The researchers said that the results of the study, published in the journal Current Biology, highlighted the critical role that rest may play in learning.

“Everyone thinks you need to ‘practice, practice, practice’ when learning something new. Instead, we found that resting, early and often, may be just as critical to learning as practice,” said Leonardo G. Cohen, M.D., Ph.D., senior investigator at NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and a senior author of the paper. “Our ultimate hope is that the results of our experiments will help patients recover from the paralyzing effects caused by strokes and other neurological injuries by informing the strategies they use to relearn lost skills.”

The study was led by Marlene Bönstrup, M.D., a postdoctoral fellow in Cohen’s lab. Like many scientists, she held the general belief that our brains needed long periods of rest, such as a good night’s sleep, to strengthen the memories formed while practicing a newly learned skill. But she started to question that idea after looking at brain waves recorded from healthy volunteers in learning and memory experiments at the NIH Clinical Center.

The researchers used a highly sensitive scanning technique called magnetoencephalography to record the waves from right-handed volunteers. The subjects sat in a chair facing a computer screen and under a long cone-shaped brain scanning cap. They were shown a series of numbers on a screen and asked to type the numbers as many times as possible with their left hands for 10 seconds; take a 10 second break; and then repeat this trial cycle of alternating practice and rest 35 more time.

As expected, the volunteers’ speed at which they correctly typed the numbers improved dramatically during the first few trials and then leveled off around the 11th cycle. And when Bönstrup looked at the volunteers’ brain waves, she observed something interesting.

“Participants’ waves seemed to change much more during the rest periods than during the typing sessions.”

“I noticed that participants’ brain waves seemed to change much more during the rest periods than during the typing sessions,” Bönstrup said. “This gave me the idea to look much more closely for when learning was actually happening. Was it during practice or rest?”

By reanalyzing the data of participants’ brain waves during and after typing, she and her colleagues made two key findings. First, they found that the volunteers’ performance improved primarily during the short rests, and not during typing. The improvements made during the rest periods added up to the overall gains the volunteers made that day. Moreover, these gains were much greater than the ones seen after the volunteers returned the next day to try again. That suggested the early breaks played as critical a role in learning as the practicing itself.

Second, by looking at the brain waves, Bönstrup found activity patterns that suggested the volunteers’ brains were consolidating, or solidifying, memories during the rest periods. Specifically, they found that the changes in the size of brain waves, called beta rhythms, correlated with the improvements the volunteers made during the rests.

Further analysis suggested that the changes primarily happened in the right hemispheres of the volunteers’ brains and along neural networks connecting the frontal and parietal lobes that are known to help control the planning of movements. These changes happened only during the breaks and were the only brain wave patterns that correlated with performance.

“Our results suggest that it may be important to optimize the timing and configuration of rest intervals when implementing rehabilitative treatments in stroke patients or when learning to play the piano in normal volunteers,” Cohen said. “Whether these results apply to other forms of learning and memory formation remains an open question.”

Cohen’s team plans to explore, in greater detail, the role of these early resting periods in learning and memory.

The word-recall quiz accurately predicted whether people had elevated brain levels of beta-amyloid, a protein that has been linked with the increased risk of mild cognitive impairment and the development of Alzheimer’s.

The investigators say they hope the procedure, which puts pressure on memory, could help identify signs that might have been missed by standard memory tests.

The test, known as the Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L), was developed by a group of researchers led by Dr. David Loewenstein of the Center for Cognitive Neurosciences and Aging and the University of Miami Miller School of Medicine.

The team’s preliminary findings were published in the journal Neurology.

Investigators used answers on a simple word quiz to evaluate the degree of cognitive impairment.

Here’s how it works: Study participants listen to a list of categorized objects (fruits, musical instruments, or clothing) and then after a brief delay, repeat as many of the words as they can recall. Shortly afterwards, they repeat the process with a different list of words from the same category. The research team found that “semantic intrusions”—recalling either a word from the previous list, or a word that fits the category but was not on either list—can indicate potential problems with memory, cognition, or control of verbal inhibition.

