Posts tagged neuroscience
Articles and news from the latest research reports.
Brain stimulation affects compliance with social norms
Neuroeconomists at the University of Zurich have identified a specific brain region that controls compliance with social norms. They discovered that norm compliance is independent of knowledge about the norm and can be increased by means of brain stimulation.
How does the human brain control compliance with social norms? The biological mechanisms that underlie norm compliance are still poorly understood. In a new study, Christian Ruff, Giuseppe Ugazio, and Ernst Fehr from the University of Zurich show that the lateral prefrontal cortex plays a central role in norm compliance.
Prefrontal cortex controls norm behavior
For the study, 63 participants took part in an experiment in which they received money and were asked to decide how much of it they wanted to share with an anonymous partner. A prevalent fairness norm in Western cultures dictates that the money should be evenly split between the two players. However, this contrasts with the participants’ self-interest to keep as much money as possible for themselves. In another experiment, the participants were faced with the same decision, but knew in advance that they could be punished by the partner for an unfair proposal.
By means of a technique called “transcranial direct current stimulation,” which sends weak and painless electric currents through the skull, the excitability of specific brain regions can be modulated. During this experiment, the scientists used this technique to increase or decrease neural activity at the front of the brain, in the right lateral prefrontal cortex. Christian Ruff, Professor of Neuroeconomics and Decision Neuroscience at the University of Zurich, said: “We discovered that the decision to follow the fairness norm, whether voluntarily or under threat of sanctions, can be directly influenced by neural stimulation in the prefrontal cortex.”
Brain stimulation affects normative behavior
When neural activity in this part of the brain was increased via stimulation, the participants’ followed the fairness norm more strongly when sanctions were threatened, but their voluntary norm compliance in the absence of possible punishments decreased. Conversely, when the scientists decreased neural activity, participants followed the fairness norm more strongly on a voluntary basis, but complied less with the norm when sanctions were threatened. Moreover, neural stimulation influenced the participants’ behavior, but it did not affect their perception of the fairness norm. It also did not alter their expectations about whether and how much they would be punished for violating the norm.
"We found that the brain mechanism responsible for compliance with social norms is separate from the processes that represent one’s knowledge and beliefs about the social norm," says Ernst Fehr, Chairman of the Department of Economics at the University of Zurich. "This could have important implications for the legal system as the ability to distinguish between right and wrong may not be sufficient for the ability to comply with social norms." Christian Ruff adds: "Our findings show that a socially and evolutionarily important aspect of human behavior depends on a specific neural mechanism that can be both up- and down-regulated with brain stimulation."
Literature:
Christian C. Ruff, Giuseppe Ugazio und Ernst Fehr. Changing Social Norm Compliance With Noninvasive Brain Stimulation. Science. October 3, 2013.
(Image: iStockphoto)
To predict, perchance to update: Neural responses to the unexpected
Among the brain’s many functions is the use of predictive models to processing expected stimuli or actions. In such a model, we experience surprise when presented with an unexpected stimulus – that is, one which the model evaluates as having a low probability of occurrence. Interestingly, there can be two distinct – but often experimentally correlated – responses to a surprising event: reallocating additional neural resources to reprogram actions, and updating the predictive model to account for the new environmental stimulus. Recently, scientists at Oxford University used brain imaging to identify separate brain systems involved in reprogramming and updating, and created a mathematical and neuroanatomical model of how brains adjust to environmental change, Moreover, the researchers conclude that their model may also inform models of neurological disorders, such as extinction, Balint syndrome and neglect, in which this adaptive response to surprise fails.
Research Fellow Jill X. O’Reilly discussed the research she and her colleagues conducted with Medical Xpress. “Sometimes we think of the brain as an input-output device which takes sensory information, processes it, and produces actions appropriately – but in fact, brains don’t passively ‘sit around’ waiting for sensory input,” O’Reilly explains. “Rather, they actively predict what is going to happen next, because by being prepared, they can process stimuli more efficiently.”
