Category: Neurology

New Non-invasive Brain Stimulation may One Day Treat Addiction, Depression and OCD

Source: CC0

Neurological disorders, such as addiction, depression, and obsessive-compulsive disorder (OCD), affect millions of people worldwide and are often characterised by complex pathologies involving multiple brain regions and circuits. These conditions are notoriously difficult to treat due to the intricate and poorly understood nature of brain functions and the challenge of delivering therapies to deep brain structures without invasive procedures.

In the rapidly evolving field of neuroscience, non-invasive brain stimulation enables the understanding and treating a myriad of neurological and psychiatric conditions, free of surgery or implants. Researchers, led by Friedhelm Hummel, who holds the Defitchech Chair of Clinical Neuroengineering at EPFL’s School of Life Sciences, and postdoc Pierre Vassiliadis, are pioneering a new approach in the field.

Their research, which is described in Nature Human Behaviour, makes use of transcranial Temporal Interference Electric Stimulation (tTIS). The approach specifically targets deep brain regions serving as control centres of several important cognitive functions and involved in different neurological and psychiatric pathologies.

“Invasive deep brain stimulation (DBS) has already successfully been applied to the deeply seated neural control centers in order to curb addiction and treat Parkinson, OCD or depression,” says Hummel. “The key difference with our approach is that it is non-invasive, meaning that we use low-level electrical stimulation on the scalp to target these regions.”

The innovative technique is based on the concept of temporal interference, initially explored in rodent models, and now successfully translated to human applications by the EPFL team. In this experiment, one pair of electrodes is set to a frequency of 2000Hz, while another is set to 2080Hz. Thanks to detailed computational models of the brain structure, the electrodes are specifically positioned on the scalp to ensure that their signals intersect in the target region.

It is at this juncture that the magic of interference occurs: the slight frequency disparity of 80Hz between the two currents becomes the effective stimulation frequency within the target zone. The brilliance of this method lies in its selectivity; the high base frequencies (eg, 2000Hz) do not stimulate neural activity directly, leaving the intervening brain tissue unaffected and focusing the effect solely on the targeted region.

The focus of this latest research is the human striatum, a key player in reward and reinforcement mechanisms. “We’re examining how reinforcement learning, essentially how we learn through rewards, can be influenced by targeting specific brain frequencies,” says Vassiliadis. By applying stimulation of the striatum at 80Hz, the team found they could disrupt its normal functioning, directly affecting the learning process.

The therapeutic potential of their work is immense, particularly for conditions like addiction, apathy and depression, where reward mechanisms play a crucial role. “In addiction, for example, people tend to over-approach rewards. Our method could help reduce this pathological overemphasis,” Vassiliadis, who is also a researcher at UCLouvain’s Institute of Neuroscience, points out.

Vassiliadis, lead author of the paper, a medical doctor with a joint PhD, describes tTIS as using two pairs of electrodes attached to the scalp to apply weak electrical fields inside the brain. “Up until now, we couldn’t specifically target these regions with non-invasive techniques, as the low-level electrical fields would stimulate all the regions between the skull and the deeper zones – rendering any treatments ineffective. This approach allows us to selectively stimulate deep brain regions that are important in neuropsychiatric disorders,” he explains.

Furthermore, the team is exploring how different stimulation patterns can not only disrupt but also potentially enhance brain functions. “This first step was to prove the hypothesis of 80Hz affecting the striatum, and we did it by disrupting it’s functioning. Our research also shows promise in improving motor behaviour and increasing striatum activity, particularly in older adults with reduced learning abilities,” Vassiliadis adds.

Hummel, a trained neurologist, sees this technology as the beginning of a new chapter in brain stimulation, offering personalised treatment with less invasive methods. “We’re looking at a non-invasive approach that allows us to experiment and personalise treatment for deep brain stimulation in the early stages,” he says. Another key advantage of tTIS is its minimal side effects. Most participants in their studies reported only mild sensations on the skin, making it a highly tolerable and patient-friendly approach.

Hummel and Vassiliadis are optimistic about the impact of their research. They envision a future where non-invasive neuromodulation therapies could be readily available in hospitals, offering a cost-effective and expansive treatment scope.

Original written by Michael David Mitchell. The original text of this story is licensed under Creative Commons CC BY-SA 4.0. Edited for style and length.

