Feeling Fatigue - Conscious Organoids? - Switch Off Pain? - Cannabis Review

[Breedlove, S]

https://www.nature.com/articles/d41586-025-03974-w

Is your brain tired? Researchers are discovering the roots of mental fatigue

    Lynne Peeples 

Near the end of his first series of chess matches against IBM’s Deep Blue computer in 1996, the Russian grandmaster Garry Kasparov lamented what he saw as an unfair disadvantage: “I’m really tired. These games took a lot of energy. But if I play a normal human match, my opponent would also be exhausted.”

Why thinking hard makes us feel tired

Whereas machine intelligence can keep running as long as it has a power supply, a human brain will become fatigued — and you don’t have to be a chess grandmaster to understand the feeling. Anyone can end up drained after a long day of work, at school or juggling the countless decisions of daily life. This mental exhaustion can sap motivation, dull focus and erode judgement. It can raise the odds of careless mistakes. Especially when combined with sleep loss or circadian disruption, cognitive fatigue can also contribute to deadly medical errors and road traffic accidents.

It was partly Kasparov’s weary comments that inspired Mathias Pessiglione, a cognitive neuroscientist and research director at the Paris Brain Institute, to study the tired brain. He wanted to know: “Why is this cognitive system prone to fatigue?”

Researchers and clinicians have long struggled to define, measure and treat cognitive fatigue — relying mostly on self-reports of how tired someone says they feel. Now, however, scientists from across disciplines are enlisting innovative experimental approaches and biological markers to probe the metabolic roots and consequences of cognitive fatigue.

The efforts are getting a boost in attention and funding in large part because of long COVID, which afflicts roughly 6 in every 100 people after infection with the coronavirus SARS-CoV-2, says Vikram Chib, a biomedical engineer at Johns Hopkins University in Baltimore, Maryland. “The primary symptom of long COVID is fatigue,” says Chib. “I think that has opened a lot of people’s eyes.”

© 2025 Springer Nature Limited

--------------------


https://undark.org/2025/12/12/interview-matthew-owen/

 Why Lab-Grown Brain Cells Might Never Become Conscious

By Sara Talpos

It’s been more than a decade since scientists first started publishing papers on neural organoids, the small clusters of cells grown in labs and designed to mimic various parts of the human brain. Since then, organoids have been used to study everything from bipolar disorder and Alzheimer’s disease, to tumors and parasitic infections. Because these new tools have the potential to reduce the use of animals in research — a goal of the current Trump administration — the field’s future may be more financially secure than other areas of scientific research. In September, for example, the federal government announced an $87 million investment into organoid research broadly.

Matthew Owen brings a unique perspective to this emerging field. As a philosopher of mind, he focuses on trying to understand both what the mind is and how it relates to the body and the brain. He draws on the work of historical philosophers and applies some of their ideas to modern-day science. In 2020, as a visiting scholar in a neuroscience lab at McGill University, he was introduced to researchers working with organoids. Owen, who also does research in bioethics, wanted to help them address a perhaps unsettling question: Could these miniature cell clusters ever develop consciousness?

Some experts believe that organoid consciousness is not likely to happen anytime in the near future, if at all. Still, certain experiments are prompting the question. In 2022, for example, researchers, including Brett Kagan of the Australian start-up Cortical Labs, published a paper explaining how they had taught their lab-grown brain cells to play a ping-pong-like video game. (Because the cells were placed in a single layer, the structures were not technically organoids, though they are expected to have similar capabilities.) In the process, the authors wrote, the tiny cell clusters displayed “sentience.” Undark recently spoke with Owen about this particular experiment and about his own writing on organoids.

--------------------


https://www.nytimes.com/2025/12/11/well/mind/antidepressant-duration.html

How Long Can You Stay on Antidepressants?

By Christina Caron

When Marjorie Isaacson first started taking medication for depression in her late 20s, she considered it lifesaving.

At the time, she had been dealing with a rocky marriage and struggling to eat. The drug, she found, helped her gain equilibrium. “I was really grateful just to be able to function,” she said.

But recently, Ms. Isaacson, 69, has been considering whether she wants to stay on antidepressants for the rest of her life.

Specifically, Ms. Isaacson wonders about the long-term effects of her medication, a serotonin-norepinephrine reuptake inhibitor that is known to raise blood pressure. And she feels unsettled by the emerging backlash against psychiatric drugs that has condemned their side effects and difficult withdrawal symptoms.

“As the years have passed, things have changed from ‘Take it and see how it goes, no need now to be concerned’ to ‘Well, it’s turning out things might be kinda complicated,’” she said. “That is worrisome.”

Antidepressants are among the most prescribed and easily accessible drugs in the United States, and many people take them for years.

But even though modern-day antidepressants have been around for decades — the Food and Drug Administration approved Prozac for depression treatment in 1987 — there is very little information about long-term use. The F.D.A. approved the drugs based on trials that lasted, at most, a few months, and randomized controlled trials of antidepressants have typically spanned only two years or less. Current clinical guidelines do not specify the optimal amount of time they should be taken for.

The lack of data can make it hard for people to know when — or whether — to quit. So we asked psychiatrists: How long should someone stay on antidepressants?
   © 2025 The New York Times Company
--------------------


https://www.science.org/content/article/can-adding-light-sensors-nerve-cells-switch-pain-epilepsy-and-other-disorders

Can adding light sensors to nerve cells switch off pain, epilepsy, and other disorders?