O’Reilly cites an important example of predictive processing, which the researchers used in their study: the control of eye movements. “You can actually only process quite a small portion of visual space accurately at any one time, which is why people tend to actively look at interesting objects,” O’Reilly tells Medical Xpress. “Parts of the brain that control eye movements – for example, the parietal cortex – are actively involved in trying to predict where visual objects that are worth looking at will occur next, in order to respond to them quickly and effectively.” Since the scientists were interested in how the brain forms predictions – such as where eye movements should be directed – they designed an experiment in which people’s expectations about where they should make eye movements were built up over time and then suddenly changed. (They did this moving the stimuli participants’ were instructed to fixate on to a different part of the computer screen.)
"However," notes O’Reilly, "we know from previous work that activity in many brain areas is evoked when people are expecting to make an eye movement to one place, and actually they have to make an eye movement to another. A lot of this brain activity has to do with reprogramming the eye movement itself, rather than learning about the changed environment. That means we needed to design an experiment in which re-planning of eye movements was sometimes accompanied by learning, and sometimes not." The researchers accomplished this by color-coding stimuli: participants knew that colorful stimuli indicated a real change in the environment, while grey stimuli were to be ignored.
To quantify how much participants learned on each trial of the experiment, the team constructed a computer participant that learned about the environment in the same way the real, human participants did. Because they could determine exactly what the computer participant knew or believed about the environment – that is, where it would need to look – on each trial, we could get mathematical measures of how surprising it found each stimulus (defined as how far the stimulus location was from where the computer participant expected it to be) and how much it learned on each trial.
Therefore, the computer participant allowed the scientists to separately measure the degree to which human participants had to respond to surprise in terms of reprogramming eye movements, and how much they learned on each trial. “We then needed to work out whether some parts of the brain were specifically involved in each of these processes,” O’Reilly continues. “To do this we used fMRI and looked for areas that increased their activity in proportion to how much the computer participant, and thereby the real participants, would need to reprogram their eye movements for each surprising stimulus – as well as the extent to which they’d have to update their predictions about future stimulus locations – on each trial.”
O’Reilly stresses that the computer participant was critical to addressing the challenges they encountered. “We had access to a complete model of what participants could know or should believe about where stimuli were expected to appear on each trial. That meant we could make very specific predictions about how much they should be surprised by certain stimuli and how much they learned from each stimulus.” The team checked these predictions by looking at behavioral measures like reaction time (participants were slower to move their eyes to surprising stimuli) and gaze dwell time (participants looked at stimuli for longer when the stimuli carried information about the possible locations of future stimuli).
O’Reilly describes how their study may inform understanding of neurological disorders in which this adjustment process fails by observing that a second saccade-sensitive region in the inferior posterior parietal cortex was activated by surprise and modulated by updating. “Some stroke victims are unable to move their eyes in order to look at stimuli that show up in their visual periphery, which turns out to be similar to the process of reprogramming to surprising stimuli in our model. In contrast,” she continues, “people with brain lesions in a slightly different brain region are able to move their eyes to look at stimuli, but seem unable to learn that stimuli could occur in some parts of space – usually towards the left of the body – even if given lots of hints and training.” Because the brain regions damaged in these two patient groups map onto the regions of parietal cortex active in the experiment’s reprogramming and updating conditions, the researchers think these two processes could be differentially affected in the two patient groups.
Moving forward, the researchers would like to test their paradigm in patients who have had strokes that damaged the different brain regions activated in their study. “We’d expect to find a difference between patients with damage in different parts of parietal cortex, such that one group might be slower to reprogram eye movements to all surprising stimuli whether these stimuli are informative about future stimulus locations or not,” O’Reilly concludes, “whereas the other group might have trouble learning that the location where stimuli are going to appear has changed.”
