This novel brain-computer interface has thus far been tested in rodents. The details were published online on February 25 in the journal Advanced Functional Materials. This work is led by a team in the lab of electrical engineering professor Shadi Dayeh at the University of California San Diego, together with researchers at Boston University led by biomedical engineering professor Anna Devor.

This new brain-computer interface is on par with and outperforms the “Utah Array,” which is the existing gold standard for brain-computer interfaces with penetrating microneedles. The Utah Array has been demonstrated to help stroke victims and people with spinal cord injury. People with implanted Utah Arrays are able to use their thoughts to control robotic limbs and other devices in order to restore some everyday activities such as moving objects.

The backing of the new brain-computer interface is flexible, conformable, and reconfigurable, while the Utah Array has a hard and inflexible backing. The flexibility and conformability of the backing of the novel microneedle-array favors closer contact between the brain and the electrodes, which allows for better and more uniform recording of the brain-activity signals. Working with rodents as model species, the researchers have demonstrated stable broadband recordings producing robust signals for the duration of the implant which lasted 196 days.

In addition, the way the soft-backed brain-computer interfaces are manufactured allows for larger sensing surfaces, which means that a significantly larger area of the brain surface can be monitored simultaneously. In the Advanced Functional Materials paper, the researchers demonstrate that a penetrating microneedle array with 1,024 microneedles successfully recorded signals triggered by precise stimuli from the brains of rats. This represents ten times more microneedles and ten times the area of brain coverage, compared to current technologies.

Thinner and transparent backings

These soft-backed brain-computer interfaces are thinner and lighter than the traditional, glass backings of these kinds of brain-computer interfaces. The researchers note in their Advanced Functional Materials paper that light, flexible backings may reduce irritation of the brain tissue that contacts the arrays of sensors.

The flexible backings are also transparent. In the new paper, the researchers demonstrate that this transparency can be leveraged to perform fundamental neuroscience research involving animal models that would not be possible otherwise. The team, for example, demonstrated simultaneous electrical recording from arrays of penetrating micro-needles as well as optogenetic photostimulation.

Two-sided lithographic manufacturing

The flexibility, larger microneedle array footprints, reconfigurability and transparency of the backings of the new brain sensors are all thanks to the double-sided lithography approach the researchers used.

Conceptually, starting from a rigid silicon wafer, the team’s manufacturing process allows them to build microscopic circuits and devices on both sides of the rigid silicon wafer. On one side, a flexible, transparent film is added on top of the silicon wafer. Within this film, a bilayer of titanium and gold traces is embedded so that the traces line up with where the needles will be manufactured on the other side of the silicon wafer.

Working from the other side, after the flexible film has been added, all the silicon is etched away, except for free-standing, thin, pointed columns of silicon. These pointed columns of silicon are, in fact, the microneedles, and their bases align with the titanium-gold traces within the flexible layer that remains after the silicon has been etched away. These titanium-gold traces are patterned via standard and scalable microfabrication techniques, allowing scalable production with minimal manual labor. The manufacturing process offers the possibility of flexible array design and scalability to tens of thousands of microneedles.

Toward closed-loop systems

Looking to the future, penetrating microneedle arrays with large spatial coverage will be needed to improve brain-machine interfaces to the point that they can be used in “closed-loop systems” that can help individuals with severely limited mobility. For example, this kind of closed-loop system might offer a person using a robotic hand real-time tactical feedback on the objects the robotic hand is grasping.

Tactile sensors on the robotic hand would sense the hardness, texture, and weight of an object. This information recorded by the sensors would be translated into electrical stimulation patterns which travel through wires outside the body to the brain-computer interface with penetrating microneedles. These electrical signals would provide information directly to the person’s brain about the hardness, texture, and weight of the object. In turn, the person would adjust their grasp strength based on sensed information directly from the robotic arm.

This is just one example of the kind of closed-loop system that could be possible once penetrating microneedle arrays can be made larger to conform to the brain and coordinate activity across the “command” and “feedback” centers of the brain.

Previously, the Dayeh laboratory invented and demonstrated the kinds of tactile sensors that would be needed for this kind of application, as highlighted in this video.