As part of the study, the scientists also conducted PET and MRI scans on 88 participants. The scans showed that those who had more semantic intrusions on the word test also had higher levels of beta-amyloid.

Overall, the study showed that semantic intrusions on the LASSI-L helped researchers separate participants who were cognitively normal from those with harder to detect cognitive impairment. Previous memory test methods likely would have labelled the latter group as cognitively unimpaired since only their correct memory test results were counted.

Since it offers a potentially faster and less expensive way to screen people for high amyloid burden than current tests, the researchers hope to make LASSI-L a low-tech tool to assist in medical evaluations and clinical trial recruitment. Still to be done: additional research with larger numbers of participants.

The study appeared in the journal Frontiers in Molecular Neuroscience.

The activity of the microglial (immune) cells plays an important role in brain aging. These cells are part of the brain’s immune defense: For example, they detect and digest bacteria and eliminate diseased or defective nerve cells. They also use messenger substances to alert other defense cells and thus initiate a concerted campaign to protect the brain from dangerous inflammation.

But this protective mechanism has undesirable side effects; it can also cause damage to healthy brain tissue. “We know that so-called endocannabinoids [the receptor found in cannabis] play an important role in this,” said Dr. Andras Bilkei-Gorzo from the Institute of Molecular Psychiatry at the University of Bonn. “These are messenger substances produced by the body that act as a kind of brake signal: They prevent the inflammatory activity of the glial cells.”

Endocannabinoids develop their effect by binding to special receptors. There are two different types, called CB1 and CB2. “However, microglial cells have virtually no CB1 and very low level of CB2 receptors,” Bilkei-Gorzo said. “They are therefore deaf on the CB1 ear. And yet they react to the corresponding brake signals – why this is the case, has been puzzling so far.”

The scientists at the University of Bonn have now been able to shed light on this puzzle. Their findings indicate that the brake signals do not communicate directly with the glial cells, but via middlemen – a certain group of neurons, because this group has a large number of CB1 receptors. “We have studied laboratory mice in which the receptor in these neurons was switched off,” Bilkei-Gorzo said. “The inflammatory activity of the microglial cells was permanently increased in these animals.”

In contrast, in control mice with functional CB1 receptors, the brain’s own defense forces were normally inactive. This only changed in the present of inflammatory stimulus. “Based on our results, we assume that CB1 receptors on neurons control the activity of microglial cells,” said Bilkei-Gorzo. “However, we cannot yet say whether this is also the case in humans.”

This is how it might work in mice: As soon as microglial cells detect a bacterial attack or neuronal damage, they switch to inflammation mode. They produce endocannabinoids, which activate the CB1 receptor of the neurons in their vicinity. This way, they inform the nerve cells about their presence and activity. The neurons may then be able to limit the immune response. The scientists were able to show that neurons similarly regulate the other major glial cell type, the astroglial cells.

During aging, the production of cannabinoids declines, reaching a low level in older people. This could lead to a kind of vicious circle, Bilkei-Gorzo suspects: “Since the neuronal CB1 receptors are no longer sufficiently activated, the glial cells are almost constantly in inflammatory mode. More regulatory neurons die as a result, so the immune response is less regulated and may become free-running.”

It may eventually be possible to break this circle with drugs. It is, for instance, hoped that cannabis will help slow the progression of dementia. Its ingredient, tetrahydrocannabinol (THC), is a powerful CB1 receptor activator – even in low doses free from intoxicating effect. Last year, the researchers from Bonn and colleagues from Israel were able to demonstrate that cannabis can reverse the aging processes in the brains of mice. This result now suggest that an anti-inflammatory effect of THC may play a role in its positive effect on the aging brain.

The discovery was made by investigators in the Department of Physical Medicine and Rehabilitation at Johns Hopkins Medicine.

