The study, conducted by researchers at Georgetown University Medical Center in collaboration with Trinity College Dublin, Ireland, is reported January 16, 2024, in the Journal of Neuroscience.

Importantly for diagnostic and treatment purposes, the researchers found that the memory loss attributed to head injury was not a permanent pathological event driven by a neurodegenerative disease. Indeed, the researchers could reverse the amnesia to allow the mice to recall the lost memory, potentially allowing cognitive impairment caused by head impact to be clinically reversed.

The Georgetown investigators had previously found that the brain adapts to repeated head impacts by changing the way the synapses in the brain operate. This can cause trouble in forming new memories and remembering existing memories. In their new study, investigators were able to trigger mice to remember memories that had been forgotten due to head impacts.

“Our research gives us hope that we can design treatments to return the head-impact brain to its normal condition and recover cognitive function in humans that have poor memory caused by repeated head impacts,” says the study’s senior investigator, Mark Burns, PhD, a professor and Vice-Chair in Georgetown’s Department of Neuroscience and director of the Laboratory for Brain Injury and Dementia.

In the new study, the scientists gave two groups of mice a new memory by training them in a test they had never seen before. One group was exposed to a high frequency of mild head impacts for one week (similar to contact sport exposure in people) and one group were controls that didn’t receive the impacts. The impacted mice were unable to recall the new memory a week later.

“Most research in this area has been in human brains with chronic traumatic encephalopathy (CTE), which is a degenerative brain disease found in people with a history of repetitive head impact,” said Burns. “By contrast, our goal was to understand how the brain changes in response to the low-level head impacts that many young football players regularly experience.”

Researchers have found that, on average, college football players receive 21 head impacts per week with defensive ends receiving 41 head impacts per week. The number of head impacts to mice in this study were designed to mimic a week of exposure for a college football player, and each single head impact by itself was extraordinarily mild.

Using genetically modified mice allowed the researchers to see the neurons involved in learning new memories, and they found that these memory neurons (the “memory engram”) were equally present in both the control mice and the experimental mice.

To understand the physiology underlying these memory changes, the study’s first author, Daniel P. Chapman, Ph.D., said, “We are good at associating memories with places, and that’s because being in a place, or seeing a photo of a place, causes a reactivation of our memory engrams. This is why we examined the engram neurons to look for the specific signature of an activated neuron. When the mice see the room where they first learned the memory, the control mice are able to activate their memory engram, but the head impact mice were not. This is what was causing the amnesia.”

The researchers were able to reverse the amnesia to allow the mice to remember the lost memory using lasers to activate the engram cells. “We used an invasive technique to reverse memory loss in our mice, and unfortunately this is not translatable to humans,” Burns adds. “We are currently studying a number of non-invasive techniques to try to communicate to the brain that it is no longer in danger, and to open a window of plasticity that can reset the brain to its former state.”

In addition to Burns and Chapman the authors include Stefano Vicini at Georgetown University and Sarah D. Power and Tomás J. Ryan at Trinity College Dublin, Ireland.

This work was supported by the Mouse Behavior Core in the Georgetown University Neuroscience Department and by the National Institutes of Health (NIH) / National Institute of Neurological Disorders and Stroke (NINDS) grants R01NS107370 & R01NS121316. NINDS also supported F30 NS122281 and the Neural Injury and Plasticity Training Grant housed in the Center for Neural Injury and Recovery at Georgetown University (T32NS041218). Seed funding is from the CTE Research Fund at Georgetown.

The authors report having no personal financial interests related to the study.

The scientists are not armed with parkas and shovels. Instead, they have tapped into data from GPS satellite radiometers, capturing the sunlight bouncing off the Arctic. This data dive could be the key to cracking the Arctic amplification code.

“The uneven warming in the Arctic is both a scientific curiosity and a pressing concern, leading us to question why this landscape has been changing so dramatically,” said Erika Roesler, an atmospheric and climate scientist at Sandia.

Previous studies have suggested that sea-ice albedo feedbacks are likely driving Arctic amplification. These albedo feedbacks can be broken down into two main areas. First, there’s an overall reduction in sea ice, leading to more exposure of the dark ocean. This absorbs more sunlight than snow-covered ice and raises temperatures. The second factor is the reflectivity of the remaining sea ice, or local albedo, which includes ponding water on ice due to melting.

Sandia researchers aimed to gain a better understanding of the reduction in reflectivity in the Arctic. Senior scientist Phil Dreike collaborated with the U.S. Space Force to obtain permission for Sandia to analyze previously unpublished data from the radiometers on GPS satellites.