International research collaboration reveals the mechanism of the sodium-potassium pump
It’s not visible to the naked eye and you can’t feel it, but up to 40 per cent of your body’s energy goes into supplying the microscopic sodium-potassium pump with the energy it needs. The pump is constantly doing its job in every cell of all animals and humans. It works much like a small battery which, among other things, maintains the sodium balance which is crucial to keep muscles and nerves working.
The sodium-potassium pump transports sodium out and potassium into the cell in a fixed cycle. During this process the structure of the pump changes. It is well-established that the pump has a sodium and a potassium form. But the structural differences between the two forms have remained a mystery, and researchers have been unable to explain how the pump distinguishes sodium from potassium.
Structure solves the mystery
Thanks to the international collaboration between Professor Chikashi Toyoshima’s group at the University of Tokyo and researchers from Aarhus University, the structure of the sodium-bound form of the protein has now been described. For the first time ever, the sodium ions can be studied at a resolution so high - 0.28 nanometres - that researchers can actually see the sodium ions and observe where they bind in the structure of the pump. In 2000, Professor Chikashi Toyoshima’s group described the structure of a calcium-pump for the first time, and in 2007 and 2009 research groups from Aarhus University and Toyoshima’s group described the potassium-bound form of the sodium-potassium pump.
"The new protein structure shows how the smaller sodium ions are bound and subsequently transported out of the cell, whereas the access of the slightly larger potassium ions is blocked. We now understand how the pump distinguishes between sodium and potassium at the molecular level. This is a great leap forward for research into ion pumps and may help us understand and treat serious neurological conditions associated with mutations of the sodium-potassium pump, including a form of Parkinsonism and alternating hemiplegia of childhood in which sodium binding is defective," explains Bente Vilsen, a professor at Aarhus University who spearheaded the project’s activities in Aarhus with Associate Professor Flemming Cornelius.
Impressed Nobel Prize winner
The vital pump was discovered in 1957 by Professor Jens Christian Skou of Aarhus University, who received the Nobel Prize for his discovery in 1997. The new result is the culmination of five or six decades of research aimed at the mechanism behind this vital motor of the cells.
"Years ago, when the first electron microscopic images were taken in which the enzyme was but a millimetre-sized dot at 250,000 magnifications, I thought, how on earth will we ever be able to establish the structure of the enzyme. The pump transports potassium into and sodium out of the cells, so it must be capable of distinguishing between the two ions. But until now, it has been a mystery how this was possible," says retired Professor Jens Christian Skou, who - even at 94 years of age - keeps up to date with new developments in the field of research which he initiated more than 50 years ago.
"Now, the researchers have described the structure that allows the enzyme to identify sodium and this may pave the way for a more detailed understanding of how the pump works. It is an impressive achievement and something I haven’t even dared dream of," concludes Jens Christian Skou.
(Source: eurekalert.org)
Researchers Uncover 48 New Genetic Variants Associated with Multiple Sclerosis
Study brings to 110 known risk factors and provides important insight into disease mechanism
Scientists of the International Multiple Sclerosis Genetics Consortium (IMSGC) have identified an additional 48 genetic variants influencing the risk of developing multiple sclerosis. This work nearly doubles the number of known genetic risk factors and thereby provides additional key insights into the biology of this debilitating neurological condition. The genes implicated by the newly identified associations underline the central role played by the immune system in the development of multiple sclerosis and show substantial overlap with genes known to be involved in other autoimmune diseases.
Published online September 29 in the journal Nature Genetics, the study, “Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis,” is the largest investigation of multiple sclerosis genetics to date. Led by the University of Miami Miller School of Medicine, this study relied upon an international team of 193 investigators from 84 research groups in 13 countries and was funded by more than 40 local and national agencies and foundations.