Source: Ecole Polytechnique Fédérale de Lausanne

Differences in Cortical Development Seen for Autistic Boys and Girls

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A new study led by UC Davis researchers finds widespread differences in brain development between autistic boys and girls ages 2-13. The study, published recently in Molecular Psychiatry, found sex-specific changes in the thickness of the brain’s cortex, or outer layer.

The findings are notable because so few studies have addressed cortical development in autistic girls, who are diagnosed with autism less often than males. Nearly four males are diagnosed with autism for every one female.

“It is clear that this sex bias is due, in part, to underdiagnosis of autism in females,” said Christine Wu Nordahl, a professor in the Department of Psychiatry and Behavioral Sciences and the UC Davis MIND Institute and a senior author on the paper.

“But this study suggests that differences in diagnosis are not the full story – biological differences also exist.”

The cortex is made up of distinct layers comprised of millions of neurons. Until about age 2, the cortex rapidly thickens as new neurons are created. After this peak, the outer cortical layer thins. Previous studies have found that this thinning process is different in autistic children than non-autistic children, but whether autistic boys and girls share the same differences had not been examined.

“It’s important to learn more about how sex differences in brain development may interact with autistic development and lead to different developmental outcomes in boys and girls,” explained Derek Andrews, lead author on the study and an assistant project scientist in the Department of Psychiatry and Behavioral Sciences and at the MIND Institute.

A changing cortex in childhood

The research team studied the brain scans of 290 autistic children – 202 males and 88 females, and 139 non-autistic, typically developing individuals – 79 males and 60 females.

All participants were in the MIND Institute’s Autism Phenome Project (APP), one of the largest longitudinal autism studies in the world.

The project includes the Girls with Autism Imaging of Neurodevelopment (GAIN) study, launched to increase the number of females represented in research.

The researchers took MRI scans at up to four time periods between the ages of 2 and 13.

They found that at age 3, autistic girls had a thicker cortex than non-autistic girls of the same age, comprising about 9% of the total cortical surface. Differences in autistic males when compared to non-autistic males of the same age were much less widespread.

In addition, when compared to males, autistic females had faster rates of cortical thinning into middle childhood. The cortical differences were present across multiple neural networks.

“We found differences in the brain associated with autism across nearly all networks in the brain,” Andrews said.

He noted that it was a surprise at first that the differences were greatest at younger ages. Because autistic girls had a more rapid rate of cortical thinning, by middle childhood, the differences between autistic males and females were much less pronounced.

“We typically think of sex differences as being larger after puberty. However, brain development around the ages of 2-4 is highly dynamic, so small changes in timing of development between the sexes could result in large differences that then converge later,” Andrews explained.

The importance of long-term studies of both sexes

These findings make it clear that longitudinal studies that include both sexes are necessary, Nordahl said.

“If we had only looked at boys at age 3, we may have concluded that there were no differences. If we had both boys and girls, but only investigated differences at 11 years of age, we may have concluded that there were very few sex differences in the cortex. We needed to follow both boys and girls across development to see the full picture,” she explained.

This was why Nordahl, who now directs the APP, launched the GAIN study in 2014. “The APP had a wonderfully large sample of about 150 autistic boys, but only about 30 autistic girls. This was too few autistic girls to really examine how they might be similar or different to boys, so we worked to increase the representation of autistic females in our research,” she said.

GAIN is unique, and Andrews said he hopes other researchers will follow suit in including more autistic girls in autism research. “Autistic females represent about 20% of the autistic population. Any successful effort to understand autism will need to include autistic females.”

Source: University of California – Davis Health

How Zebrafish Heal from Spinal Cord Injury could Help Humans

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Zebrafish have a remarkable ability to heal their spinal cord after injury. Now, researchers at Karolinska Institutet have uncovered an important mechanism behind this phenomenon – a finding that could have implications for the treatment of spinal cord injury in humans.

In a new study published in Nature Communications, researchers show that the neurons of adult zebrafish immediately start to cooperate after a spinal cord injury, keeping the cells alive and stimulating the healing process.

“We have shown that the neurons form small channels called gap junctions, which create a direct connection between the neurons and enable the exchange of important biochemical molecules, allowing the cells to communicate and protect each other,” explains Konstantinos Ampatzis, a researcher in the Department of Neuroscience at Karolinska Institutet, who led the study.