 By Kelly Servick 

In the past 20 years, mice with glowing cables sprouting from their heads have become a staple of neuroscience. They reflect the rise of optogenetics, in which neurons are engineered to contain light-sensitive proteins called opsins, allowing pulses of light to turn them on or off. The method has powered thousands of basic experiments into the brain circuits that drive behavior and underlie disease.

As this research tool matured, hopes arose for using it as a treatment, too. Compared with the electrical or magnetic brain stimulation approaches already in use, optogenetics offers a way to more precisely target and manipulate the exact cell types underlying brain disorders.

So far only one optogenetic application—addressing certain kinds of vision loss by introducing opsins into cells in the eye—has made it into human trials. But its promising early results, along with the discovery of more sensitive and sophisticated opsins, are inspiring researchers to look beyond the eye, developing treatments that would act on peripheral nerves or deep in the brain. Initial tests of these strategies in animal models of epilepsy, amyotrophic lateral sclerosis (ALS), and other neurological disorders have been encouraging, researchers reported last month at the annual meeting of the Society for Neuroscience (SfN) in San Diego. One company is hoping to launch a human trial for an optogenetic pain treatment by 2027.

“We definitely don’t want to oversell the idea of using optogenetics [on human brains] any time soon, but we also are firmly convinced that this is now the right moment to be thinking about this seriously,” University of Geneva neurologist and neuroscientist Christian Lüscher told an SfN session he chaired, in which participants presented a newly published road map for bringing optogenetics to the clinic. Still, the presenters acknowledged major remaining challenges, including possible risks of inserting genes for opsins—many of which are derived from algae or other microbes—into a person’s nerves or brain cells.
© 2025 American Association for the Advancement of Science.
--------------------


https://www.nytimes.com/2025/12/12/health/medical-cannabis-benefits.html

Review of Medical Cannabis Use Finds Little Evidence of Benefit

By Jan Hoffman

To treat their pain, anxiety and sleep problems, millions of Americans turn to cannabis, which is now legal in 40 states for medical use. But a new review of 15 years of research concludes that the evidence of its benefits is often weak or inconclusive, and that nearly 30 percent of medical cannabis patients meet criteria for cannabis use disorder.

“The evidence does not support the use of cannabis or cannabinoids at this point for most of the indications that folks are using it for,” said Dr. Michael Hsu, an addiction psychiatrist and clinical instructor at the University of California, Los Angeles, and the lead author of the review, which was published last month in the medical journal JAMA. (Cannabis refers to the entire plant; cannabinoids are its many compounds.)

The analysis arrives amid a surging acceptance and normalization of cannabis products, a $32 billion industry. For the review, addiction experts at academic medical centers across the country studied more than 2,500 clinical trials, guidelines and surveys conducted mostly in the United States and Canada. They found a wide gulf between the health purposes for which the public seeks out cannabis and what gold-standard science shows about its effectiveness.

The researchers distinguished between medical cannabis, sold at dispensaries, and pharmaceutical-grade cannabinoids — the handful of medicines approved by the Food and Drug Administration with formulations containing either low-grade THC,  a psychoactive compound, or CBD, a nonintoxicating compound. Those medicines, including Marinol, Syndros and Cesamet, are available by prescription at conventional pharmacies and have had good results in easing chemotherapy-related nausea, stimulating the appetite of patients with debilitating illnesses like H.I.V./AIDS, and easing some pediatric seizure disorders.

    © 2025 The New York Times Company
--------------------


https://www.thetransmitter.org/brain-waves/dispute-erupts-over-universal-cortical-brain-wave-claim/

Dispute erupts over universal cortical brain-wave claim

By Claudia López Lloreda

A new commentary calls into question a 2024 paper that described a universal pattern of cortical brain oscillations. But that team has provided a more expansive analysis in response and stands by its original conclusions. Both articles were published today in “Matters Arising” in Nature Neuroscience.

 Ultimately, the back-and-forth suggests that a frequency “motif” may exist, but it may not be as general as the original study proposed, says Aitor Morales-Gregorio, a postdoctoral researcher at Charles University, who was not involved with any of the work. “The [2024] conclusions are way too optimistic about how general and how universal this principle might be.”

The 2024 study identified a brain-wave motif in 14 cortical areas in macaques: Alpha and beta rhythms predominated in the deeper layers, whereas gamma bands appeared in the more superficial layers. Because this motif also showed up in marmosets and humans, the researchers speculated that it may be a universal mechanism for cortical computation in primates. 

“Results typically come with a level of variability, of noise, of uncertainty,” says 2024 study investigator Diego Mendoza-Halliday, assistant professor of neuroscience at the University of Pittsburgh. But this pattern “was just there the whole time, at all times, in many, many of the recordings.” The team leveraged the findings to create an algorithm that detects Layer 4 of the cortex.

But the pattern is “by no means universal,” according to the new commentary, which found the motif in about 60 percent of the recordings in an independent monkey dataset. Further, the algorithm trained to identify Layer 4 of the cortex is unreliable, the commentary shows.

© 2025 Simons Foundation
--------------------