“New observational climate datasets are unique,” Roesler said. “To qualify as a climate dataset, observations must span a multitude of years. Small-scale science projects are typically not that long in duration, making this dataset particularly valuable.”

Amy Kaczmarowski, an engineer at Sandia, conducted an analysis of the data spanning from 2014 to 2019.

“There have been numerous local measurements and theoretical discussions regarding the effects of water puddling on ice albedo,” Kaczmarowski said. “This study represents one of the first comprehensive examinations of year-to-year effects in the Arctic region. Sandia’s data analysis revealed a 20% to 35% decrease in total reflectivity over the Arctic summer. According to microwave sea-ice extent measurements collected during the same period, one-third of this loss of reflectivity is attributed to fully melted ice.”

The other two-thirds of the loss in reflectivity is likely caused by the weathering of the remaining sea ice.

“The key discovery here is just how much the weathered ice is reducing reflectivity,” Kaczmarowski added. Weathered ice refers to the remaining sea ice, which can be thinner and may contain melt ponds.

The GPS satellites are expected to continue providing data through 2040. The Sandia team hopes other researchers will consider their findings, recently published in the journal Nature Scientific Reports, and incorporate them into their models for Arctic amplification. They plan to continue mining the GPS data and are enthusiastic about collaborating with other climate researchers for further analysis.

“We will continue to use this data to investigate various regions of the Earth for climate applications,” Kaczmarowski said.

The rules of statistical physics address the uncertainty about the state of a system that arises when that system interacts with its environment. But they’ve long missed another kind, say SFI Professor David Wolpert and Jan Korbel, a postdoctoral researcher at the Complexity Science Hub in Vienna, Austria. In a new paper published in Physical Review Research, the pair of physicists argue that uncertainty in the thermodynamic parameters themselves — built into equations that govern the energetic behavior of the system — may also influence the outcome of an experiment.

“At present, almost nothing is known about the thermodynamic consequences of this type of uncertainty despite its unavoidability,” says Wolpert. In the new paper, he and Korbel consider ways to modify the equations of stochastic thermodynamics to accommodate it.

When Korbel and Wolpert met at a 2019 workshop on information and thermodynamics, they began talking about this second kind of uncertainty in the context of non-equilibrium systems.

“We wondered, what happens if you don’t know the thermodynamic parameters governing your system exactly?” recalls Korbel. “And then we started playing around.” The equations that describe thermodynamic systems often include precisely defined terms for things like temperature and chemical potentials. “But as an experimenter or an observer you don’t necessarily know these values” to very large precision, says Korbel.

Even more vexing, they realized that it’s impossible to measure parameters like temperature, pressure, or volume precisely, both because of the limitations of measurement and the fact that these quantities change quickly. They recognized that uncertainty about those parameters not only influences information about the original state of the system, but also how it evolves.

It’s almost paradoxical, Korbel says. “In thermodynamics, you’re assuming uncertainty about your state so you describe it in a probabilistic way. And if you have quantum thermodynamics, you do this with quantum uncertainty,” he says. “But on the other hand, you’re assuming that all the parameters are known with exact precision.”

Korbel says the new work has implications for a range of natural and engineered systems. If a cell needs to sense the temperature to carry out some chemical reaction, for example, then it will be limited in its precision. The uncertainty in the temperature measurement could mean that the cell does more work — and uses more energy. “The cell has to pay this extra cost for not knowing the system,” he says.

Optical tweezers offer another example. These are high-energy laser beams configured to create a kind of trap for charged particles. Physicists use the term “stiffness” to describe the particle’s tendency to resist being moved by the trap. To determine the optimal configuration for the lasers they measure the stiffness as precisely as possible. They typically do this by taking repeated measurements, assuming that the uncertainty arises from the measurement itself.

But Korbel and Wolpert offer another possibility — that the uncertainty arises from the fact that the stiffness itself may be changing as the system evolves. If that’s the case, then repeated identical measurements won’t capture it, and finding the optimal configuration will remain elusive. “If you keep doing the same protocol, then the particle doesn’t end up in the same point, you may have to do a little push,” which means extra work that’s not described by the conventional equations.

This uncertainty could play out at all scales, Korbel says. What’s often interpreted as uncertainty in measurement may be uncertainty in the parameters in disguise. Maybe an experiment was done near a window where the sun was shining, and then repeated when it was cloudy. Or perhaps the air conditioner kicked on between multiple trials. In many situations, he says, “it’s relevant to look at this other type of uncertainty.”

