How do directional connections shape complex dynamics in neuronal networks?

Uncovering the relationship between structure (connectivity) and function (neuronal activity) is a fundamental question across many areas of biology. However, investigating this directly in animal brains is challenging because of the immense complexity of their neural connections and the invasive surgeries that are typically needed. Lab-grown neurons with artificially-controlled connections have the possibility of becoming a useful alternative to animal testing, particularly as we learn how to accurately characterize their behaviour.

A research team at Tohoku University used microfluidic devices to reveal how directional connections shape the complex dynamics of neuronal networks. They also developed mathematical models based on experimental data to predict how connectivity influences activity across space and time.

The results were published in Neural Networks on November 28, 2024.

Like a river current, directional connections in neuronal networks propagate signals in a downstream flow from one area to another. A microfluid device has tiny channels that can precisely direct the flow, which can help fabricate neurons that react more similarly to in-vivo models. By studying in-vitro neurons in a lab environment, the research team was able to efficiently and constructively explore whether one-way connections play other fundamental roles in shaping brain dynamics.

“The brain is difficult to understand, in part, because it is dynamic — it can learn to respond differently to the same stimuli over time based on a number of factors,” says lead author Nobuaki Monma.

The research team fabricated neuronal networks bearing modular connectivity (as observed in animals’ nervous systems) and embedded directional connections between modules using microchannels. The connections were embedded in a feedforward manner to minimize excessive excitatory reactions. Using calcium imaging to record spontaneous activity exhibited by the neuronal network, they found that networks incorporating directional connections exhibited more complex activity patterns compared to networks without directionality.

In addition, the researchers developed two mathematical models to clarify the underlying network mechanisms behind biological observations and to predict configurations that would yield greater dynamical complexity. The models determined that the interplay between modularity and connectivity fostered more complex activity patterns.

“The findings of this study are expected not only to deepen our fundamental understanding of neuronal networks in the brain, but also to find applications in fields such as medicine and machine learning,” proposes Associate Professor Hideaki Yamamoto.

This may also offer an in-vitro model for developing biologically plausible artificial neural networks. Further theoretical advancements would also contribute to modeling large-scale networks, which may provide insights to future connectome analysis of the brain. The more thoroughly we understand these neuronal networks, the more it could be used as a trusty tool to unlock the many mysteries of the brain.

Share Button

Child mental health crisis: Better resilience is the solution, say experts

The surge in mental health referrals among young people has prompted debate among experts about the cause – and the most effective solution

Share Button

AI slashes cost and time for chip design, but that is not all

Specialized microchips that manage signals at the cutting edge of wireless technology are astounding works of miniaturization and engineering. They’re also difficult and expensive to design.

Now, researchers at Princeton Engineering and the Indian Institute of Technology have harnessed artificial intelligence to take a key step toward slashing the time and cost of designing new wireless chips and discovering new functionalities to meet expanding demands for better wireless speed and performance. In an article published Dec. 30 in Nature Communications, the researchers describe their methodology, in which an AI creates complicated electromagnetic structures and associated circuits in microchips based on the design parameters. What used to take weeks of highly skilled work can now be accomplished in hours.

What is more, the AI behind the new system has produced strange new designs featuring unusual patterns of circuitry. Kaushik Sengupta, the lead researcher, said the designs were unintuitive and unlikely to be developed by a human mind. But they frequently offer marked improvements over even the best standard chips.

“We are coming up with structures that are complex and looks random shaped and when connected with circuits, they create previously unachievable performance. Humans cannot really understand them, but they can work better,” said Sengupta, a professor of electrical and computer engineering and co-director of NextG, Princeton’s industry partnership program to develop next-generation communications.

These circuits can be engineered towards more energy efficient operation or to make them operable across an enormous frequency range that is not currently possible. Furthermore, the method synthesizes inherently complex structures in minutes, while conventional algorithms may take weeks. In some cases, the new methodology can create structures that are impossible to synthesize with current techniques.

