At the age of 29, Brittany Maynard was newly married and thought that she had her whole life ahead of her. That was when she was diagnosed with grade II astrocytoma, a serious brain tumor giving her ten years to live. Shortly after, she was told she had glioblastoma multiforme (GBM), the deadliest type of brain cancer there is. She was told that patients live an average of six months with the condition, and those final months are painful. That’s when she and her husband made the decision to move to Oregon, one of the five states that allow doctor-assisted suicide, so that she could choose her own passing.
“Seize the day. What’s important to you, what do you care about, what matters. Pursue that–forget the rest.”
Wise words from a brave woman.
For more information about The Brittany Fund, check out its website here.
Scientists at Seattle Children’s Research Institute have discovered an area of the brain that could control a person’s motivation to exercise and participate in other rewarding activities – potentially leading to improved treatments for depression.
Dr. Eric Turner, a principal investigator in Seattle Children’s Research Institute’s Center for Integrative Brain Research, together with lead author Dr. Yun-Wei (Toni) Hsu, have discovered that a tiny region of the brain – the dorsal medial habenula – controls the desire to exercise in mice. The structure of the habenula is similar in humans and rodents and these basic functions in mood regulation and motivation are likely to be the same across species.
Exercise is one of the most effective non-pharmacological therapies for depression. Determining that such a specific area of the brain may be responsible for motivation to exercise could help researchers develop more targeted, effective treatments for depression.
“Changes in physical activity and the inability to enjoy rewarding or pleasurable experiences are two hallmarks of major depression,” Turner said. “But the brain pathways responsible for exercise motivation have not been well understood. Now, we can seek ways to manipulate activity within this specific area of the brain without impacting the rest of the brain’s activity.”
Dr. Turner’s study, titled “Role of the Dorsal Medial Habenula in the Regulation of Voluntary Activity, Motor Function, Hedonic State, and Primary Reinforcement,” was published today by the Journal of Neuroscience and funded by the National Institute of Mental Health and National Institute on Drug Abuse. The study used mouse models that were genetically engineered to block signals from the dorsal medial habenula. In the first part of the study, Dr. Turner’s team collaborated with Dr. Horacio de la Iglesia, a professor in University of Washington’s Department of Biology, to show that compared to typical mice, who love to run in their exercise wheels, the genetically engineered mice were lethargic and ran far less. Turner’s genetically engineered mice also lost their preference for sweetened drinking water.
“Without a functioning dorsal medial habenula, the mice became couch potatoes,” Turner said. “They were physically capable of running but appeared unmotivated to do it.”
In a second group of mice, Dr. Turner’s team activated the dorsal medial habenula using optogenetics – a precise laser technology developed in collaboration with the Allen Institute for Brain Science. The mice could “choose” to activate this area of the brain by turning one of two response wheels with their paws. The mice strongly preferred turning the wheel that stimulated the dorsal medial habenula, demonstrating that this area of the brain is tied to rewarding behavior.
Past studies have attributed many different functions to the habenula, but technology was not advanced enough to determine roles of the various subsections of this area of the brain, including the dorsal medial habenula.
“Traditional methods of stimulation could not isolate this part of the brain,” Turner said. “But cutting-edge technology at Seattle Children’s Research Institute makes discoveries like this possible.”
As a professor in the University of Washington Department of Psychiatry and Behavioral Sciences, Dr. Turner treats depression and hopes this research will make a difference in the lives of future patients.
“Working in mental health can be frustrating,” Turner said. “We have not made a lot of progress in developing new treatments. I hope the more we can learn about how the brain functions the more we can help people with all kinds of mental illness.”
The above story is based on materials provided by Seattle Children’s Hospital. Note: Materials may be edited for content and length.
Although we all know that sneezes and coughs transmit infections, little research had been done to model how they work. To address this knowledge gap, Dr. Lydia Bourouiba and Dr. John Bush of MIT’s Applied Mathematics Lab used high speed cameras and fluid mechanics to reveal why we’ve grossly underestimated the role of gas clouds in these violent expirations.
