The Influence of Spatiotemporal Structure of Noisy Stimuli in Decision Making
Decision making is a process of utmost importance in our daily lives, the study of which has been receiving notable attention for decades. Nevertheless, the neural mechanisms underlying decision making are still not fully understood. Computational modeling has revealed itself as a valuable asset to address some of the fundamental questions. Biophysically plausible models, in particular, are useful in bridging the different levels of description that experimental studies provide, from the neural spiking activity recorded at the cellular level to the performance reported at the behavioral level. In this article, we have reviewed some of the recent progress made in the understanding of the neural mechanisms that underlie decision making. We have performed a critical evaluation of the available results and address, from a computational perspective, aspects of both experimentation and modeling that so far have eluded comprehension. To guide the discussion, we have selected a central theme which revolves around the following question: how does the spatiotemporal structure of sensory stimuli affect the perceptual decision-making process? This question is a timely one as several issues that still remain unresolved stem from this central theme. These include: (i) the role of spatiotemporal input fluctuations in perceptual decision making, (ii) how to extend the current results and models derived from two-alternative choice studies to scenarios with multiple competing evidences, and (iii) to establish whether different types of spatiotemporal input fluctuations affect decision-making outcomes in distinctive ways. And although we have restricted our discussion mostly to visual decisions, our main conclusions are arguably generalizable; hence, their possible extension to other sensory modalities is one of the points in our discussion.
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Filed under decision making neural networks computational models neurons neuroscience science
Study finds almost half of homeless men had traumatic brain injury in their lifetime, vast majority before they lost their homes
Almost half of all homeless men who took part in a study by St. Michael’s Hospital had suffered at least one traumatic brain injury in their life and 87 per cent of those injuries occurred before the men lost their homes.
While assaults were a major cause of those traumatic brain injuries, or TBIs, (60 per cent) many were caused by potentially non-violent mechanisms such as sports and recreation (44 per cent) and motor vehicle collisions and falls (42 per cent).
The study, led by Dr. Jane Topolovec-Vranic, a clinical researcher in the hospital’s Neuroscience Research Program, was published in the journal CMAJ Open.
Dr. Topolovec-Vranic said it’s important for health care providers and others who work with homeless people to be aware of any history of TBI because of the links between such injuries and mental health issues, substance abuse, seizures and general poorer physical health.
The fact that so many homeless men suffered a TBI before losing their home suggests such injuries could be a risk factor for becoming homeless, she said. That makes it even more important to monitor young people who suffer TBIs such as concussions for health and behavioural changes, she said.
Dr. Topolovec-Vranic looked at data on 111 homeless men aged 27 to 81 years old who were recruited from a downtown Toronto men’s shelter. She found that 45 per cent of these men had experienced a traumatic brain injury, and of these, 70 per cent were injured during childhood or teenage years and 87 per cent experienced an injury before becoming homeless.
In men under age 40, falls from drug/alcohol blackouts were the most common cause of traumatic brain injury while assault was the most common in men over 40 years old.
Recognition that a TBI sustained in childhood or early teenage years could predispose someone to homelessness may challenge some assumptions that homelessness is a conscious choice made by these individuals, or just the result of their addictions or mental illness, said Dr. Topolovec-Vranic.
This study received funding from the Canadian Institutes of Health Research and the Ontario Neurotrauma Foundation.
Separately, a recent study by Dr. Stephen Hwang of the hospital’s Centre for Research on Inner City Health, found the number of people who are homeless or vulnerably housed and who have also suffered a TBI may be as high as 61 per cent—seven times higher than the general population.
Dr. Hwang’s study, published in the Journal of Head Trauma Rehabilitation, is one of the largest studies to date investigating TBI in homeless populations. The findings come from the Health and Housing in Transition Study, which tracks the health and housing status of homeless and vulnerably housed people in Toronto, Vancouver and Ottawa.
(Source: stmichaelshospital.com)
Filed under TBI brain injury homeless people mental health neuroscience science
Methylphenidate, also known as Ritalin, may prevent the depletion of self-control, according to research published in Psychological Science, a journal of the Association for Psychological Science.
