UK and Chinese scientists have demonstrated that laser light therapy is effective in improving short term memory in a study published in Science Advances. The innovative, non-invasive therapy could improve short term, or working memory in people by up to 25%.
The treatment, termed transcranial photobiomodulation (tPBM), is applied to the right prefrontal cortex, an area important for working memory. In their experiment, the team showed how working memory improved among research participants after several minutes of treatment. They were also able to track the changes in brain activity using electroencephalogram (EEG) monitoring during treatment and testing.
Previous studies have shown that laser light treatment will improve working memory in mice, and human studies have shown tPBM treatment can improve accuracy, speed up reaction time and improve high-order functions such as attention and emotion. This is the first study, however, to confirm a link between tPBM and working memory in humans.
Co-author Dongwei Li, a visiting PhD student, said, “People with conditions like ADHD (attention deficit hyperactivity disorder) or other attention-related conditions could benefit from this type of treatment, which is safe, simple and non-invasive, with no side-effects.”
In the study researchers at Beijing Normal University carried out experiments with 90 male and female participants aged between 18 and 25. Participants were treated with laser light to the right prefrontal cortex at wavelengths of 1064 nm, while others were treated at a shorter wavelength, or treatment was delivered to the left prefrontal cortex. Each participant was also treated with a sham, or inactive, tPBM to rule out the placebo effect.
After tPBM treatment over 12 minutes, the participants were asked to remember the orientations or colour of a set of items displayed on a screen. The participants treated with laser light to the right prefrontal cortex at 1064 nm showed clear improvements in memory over those who had received the other treatments. While participants receiving other treatment variations were about to remember between three and four of the test objects, those with the targeted treatment were able to recall between four and five objects.
Data, including from electroencephalogram (EEG) monitoring during the experiment was analysed at the University of Birmingham and showed changes in brain activity that also predicted the improvements in memory performance.
The researchers do not yet know precisely why the treatment results in positive effects on working memory, nor how long the effects will last. Further research is planned to investigate these aspects.
Professor Ole Jensen, also at the Center for Human Brain Health, said, “We need further research to understand exactly why the tPBM is having this positive effect, but it’s possible that the light is stimulating the astrocytes –the powerplants – in the nerve cells within the prefrontal cortex, and this has a positive effect on the cells’ efficiency. We will also be investigating how long the effects might last. Clearly if these experiments are to lead to a clinical intervention, we will need to see long-lasting benefits.”
A widely reported study published in Science that presented evidence for a distributed, ‘stepwise’ origin for Omicron across the African continent has drawn criticism from a number of prominent scientists.
Dr Tulio Oliveira, the director of CERI (Centre for Epidemic Response & innovation) and KRISP (KZN Research Innovation & Sequencing Platform) was one of these scientists expressing their doubts over Twitter.
Dr Oliveira tweeted that, like many other scientists, he was sceptical of the Science paper’s narrative of a stepwise emergence of Omicron in Africa.
“First, the ‘fishing’ of intermediates in Africa should also have been performed in Europe and the USA, which were the regions of the world that introduced the majority of Omicron lineages to Africa -“
He also questioned the accuracy of their results due to possible contamination, and also the strength of their analyses, noting that phylogenetic analyses are weak.
For his fourth point, he says that “the Benin sequences could be recombinants of Delta and Omicron, real recombination, or recombination through contamination of the sequencing process.” He was unable to check for the prevalence of mutations.
He also makes a very simple observation regarding the timing of waves: if Omicron arose first in West Africa, why then did South Africa experience the Omicron wave before them?
The paper was also not presented as a preprint to allow for the research community to give feedback and improved the manuscript, a criticism echoed by biologist and physicist Richard Neher.
“Lastly, the results presented do not reject any of the three hypotheses of Omicron evolution (i.e. unsampled location, immune suppressed individual, animal reservoir).”
Nevertheless, he says that “I have many colleagues and collaborators in this paper and would like to recognize that the allele qPCR system to identify BA.1 is a great tool. Also that their mutation analyses are also good.”
Ketamine, an established anaesthetic and increasingly popular antidepressant, dramatically reorganises activity in the brain, as if a switch had been flipped on its active circuits, according to a new study published in a Nature Neuroscience paper.