The risks of cardiac conditions associated with the use of antipsychotics have been a concern for the last 30 years. Drugs have previously been either removed from the market or had their use restricted due to an unacceptably high risk of lethal ventricular arrhythmias. Drug-induced cardiac arrhythmias, however, remain an important clinical issue because there are drugs that increase the risk of SCD, but remain on the market because they serve an important clinical need and there are no safer alternatives.

Professor Jamie Vandenberg, PhD, MBBS, FHRS, of the Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia, co-author of the editorial accompanying the study, explains, “Of the 41 drugs on the market in the United States that are listed as having known risk of heart rhythm disorders, five are antipsychotic drugs, the mainstay of treatment for schizophrenia and psychosis. The use of antipsychotic drugs is associated with an approximately two-fold increased risk of sudden cardiac death. If we cannot eliminate this risk, then at the least, we need to minimize the risk by identifying those patients who are at highest risk and managing them more closely.”

Lead investigator of the study Shang-Hung Chang, MD, PhD, of the Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan, adds, “The use of the antipsychotics quetiapine and haloperidol to treat mental disorders is widespread. In an effort to enhance patient safety and optimize the management of individuals receiving these medications, we have investigated the incidences, risk factors, and clinical outcomes of severe QT prolongation to provide valuable insights for healthcare professionals, patients, and caregivers.”

The research involved a retrospective analysis of electronic medical records of a large cohort of patients from a healthcare provider in Taiwan who received quetiapine or haloperidol therapy. Investigators evaluated the incidences, risk factors, and clinical correlates of severe QT prolongation (i.e., ventricular arrhythmias and sudden cardiac death) in these patients. The most significant results of the study were that more than 10% of patients developed severe QT prolongation during follow-up and the increased risk of ventricular arrhythmias and sudden cardiac death in quetiapine or haloperidol users who developed severe QT prolongation.

Co-author Chun-Li Wang, MD, of the Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan, says the findings underscore the importance of closely monitoring patients receiving these medications and implementing appropriate risk mitigation strategies to ensure patient safety. “Clinicians should be aware of the potential risks associated with quetiapine use, particularly the risk of severe QT prolongation and its associated outcomes, including ventricular arrhythmias and sudden cardiac death.”

Professor Vandenberg comments, “It would be prudent to undertake an ECG before and after commencement of an antipsychotic drug. If it is an option, one could stop a drug causing QT prolongation and try a different antipsychotic. But if this is not practical, one should pay particular attention to reducing other risk factors, such as prescription of other drugs that may exacerbate QT prolongation and be vigilant for hypokalemia.”

The study found that, due in part to the challenges of extracting groundwater, an aquifer’s depletion can curb crop yields even when it appears saturated enough to continue meeting the demands of irrigation. Those agricultural losses escalate as an aquifer dwindles, the researchers reported, so that its depletion exerts a greater toll on corn and soybean yields when waning from, say, 100 feet thick to 50 than from 200 feet to 150.

That reality should encourage policymakers, resource managers and growers to reconsider the volume of crop-quenching groundwater they have at their disposal, the team said, especially in the face of fiercer, more frequent drought.

“As you draw down an aquifer to the point that it’s quite thin, very small changes in the aquifer thickness will then have progressively larger and larger impacts on your crop production and resilience,” said Nick Brozović, director of policy at the Daugherty Water for Food Global Institute. “And that’s a thing that we don’t predict well, because we tend to predict based on the past. So if we base what’s going to happen on our past experience, we’re always going to underpredict. We’re always going to be surprised by how bad things get.”

The team came to its conclusions after analyzing yields, weather and groundwater data from the High Plains Aquifer, which, as the largest in the United States, underlies portions of eight states — including nearly all of Nebraska. Some areas of the aquifer, especially those beneath Texas and Kansas but also the Cornhusker State, have diminished considerably over the past several decades, pumped for the sake of irrigating land that would otherwise stand little chance of sustaining crops.

“In terms of things that let you address food security under extreme conditions — in particular, drought and climate change — we really can’t do without irrigation,” said Brozović, professor of agricultural economics at the University of Nebraska-Lincoln. “If we want to feed the world with high-quality, nutritious food and a stable food supply, we need to irrigate.”

Brozović and Husker colleague Taro Mieno had already constructed plenty of models, and run plenty of simulations, on how the High Plains Aquifer responds to drought and dry conditions. But talking with farmers revealed that the models were not addressing their primary concern: well yield, or the amount of groundwater that growers can expect to continuously draw when trying to buffer their crops against drought.