Self-control can be difficult — sticking with a diet or trying to focus attention on a boring textbook are hard things to do. Considerable research suggests one potential explanation for this difficulty: Exerting self-control for a long period seems to “deplete” our ability to exert self-control effectively on subsequent tasks.
“It is as if self-control is a limited resource that ‘runs out’ if it is used too much,” says lead researcher Chandra Sripada of the University of Michigan. “If we could figure out the brain mechanisms that cause regulatory depletion, then maybe we could find a way to prevent it.”
Previous research has implicated the neurotransmitters dopamine and norepinephrine in regulatory processing. Sripada and University of Michigan collaborators Daniel Kessler and John Jonides decided to see whether manipulating levels of these transmitters might affect regulatory depletion.
The researchers tested 108 adult participants, all of whom took a drug capsule 60 minutes prior to testing. Half of the participants received a capsule that contained methylphenidate, a medication used to treat ADHD that increases brain dopamine and norepinephrine. The other half received a placebo capsule. The study was double-blind, so neither the participants nor the researchers knew at the time of testing who had received which capsule.
The participants then completed a computer-based task in which they were required to press a button when a word containing the letter e appeared on screen. Some were given modified instructions that asked them to refrain from pressing the button if the letter e was next to or one extra letter away from another vowel — this version of the task was designed to tax participants’ self-control.
All of the participants then completed a second computer task aimed at testing their ability to process competing information and exert regulatory control in order to make a correct response.
In line with the researchers’ hypotheses, participants who received the placebo and performed the taxing version of the first task showed greater variability in how quickly they responded in the second task, compared to those whose self-control hadn’t been depleted in the first task.
But for those participants who took the methylphenidate capsule, the first task didn’t have an effect on later performance — the methylphenidate seemed to counteract the self-regulatory depletion incurred by the harder version of the first task.
“These results indicate that depletion of self-control due to prior effort can be fully blocked pharmacologically,” says Sripada. “The task we give people to deplete their self-control is pretty cognitively demanding, so we were surprised at how effective methylphenidate was in blocking depletion of self-control.”
Sripada and colleagues suggest that methylphenidate may help to boost performance of the specific circuits in the brain’s prefrontal cortex that are normally compromised after sustained exertion of self-control.
This doesn’t mean, however, that those of us looking to boost our self-control should go out and get some Ritalin:
“Methylphenidate is a powerful psychotropic medicine that should only be taken with a prescription,” says Sripada. “We want to use this research to better understand the brain mechanisms that lead to depletion of self-control, and what interventions — pharmacological or behavioral — might prevent this.”
Filed under ADHD methylphenidate self-control cognitive control attention psychology neuroscience science
With a new generation of military veterans returning home from Iraq and Afghanistan, post-traumatic stress disorder (PTSD) has become a prominent concern in American medical institutions and the culture at-large. Estimates indicate that as many as 35 percent of personnel deployed to Iraq and Afghanistan suffer from PTSD. New research from the University of South Carolina School of Medicine is shedding light on how PTSD is linked to other diseases in fundamental and surprising ways.
The rise in PTSD has implications beyond the impact of the psychiatric disorder and its immediate consequences, which include elevated suicide risk and inability to lead a normal life, that result in approximately $3 billion in lost productivity every year. Over time, these PTSD patients will continue to experience increased risks of a myriad of medical conditions like cardiovascular disease, diabetes, gastrointestinal disease, fibromyalgia, musculoskeletal disorders and others, all of which share chronic inflammation as a common underlying cause.
The mechanisms that trigger PTSD, and that cause PTSD patients to suffer from higher rates of chronic-inflammation-related medical conditions remain unknown. Additionally, PTSD is incurable, and though there are available treatments, they are often not completely effective. In an effort to get to the root of PTSD, and begin to understand the links between PTSD and the secondary diseases that often come with it, a team at the University of South Carolina School of Medicine is investigating PTSD through the lens of inflammation. They have recently published findings of a new study, “Dysregulation in microRNA Expression is Associated with Alterations in Immune Functions in Combat Veterans with Post-traumatic Stress Disorder,” in the journal PLOS ONE.