Researchers observed greatly altered patterns of neuronal activity in the cerebral cortex of animal models after ketamine administration – normally active neurons were silenced while another set that were normally quiet suddenly sprang to action.
This ketamine-induced activity switch in key brain regions tied to depression may impact our understanding of ketamine’s treatment effects and future research in the field of neuropsychiatry.
“Our surprising results reveal two distinct populations of cortical neurons, one engaged in normal awake brain function, the other linked to the ketamine-induced brain state,” said the co-lead and co-senior author Joseph Cichon, MD, PhD, an assistant professor at the University of Pennsylvania. “It’s possible that this new network induced by ketamine enables dreams, hypnosis, or some type of unconscious state. And if that is determined to be true, this could also signal that it is the place where ketamine’s therapeutic effects take place.”
Anaesthesiologists routinely deliver anesthetic drugs before surgeries to reversibly alter activity in the brain so that it enters its unconscious state. Since its synthesis in the 1960s, ketamine has been a mainstay in anaesthesia practice because of its reliable physiological effects and safety profile. One of ketamine’s signature characteristics is that it maintains some activity states across the surface of the brain (the cortex). This contrasts with most anaesthetics, which work by totally suppressing brain activity. It is these preserved neuronal activities that are thought to be important for ketamine’s antidepressant effects in key brain areas related to depression. But, to date, how ketamine exerts these clinical effects remains mysterious.
In their new study, the researchers analysed mouse behaviours before and after they were administered ketamine, comparing them to control mice who received placebo saline. One key observation was that those given ketamine, within minutes of injection, exhibited behavioural changes consistent with what is seen in humans on the drug, including reduced mobility, impaired responses to sensory stimuli, which are collectively termed “dissociation.”
“We were hoping to pinpoint exactly what parts of the brain circuit ketamine affects when it’s administered so that we might open the door to better study of it and, down the road, more beneficial therapeutic use of it,” said co-lead and co-senior author Alex Proekt, MD, PhD, an associate professor at Penn.
Two-photon microscopy was used to image cortical brain tissue before and after ketamine treatment. By following individual neurons and their activity, they found that ketamine turned on silent cells and turned off previously active neurons.
The neuronal activity observed was traced to ketamine’s ability to block the activity of synaptic receptors called NMDA receptors and ion channels called HCN channels. The researchers found that they could recreate ketamine’s effects without the medications by simply inhibiting these specific receptors and channels in the cortex. The scientists showed that ketamine weakens several sets of inhibitory cortical neurons that normally suppress other neurons. This allowed the normally quiet neurons, the ones usually being suppressed when ketamine wasn’t present, to become active.
The study showed that this dropout in inhibition was necessary for the activity switch in excitatory neurons – the neurons forming communication highways, and the main target of commonly prescribed antidepressant medications. More work will need to be undertaken to determine whether the ketamine-driven effects in excitatory and inhibitory neurons are the ones behind ketamine’s rapid antidepressant effects.
“While our study directly pertains to basic neuroscience, it does point at the greater potential of ketamine as a quick-acting antidepressant, among other applications,” said co-author Max Kelz, MD, PhD. “Further research is needed to fully explore this, but the neuronal switch we found also underlies dissociated, hallucinatory states caused by some psychiatric illnesses.”
In August 2007, a soccer match took place that fans of the club Sevilla FC will not forget: the 22-year-old Antonio Puerta suffered a cardiac arrest and collapsed on the field, passing away in hospital a few days later. It was later discovered that the player was affected from a condition named arrhythmogenic cardiomyopathy.
Arrhythmogenic cardiomyopathy can lead to sudden death, and it particularly affects young athletes. Using genetically modified mice, which develop a similar disease to humans, researchers identified previously unknown mechanisms and potential therapeutic targets. Their results were published in the journal Circulation.
This inherited disease is estimated to occur at 1 in every 5000, with men being more commonly affected than women. “Arrhythmogenic cardiomyopathy leads to arrhythmia with a loss of cardiac muscle cells, deposits of connective tissue and fat within the cardiac muscle. This can cause sudden cardiac death, often during exercise,” says Volker Spindler, anatomist and head of the Cell Adhesion group at the University of Basel’s Department of Biomedicine.