Multiple sclerosis (MS) is a chronic disabling neurological condition that affects over 2.5 million individuals worldwide. The disease results in patchy inflammation and damage to the central nervous system that causes problems with mobility, balance, sensation and cognition depending upon where the damage to the central nervous system occurs. Neurological symptoms are often intermittent in the early stages of the disease but tend to persist and progressively worsen with the passage of time for the majority of patients. The risk of developing multiple sclerosis is increased in those who have a family history of the disease. Research studies in twins and adopted individuals have shown that this increased risk is primarily the result of genetic risk factors.
The findings released in this study nearly double the number of confirmed susceptibility loci, underline the critical role played by the immune system in the development of multiple sclerosis, and highlight the marked similarities between the genetic architecture underlying susceptibility to this and the many other autoimmune diseases.
The present study takes advantage of custom designed technology known as ImmunoChip—a high-throughput genotyping array specifically designed to interrogate a targeted set of genetic variants linked to one or more autoimmune diseases. IMSGC researchers used the ImmunoChip platform to analyze the DNA from 29,300 individuals with multiple sclerosis and 50,794 unrelated healthy controls, making this the largest genetics study ever performed for multiple sclerosis. In addition to identifying 48 new susceptibility variants, the study also confirmed and further refined a similar number of previously identified genetic associations.
With these new findings, there are now 110 genetic variants associated with MS. Although each of these variants individually confers only a very small risk of developing multiple sclerosis, collectively they explain approximately 20 percent of the genetic component of the disease.
Explaining the significance of the work and the nature of the collaboration, the Miller School’s Jacob McCauley, Ph.D., who led the study on behalf of the IMSGC, said, “With the release of these new data, our ongoing effort to elucidate the genetic components of this complex disease has taken a major step forward. Describing the genetic underpinnings of any complex disease is a complicated but critical step. By further refining the genetic landscape of multiple sclerosis and identifying novel genetic associations, we are closer to being able to identify the cellular and molecular processes responsible for MS and therefore the specific biological targets for future drug treatment strategies. These results are the culmination of a thoroughly collaborative effort. A study of this size and impact is only possible because of the willingness of so many hard working researchers and thousands of patients to invest their time and energy in a shared goal.”
(Source: med.miami.edu)
Well-connected hemispheres of Einstein’s brain may have sparked brilliance
The left and right hemispheres of Albert Einstein’s brain were unusually well connected to each other and may have contributed to his brilliance, according to a new study conducted in part by Florida State University evolutionary anthropologist Dean Falk.
"This study, more than any other to date, really gets at the ‘inside’ of Einstein’s brain," Falk said. "It provides new information that helps make sense of what is known about the surface of Einstein’s brain."
The study, “The Corpus Callosum of Albert Einstein’s Brain: Another Clue to His High Intelligence,” was published in the journal Brain. Lead author Weiwei Men of East China Normal University’s Department of Physics developed a new technique to conduct the study, which is the first to detail Einstein’s corpus callosum, the brain’s largest bundle of fibers that connects the two cerebral hemispheres and facilitates interhemispheric communication.
"This technique should be of interest to other researchers who study the brain’s all-important internal connectivity," Falk said.
Men’s technique measures and color-codes the varying thicknesses of subdivisions of the corpus callosum along its length, where nerves cross from one side of the brain to the other. These thicknesses indicate the number of nerves that cross and therefore how “connected” the two sides of the brain are in particular regions, which facilitate different functions depending on where the fibers cross along the length. For example, movement of the hands is represented toward the front and mental arithmetic along the back.
In particular, this new technique permitted registration and comparison of Einstein’s measurements with those of two samples — one of 15 elderly men and one of 52 men Einstein’s age in 1905. During his so-called “miracle year” at 26 years old, Einstein published four articles that contributed substantially to the foundation of modern physics and changed the world’s views about space, time, mass and energy.
The research team’s findings show that Einstein had more extensive connections between certain parts of his cerebral hemispheres compared to both younger and older control groups.