Pathway to commercialization

The advanced dual-side lithographic microfabrication processes described in this paper are patented (US 10856764). Dayeh co-founded Precision Neurotek Inc. to translate technologies innovated in his laboratory to advance state of the art in clinical practice and to advance the fields of neuroscience and neurophysiology.

Binge eating disorder, which affects about 3-5% of the U.S. population, is characterized by frequent episodes of eating large amounts of food and a sense of having no control over the behavior. The study’s findings suggest that abnormal development in the brain’s centers for reward and inhibition may play a role.

The recently published study is available online in the journal Psychiatry Research.

“In children with binge eating disorder, we see abnormality in brain development in brain regions specifically linked to reward and impulsivity, or the ability to inhibit reward,” said lead author Stuart Murray, Della Martin Associate Professor of Psychiatry and the Behavioral Sciences at the Keck School of Medicine of USC, where he serves as director of the Eating Disorders Program.

“These kids have a very, very heightened reward sensitivity, especially toward calorically dense, high-sugar foods. The findings underscore the fact that this is not a lack of discipline for these kids.”

Pandemic saw increase in eating disorders among young people

Experts say eating disorders in young people soared during the pandemic, along with steep increases in hospitalizations. Social isolation, stress, disruption of routine and a social media-fueled quest for perfection all exacerbated disorders such as anorexia, muscle dysmorphia and binge eating.

Binge eating disorder puts people at risk for obesity, metabolic syndrome, abnormal cardiac function and suicidal thoughts. Treatment goals include reducing the frequency of binge eating episodes by removing “trigger” foods, as well as addressing underlying anxiety or depression. Treatment with medication and talk therapy is effective about only half the time, Murray said.

For this study, Murray and his colleagues analyzed brain scans and other data from 71 children with diagnosed binge eating disorder and 74 children without binge eating disorder, who are part of a large longitudinal study called the Adolescent Brain and Cognitive Development Study. That study includes data of 11,875 children ages 9-10 who were enrolled in 2016-2018 and recruited from 21 sites around the U.S.

In the children with binge eating disorder, they saw elevations in gray matter density in areas that are typically “pruned” during healthy brain development. Synaptic pruning, a development phase that occurs between ages 2 and 10, eliminates synapses that are no longer used, making the brain more efficient. Disturbed synaptic pruning is linked to a number of psychiatric disorders.

“This study suggests to me that binge eating disorder is wired in the brain, even from a very, very early age,” Murray said. “The question that we don’t know, which is something that we will address in time, is whether successful treatment of binge eating disorder in kids helps correct brain development. The prognosis of almost all psychiatric diseases is better if you can treat them in childhood.”

About the study

In addition to Murray, other authors were Christina Duval, Ane Balkchyan and Steven Siegel of the Department of Psychiatry and the Behavioral Sciences at the Keck School of Medicine; Ryan Cabeen, Arthur Toga and Kay Jann of the USC Mary and Mark Stevens Neuroimaging and Informatics Institute at the Keck School of Medicine; and Jason Nagata of University of California, San Francisco.

USC’s Department of Psychiatry and the Behavioral Sciences includes about 200 faculty members who provide services to patients at Children’s Hospital Los Angeles, Los Angeles County+USC Medical Center, Keck Hospital of USC, USC Norris Comprehensive Cancer Center and USC Student Health.

The study was supported by grants from the National Institutes of Health, including the National Institute of Mental Health (K23MH115184)

Diseases caused by a combination of bacteria, viruses, fungi and parasites — also known as polymicrobial infections — are challenging to treat because scientists don’t fully understand how pathogens interact during infection and how these interactions impact the drugs used to treat them.

In a study published in the journal Infection and Immunity, researchers in the Molecular & Biomedical Sciences Department looked at two pathogens that often occur at similar sites, particularly in cystic fibrosis and mechanically ventilated patients: Candida albicans and Pseudomonas aeruginosa.