“Everybody’s interested in how aquifer depletion affects the resiliency of irrigated agriculture in the region,” said Mieno, an associate professor of agricultural economics and lead author of the study, which was published in the journal Nature Water.

So the researchers consulted annual estimates of the High Plains Aquifer’s thickness, which date back to 1935, along with county-level yields of corn and soybean from 1985 through 2016. Meteorological data, meanwhile, allowed the team to calculate seasonal water deficits, or the difference between the water gained from precipitation and the amount that crops lost via evaporation and transpiration.

When the latter exceeds the former, farmers often turn to aquifers for help in making up the difference, the researchers knew. What they didn’t know: Under what conditions, and to what extent, would an aquifer’s depletion make pumping its water too difficult or expensive to undertake? And how much would the resulting decisions — to reduce the amount of irrigation per acre, to cease irrigating certain plots all together — influence corn and soybean yields?

Farmers fortunate enough to be growing corn and soybean above the most saturated swaths of the High Plains Aquifer — roughly 220 to 700 feet thick — continued to enjoy high irrigated yields even in times of extreme water deficits, the team found. By contrast, those depending on the least saturated areas — between 30 and 100 feet — saw their irrigated yields begin trending downward when water deficits reached just 400 millimeters, a common occurrence in Nebraska and other Midwestern states.

In years when the deficit approached or exceeded 700 millimeters, irrigated fields residing above the thickest groundwater yielded markedly more corn than those sitting above the thinnest. The results were starker during a 950-millimeter water deficit, which corresponds with extreme drought: Fields atop the least saturated stretches of aquifer yielded roughly 19.5 fewer bushels per acre.

“Because of the way that aquifers work, even if there’s a lot of water there, as they deplete, you actually lose the ability to meet those crop water needs during the driest periods, because well yield tends to decline as you deplete an aquifer,” Brozović said. “That has an economic consequence and a resilience consequence.”

The study captured another telling link between the water residing underground and that applied at the surface. When atop groundwater roughly 330 feet thick, farmers irrigated 89% of their acres dedicated to growing corn. Where the aquifer was a mere 30 feet thick? Just 70% of those acres received irrigation. That’s likely a result of lower well yield driving farmers to irrigate only some of their fields, Taro said, or even give up on irrigation.

To better understand how that reduced irrigation was contributing to agricultural losses amid dry conditions, the researchers then factored in yields from both irrigated and non-irrigated fields, the latter of which rely on precipitation alone. That analysis pegged yields as even more sensitive to even smaller water deficits, suggesting that the decline in irrigated land was compounding the losses endured on still-irrigated plots.

And it illustrated the runaway threat posed when an aquifer’s average thickness drops below certain thresholds. At a water deficit of 950 millimeters, reducing an aquifer’s thickness from roughly 330 to 230 feet was estimated to initiate an average loss of about 2.5 corn bushels per acre, what the authors called a “negligible difference.” The same absolute decrease, but from 230 to 130 feet, led to an estimated loss of 15 bushels per acre.

“As a consequence, your resilience to climate decreases rapidly,” Mieno said. “So when you’re operating on an aquifer that is very thick right now, you’re relatively safe. But you want to manage it in a way that you don’t go past that threshold, because from there, it’s all downhill.

“And the importance of aquifers is going to increase as climate change progresses in the future, for sure. As it gets hotter, you typically need more water. That means you need more irrigation, and you’re going to deplete the aquifer even faster, and things can get worse and worse.”

Nebraska is lucky, Brozović said, in that it sits above such a massive reservoir and has established a governance system designed to conserve it at a local scale. But most regulations focus on mandating how much and when groundwater gets pumped, not safeguarding the aquifer’s saturation level or the corresponding ability to extract water from it.

Brozović conceded that convincing policymakers to consider revising those parameters now, when much of the state still boasts sufficient groundwater, is “perhaps a tough sell.” He’s hopeful that the new study can at least help put that conversation on the table.

“Once you have a problem — once well yields are already declining and the aquifer’s really thin — even if you put in policies, you still get a lot of the (negative) impacts,” he said. “So the time to really put in meaningful policies is before things have gone off the cliff.

“First, you have to understand, you have to measure, you have to educate. You have to understand what you’re preserving, and why. The more you can provide the quantitative evidence for why it’s worth going to the trouble of doing all of this, and what’s at stake,” he said, “the easier that conversation is.”

Brozović and Mieno authored the Nature Water study with the University of Manchester’s Timothy Foster and the University of Minnesota’s Shunkei Kakimoto. The researchers received support in part from the U.S. Department of Agriculture.