be easily put on and taken off. They also aim to develop a system that can be controlled with a tablet rather than a computer, making it smaller and more portable.

“It has been amazing to see the possibilities of sensory information coming from a device that was originally created to only allow me to control my hand in a one-way direction,” Burkhart says.

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This study was supported by Battelle Memorial Institute and The Ohio State University Center for Neuromodulation.

Cell, Ganzer et al.: “Restoring the Sense of Touch Using a Sensorimotor Demultiplexing Neural Interface” https://www.cell.com/cell/fulltext/S0092-8674(20)30347-0

For most adults who lose their vision, blindness results from damage to the eyes or optic nerve while the brain remains intact. For decades, researchers have proposed developing a device that could restore sight by bypassing damaged eyes and delivering visual information from a camera directly to the brain. In a paper publishing in the journal Cell on May 14, a team of investigators at Baylor College of Medicine in Houston report that they are one step closer to this goal. They describe an approach in which implanted electrodes are stimulated in a dynamic sequence, essentially “tracing” shapes on the surface of the visual cortex that participants were able to “see.”

“When we used electrical stimulation to dynamically trace letters directly on patients’ brains, they were able to ‘see’ the intended letter shapes and could correctly identify different letters,” senior author Daniel Yoshor says. “They described seeing glowing spots or lines forming the letters, like skywriting.”

Previous attempts to stimulate the visual cortex have been less successful. Earlier methods treated each electrode like a pixel in a visual display, stimulating many of them at the same time. Participants could detect spots of light but found it hard to discern visual objects or forms. “Rather than trying to build shapes from multiple spots of light, we traced outlines,” says first author Michael Beauchamp. “Our inspiration for this was the idea of tracing a letter in the palm of someone’s hand.”

The investigators tested the approach in four sighted people who had electrodes implanted in their brains to monitor epilepsy and two blind people who had electrodes implanted over their visual cortex as part of a study of a visual cortical prosthetic device. Stimulation of multiple electrodes in sequences produced perceptions of shapes that subjects were able to correctly identify as specific letters.

The approach, the researchers say, demonstrates that it could be possible for blind people to regain the ability to detect and recognize visual forms by using technology that inputs visual information directly into the brain, should they wish to. The researchers note, however, that several obstacles must be overcome before this technology could be implemented in clinical practice.

“The primary visual cortex, where the electrodes were implanted, contains half a billion neurons. In this study we stimulated only a small fraction of these neurons with a handful of electrodes,” Beauchamp says. “An important next step will be to work with neuroengineers to develop electrode arrays with thousands of electrodes, allowing us to stimulate more precisely. Together with new hardware, improved stimulation algorithms will help realize the dream of delivering useful visual information to blind people.”

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This work was supported by the National Institutes of Health.

Cell, Beauchamp et al.: “Dynamic Stimulation of Visual Cortex Produces Form Vision in Sighted and Blind Humans” https://www.cell.com/cell/fulltext/S0092-8674(20)30496-7

The expression “once bitten, twice shy” is an illustration of how a bad experience can induce fear and caution. How to effectively reduce the memory of aversive events is a fundamental question in neuroscience. Scientists in China are reporting that by transplanting mouse embryonic interneurons into the brains of mice and combining that procedure with training to lessen fear, they can help to reduce the fear response. The study is being published December 8 in Neuron.

“Anxiety and fear-related disorders such as post-traumatic stress disorder [PTSD] cause great suffering and impose high costs to society,” says Yong-Chun Yu, a professor at the Institutes of Brain Science at Fudan University in Shanghai and the study’s senior author. “Pharmacological and behavioral treatments of PTSD can reduce symptoms, but many people tend to relapse. There’s a pressing need for new strategies to treat these refractory cases.”

In the study, the researchers used traditional conditioning to instill fear in the mice. They exposed them to a sound as a neutral stimulus, followed by a mild shock to the foot. To determine the level of fear, they measured the amount of time the mice exhibited freezing behavior–the natural sympathetic fear response in prey animals that is indicated by crouching. They then conducted fear extinction training, in which the mice were exposed to the sound but not the shock. After a few rounds, the freezing response times were significantly reduced.

To determine the contribution that transplanting immature interneurons into the amygdala–a brain structure known to be involved in processing of fear and other emotions–could have on fear extinction training, they inserted medial ganglionic eminence (MGE) cells taken from embryos into the amygdala regions of mature mice. The transplanted cells were labeled with green fluorescent protein, enabling the researchers to experimentally confirm that the new cells were integrating into the brains’ circuits.

“We found that although the transplanted interneurons did not alter the formation of fear memories, they reduced recovery and renewal of fear after extinction training,” Yu says. However, transplantation of the neurons alone was not enough to reduce fear memories, indicating that the MGE cells were boosting the effectiveness of that training.

“Unexpectedly, we observed that the erasure of fear memory is facilitated only by transplanted immature interneurons–two weeks after transplantation,” he adds. “Previous studies had indicated that transplanted MGE cells induce plasticity when they are relatively mature–four weeks after transplantation.”

Further studies indicated that the transplanted immature interneurons reactivated a juvenile-like plasticity in the mature amygdala. “Likely related to the changes in the expression of perineuronal nets (PNNs), which are responsible for synaptic stabilization, we found that transplanted immature neurons enhance synaptic plasticity in the amygdala’s circuits by disrupting PNNs, converting the amygdala to a juvenile stage,” Yu says.

Additional experiments are required to determine how these transplanted immature interneurons rejuvenate the mature circuits. “We still don’t know the mechanism by which these immature neurons modulate the fear extinction behavior in the mice,” he concludes. “We also need to determine the exact subtype of transplanted interneurons and the exact subregion in the amygdala that are responsible for these behavioral effects.”