The research of Einstein’s corpus callosum was initiated by Men, who requested the high-resolution photographs that Falk and other researchers published in 2012 of the inside surfaces of the two halves of Einstein’s brain. In addition to Men, the current research team included Falk, who served as second author; Tao Sun of the Washington University School of Medicine; and, from East China Normal University’s Department of Physics, Weibo Chen, Jianqi Li, Dazhi Yin, Lili Zang and Mingxia Fan.
(Image: National Museum of Health and Medicine)
Get the picture? New high-res images show brain activity like never before
In the middle of the human brain there is a tiny structure shaped like an elongated donut that plays a crucial role in managing how the body functions. Measuring just 10 millimeters in length and six millimeters in diameter, the hollow structure is involved in a complex array of behavioral, cognitive, and affective phenomena, such as the fight or flight response, pain regulation, and even sexual activity, according to Northeastern senior research scientist Ajay Satpute.
With a name longer than the structure itself, the “midbrain periaqueductal gray region,” or PAG, is extraordinarily difficult to investigate in humans because of its size and intricate structure, he said.
In research published online this week in the journal Proceedings of the National Academy of Science, Satpute and his colleagues at Northeastern’s Interdisciplinary Affective Science Laboratory explain how they hurdled these challenges by using state-of-the art imaging to capture this complex neural activity. The research could ultimately help scientists explore the grounds of human emotion like never before.
“The PAG’s functional properties occur at such small spatial scales that we need to capture its activity at very high resolution in order to understand it,” he explained.
Until recently, neuroimaging studies have been carried out on functional magnetic resonance imaging, or fMRI, instruments containing magnets of up to three Teslas, a measure of magnetic field strength. These instruments provide critical data for understanding how the brain’s different areas respond to different stimuli, but when those areas become sufficiently small and complicated, their resolution falls short.
In the case of the tiny PAG, this problem is paramount because the PAG wraps around a hollow core, or “aqueduct,” containing cerebrospinal fluid, Satpute said. Traditional fMRI instruments cannot distinguish neural activity occurring in the PAG from that occurring in the CS fluid. Even more difficult is identifying where within the PAG itself specific responses originate.
In collaboration with researchers at the Massachusetts General Hospital in Boston, Satpute and his colleagues used a high-tech fMRI instrument that contains a seven-Tesla magnet. The force of the instrument is so strong (albeit harmless) that one can feel its pull when simply walking by. Coupled with painstaking manual data analyses, Satpute was able to resolve activity in sub-regions of the PAG with more precision than ever before.
With their method in hand, the research team showed 11 human research subjects images of burn victims, gory injuries, and other content related to threat, harm, and loss while keeping tabs on the PAG’s activity. Researchers also showed the subjects neutral images such and then compared results between the two scenarios.
The proof-of-concept study showed emotion-related activity concentrated in particular areas of the PAG. While similar results have been demonstrated in animal models, nothing like it had previously been shown in human brains.
Using this methodology, the researchers said they would not only gain a better understanding of the PAG but also be able to investigate a range of brain-related research questions beyond this particular structure.
Seven-Tesla brain imaging provides an unprecedented view of regions like the PAG while they respond to stimuli, said Lisa Feldman Barrett, director of the Interdisciplinary Affective Science Laboratory. “Studies like this are a critical step forward in bridging human and nonhuman animal studies of emotion, because they offer a level of resolution in human brains that was previously possible only in studies of non-human animal,” she said.
Is the human brain capable of identifying a fake smile?
Since Leonardo Da Vinci painted the Mona Lisa, much has been said about what lies behind her smile. Now, Spanish researchers have discovered how far this attention-grabbing expression confuses our emotion recognition and makes us perceive a face as happy, even if it is not.
Human beings deduce others´ state of mind from their facial expressions. “Fear, anger, sadness, displeasure and surprise are quickly inferred in this way,” David Beltrán Guerrero, researcher at the University of La Laguna, explains to SINC. But some emotions are more difficult to perceive.