Candida is the fourth most common hospital-acquired pathogen, and is particularly difficult to treat. It is targeted by a number of antifungal agents, but some only slow it rather than kill it outright. Meanwhile, P. aeruginosa infects 90% of all adult cystic fibrosis patients. Combined, C. albicans and P. aeruginosa cause more serious disease in cystic fibrosis and ventilated patients.

The researchers investigated the effectiveness of an antifungal drug, fluconazole, in the test tube and during infection of the zebrafish with both pathogens. Fluconazole is known to slow fungal growth, but Candida can become tolerant to the drug and not only survive, but also develop tolerance that leads to failed therapy and, potentially, death.

What the study found was promising. The results showed that P. aeruginosa works with fluconazole to eliminate drug tolerance and clear the C. albicans infection in the culture and the zebrafish.

“Polymicrobial infections are challenging to treat not only because of the lack of understanding of how invading microorganisms interact but also because we don’t know how these interactions affect treatment efficacy. Our work demonstrates that polymicrobial interactions can indeed affect treatment efficacy and, most importantly, it highlights the importance of nutrient availability in the environment — such as iron in our study — and how it modulates treatment efficacy,” says Siham Hattab, lead author of the study who conducted the research as part of her Ph.D. in the Department of Molecular and Biomolecular Sciences.

What’s more, the bacteria also enhance the drug’s ability against a second pathogenic Candida species that tends to be more resistant to the drug.

The increased effectiveness of the drug suggests to the researchers that there is still much more to learn about how current drugs work when targeting these dangerous and complex polymicrobial infections. “We are really excited to have revealed that sometimes drugs against fungal infection can work even better in a more ‘real-world’ situation than in the test tube. There is still a lot to learn about how pathogens interact during infection, and it will be interesting to see how the bacteria manage to work with the drugs to target Candida,” says Robert Wheeler, associate professor of microbiology and senior author of the study.

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Researchers from half a dozen universities investigated what the future might hold in terms of rainfall and soil moisture, two measurements of drought. The team, led by UC Santa Barbara’s Samantha Stevenson, found that many regions of the world will enter permanent dry or wet conditions in the coming decades, under modern definitions. The findings, published in the Proceedings of the National Academy of Sciences, reveal the importance of rethinking how we classify these events as well as how we respond to them.

“Essentially, we need to stop thinking about returning to normal as a thing that is possible,” said Stevenson, an assistant professor in the Bren School of Environmental Science & Management. This idea affects both how we define drought and pluvial (abnormally wet) events and how we adapt to a changing environment.

A drought is when conditions are drier than expected. But this concept becomes vague when the baseline itself is in flux. Stevenson suggests that, for some applications, it’s more productive to frame drought relative to this changing background state, rather than a region’s historical range of water availability.

To predict future precipitation and soil moisture levels, Stevenson and her colleagues turned to a new collection of climate models from different research institutions. Researchers had run each model many times with slightly different initial conditions, in what scientists call an “ensemble.” Since the climate is an inherently chaotic system, researchers use ensembles to account for some of this unpredictability.

The results show a world where certain regions are in permanent drought while others experience perennial pluvial for the rest of the 21^st century. The team calculated the year in which average soil moisture will exceed the threshold that defines either a megadrought or a megapluvial. “In other words, at what point do average conditions exceed what we would consider a megadrought if it happened now, [and never return to ‘normal’]” Stevenson said.

The western United States has already crossed this benchmark, and there are other places headed that way as well, including Australia, southern Africa and western Europe. “But, again, that’s if we use today’s definition of a drought,” Stevenson said.

The authors argue that we need to move away from fixed definitions toward a more nuanced account of drought and pluvial. “Our idea of normal is, in a sense, meaningless when ‘normal’ is continuously changing,” Stevenson added.

Climate models indicate that average soil moisture in many regions will continue to drop. That said, the team’s ensembles suggests that soil moisture will continue to experience drought-related variation similar to today, relative to the ever-drier baseline.

The fluctuation highlights the need to consider both long term changes and the usual ups and downs associated with historic droughts and pluvials. “The most important management challenge will be to adjust for the relentless declines in water availability, as this exceeds the expected impact of future megadroughts,” said co-author Julia Cole, a professor at the University of Michigan.