The researchers will further investigate the exact mechanisms behind this protective strategy in zebrafish and hope this knowledge will lead to new ways of treating spinal cord injury in humans.

“Spinal cord injuries are a major burden for sufferers and their families,” says Konstantinos Ampatzis. “What if we could get human neurons to adopt the same survival strategy and behave like zebrafish neurons after an injury? This could be the key to developing new effective treatments.”

Source: Karolinka Institutet

Concussion is Associated with Iron Accumulation in Certain Brain Areas

Photo by Anna Shvets

People who suffer from headaches after experiencing concussions may also be more likely to have higher levels of iron in areas of the brain – a sign of injury to brain cells, according to a preliminary study presented at the American Academy of Neurology’s 76th Annual Meeting.

“These results suggest that iron accumulation in the brain can be used as a biomarker for concussion and post-traumatic headache, which could potentially help us understand the underlying processes that occur with these conditions,” said study author Simona Nikolova, PhD, of the Mayo Clinic in Phoenix, Arizona, and a member of the American Academy of Neurology.

The study involved 120 participants, 60 of whom who had post-traumatic headache (PTH) due to mild traumatic brain injury (mTBI), and 60 healthy controls. The injuries were due to a fall for 45% of the people, 30% were due to a motor vehicle accident and 12% were due to a fight. Other causes were the head hitting against or by an object and sports injuries. A total of 46% of the people had one mild traumatic brain injury in their lifetime, 17% had two, 16% had three, 5% had four and 16% had five or more mild traumatic brain injuries.

Participants underwent 3T brain magnetic resonance imaging (T2* maps). T2* differences were determined using age-matched paired t-tests. For the PTH group, scans were done an average of 25 days after injury. T2* correlations with headache frequency, number of lifetime mTBIs, time since most recent mTBI, and Sport Concussion Assessment Tool (SCAT) severity scale scores,

The researchers observed lower T2* values in PTH participants relative to HC in the right supramarginal area, left occipital, bilateral precuneus, right cuneus, right cerebellum, right temporal, bilateral caudate, genu of the corpus callosum, right anterior cingulate cortex and right rolandic operculum (p < 0.001).

Within PTH subjects, there were positive correlations with iron accumulation between lifetime mTBIs, the time since most recent mTBI and headache frequency in certain areas of the brain. For example, T2* levels in headache frequency with T2* in the posterior corona radiata, bilateral temporal, right frontal, bilateral supplemental motor area, left fusiform, right hippocampus, sagittal striatum, and left cerebellum were associated with headache frequency.

“Previous studies have shown that iron accumulation can affect how areas of the brain interact with each other,” Nikolova said. “This research may help us better understand how the brain responds and recovers from concussion.”

Nikolova said that using the indirect measure of iron burden also means that the change in that measure could be due to other factors such as haemorrhage or changes in tissue water rather than iron accumulation.

Source: American Academy of Neurology

Singing Repairs the Language Network of the Brain after Stroke

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Cerebrovascular accidents, or strokes, are the most common cause of aphasia, a speech disorder of cerebral origin. People with aphasia have a reduced ability to understand or produce speech or written language. An estimated 40% of people who have had a stroke have aphasia. As many as half of them experience aphasia symptoms even a year after the original attack.

Researchers at the University of Helsinki previously found that sung music helps in the language recovery of patients affected by strokes. Now, the researchers have uncovered the reason for the rehabilitative effect of singing. The recently completed study was published in the eNeuro journal.

According to the findings, singing, as it were, repairs the structural language network of the brain. The language network processes language and speech in the brain, which has been damaged.

“For the first time, our findings demonstrate that the rehabilitation of patients with aphasia through singing is based on neuroplasticity changes, that is, the plasticity of the brain,” says University Researcher Aleksi Sihvonen from the University of Helsinki.

Singing improves language network pathways

The language network encompasses the cortical regions of the brain involved in the processing of language and speech, as well as the white matter tracts that convey information between the different end points of the cortex.

According to the study results, singing increased the volume of grey matter in the language regions of the left frontal lobe and improved tract connectivity especially in the language network of the left hemisphere, but also in the right hemisphere.

“These positive changes were associated with patients’ improved speech production,” Sihvonen says.

