‘Exploding head syndrome’ a real, overlooked sleep disorder

It sounds like a phrase from Urban Dictionary or the title of an animated gif, but a Washington State University researcher says “exploding head syndrome” is an authentic and largely overlooked phenomenon that warrants a deeper look.

“It’s a provocative and understudied phenomenon,” said Brian Sharpless, a WSU assistant professor and director of the university psychology clinic who recently reviewed the scientific literature on the disorder for the journal Sleep Medicine Reviews. “I’ve worked with some individuals who have it seven times a night, so it can lead to bad clinical consequences as well.”

People with the syndrome typically perceive abrupt, loud noises—door slams, fireworks, gunshots—as they are going to sleep or waking up. While harmless, the episodes can be frightening.

“Some people start to become anxious when they go into their bedroom or when they try to go to sleep,” said Sharpless. “Daytime sleepiness can be another problem.”

Some patients report mild pain. Some hear an explosion in one ear, others in both ears and yet others within their heads. Some also see what looks like lightning or bright flashes.

Researchers do not know how widespread the problem is, but Sharpless is fielding enough reports of people with the disorder that he thinks it is more widespread than presumed. Just this week, a story on the disorder in Britain’s Daily Mail prompted several people with the syndrome to contact him. (See http://www.dailymail.co.uk/health/article-2620837/Is-exploding-head-syndrome-reason-sleep.html)

The term “exploding head syndrome” dates to a 1988 article in Lancet, but it was described clinically as “snapping of the brain” in 1920. Silas Weir Mitchell, an American physician, wrote in 1876 of two men who experienced explosive-sounding “sensory discharges.”

While the syndrome is recognized in the International Classification of Sleep Disorders, studies using electroencephalogram recordings have only documented the disruptions in periods of relaxed but awake drowsiness.

As with many sleep phenomena, it is largely mysterious.

“In layman’s terms, our best guess is that it occurs when the body doesn’t shut down for sleep in the correct sequence,” said Sharpless. “Instead of shutting down, certain groups of neurons actually get activated and have us perceive the bursts of noise. Behavioral and psychological factors come into play as well, and if you have normally disrupted sleep, the episodes will be more likely to occur.”

Judging from the limited scientific literature and available statistics, Sharpless said the syndrome is more common in women than men. Some medical treatments are available for it, but one possible intervention can be simply reassuring a patient that it is not a dangerous condition.

(Image caption: Uncinate fasiculus, an important tract with the greatest concentration of progesterone receptors, show greater injury in males than females after mild traumatic brain injury (mTBI). (a) Axial and (b) coronal images show regions of decreased fractional anisotropy in male patients with mTBI relative to female mTBI patients, involving the uncinate fasiculus (red) bilaterally.)

Gender May Contribute to Recovery Time After Concussion

A study of concussion patients using diffusion tensor imaging (DTI) found that males took longer to recover after concussion than females did. Results of the study, which show that DTI can be used as a bias-free way to predict concussion outcome, are published online in the journal Radiology.

Each year, more than 17 million Americans suffer a mild traumatic brain injury (mTBI), more commonly known as a concussion, of which approximately 15 percent suffer persistent symptoms beyond three months.

Assessing outcomes and recovery time after concussion can be very subjective. Typically, physicians must rely on patient cooperation to assess injury severity.

"MRI and CT brain images of concussion patients are often normal," said Saeed Fakhran, M.D., assistant professor of neuroradiology at the University of Pittsburgh School of Medicine. "Diffusion tensor imaging is the first imaging technique that shows abnormalities associated with concussion, because it is able to see white matter tracts at a microscopic level."

DTI is an advanced form of MRI that allows researchers to assess microscopic changes in the brain’s white matter. The brain’s white matter is composed of millions of nerve fibers called axons that act like communication cables connecting various regions of the brain. DTI produces a measurement, called fractional anisotropy (FA), of the movement of water molecules along axons. In healthy white matter, the direction of water movement is fairly uniform and measures high in FA. When water movement is more random, FA values decrease. Abnormally low FA is associated with cognitive impairment in patients with brain injuries.