In this study, led by Drs. Prakash Nagarkatti and Mitzi Nagarkatti, the authors investigated microRNA profiles and tried to establish a link between the microRNA and inflammation in combat veterans of the Persian Gulf, Iraq and Afghanistan wars who are PTSD patients at the Dorn VA Medical Center. MicroRNA are small, noncoding RNA that can switch human genes on and off, effectively controlling gene expression. Some specific types of microRNA are known to regulate genes involved in inflammation, making them a kind of marker that can indicate when inflammation is present.
The microRNA role in PTSD has not been investigated previous to this study, which found that the PTSD patients had significant alterations in microRNA expression. The study analyzed 1163 microRNA and found that the expression of microRNA that regulate genes involved in inflammation were altered in PTSD patients. The alterations were found to be linked to heightened inflammation in these patients.
Dr. Mitzi Nagarkatti sums up the significance of this study as follows: “We are very excited about these results. Thus far, no one had looked at the role of microRNA in the blood of PTSD patients. Thus, our finding that the alterations in these small molecules are connected to higher inflammation seen in these patients is very interesting and helps establish the connection between war trauma and microRNA changes.”
In addition to the alterations in microRNA expression, the study also found that PTSD patients had higher levels of inflammation caused by certain types of immune cells called T cells. These T cells produced higher levels of inflammatory mediators called cytokines, specifically interferon-gamma and interleukin-17. This finding was especially interesting because one of the inflammation-associated microRNAs, miR-125a, which specifically targets increased production of interferon-gamma, was found to have decreased expression in the PTSD patients studied. Overall, these results suggested that trauma may cause alterations in the expression of microRNA which promote inflammation in PTSD patients.
Commenting on this, Dr. Prakash Nagarkatti said, “These studies form the foundation to further analyze the role of microRNA in PTSD. Trauma experienced during war may trigger changes in microRNA which may in turn cause various clinical disorders seen in PTSD patients. Our long-term goal is to identify whether PTSD patients express a unique signature profile of microRNA which can be used towards early detection, prevention and treatment of PTSD.”
(Source: eurekalert.org)
Filed under PTSD inflammation microRNA cytokines T cells miR-125a depression neuroscience science
Pain curbs sex drive in female mice, but not in males
“Not tonight, dear, I have a headache.” Generally speaking, that line is attributed to the wife in a couple, implying that women’s sexual desire is more affected by pain than men’s.
Now, researchers from McGill University and Concordia University in Montreal have investigated, possibly for the first time in any species, the direct impact of pain on sexual behaviour in mice. Their study, published in the April 23 issue of The Journal of Neuroscience, found that pain from inflammation greatly reduced sexual motivation in female mice in heat — but had no such effect on male mice.
“We know from other studies that women’s sexual desire is far more dependent on context than men’s – but whether this is due to biological or social/cultural factors, such as upbringing and media influence, isn’t known,” says Jeffrey Mogil, a psychology professor at McGill and corresponding author of the new study. “Our finding that female mice, too, show pain-inhibited sexual desire suggests there may be an evolutionary biology explanation for these effects in humans – and not simply a sociocultural one.”
To conduct the study, the researchers placed mice in a mating chamber divided by a barrier with openings too small for male mice to squeeze through. This enabled the females to decide whether, and for how long, to spend time with a male partner. Female mice in pain spent less time on the “male side” of the testing chamber, and as a result less sexual behaviour occurred. The researchers found that the sexual motivation of the female mice could be revived, however with a pain-relieving drug (pregabalin) or with either of two known desire-enhancing drugs.
Male mice, for their part, were tested in an undivided chamber in which they had free access to a female partner in heat. Their sexual behaviour was entirely unaffected by the same inflammatory pain. There were no differences in pain perception between the sexes, the researchers determined.
“Chronic pain is very often accompanied by sexual problems in humans,” says Prof. Yitzchak Binik, a professor of psychology at McGill and Director of the Sex and Couple Therapy Service at the McGill University Health Center. “This research provides an animal model of pain-inhibited sexual desire that will help scientists study this important symptom of chronic pain.”