Today, a range of gene mutations are known to trigger the condition. However, even with an early diagnosis there is no cure, only options for the management of symptoms are available. “Patients are advised to avoid any competitive or endurance sports and have to take medications such as beta blockers. Where appropriate, a catheter ablation may be performed or an implantable defibrillator may be used” says the cardiologist Gabriela Kuster, who heads the Myocardial Research group at the Department of Biomedicine. Sometimes the only option is a heart transplant.
Cardiac muscle cells become less ‘sticky’
The starting point for the project was the notion that many of the mutations affect structures known as the desmosomes. These are protein clusters on the surface of cardiac muscle cells that ensure a tight connection between the cells. “You can imagine these clusters to act like a piece of Velcro,” says the physician Dr Camilla Schinner, first author of the study. This led to the theory that the mutations reduce adhesion between the cells, thus weakening the cardiac muscle.
To test this hypothesis, Spindler’s team introduced a mutation similar to that found in patients into the genome of mice. The cardiac function of these animals was then examined by Kuster’s group. The result: the genetically modified animals showed a heart disease with arrhythmia that resembled arrhythmogenic cardiomyopathy in humans. In addition, microscopic and biochemical analysis indeed showed reduced adhesion between the cardiac muscle cells. The researchers also observed the scarring of the cardiac muscle typical for this disease.
Preventing cardiac tissue damage
Their next step was to investigate how diseased cardiac muscle differed from healthy conditions at the molecular level. Mice with the mutation showed an increased amount of a particular protein at the Velcro-like structures of the heart muscle cells. This leads, via a series of events, to connective tissue deposition and scarring of the heart. The addition of a substance which blocks this cascade prevented disease progression – which is why Spindler here sees a potential new treatment approach.
“Nevertheless, there is still a long way to go until an application in humans may be considered,” he points out. “But we now have better options to study the disease in more detail to improve our understanding of the underlying mechanisms.”
Many people struggle with feeling groggy in the morning until they get their first coffee, but those who wake up feeling refreshed each day is not just merely a fluke of genetics. Scientists report in the journal Nature Communications that people can wake up each morning without feeling sluggish by paying attention to three key factors: sleep, exercise and the nutritional composition of their breakfast.
The findings come from a study of 833 participants who, over a two-week period, were given a variety of breakfast meals; wore wristwatches to record their physical activity and sleep quantity, quality, timing and regularity; kept diaries of their food intake; and recorded their alertness levels from the moment they woke up and throughout the day. The study included both fraternal and identical twins to disentangle the influence of genes from environment and behaviour.
The researchers found that the secret to alertness is a three-part prescription requiring substantial exercise the previous day, sleeping longer and later into the morning, and eating a breakfast high in complex carbohydrates, with limited sugar. The researchers also discovered that a healthy controlled blood glucose response after eating breakfast is key to waking up more effectively.
“All of these have a unique and independent effect,” said UC Berkeley postdoctoral fellow Raphael Vallat, first author of the study. “If you sleep longer or later, you’re going to see an increase in your alertness. If you do more physical activity on the day before, you’re going to see an increase. You can see improvements with each and every one of these factors.”
Morning grogginess is more than just an annoyance. It has major societal consequences: Many auto accidents, job injuries and large-scale disasters are caused by people who cannot shake off sleepiness. The Exxon Valdez oil spill in Alaska, the Three Mile Island nuclear meltdown in Pennsylvania and an even worse nuclear accident in Chernobyl, Ukraine, are well-known examples.
“Many of us think that morning sleepiness is a benign annoyance. However, it costs developed nations billions of dollars every year through loss of productivity, increased health care utilisation, work absenteeism. More impactful, however, is that it costs lives – it is deadly,” said senior author Matthew Walker, UC Berkeley professor of neuroscience and psychology. “From car crashes to work-related accidents, the cost of sleepiness is deadly. As scientists, we must understand how to help society wake up better and help reduce the mortal cost to society’s current struggle to wake up effectively each day.”
Personalised approach to eating
Walker and Vallat teamed up with researchers in the UK, the US and Sweden to analyse data acquired by a UK company, Zoe Ltd., that has followed hundreds of people for two-week periods in order to learn how to predict individualised metabolic responses to foods based on a person’s biological characteristics, lifestyle factors and the foods’ nutritional composition.