The findings add another clue to a growing body of research on how the brain generates movement in the first place, according to a news release from Johns Hopkins Medicine. That knowledge could eventually help scientists understand how brain-controlled motor responses go awry after neurologic disease or injuries such as strokes.

Since the early 1950s, researchers have known that repeating a movement can improve the reaction time, said study author Adrian Mark Haith, Ph.D., assistant professor of neurology at the Johns Hopkins University School of Medicine. This effect has long been attributed to “anticipation”–being prepared to repeat a movement by default in accordance with expectations about which movement would most likely be required.

However, other experiments using transcranial magnetic stimulation–a technique that uses magnetic pulses to stimulate the brain and record responses–show that repeating movements can actually bias the movements that occur when stimulating the brain’s motor cortex, making typically random movements more like the one that was practiced.

“These studies suggest that something other than anticipation might be happening with repetition,” Haith said.

In a study designed to clarify how repeated movements might influence motor response, Haith, along with colleagues Pablo A. Celnik, M.D., professor of physical medicine and rehabilitation, neurology, and neuroscience at the Johns Hopkins University School of Medicine; Firas Mawase, Ph.D., a former postdoctoral fellow in Celnik’s lab; and Daniel Lopez, B.S., a research assistant at the Johns Hopkins University School of Medicine, devised a set of experiments to tease out whether or not practice might affect movement through anticipation or another mechanism.

The researchers recruited 36 right-handed adult volunteers, 22 of whom were women, ranging in age from 19 to 30 years. Each of the volunteers sat at a desk in front of a large computer screen. On the desktop was a touch-responsive tablet. When a target appeared on the screen, the volunteers were asked to move a cursor to touch the target as quickly as possible using a stylus on the tablet.

In initial tests, the volunteers took about 215 milliseconds (each millisecond is 1/1000th of a second) to respond and reach the changing target, no matter what direction they moved their hands. However, after practicing moving the cursor hundreds of times in just a single direction, the volunteers became significantly faster at responding and moving the cursor toward the target in that direction, even though their reaction times stayed the same when the target appeared in other directions.

“The benefit you get is 20 to 30 milliseconds,” says Celnik. “It sounds small, but when you’re looking at performance that can make a difference in sports and other areas that require quick motor movements, that time increment might mean the divide between a winner and a loser.”

The scientists reasoned that there were two possibilities for the subjects’ decreased reaction times: One idea is that they had learned to anticipate the movement and were guessing that the target would appear in the preferential (usual) direction from force of habit. Another is that repetitive practice somehow trained their brains to select the practiced movement more quickly in the future while still allowing the subjects the same amount of flexibility as before they practiced to choose other targets.

To tease apart those possibilities, the researchers tried another experiment much like the previous ones in which the subjects were asked to move their hand toward a target that appeared on the screen, but with a twist: they were asked to move their hand on every fourth beat of a metronome, whether the target appeared or not. When the target did appear, it showed up in various time intervals right before the fourth beat, effectively imposing a reaction time on each trial.

If, as previous theories held, the subjects were anticipating movement in the practiced direction, the researchers reasoned they’d preferentially move their hand in that direction when the target failed to show up, or when the reaction time was so narrow that they wouldn’t have time to accurately hit the target. However, that wasn’t the case, said Firas.

“The subjects did have preferred directions for moving their hands when they had to guess, but it was mostly directions comfortable for right-handed people,” he said. “They either chose up and to the right or down and to the left, rather than in the direction they’d practiced.”

Together, the researchers concluded that these results, published in the July 24, 2018 issue of Cell Reports, suggest that repeating a movement many times somehow primes the brain to be more efficient at making that movement in the future.

Celnik said he and his team plan to investigate what’s happening in the brain itself to better understand this effect. Gaining insight on the neural mechanisms behind the phenomenon, he added, could lead to more effective therapies for stroke and other disorders that affect the brain’s control over body movement.