A total of 54 aphasia patients participated in the study, of whom 28 underwent MRI scans at the beginning and end of the study. The researchers investigated the rehabilitative effect of singing with the help of choir singing, music therapy and singing exercises at home.

Singing is a cost-effective treatment

Aphasia has a wide-ranging effect on the functional capacity and quality of life of affected individuals and easily leads to social isolation.

According to Sihvonen, singing can be seen as a cost-effective addition to conventional forms of rehabilitation, or as rehabilitation for mild speech disorders in cases where access to other types of rehabilitation is limited.

“Patients can also sing with their family members, and singing can be organised in healthcare units as a group-based, cost-efficient rehabilitation,” Sihvonen says.

Source: University of Helsinki

Difference in Brain Structures may Explain Concussion Outcomes for Males and Females

Coup and contrecoup brain injury. Credit: Scientific Animations CC4.0

Important brain structures that are key for signalling in the brain are narrower and less dense in females, and more likely to be damaged by brain injuries, such as concussion. Long-term cognitive deficits occur when the signals between brain structures weaken due to the injury. These structural differences in male and female brains might explain why females are more prone to concussions and experience longer recovery from the injury than their male counterparts, according to a University of Pennsylvania-led preclinical study published in Acta Neuropathologica.

Each year, approximately 50 million individuals worldwide suffer a concussion, also referred to as mild traumatic brain injury (TBI). For more than 15% of individuals who suffer persisting cognitive dysfunction, which includes difficulty concentrating, learning and remembering new information, and making decisions.

Although males make up the majority of emergency department visits for concussion, this has been primarily attributed to their greater exposure to activities with a risk of head impacts compared to females. In contrast, it has recently been observed that female athletes have a higher rate of concussion and appear to have worse outcomes than their male counterparts participating in the same sport.

“Clinicians have observed for a long time that females suffer from concussion at higher rates than males in the same sports, and that they take longer to recover cognitive function, but couldn’t explain the underlying mechanisms of this phenomenon,” said senior author Douglas Smith, MD, a professor of Neurosurgery and director of Penn’s Center for Brain Injury and Repair. “The variances in brain structures of females and males not only illuminate why this disparity exists, but also exposes biomarkers, such as axon protein fragments, that can be measured in the blood to determine injury severity, monitor recovery, and eventually help identify and develop treatments that help patients repair these damaged structures and restore cognitive function.”

Axons connect neurons, allowing communication across the brain. These axons form bundles that make up white matter in the brain and play a large role in learning and communication between different brain regions. Axons are delicate structures and are vulnerable to damage from concussion.

Communication between axons in the brain is powered by sodium channels that serve as the brain’s electric grid. When axons are damaged, these sodium channels are also impaired, which causes loss of signaling in the brain. The loss of signaling causes the cognitive impairment experienced by individuals after concussion.

In this study, researchers used large animal models of concussion to identify differences in brains of males and females after a concussion. They found that females had a higher population of smaller axons, which researchers demonstrated are more vulnerable to injury. They also reported that in these models, females had greater loss of sodium channels after concussion.

“The differences in brain structure not only tell us a lot about how brain injury affects males and females differently but could offer insights in other brain conditions that impact axons, like Alzheimer’s and Parkinson’s disease,” said Smith. “If female brains are more vulnerable to damage from concussion, they might also be more vulnerable to neurodegeneration, and it’s worth further research to understand how sex influences the structure and functions of the brain.”

Source: University of Pennsylvania School of Medicine

Study Finds Some TBI Patients Could have Recovered if Life Support was Kept on

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Severe traumatic brain injury (TBI) is a major cause of hospitalisations and deaths around the world, affecting more than five million people each year. Predicting outcomes following a brain injury can be challenging, yet families are asked to make decisions about continuing or withdrawing life-sustaining treatment within days of injury.

In a new study published in the Journal of Neurotrauma, Mass General Brigham investigators analysed potential clinical outcomes for TBI patients enrolled in the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study for whom life support was withdrawn. The investigators found that some patients for whom life support was withdrawn may have survived and recovered some level of independence a few months after injury. These findings suggest that delaying decisions on withdrawing life support might be beneficial for some patients.

Families are often asked to make decisions to withdraw life support measures, such as mechanical breathing, within 72 hours of a brain injury. Information relayed by physicians suggesting a poor neurologic prognosis is the most common reason families opt for withdrawing life support measures. However, there are currently no medical guidelines or precise algorithms that determine which patients with severe TBI are likely to recover.