Precipitation patterns, on the other hand, will become much more extreme. Warm air holds more moisture than cold air. So as the atmosphere heats up, it’ll be able to suck more moisture from dry areas and dump more precipitation on wet regions.

“We wanted to consider both precipitation and soil moisture at the same time because that can be important for water management,” Stevenson said. For instance, we will need to adapt infrastructure to more arid conditions in the American West, but that infrastructure will also need to handle more intense rainfall.

“When we talk about being in a drought, the presumption is that eventually the drought will end, and conditions will return to normal,” Stevenson said. “But if we’re never returning to normal, then we need to adapt all of the ways that we manage water with the expectation that normal will continually be drier and drier every year.”

The discovery, published in the scientific journal Cell, results from a collaboration of scientists at the Max Planck Florida Institute for Neuroscience, HHMI’s Janelia Research Campus, the Allen Institute for Brain Science, and others. Led by co-first authors Dr. Hidehiko Inagaki and Dr. Susu Chen and senior author Dr. Karel Svoboda, the scientists set out to understand how cues in our environment can trigger planned movement.

“The brain is like an orchestra,” said Dr. Inagaki. “In a symphony, instruments play diverse tunes with different tempos and timbres. The collective of these sounds shapes a musical phrase. Similarly, neurons in the brain are active with diverse patterns and timing. The ensemble of neuronal activities mediates specific aspects of our behavior.”

For example, the motor cortex is a brain area that controls movement. Activity patterns in the motor cortex are dramatically different between the planning and execution phases of movement. The transition between these patterns is critical to trigger movement. Yet, the brain areas controlling this transition were unknown. “There must be brain areas acting as the conductor,” described Dr. Inagaki. “Such areas monitor environmental cues and orchestrate neuronal activities from one pattern to the other. The conductor ensures that plans are converted into action at the right time.”

To identify the neural circuit that serves as the conductor to initiate planned movement, the team simultaneously recorded the activity of hundreds of neurons while a mouse performed a cue-triggered movement task. In this task, mice were trained to lick to the right if whiskers were touched or to the left if whiskers were not touched. If the animals licked in the correct direction, they received a reward. However, there was a catch. The animals had to delay their movement until a tone, or “go cue,” was played. Only correct movements after the go cue would be rewarded. Therefore, mice maintain a plan of the direction they will lick until the go cue and execute the planned lick after.

The scientists then correlated complex neuronal activity patterns to relevant stages of the behavioral task. The researchers found brain activity occurring immediately after the go cue and during the switch between motor planning and execution. This brain activity arose from a circuit of neurons in the midbrain, thalamus, and cortex.

To test whether this circuit acted as a conductor, the team used optogenetics. This approach enabled the scientists to activate or inactivate this circuit using light. Activating this circuit during the planning phase of the behavioral task switched the mouse’s brain activity from motor planning to execution and caused the mouse to lick. On the other hand, turning off the circuit while playing the go cue suppressed the cued movement. The mice remained in a motor planning stage as if they had not received the go cue.

This work by Dr. Inagaki and his colleagues identified a neural circuit critical for triggering movement in response to environmental cues. Dr. Inagaki explains how their findings demonstrate generalizable features of behavioral control. “We have found a circuit that can change the activity of the motor cortex from motor planning to execution at the appropriate time. This gives us insight into how the brain orchestrates neuronal activity to produce complex behavior. Future work will focus on understanding how this circuit and others reorganize neuronal activity across many brain regions.”

In addition to these fundamental advances in understanding how the brain functions, this work has important clinical implications. In motor disorders, such as Parkinson’s disease, patients experience difficulty in self-initiated movement, including difficulty in walking. However, adding environmental cues to trigger movements, such as lines on the floor or auditory tones, can dramatically improve a patient’s mobility. This phenomenon, known as paradoxical kinesia, suggests that different mechanisms in the brain are recruited for self-initiated movement and cue-triggered movement. Discovering the brain networks involved in cue-triggered movements, which are relatively spared in Parkinson’s disease, may help to optimize treatment.