“There is a wide range of more ambiguous expressions, from which it is difficult to deduce the underlying emotional state. A typical example is the expression of happiness,” says Beltrán, who is part of a group of experts at the Canarian institution who have analyzed, in three scientific articles, the smile’s capacity to distort people’s innate deductive ability.
“The smile plays a key role in recognizing others´ happiness. But, as we know, we are not really happy every time we smile,” he adds. In some cases, a smile merely expresses politeness or affiliation. In others, it may even be a way of hiding negative feelings and incentives, such as dominance, sarcasm, nervousness or embarrassment.
To develop this line of research, the authors created faces comprising smiling mouths and eyes expressing non-happy emotions, and compared them with faces in which both mouths and eyes expressed the same type of emotional state.
The main objective was to discover how far the smile skews the recognition of ambiguous expressions, making us identify them with happiness even though they are accompanied by eyes which clearly express a different feeling.
The power of a smile
“The influence of the smile is highly dependent on the type of task given to participants and, therefore, on the type of activity we are involved in when we come across this type of expression,” Beltrán notes.
Thus when the task is purely perceptive – like the detection of facial features - the smile has a very strong influence, to the extent that differences between ambiguous expressions (happy mouth and non-happy eyes) and genuinely happy expressions (happy mouth and eyes) are not distinguished.
On the other hand, when the task involves categorizing expressions, that is recognizing if they are happy, sad or any other emotion, the influence of the smile weakens, although it is still important, since 40% of the time, participants identify ambiguous expressions as genuinely happy.
However, the influence of the smile disappears in emotional assessment, that is when someone is asked to assess whether a facial expression is positive or negative: “A smile can cause us to interpret a non-happy expression as happy, except when we are involved in the emotional assessment of said expression,” he highlights.
A stimulus which is difficult to assess
According to the authors, the reason why a smile sometimes leads to the incorrect categorization of an expression is related to its high visual “salience”– its attention-grabbing capacity – and its almost exclusive association with the emotional state of happiness.
In a recent study, it was found that the smile dominates many of the initial stages of the brain processing of faces, to the extent that it prompts similar electrical activity in the brain for genuinely happy expressions and ambiguous expressions with smiles and non-happy eyes.
By measuring eye movements, it was observed that an ambiguous expression is confused and categorized as happy if the first gaze falls on the area of the smiling mouth, rather than the area of the eyes.
However, curiously the influence of the smile in these assessments is not the same for everyone. “Another study showed that people with social anxiety tend to confuse ambiguous expressions with genuinely happy expressions less frequently,” Beltrán concludes.
References:
Manuel G. Calvo, Hipólito Marrero, David Beltrán. “When does the brain distinguish between genuine and ambiguous smiles? An ERP study”. Brain and Cognition 81 (2013) 237–246.
Manuel G. Calvo, Andrés Fernández-Martín, Lauri Nummenmaa. “Perceptual, categorical, and affective processing of ambiguous smiling facial expressions”. Cognition 125 (2012) 373–393.
Manuel G. Calvo; Aida Gutiérrez-García; Pedro Avero; Daniel Lundqvist. “Attentional Mechanisms in Judging Genuine and Fake Smiles: Eye-Movement Patterns”. Emotion 2013, Vol. 13 (2013), No. 4, 792–802.
To pinpoint why depression messes with memory, researchers took a page from Sesame Street’s book.
The show’s popular game “One of these things is not like the others” helps young viewers learn to differentiate things that are similar – a process known as “pattern separation.”
A new Brigham Young University study concludes that this same skill fades in adults in proportion to the severity of their symptoms of depression. The more depressed someone feels, the harder it is for them to distinguish similar experiences they’ve had.
If you’ve ever forgotten where you parked the car, you know the feeling (though it doesn’t mean you have depression).
“That’s really the novel aspect of this study – that we are looking at a very specific aspect of memory,” said Brock Kirwan, a psychology and neuroscience professor at BYU.