Using data collected over a 7.5-year period on 1392 TBI patients in intensive care units at 18 US trauma centres, the researchers created a mathematical model to calculate the likelihood of withdrawal of life-sustaining treatment, based on properties like demographics, socioeconomic factors and injury characteristics. Then, they paired individuals for whom life-sustaining treatment was not withdrawn (WLST-) to individuals with similar model scores, but for whom life-sustaining treatment was withdrawn (WLST+).

Based on follow-up of their WLST- paired counterparts, the estimated six-month outcomes for a substantial proportion of the WLST+ group was either death or recovery of at least some independence in daily activities. Of survivors, more than 40%of the WLST- group recovered at least some independence. In addition, the research team found that remaining in a vegetative state was an unlikely outcome by six-months after injury. Importantly, none of the patients who died in this study were pronounced brain dead, and thus the results are not applicable to brain death.

According to the authors, the findings suggest there is a cyclical, self-fulfilling prophecy taking place: Clinicians assume patients will do poorly based on outcomes data. This assumption results in withdrawal of life support, which in turn increases poor outcomes rates and leads to even more decisions to withdraw life support.

The authors suggest that further studies involving larger sample sizes that allow for more precise matching of WLST+ and WLST- cohorts are needed to understand variable recovery trajectories for patients who sustain traumatic brain injuries.

“Our findings support a more cautious approach to making early decisions on withdrawal of life support,” said corresponding author Yelena Bodien, PhD, of the Department of Neurology’s Center for Neurotechnology and Neurorecovery at Massachusetts General Hospital and of the Spaulding-Harvard Traumatic Brain Injury Model Systems. “Traumatic brain injury is a chronic condition that requires long term follow-ups to understand patient outcomes. Delaying decisions regarding life support may be warranted to better identify patients whose condition may improve.”

Read more in the study, published May 13, in the Journal of Neurotrauma.

Nutrient’s Pathway into the Brain could be Used to Treat Neurological Disorders

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A University of Queensland researcher has found molecular doorways that could be used to help deliver drugs into the brain to treat neurological disorders. Dr Rosemary Cater from UQ’s Institute for Molecular Bioscience led a team which discovered that an essential nutrient called choline is transported into the brain by a protein called FLVCR2.

“Choline is a vitamin-like nutrient that is essential for many important functions in the body, particularly for brain development,” Dr Cater said.

“We need to consume 400-500mg of choline per day to support cell regeneration, gene expression regulation, and for sending signals between neurons.”

Dr Cater said that until now, little was known about how dietary choline travels past the layer of specialised cells that separates the blood from the brain.

“This blood-brain barrier prevents molecules in the blood that are toxic to the brain from entering,” she explained. “The brain still needs to absorb nutrients from the blood, so the barrier contains specialised cellular machines – called transporters – that allow specific nutrients such as glucose, omega-3 fatty acids and choline to enter. While this barrier is an important line of defence, it presents a challenge for designing drugs to treat neurological disorders.”

Dr Cater was able to show that choline sits in a cavity of FLVCR2 as it travels across the blood-brain barrier and is kept in place by a cage of protein residues.

“We used high-powered cryo-electron microscopes to see exactly how choline binds to FLVCR2,” she said. “This is critical information for understanding how to design drugs that mimic choline so that they can be transported by FLVCR2 to reach their site of action within the brain. These findings will inform the future design of drugs for diseases such as Alzheimer’s and stroke.”

The research also highlights the importance of eating choline-rich foods – such as eggs, vegetables, meat, nuts and beans.

The research is published in Nature and funded by the National Institutes of Health.

Source: University of Queensland

Neuron Cluster may Create a Little-understood Form of Chronic Pain

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Stimulating a small cluster of neurons in the brain appears to create a response in mice that mimics nociplastic pain, a type of unexplained chronic pain, researchers at the University of Washington School of Medicine in Seattle have found. 