Uday Khankhoje, a co-author and associate professor of electrical engineering at IIT Madras, said the new technique not only delivers efficiency but promises to unlock new approaches to design challenges that have been beyond the capability of engineers.

“This work presents a compelling vision of the future,” he said. “AI powers not just the acceleration of time-consuming electromagnetic simulations, but also enables exploration into a hitherto unexplored design space and delivers stunning high-performance devices that run counter to the usual rules of thumb and human intuition.”

Wireless chips are a combination of standard electronic circuits like those in computer chips and electromagnetic structures including antennas, resonators, signal splitters, combiners and others. These combinations of elements are put together in every circuit block, carefully handcrafted and co-designed to operate optimally. This method is then scaled to other circuits, sub-systems and systems, making the design process extremely complex and time consuming, particularly for modern, high-performance chips behind applications like wireless communication, autonomous driving, radar and gesture recognition.

“Classical designs, carefully, put these circuits and electromagnetic elements together, piece by piece, so that the signal flows in the way we want it to flow in the chip. By changing those structures, we incorporate new properties,” Sengupta said. “Before, we had a finite way of doing this, but now the options are much larger.”

It can be hard to comprehend the vastness of a wireless chip’s design space. The circuitry in an advanced chip is so small, and the geometry so detailed, that the number of possible configurations for a chip exceeds the number of atoms in the universe, Sengupta said. There is no way for a person to understand that level of complexity, so human designers don’t try. They build chips from the bottom up, adding components as needed and adjusting the design as they build.

The AI approaches the challenge from a different perspective, Sengupta said. It views the chip as a single artifact. This can lead to strange, but effective arrangements. He said humans play a critical role in the AI system, in part because that AI can make faulty arrangements as well as efficient ones. It is possible for AI to hallucinate elements that don’t work, at least for now. This requires some level of human oversight.

“There are pitfalls that still require human designers to correct,” Sengupta said. “The point is not to replace human designers with tools. The point is to enhance productivity with new tools. The human mind is best utilized to create or invent new things, and the more mundane, utilitarian work can be offloaded to these tools.”

The researchers have used AI to discover and design complex electromagnetic structures that are-co-designed with circuits to create broadband amplifiers. Sengupta said future research will involve linking multiple structures and designing entire wireless chips with the AI system.

“Now that this has shown promise, there is a larger effort to think about more complicated systems and designs,” he said. “This is just the tip of the iceberg in terms of what the future holds for the field.”

Share Button

Elderly patients’ five-day wait in ‘intolerable’ A&E

At 17:00 GMT on Monday, 1,052 people were in Northern Ireland’s nine EDs, up from 797 on Sunday night.

Share Button

Starmer’s NHS waiting list plan – will it work?

Lack of staff and money could make it difficult for government to achieve its aims.

Share Button

Major Blow To Keir Starmer As Poll Finds 1 In 4 Brits Regret Voting For Labour

One in four voters who backed Keir Starmer at the general election now regret it, according to a new poll.

Research by think tank More in Common and published by LBC found 56% of voters now have a lower opinion of the government after six months in power.

It seems that three policies drove this frustrated response to Labour – the government’s decision to reduce the number of pensioners eligible for the winter fuel allowance, cut inheritance tax relief for farmers and its refusal to compensate WASPI women over pension changes.

Some voters said these choices were more damaging to the governing party than partygate – the repeated breach of their own lockdown rules which helped oust Boris Johnson from No.10 – was to the Conservatives.

To make matters even worse for the prime minister, 54% of respondents said they were pessimistic Labour can deliver the change they promised in the election.

A quarter of participants also said they regret voting for Starmer – and that fraction creeps up to two in five (41%) among the 65 to 74 year olds.

Starmer did secure a landslide victory in July’s general election, taking a staggering 411 seats, but, while his success was widespread, it was shallow. Many Labour MPs won their constituencies on relatively narrow majorities.

Asked how the government would win the electorate back after this devastating poll, health minister Karin Smyth told LBC: “We have to deliver.