The participants were given pre-prepared meals, with different amounts of nutrients incorporated into muffins, for the entire two weeks to see how they responded to different diets upon waking. A standardised breakfast, with moderate amounts of fat and carbohydrates, was compared to a high protein (muffins plus a milkshake), high carbohydrate or high sugar (glucose drink) breakfast. The subjects also wore continuous glucose monitors to measure blood glucose levels throughout the day.
The worst type of breakfast, on average, contained high amounts of simple sugar; it was associated with an inability to wake up effectively and maintain alertness. When given this sugar-infused breakfast, participants struggled with sleepiness.
In contrast, the high-carbohydrate breakfast was linked to individuals revving up their alertness quickly in the morning and sustaining that alert state.
“A breakfast rich in carbohydrates can increase alertness, so long as your body is healthy and capable of efficiently disposing of the glucose from that meal, preventing a sustained spike in blood sugar that otherwise blunts your brain’s alertness,” Vallat said
“We have known for some time that a diet high in sugar is harmful to sleep, not to mention being toxic for the cells in your brain and body,” Walker added. “However, what we have discovered is that, beyond these harmful effects on sleep, consuming high amounts of sugar in your breakfast, and having a spike in blood sugar following any type of breakfast meal, markedly blunts your brain’s ability to return to waking consciousness following sleep.”
It wasn’t all about food, however. Sleep mattered significantly. In particular, Vallat and Walker discovered that sleeping longer than you usually do, and/or sleeping later than usual, resulted in individuals ramping up their alertness very quickly after awakening from sleep. According to Walker, between seven and nine hours of sleep is ideal for ridding the body of “sleep inertia” – the inability to reach functional cognitive alertness after waking up. Most people need this amount of sleep to remove adenosine, a chemical that accumulates in the body throughout the day and brings on sleepiness in the evening, something known as sleep pressure.
“Considering that the majority of individuals in society are not getting enough sleep during the week, sleeping longer on a given day can help clear some of the adenosine sleepiness debt they are carrying,” Walker speculated.
“In addition, sleeping later can help with alertness for a second reason,” he said. “When you wake up later, you are rising at a higher point on the upswing of your 24-hour circadian rhythm, which ramps up throughout the morning and boosts alertness.”
It’s unclear, however, what physical activity does to improve alertness the following day.
“It is well known that physical activity, in general, improves your alertness and also your mood level, and we did find a high correlation in this study between participants’ mood and their alertness levels,” Vallat said. “Participants that, on average, are happier also feel more alert.”
But Vallat also noted that exercise is generally associated with better sleep and a happier mood.
“It may be that exercise-induced better sleep is part of the reason exercise the day before, by helping sleep that night, leads to superior alertness throughout the next day,” Vallat said.
Walker noted that the restoration of consciousness from non-consciousness — from sleep to wake — is unlikely to be a simple biological process.
“If you pause to think, it is a non-trivial accomplishment to go from being nonconscious, recumbent and immobile to being a thoughtful, conscious, attentive and productive human being, active, awake, and mobile. It’s unlikely that such a radical, fundamental change is simply going to be explained by tweaking one single thing,” he said. “However, we have discovered that there are still some basic, modifiable yet powerful ingredients to the awakening equation that people can focus on — a relatively simple prescription for how best to wake up each day.”
It’s not in your genes
Comparisons of data between pairs of identical and non-identical twins showed that genetics plays only a minor and insignificant role in next-day alertness, explaining only about 25% of the differences across individuals.
“We know there are people who always seem to be bright-eyed and bushy-tailed when they first wake up,” Walker said. “But if you’re not like that, you tend to think, ‘Well, I guess it’s just my genetic fate that I’m slow to wake up. There’s really nothing I can do about it, short of using the stimulant chemical caffeine, which can harm sleep.
“But our new findings offer a different and more optimistic message. How you wake up each day is very much under your own control, based on how you structure your life and your sleep. You don’t need to feel resigned to any fate, throwing your hands up in disappointment because, ‘… it’s my genes, and I can’t change my genes.’ There are some very basic and achievable things you can start doing today, and tonight, to change how you awake each morning, feeling alert and free of that grogginess.”
Walker, Vallat and their colleagues continue their collaboration with the Zoe team, examining novel scientific questions about how sleep, diet and physical exercise change people’s brain and body health, steering them away from disease and sickness.