“When we stimulate these neurons, the mouse behaves as though gentle touch is very painful, which is one of the characteristics of nociplastic pain,” said Richard Palmiter, a professor of biochemistry and investigator of the Howard Hughes Medical Institute. Dr Logan Condon, who spearheaded this research as a PhD student at UW, was lead author on the paper, which was published in Cell Reports

Chronic pain can arise from ongoing injury or persistent damage to the nervous system. Pain caused by injury is called nociceptive from the Latin nocere “to harm.” Pain due to nerve damage is called neuropathic. But these categories do not explain a common form of chronic pain the persists even after an injury has fully healed and there is no evidence of neurological damage. This led the International Association for the Study of Pain to define a new category called nociplastic pain, meaning “able to be moulded.” 

Although the cause of nociplastic pain is unknown, scientists think it involves changes in pain circuits in the spinal cord and brain. These changes result in the perception of pain even when no nerve injury exists. 

In the new study, researchers demonstrated that stimulating a cluster of cells in the brain’s parabrachial nucleus can generate chronic pain behaviour typical of nociplastic pain. They also showed that inhibiting these cells can prevent pain from nerve injury. 

The parabrachial nucleus is in an area of the brain known as the pons. It acts as a hub that relays aversive sensory information from the body to different parts of the brain. The parabrachial neurons found to create nociplastic pain are called Calca neurons, named for a defining gene for these cells. 

“You can think of these Calca neurons as a warning system for the brain,” said Palmiter. “They respond to any aversive event you can think of – a pinch, a visual threat, a bad odour, a loud noise – and they tell your brain that something bad is happening in the environment and you’d better do something about it.”

It is possible to manipulate genetically defined neurons using viral techniques to express molecules that activate, or inhibit, those neurons. 

The researchers also found that the nociplastic pain behaviour continues even after the Calca-neuron activation has stopped. This suggests signals from the stimulated Calca neurons cause persistent effects – a sign of plasticity – in the nerve circuits leading to the spinal cord. 

They also showed that it was possible to create nociplastic behaviours in the mice by exposing them to unpleasant, aversive experiences like nausea, chemotherapy drugs or migraine-like conditions. 

Palmiter’s team is currently focusing on the neural circuits and plasticity that arises when parabrachial Calca neurons are activated.

“The brain is somehow sending signals to the spinal cord,” he said. “We want to figure out the pathway for those signals.”

Source: University of Washington

The First Half of a Night’s Sleep Resets Brain Connections

…but not the second half

Source: CC0

During a night’s sleep, the brain weakens the new connections between neurons that had been forged while awake – but only during the first half, according to a new study in fish by UCL scientists.

The researchers say that their findings, published in Nature, provide insight into the role of sleep, but still leave an open question around what function the latter half of a night’s sleep serves.

The researchers say the study supports the Synaptic Homeostasis Hypothesis, a key theory on the purpose of sleep which proposes that sleeping acts as a reset for the brain.

Lead author Professor Jason Rihel (UCL Cell & Developmental Biology) said: “When we are awake, the connections between brain cells get stronger and more complex. If this activity were to continue unabated, it would be energetically unsustainable. Too many active connections between brain cells could prevent new connections from being made the following day.

“While the function of sleep remains mysterious, it may be serving as an ‘off-line’ period when those connections can be weakened across the brain, in preparation for us to learn new things the following day.”

For the study, the scientists used optically translucent zebrafish, with genes enabling synapses to be easily imaged. The research team monitored the fish over several sleep-wake cycles.

The researchers found that brain cells gain more connections during waking hours, and then lose them during sleep. They found that this was dependent on how much sleep pressure (need for sleep) the animal had built up before being allowed to rest; if the scientists deprived the fish from sleeping for a few extra hours, the connections continued to increase until the animal was able to sleep.

Professor Rihel added: “If the patterns we observed hold true in humans, our findings suggest that this remodelling of synapses might be less effective during a mid-day nap, when sleep pressure is still low, rather than at night, when we really need the sleep.”

The researchers also found that these rearrangements of connections between neurons mostly happened in the first half of the animal’s nightly sleep. This mirrors the pattern of slow-wave activity, which is part of the sleep cycle that is strongest at the beginning of the night.

First author Dr Anya Suppermpool (UCL Cell & Developmental Biology and UCL Ear Institute) said: “Our findings add weight to the theory that sleep serves to dampen connections within the brain, preparing for more learning and new connections again the next day. But our study doesn’t tell us anything about what happens in the second half of the night. There are other theories around sleep being a time for clearance of waste in the brain, or repair for damaged cells – perhaps other functions kick in for the second half of the night.”

Source: University College London