“That’s disappointing to hear, but we’re just six months in, we know the awful inheritance that we have to deal with.

“Things like today, delivering on those [NHS] waiting lists, getting more money in people’s pockets, better lives, better education for their children, getting those waiting lists down and crucially being able to see a GP – we know that delivery is what matters.

“That’s why Keir Starmer is out today, setting out, in the start of this new year, our plan for reducing those waiting lists, we’re very conscious of that.”

The prime minister has pledged today to introduce half a million more appointments as part of the government’s plan to cut maximum waiting times from 18 months to 18 weeks by the next election.

Starmer announced his plans to reform the country at the end of 2024 with his six milestones, including putting more police officers on the street, building 1.5 million homes and putting more money in people’s pockets.

Share Button

Age matters: Kidney disorder indicator gains precision

Annual health checkups regularly include urine tests that serve several purposes, including checking for symptoms of kidney disease. The presence of albumin in the urine is one indicator as is glomerular filtration rate. In diabetic nephropathy, albuminuria first appears, leading to excessive filtration and eventually a decrease in GFR.

In the elderly, however, excessive filtration cannot be detected due to age-related GFR decline. To accurately assess GFR, Osaka Metropolitan University researchers have come up with a new calculation method.

The group led by Dr. Akihiro Tsuda, a lecturer at the Graduate School of Medicine, assessed 180 kidney transplant donor candidates to define a new formula for determining the threshold value for hyperfiltration based on age and GFR values.

Among other findings, the conventional method of correcting for body surface area in obese patients was determined to be inaccurate as excessive filtration cannot be detected. The researchers suggest calculating GFR without the correction but by taking into account the decline in the filtration rate due to aging.

“Since hyperfiltration is a precursor to diabetic nephropathy, we hope that using this new formula will more accurately diagnose the condition, leading to early detection and treatment,” stated Dr. Tsuda.

The findings were published in Hypertension Research.

Share Button

Government unveils plan to cut NHS waiting list backlog

The government pledged to cut the list of patients waiting more than 18 weeks for treatment in England by nearly half a million over the next year.

Share Button

NHS App upgrade to give patients more choice over treatment

Plans for an upgraded NHS app to allow more patients in England to book treatments will be announced by the health secretary on Monday.

Share Button

If Your Poo Looks Like This, It’s Time To See A Doctor

(This story was originally published in 2019.)

It can be pretty, um, crappy dealing with bowel issues.

Figuring out what’s normal and what isn’t can be a challenge if you don’t know what to look for. Stools come in all shapes and sizes and can shift forms depending on what you’re eating or what is going on in your life at the moment.

“Bowel movements change from person to person depending on his or her diet, physical activity, how much water they consume and what medications they take,” said M. Nuri Kalkay, a retired gastroenterologist and health blogger.

Everyone has their own barometer of how often their body is used to going and what a typical stool looks like for them. But what if things change and you see something beyond the norm in the toilet? We chatted with some experts to determine what bowel habits are aren’t so ordinary and might require a trip to the doctor.

Black and/or tarry stools

Jeffery M. Nelson, surgical director at the Center for Inflammatory Bowel and Colorectal Diseases at Baltimore’s Mercy Medical Center, said if your poo is black, “not just dark brown,” you should be concerned.

“This means bleeding is happening from an upper GI source like the esophagus, stomach or small bowel,” he explained.

There are some exceptions to this: If you’re taking iron supplements, for example, your stools may appear dark green to the point where they almost look black. If you’ve taken bismuth medication like Pepto Bismol, that can also make your stools look almost black. It’s always best to check with a doctor if you’re unsure.

Bright red blood in your stools

If you find blood in your stool either by itself on the toilet paper, in the water or streaked in the stools, this can indicate a bleeding source from the anal canal or a low rectal source.

“Things like internal haemorrhoids, anal fissures, rectal polyps or rectal cancers can all do this,” said Nelson. All of these are reasons to see a doctor.