The research team examined the medical records and imaging results of 69 patients diagnosed with mTBI between 2006 and 2013, including 47 males and 22 females, and 21 controls consisting of 10 males and 11 females (median age of males: 17; median age of females: 16). Of the 47 males with mTBI, 32 (68 percent) were injured while playing a sport, as were 10 of the 22 females (45 percent).

All patients underwent the same evaluation, including a computerized neurocognitive test and DTI of the brain. The DTI scans of the mTBI patients revealed abnormalities within the uncinate fasciculi (UF), a white matter tract that connects the frontal and temporal lobes of the brain. Although its exact role is controversial, the UF tract is believed to allow temporal lobe-based memory associations to modify behavior though interactions with another area of the brain.

The DTI scans revealed that compared to the female mTBI patients, the male mTBI patients had significantly decreased UF FA values.

"In the future, we would like to look at the issue of gender and concussions more in depth to determine who does better and why," Dr. Fakhran said.

A statistical analysis of the data revealed that UF FA value was a stronger predictor of recovery time than initial symptom severity based on neurocognitive testing. The most substantial risk factor for a recovery time longer than three months was decreased UF FA. Male gender also directly correlated with increased recovery time.

"The potential of DTI and UF FA to predict outcome after concussion has great clinical impact," Dr. Fakhran said. "Currently, we are heavily reliant on patient reporting, and patients may have ulterior motives, such as wanting to get back to play. But you can’t trick an MR scanner."

The average time to symptom recovery for all concussion patients was 54 days. However, compared to the female patients who recovered in an average of 26.3 days, recovery was significantly longer for the male patients (an average of 66.9 days), irrespective of initial symptom severity.

"Male gender and UF FA values are independent risk factors for persistent post-concussion symptoms after three months and stronger predictors of time to recovery than initial symptom severity or neurocognitive test results," Dr. Fakhran said.

He said results of the study indicate a potential role for UF FA values in triaging concussion patients in the future.

"There’s prognostic value in DTI for both children participating in sports as well as for professional athletes," he said. "Lower FA values in the uncinate fasciculi could offer a metric for evaluating the severity of mild traumatic brain injuries and predicting clinical outcome. We’re not at the point where DTI can provide individual prognoses yet, but that’s the hope and goal."

Molecular Switches for Age-Related Memory Decline? A Genetic Variant Protects Against Brain Aging

Even among the healthiest individuals, memory and cognitive abilities decline with age. This aspect of normal aging can affect an individual’s quality of life and capability to live independently but the rate of decline is variable across individuals. There are many factors that can influence this trajectory, but perhaps none more importantly than genetics.

Scientists are seeking to identify key molecular switches that control age-related memory impairment. When new molecules are identified as critical to the process of memory consolidation, they are then tested to determine whether they contribute to the memory problems of the elderly.

One of these proteins is called KIBRA and the gene responsible for its production is WWC1. KIBRA is known to play a role in human memory and so researchers at the Lieber Institute for Brain Development and the National Institute of Mental Health, led by senior author Dr. Venkata Mattay, conducted a study to determine the effects of genetic variants in WWC1 on memory. Their findings are published in the current issue of Biological Psychiatry.

“Identifying these genetic factors, while helping us better understand the neurobiology of cognitive aging, will also aid in identifying mechanisms that confer individuals with resilience to withstand the inevitable age-related changes in neural architecture and function,” explained Mattay.

Using imaging genetics, a method that combines genetics with brain imaging technology, the team explored the effect of a variant in the WWC1 gene on age-related changes in memory function. The particular WWC1 variant under investigation has three potential forms – CC, TT, or CT.

They recruited 233 healthy volunteers, who ranged in age from 18-89 years. The volunteers completed a battery of cognitive tests, underwent genotyping, and completed a memory task during a brain imaging scan.

They found that individuals who carry the T allele, as either CT or TT, performed better on the memory task and showed more active engagement in the hippocampus, a vital brain region for memory, with increasing age.

“Our results show a dynamic relationship between this gene and increasing age on hippocampal function and episodic memory with the non-T allele group showing a significant decline across the adult life span,” said Mattay. “A similar relationship was not observed in the T-allele carrying group suggesting that this variant of the gene may confer a protective effect.”