Only 8.2% of human DNA is likely to be doing something important – is ‘functional’ – say Oxford University researchers.
This figure is very different from one given in 2012, when some scientists involved in the ENCODE (Encyclopedia of DNA Elements) project stated that 80% of our genome has some biochemical function.
That claim has been controversial, with many in the field arguing that the biochemical definition of ‘function’ was too broad – that just because an activity on DNA occurs, it does not necessarily have a consequence; for functionality you need to demonstrate that an activity matters.
To reach their figure, the Oxford University group took advantage of the ability of evolution to discern which activities matter and which do not. They identified how much of our genome has avoided accumulating changes over 100 million years of mammalian evolution – a clear indication that this DNA matters, it has some important function that needs to be retained.
‘This is in large part a matter of different definitions of what is “functional” DNA,’ says joint senior author Professor Chris Pointing of the MRC Functional Genomics Unit at Oxford University. ‘We don’t think our figure is actually too different from what you would get looking at ENCODE’s bank of data using the same definition for functional DNA.
‘But this isn’t just an academic argument about the nebulous word “function”. These definitions matter. When sequencing the genomes of patients, if our DNA was largely functional, we’d need to pay attention to every mutation. In contrast, with only 8% being functional, we have to work out the 8% of the mutations detected that might be important. From a medical point of view, this is essential to interpreting the role of human genetic variation in disease.’
The researchers Chris Rands, Stephen Meader, Chris Ponting and Gerton Lunter report their findings in the journal PLOS Genetics. They were funded by the UK Medical Research Council and the Wellcome Trust.
The researchers used a computational approach to compare the complete DNA sequences of various mammals, from mice, guinea pigs and rabbits to dogs, horses and humans.
Dr Gerton Lunter from the Wellcome Trust Centre for Human Genetics at Oxford University, the other joint senior author, explained: ‘Throughout the evolution of these species from their common ancestors, mutations arise in the DNA and natural selection counteracts these changes to keep useful DNA sequences intact.’
The scientists’ idea was to look at where insertions and deletions of chunks of DNA appeared in the mammals’ genomes. These could be expected to fall approximately randomly in the sequence – except where natural selection was acting to preserve functional DNA, where insertions and deletions would then lie further apart.
‘We found that 8.2% of our human genome is functional,’ says Dr Lunter. ‘We cannot tell where every bit of the 8.2% of functional DNA is in our genomes, but our approach is largely free from assumptions or hypotheses. For example, it is not dependent on what we know about the genome or what particular experiments are used to identify biological function.’
The rest of our genome is leftover evolutionary material, parts of the genome that have undergone losses or gains in the DNA code – often called ‘junk’ DNA.
‘We tend to have the expectation that all of our DNA must be doing something. In reality, only a small part of it is,’ says Dr Chris Rands, first author of the study and a former DPhil student in the MRC Functional Genomics Unit at Oxford University.
Not all of the 8.2% is equally important, the researchers explain.
A little over 1% of human DNA accounts for the proteins that carry out almost all of the critical biological processes in the body.
The other 7% is thought to be involved in the switching on and off of genes that encode proteins – at different times, in response to various factors, and in different parts of the body. These are the control and regulation elements, and there are various different types.
‘The proteins produced are virtually the same in every cell in our body from when we are born to when we die,’ says Dr Rands. ‘Which of them are switched on, where in the body and at what point in time, needs to be controlled – and it is the 7% that is doing this job.’
In comparing the genomes of different species, the researchers found that while the protein-coding genes are very well conserved across all mammals, there is a higher turnover of DNA sequence in the regulatory regions as this sequence is lost and gained over time.
Mammals that are more closely related have a greater proportion of their functional DNA in common.