Melissa Farmer, now a postdoctoral fellow at Northwestern University, led the study as a doctoral student at McGill under the supervision of Prof. Mogil, a pain researcher, and Prof. Binik, a human sexual-disorder researcher.
Prof. James Pfaus of Concordia University’s Centre for Studies in Behavioral Neurobiology, an expert on rodent sexual behaviour, also co-authored the study. “The sex differences in pain reactivity open new doors to understanding how sexual responses are organized in the brain,” Prof. Pfaus said. “In fact, the growing trend towards personalized medicine requires us to understand how particular ailments, along with their treatments, might impact the sexual lives of women and men.“
Filed under sexual behavior mating sex differences pain chronic pain neuroscience science
Researchers at Aarhus University, Denmark, have drawn up the most detailed ‘image of the enemy’ to date of one of the body’s most important players in the development of Parkinson’s disease. This provides much greater understanding of the battle taking place when the disease occurs – knowledge that is necessary if we are to understand and treat Parkinsonism. However, it also raises an existential question because part of the conclusion is that we do not live forever!
Parkinson’s disease is one of the most common neurological disorders, with about 7000 people suffering from the disease in Denmark alone. There is no cure, and the symptoms continue to get worse. The disease occurs because different nerves in the brain die. These include the nerve cells that form dopamine, which is known as the brain’s ‘reward substance’ and which also helps control our fine motor skills.
A group of researchers from Aarhus University, the University of Southern Denmark (SDU) and the University of Cambridge has just published two studies in the prestigious Journal of the American Chemical Society (JACS) and Angewandte Chemie. These studies provide the best insight to date into the behaviour of a particular protein state that plays an important role in Parkinson’s disease. In other words, they have created a detailed image of what is presumed to be the arch enemy we are up against in our understanding of Parkinsonism. It is an advanced antagonist, and one that functions with a considerable degree of unpredictability. “Fighting the enemy is by no means a Sunday outing,” say the main authors of the results – Professor Daniel Otzen, Aarhus University, and his colleagues Nikolai Lorenzen and Wojciech Paslawski, who recently defended their PhD dissertations on this subject at Aarhus University’s Interdisciplinary Nanoscience Centre (iNANO).
(Source: eurekalert.org)
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Filed under parkinson's disease oligomers amyloid fibrils nerve cells alpha synuclein neuroscience science
Scientists have known that abnormal brain growth is associated with autism spectrum disorder. However, the relationship between the two has not been well understood.
(Image: Thinkstock)
Now, scientists from the Florida campus of The Scripps Research Institute (TSRI) have shown that mutations in a specific gene that is disrupted in some individuals with autism results in too much growth throughout the brain, and yet surprisingly specific problems in social interactions, at least in mouse models that mimic this risk factor in humans.
“What was striking is that these were basically normal animals in terms of behavior, but there were consistent deficits in tests of social interaction and recognition—which approximate a major symptom of autism,” said Damon Page, a TSRI biologist who led the study. “This suggests that when most parts of the brain are overgrown, the brain somehow adapts to it with minimal effects on behavior in general. However, brain circuits relevant to social behavior are more vulnerable or less able to tolerate this overgrowth.”
The study, which focuses on the gene phosphatase and tensin homolog (PTEN), was recently published online ahead of print by the journal Human Molecular Genetics.
Autism spectrum disorder is a neurodevelopmental disorder involving a range of symptoms and disabilities involving social deficits and communication difficulties, repetitive behaviors and interests, and sometimes cognitive delays. The disorder affects in approximately one percent of the population; some 80 percent of those diagnosed are male.
In a previous study, Page and colleagues found that mutations in Pten causes increased brain size and social deficits, with both symptoms being exacerbated by a second “hit” to a gene that regulates levels of the neurotransmitter serotonin in the brain. In the new study, the TSRI team set out to explore whether mutations in Pten result in widespread or localized overgrowth within the brain, and whether changes in brain growth are associated with broad or selective deficits in tests of autism-relevant behaviors in genetically altered mice. The team tested mice for autism spectrum disorder-related behaviors including mood, anxiety, intellectual, and circadian rhythm and/or sleep abnormalities.