Dr. John Krystal, Editor of Biological Psychiatry, commented, “The risk mechanisms for age-related memory impairment that we identify today may become the targets for the prevention and treatment of this problem in the future.”

Engineering resilience in the brain

Penn researchers model neural structures on the smallest scales to better understand traumatic brain injury

Compared to the monumental machines of science, things like the International Space Station or the Large Hadron Collider, the human brain doesn’t look like much. However, this three-pound amalgam of squishy cells is one of the most complicated and complex structures in the known universe.

With hundreds of billions of neurons, each with its own inner world of organelles and molecular components, understanding the fundamental wiring of the brain is a major undertaking, one that has received a commitment of at least $100 million worth of federal funding from the National Science Foundation (NSF), the National Institutes of Health and the Defense Advanced Research Projects Agency.

And with all of the brain’s interconnected structures, protecting or repairing this complicated machine means thinking like an engineer.

"The idea is really quite simple," says Vivek Shenoy, an NSF-supported professor of materials science and engineering at the University of Pennsylvania’s School of Engineering and Applied Science. "All of the mechanical properties of cells come from their cytoskeleton and the molecules within it. They’re all reinforcing frames, like the frame in a building. Engineers design buildings and other structural objects to make sure they don’t fail, so it’s the same principle: structural engineering on a very, very small level."

Shenoy applies this approach to a problem very much in the public eye—traumatic brain injury. Even the mildest forms of TBI, better known as concussions, can do irreversible damage to the brain. More serious forms can be fatal.

With a background in mechanical engineering and materials science, one might think that Shenoy’s contribution to this problem involves designing new helmets or other safety devices. Instead, he and his colleagues are uncovering the fundamental math and physics behind one of the core mechanisms of the injury: swelling in axons caused by damage to internal structures known as microtubules. These neural “train tracks” transport molecular cargo from one end of a neuron to another; when the tracks break, the cargo piles up and produces bulges in the axons that are the hallmark of fatal TBIs.

Armed with a better understanding of the mechanical properties of these critical structures, Shenoy and his colleagues are laying the foundations for drugs that could one day bolster neurons’ reinforcing frames, making them more resilient when faced with a TBI-inducing impact.

Train tracks and crossties

The first step toward this understanding was resolving a paradox: Why were the microtubules, the stiffest elements of the axons, the parts that were breaking when loaded with the stress of a blow to the head?

A recent finding from Shenoy’s team shows that the answer rests with a critical brain protein known as tau, which is implicated in several neurodegenerative diseases, including Alzheimer’s. If microtubules are like train tracks, tau proteins are the crossties that hold them together. The protein’s elastic properties help explain why rapid movement of the brain, whether on a football field or a car crash, leads to TBI.

Shenoy’s colleague Douglas Smith, professor of neurosurgery in Penn’s Perelman School of Medicine and director of the Penn Center for Brain Injury and Repair, had previously studied the mechanical properties of axons, subjecting them to strains of different forces and speeds.

"What we saw is that with slow loading rates, axons can stretch up to at least 100 percent with no signs of damage," Smith said. "But at faster rates, axons start displaying the same swellings you see in the TBI patients. This process occurs even with relatively short stretches at fast rates."

To explain this rate-dependent response, Shenoy and Smith had to delve deeper inside the structure of microtubules. Based on Smith’s work, other biophysical modelers had previously accounted for the geometry and elastic properties of the axon during a stretching injury, but they did not have good data for representing tau’s role.

"You need to know the elastic properties of tau," Shenoy said, "because when you load the microtubules with stress, you load the tau as well. How these two parts distribute the stress between them is going to have major impact on the system as a whole."

Elastic properties

Shenoy and his colleagues had a sense of tau’s elastic properties but did not have hard numbers until a 2011 experiment from a Swiss and German research team physically stretched out lengths of tau by plucking it with the tip of an atomic force microscope.

"This experiment demonstrated that tau is viscoelastic," Shenoy said. "Like Silly Putty, when you add stress to it slowly, it stretches a lot. But if you add stress to it rapidly, like in an impact, it breaks."

This behavior is because the strands of tau protein are coiled up and bonded to themselves in different places. Pulled slowly, those bonds can come undone, lengthening the strand without breaking it.