But only 2.2% of human DNA is functional and shared with mice, for example – because of the high turnover in the regulatory DNA regions over the 80 million years of evolutionary separation between the two species.
‘Regulatory DNA evolves much more dynamically that we thought,’ says Dr Lunter, ‘but even so, most of the changes in the genome involve junk DNA and are irrelevant.’
He explains that although there is a lot of functional DNA that isn’t shared between mice and humans, we can’t yet tell what is novel and explains our differences as species, and which is just a different gene-switching system that achieves the same result.
Professor Ponting agrees: ‘There appears to be a lot of redundancy in how our biological processes are controlled and kept in check. It’s like having lots of different switches in a room to turn the lights on. Perhaps you could do without some switches on one wall or another, but it’s still the same electrical circuit.’
He adds: ‘The fact that we only have 2.2% of DNA in common with mice does not show that we are so different. We are not so special. Our fundamental biology is very similar. Every mammal has approximately the same amount of functional DNA, and approximately the same distribution of functional DNA that is highly important and less important. Biologically, humans are pretty ordinary in the scheme of things, I’m afraid.
‘I’m definitely not of the opinion that mice are bad model organisms for animal research. This study really doesn’t address that issue,’ he notes.
The above story is based on materials provided by University of Oxford. Note: Materials may be edited for content and length.
Credit: Robin Carhart-Harris
Psychedelic drugs alter consciousness in a profound and novel way that increases the breadth and fluency of cognition. However, until recently, we were unable to offer an explanation for how the brain was altered to account for these effects.
In a new study, published in Human Brain Mapping, we scanned the brains of volunteers who had been injected with psilocybin – the chemical found in magic mushrooms which gives a psychedelic experience – and a control group who hadn’t, and discovered two key things: that psilocybin increased the amplitude (or “volume”) of activity in regions of the brain that are reliably activated during dream sleep and form part of the brain’s ancient emotion system; and that psychedelics facilitate a state of “expanded” consciousness – meaning that the breath of associations made by the brain and the ease by which they are visited is enhanced under the drugs.
Ego and emotion
This finding of a similar pattern to dream activity is intriguing. While the psychedelic state has been previously compared with dreaming, the opposite effect has been observed in the brain network from which we get our sense of “self” (called the default-mode network or ego-system). Put simply, while activity became “louder” in the emotion system, it became more disjointed and so “quieter” in the ego system.
Evidence from this study, and also preliminary data from an ongoing brain imaging study with LSD, appear to support the principle that the psychedelic state rests on disorganised activity in the ego system permitting disinhibited activity in the emotion system. And such an effect may explain why psychedelics have been considered useful facilitators of certain forms of psychotherapy.
We also looked at the range of connectivity configurations – or “motifs” – in the emotion system and found that a broader range of motifs emerged under psilocybin, and this effect began with the onset of the drug’s psychological effects.
This is an entirely novel analysis and its validity needs to be further tested – but it may offer an initial insight into the biological basis of the often described consciousness-expansion that is one of the hallmarks of a psychedelic experience.
Building a picture
Our research into the brain effects of psychedelic drugs began at the University of Bristol in 2009 and continues today at Imperial College London and Cardiff University.
We were interested in the idea that psychedelics facilitate communication across the brain and, more specifically, how the default-mode network in the brain, arguably science’s best biological correlate of the self, normally works to constrain this.
Our first study, published in Proceedings of the National Academy of Sciences in 2012, revealed decreases in brain activity after injection of psilocybin that were localised to the default-mode network.
This finding was exciting because it synched with the idea that psychedelics cause temporary “ego dissolution”, in other words – diminishing one’s sense of having a firm and enduring personality. Our new research adds to our understanding about how this happens.
Understanding the brain mechanisms that underlie enhanced cognitive fluency under psychedelics may offer insights into how these drugs may be psychologically useful, for example in helping patients experience an emotional release in psychotherapy, and also potentially enhancing creative thinking.
Editors note: Original publication can be found here.