Maroon-coloured stools

If your stools are this colour, then they’re likely also more liquid in consistency and paired with an unpleasant, distinct odour. According to Nelson, this can indicate bleeding from the very end of the small bowel or the colon.

“Diverticulosis and arteriovenous malformations are the classic causes of this presentation,” and a reason to go to the emergency room, he said.

Pale, oily and especially foul-smelling stools

“This finding is called steatorrhea and is due to excess fat in the stool,” explained Chris Carrubba, an internal medicine doctor in Jacksonville, Florida.

Carrubba said steatorrhea is often seen with malabsorption syndromes, pancreatic insufficiency and biliary disease. “The presence of steatorrhea indicates difficulty absorbing fat and these patients are at risk of developing deficiencies in fat soluble vitamins,” like vitamins A, D, E and K, he said.

Stools that are different than your typical bowel movements

Your body is a creature of habit in a lot of ways. For example, if you consistently have smooth, long sausage-like stools and suddenly they change to a completely different size, you should speak to your doctor.

“Pencil thin versus log-like routinely could mean that an inflammatory condition may be present such as Crohn’s or infection,” said Karen Soika, a general surgeon in Greenwich, Connecticut.

If the consistency of your stools has changed to watery or diarrhoea, this could signify irritable bowel syndrome, an infectious cause or an inflammatory bowel disease such as Ulcerative colitis.

IBS or infections can also increase constipation.

Watery diarrhoea after a camping trip

This can be due to giardia, “a protozoal organism that is found in freshwater and the reason that you should always boil and sanitise water from mountain streams or lakes,” Carrubba said.

Ingestion of this organism can result in giardiasis, which leads to abdominal pain and persistent, watery diarrhoea. The issue can be treated with antimicrobials. In addition to drinking contaminated water, you can also be exposed to giardia by eating uncooked vegetables or fruits that were rinsed in contaminated water and by improperly washing hands after coming into contact with faeces or an infected human or animal.

Mucus in the stool

This is usually due to inflammation of the intestines, said Peyton Berookim, a gastroenterologist in Los Angeles. He noted that the condition can be seen in inflammatory bowel diseases like ulcerative colitis or Crohn’s. It can also be due to inflammation caused by a bacterial infection or IBS.

“Mucus associated with blood and or abdominal pain should not be ignored and requires medical attention,” he explained.

Hard or infrequent stools

This signifies constipation and is usually caused by a lack of fibre in your diet, as well as low water intake. However, this issue may also be caused by medications, blockages in the intestine, or in more rare cases, colon cancer.

“Constipation can be treated in many ways and I always begin with increasing fibre and water intake. The recommended daily intake of fibre is at least 25 grams and the amount of water needed varies from person to person,” said Jack Braha, a gastroenterologist at Brooklyn Gastroenterology and Endoscopy Associates.

Laxatives are available over-the-counter to help with this issue and work by either increasing the motility in your gut or increasing the amount of water delivered to the colon, Braha said.

“But for symptoms that do not rapidly improve or begin after the age of 50, it is important to seek advice from a gastroenterologist in order to determine if further testing like a colonoscopy is needed to check for more serious issues such as an intestinal obstruction or colon cancer,” he said.

Loose, watery or frequent stools

“Diarrhoea is common after eating bad food or from an infection and should not last more than a week in most instances,” Braha explained.

Loose stools may be a cause for concern if the diarrhoea lasts longer than two weeks or when it is in conjunction with bleeding, weight loss or symptoms that keep you awake at night.

“When diarrhoea is not from an infectious source, we look for other common causes like lactose intolerance, irritable bowel syndrome, inflammatory bowel disease or celiac disease,” Braha said. “Gastroenterologists can usually find the cause of diarrhoea by checking certain blood tests, stool tests and performing a colonoscopy.”

Generally, it’s a good idea to make an appointment with your doctor if you’re concerned about your bowel movements at all. Your poo may be trying to tell you something.

Share Button