"The damage in traumatic brain injury occurs when the microtubules stretch but the tau doesn’t, as they can’t stretch as far," Shenoy said. "If you’re in a situation where the tau doesn’t stretch, such as what happens in fast strain rates, then all the strain will transfer to the microtubules and cause them to break."

With a comprehensive model of the tau-microtubule system, the researchers were able to boil down the outcome of rapid stress loading to equations with only a handful of variables. This mathematical understanding allowed the researchers to produce a phase diagram that shows the dividing line between strain rates that leave permanent damage versus ones that are safe and reversible.

Next steps

Having this mathematical understanding of the interplay between tau and microtubules is only the beginning.

"Predicting what kind of impacts will cause these strain rates is still a complicated problem," Shenoy said. "I might be able to measure the force of the impact when it hits someone’s head, but that force then has to make its way down to the axons, which depends on a lot of different things.

"You need a multiscale model, and our work will be an input to those models on the smallest scale."

In the longer term, however, knowing the parameters that lead to irreversible damage could lead to better understanding of brain injuries and diseases and to new preventive measures. It may even be possible to design drugs that alter microtubule stability and elasticity of axons in traumatic brain injury; Smith’s group has demonstrated that treatment with the microtubule-stabilizing drug taxol reduced the extent of axon swellings and degeneration after injuries in which they are stretched.

Ultimately, insights on the molecular level will be inputs to a more comprehensive view of the brain and its many hierarchies of organizations.

"When you’re talking about something’s mechanical properties, stiffness is what comes to mind," Shenoy said. "Biochemistry is what determines that stiffness in the brain’s structures, but that’s only at the molecular level. Once you build it up and formulate things at the appropriate scale, protecting the brain becomes more of a structural engineering problem."

Yawning to cool the brain

Why do we yawn? We tend to yawn before sleep and after waking, when we are bored or under stimulated. We yawn in the anticipation of important events and when we are under stress. What do all of these have in common? Researchers from the University of Vienna, Austria, and the Nova Southeastern University and SUNY College at Oneonta, USA highlight a link with thermoregulation, and in particular, brain cooling. The results of their study have been published in the scientific journal “Physiology & Behaviour”.

Common belief is that yawning helps to increase the oxygen supply. However, previous research has failed to show an association between yawning and blood oxygen levels. New research by a team of researchers led by Psychologist Andrew Gallup of SUNY College at Oneonta, USA now reveals that yawning cools the brain.

Sleep cycles, cortical arousal and stress are all associated with fluctuations in brain temperature, Yawning subsequently functions to keep the brain temperature balanced and in optimal homeostasis. According to this theory, yawning should also be easily manipulated by ambient temperature variation, since exchange with cool ambient air temperature may facilitate lowering brain temperature. Specifically, the researchers hypothesized that yawning should only occur within an optimal range of temperatures, i.e., a thermal window.

To test this, Jorg Massen and Kim Dusch of the University of Vienna measured contagious yawning frequencies of pedestrians outdoors in Vienna, Austria, during both the winter and summer months, and then compared these results to an identical study conducted earlier in arid climate of Arizona, USA. Pedestrians were asked to view a series of images of people yawning, and then they self-reported on their own yawning behavior.

Results showed that in Vienna people yawned more in summer than in winter, whereas in Arizona people yawned more in winter than in summer. It turned out that it was not the seasons themselves, nor the amount of daylight hours experienced, but that contagious yawning was constrained to an optimal thermal zone or range of ambient temperatures around 20o C. In contrast, contagious yawning diminished when temperatures were relatively high at around 37o C in the summer of Arizona or low and around freezing in the winter of Vienna. Lead author Jorg Massen explains that where yawning functions to cool the brain, yawning is not functional when ambient temperatures are as hot as the body, and may not be necessary or may even have harmful consequences when it is freezing outside.

While most research on contagious yawning emphasizes the influence of interpersonal and emotional-cognitive variables on its expression, this report adds to accumulating research suggesting that the underlying mechanism for yawning, both spontaneous and contagious forms, is involved in regulating brain temperature. In turn, the cooling of the brain functions to improve arousal and mental efficiency. The authors of this study suggest that the spreading of this behavior via contagious yawning could therefore function to enhance overall group vigilance.