Depression has been generally linked to poor memory for a long time. To find out why, Kirwan and his former grad student D.J. Shelton put people through a computer-aided memory test. The participants viewed a series of objects on the screen. For each one, they responded whether they had seen the object before on the test (old), seen something like it (similar), or not seen anything like it (new).
With old and new items, participants with depression did just fine. They often got it wrong, however, when looking at objects that were similar to something they had seen previously. The most common incorrect answer was that they had seen the object before.
“They don’t have amnesia,” Kirwan said. “They are just missing the details.”
This can be a challenge in a number of everyday situations, such as trying to remember which friends and family members you’ve told about something personal – and which ones are still in the dark.
The findings also give an important clue about what is happening in the brain that might explain this.
“There are two areas in your brain where you grow new brain cells,” Kirwan said. “One is the hippocampus, which is involved in memory. It turns out that this growth is decreased in cases of depression.”
Because of this study, we know a little more about what these new brain cells are for: helping us see and remember new experiences. The study appears in the journal Behavioral Brain Research.
Drowsy Drosophila shed light on sleep and hunger
Scientists discover key function in molecule that regulates sleep, metabolism and hunger
Why does hunger keep us awake and a full belly make us tired? Why do people with sleep disorders such as insomnia often binge eat late at night? What can sleep patterns tell us about obesity?
Sleep, hunger and metabolism are closely related, but scientists are still struggling to understand how they interact. Now, Brandeis University researchers have discovered a function in a molecule in fruit flies that may provide insight into the complicated relationship between sleep and food.
In the October issue of the journal Neuron, Brandeis scientists report that sNPF, a neuropeptide long known to regulate food intake and metabolism, is also an important component in regulating and promoting sleep. When researchers activated sNPF in fruit flies, the insects fell asleep almost immediately, awaking only long enough to eat before nodding off again. The flies were so sleepy that once they found a food source, they slept right on top of it for days — like falling asleep on a giant hamburger bun and waking up long enough to take a few nibbles before falling back to sleep.
When researchers returned sNPF functions to normal, the flies resumed their normal level of activity, leaving behind their couch potato ways.
The researchers, led by professor of biology Leslie Griffith, concluded that sNPF has an important regulatory function in sleep in addition to its previously known function coordinating behaviors such as eating and metabolism.
"This paper provides a nice bridge between feeding behavior and sleep behavior with just a single molecule," says Nathan Donelson, a post doctoral fellow in Griffith’s lab and one of the study’s lead authors.
Neurons use neuropeptides to communicate a range of brain functions including learning, metabolism, memory and social behaviors. In humans, Neuropeptide Y functions similarly to sNPF and has been studied as a possible drug target for obesity treatment.
But scientists don’t fully understand how regulating neuropeptide function at specific times and in specific cells affects sleeping and eating. By studying sNPF in fruit flies, scientists can learn which cells, neurotransmitters and genes are involved in eating and sleeping; what processes turn on and inhibit the behaviors, and how sleep cells are relevant to hunger drive.
"Our paper makes a significant step into tying all these things together," says Donelson, "and that is extremely important down the road to our understanding of human health."
(Source: eurekalert.org)
Power of precision medicine in successful treatment of patient with disabling OCD
A multidisciplinary team led by a geneticist and psychiatrist from Cold Spring Harbor Laboratory’s (CSHL) Stanley Institute for Cognitive Genomics today publish a paper providing a glimpse of both the tremendous power and the current limitations of what is sometimes called “precision medicine.”
Precision medicine is an approach to diagnosis and treatment that tailors therapeutic care to individuals in a highly specific manner, and which brings to bear powerful new technologies that have not yet made it into the mainstream of clinical medicine, in part because they remain unproven.
Gholson J. Lyon, M.D., Ph.D., a CSHL researcher in molecular genetics and also a practicing psychiatrist, and collaborators at the University of Utah, the Utah Foundation for Biomedical Research (UFBR) and the companies Omicia, Inc. and AssureRx, report on their recruitment and treatment of a single patient with severe psychiatric illness. The man, identified as a 37-year-old U.S. military veteran, suffered from a form of obsessive-compulsive disorder (OCD) that rendered him completely disabled – profoundly compulsive and anxious, occasionally paranoid, and unable to hold a job or form meaningful relationships.
Over the past three years, the team successfully treated the man with an experimental form of electrical brain stimulation, called deep-brain stimulation (DBS). To date, DBS has been used most frequently to lessen symptoms in people with advanced Parkinson’s disease and also on an experimental basis to help lift otherwise untreatable, severe depression. Worldwide, only around 100 other people with OCD have been reported to have received DBS treatment on a trial basis. This was the first such instance, however, in which an individual with such severe mental illness, being treated with DBS, also consented to and received whole-genome sequencing, and rigorous post-sequencing analysis of the results, accompanied by genetic counseling.
Integrating the results
Each phase of the study generated significant data; but never had such data been integrated in the context of a single clinical psychiatric case. The results, which appear online today in the journal PeerJ, show that the patient was greatly helped by DBS. Over the treatment period, symptoms associated with OCD diminished to the point that the individual was able to “regain a quality of life that he had not previously experienced in over 15 years,” Dr. Lyon and colleagues report. As the electrical stimulation of his brain via DBS was optimized over time (this involved gradually increasing the voltage used in electrical stimulation), he was able to participate in regular exercise, work as a volunteer, and eventually meet someone and get married.
The researchers noted that several times during the treatment, when power from the battery that drives the DBS signals was either drained or not activated by the patient, symptoms of severe OCD returned over the course of 12-24 hours and rapidly became debilitating. This was both a powerful lesson to the patient to keep the device charged (the battery is rechargeable) and vivid evidence to the scientists regarding the device’s role in producing the patient’s observed symptomatic improvements.
Whole-genome sequencing, meantime, revealed that the patient carries at least three gene variants, or alleles, that have been associated in other studies with neuropsychiatric illness. These variants were in genes that encode proteins called BDNF, MTHFR and ChAT. The BDNF gene variant is of particular interest. Its protein is a prime growth factor essential in the early development and subsequent healthy function of the brain and nervous system. The other two variants have also been associated in past studies with possibly increasing the risks of mental illness.
Other gene variants were found that have implications for the way the patient is either able or unable to metabolize particular kinds of drugs. These and literally thousands of other bits of personal genomic information had no immediate impact on his treatment or prognosis, but were archived by Dr. Lyon’s team in the hope that at some later date they might be useful. One of the gene variants did prompt a referral for an eye exam, which revealed bilateral cataracts and poor night vision in this person, which the investigators are currently following up.
“Although we believe in archiving and managing all genetic results and not just a small subset of presently-known ‘risk genes,’ we did analyze the 57 genes in our subject’s genome that are currently recommended for ‘return of results’ to patients by the American College of Medical Genetics,” Dr. Lyon and the team notes.
“I met with this individual to go over the results with him” Dr. Lyon adds, “along with adding some of the findings into his paper-based medical record. We also contacted physicians and other officials at the US Veterans Administration office to offer to incorporate these data into the VA electronic medical record for this patient. We were told, however, that there is no current capacity at the VA to incorporate any genomic variant data.”
The inability even to enter the data in existing electronic health record databases points to the practical problems that remain in using comprehensive data sets to help evaluate and treat patients in a clinical context.
The team, however, believes its results demonstrate that “one can learn a substantial amount from detailed study of particular individuals,” and argues that “we are entering an era of precision medicine in which we can learn from and collect substantial data on informative individual cases.” They further note: “The genomic data we gathered would have been more helpful if obtained much earlier in the patient’s medical course, as it could have provided guidance on which medications to avoid or to provide in increased doses.”