The researchers found that Pten mutant mice showed altered social behavior, but few other changes—a more subtle change than would have been predicted given broad expression and critical cellular function of the gene.
Intriguingly, some of the more subtle impairments were sex-specific. In addition to social impairments, males with the mutated gene showed abnormalities related to repetitive behavior and mood/anxiety, while females exhibited additional circadian activity and emotional learning problems.
The results raise the question of how mutations in PTEN, a general regulator of growth, can have relatively selective effects on behavior and cognitive development. One idea is that PTEN mutations may desynchronize the normal pattern of growth in key cell types—the study points to dopamine neurons—that are relevant for social behavior.
“Timing is everything,” Page said. “Connections have to form in the right place at the right time for circuits to develop normally. Circuitry involved in social behavior may turn out to be particularly vulnerable to the effects of poorly coordinated growth.”
(Source: scripps.edu)
Filed under autiism ASD PTEN mutations social behavior dopamine neurons neuroscience science
Seeking the Causes of Hyperactivity
The 60 trillion cells that comprise our bodies communicate constantly. Information travels when chemical compounds released by some cells are received by receptors in the membrane of another cell. In a paper published in the Journal of Neuroscience, the OIST Cell Signal Unit, led by Professor Tadashi Yamamoto, reported that mice lacking an intracellular trafficking protein called LMTK3, are hyperactive. Hyperactivity is a behavioral disorder that shows symptoms including restlessness, lack of coordination, and aggressive behavior. Identifying the genetic factors that contribute to such behaviors may help to explain the pathological mechanisms underlying autism and Attention Deficit Hyperactivity Disorder, ADHD, in humans.
LMTK3 is abundant in two brain regions: the cerebral cortex, which coordinates perception, movement, and thought, and the hippocampus, which governs memory and learning. In the brain, neurons communicate via connections called synapses. To send a message, a nerve terminus in the pre-synapse releases neurotransmitters to be received by the post-synaptic receptors. Yamamoto’s team discovered that LMTK3 regulates trafficking of neurotransmitter receptors at synapses. In neurons of mice deficient in LMTK3, internalization of receptors are augmented in the post-synapse, suggesting that synaptic communication is impaired. The LMTK3-deficient mice exhibited various hyperactive behaviors such as restlessness and hypersensitivity to sound. Interestingly, their dopamine levels were elevated. Dopamine is a neurotransmitter known to be involved in regulation of movement and hormone levels, motivation, learning, and expression of emotion. Excessive dopamine secretion results in schizophrenia, causing a loss of integrity of neuronal activity, and abnormal thoughts and emotions. The relationships between regulation of neurotransmitter receptor expression by LMTK3, dopamine turnover, and the biochemical pathways that induce hyperactivity, remain unknown.
Functions of many human proteins are still not understood. The Cell Signal Unit continues genetic studies of intracellular proteins that maintain and regulate complex functions such as behaviors, through their activities inside cells. “We hope to advance our research in order to elucidate genetic defects that result in behavioral abnormalities,” Yamamoto said.
Filed under hyperactivity ADHD LMTK3 cerebral cortex hippocampus dopamine neuroscience science
A new study suggests that targeting B cells, which are a type of white blood cell in the immune system, may be associated with reduced disease activity for people with multiple sclerosis (MS). The study is released today and will be presented at the American Academy of Neurology’s 66th Annual Meeting in Philadelphia, April 26 to May 3, 2014.
For the study, 231 people with relapsing-remitting MS received either a placebo or one of several low dosages of the drug ofatumumab, which is an anti-B cell antibody, for 24 weeks, with the first 12 weeks making up the placebo-controlled period. The main objective was to determine the effects of ofatumumab dosing regimens compared to placebo on the total number of new brain lesions assessed every four weeks over a 12-week period.
All dose groups including placebo showed lesion activity in the first four weeks with lesion suppression in all ofatumumab dose groups from weeks four to12. Researchers measured the amount of B cells in participants and compared that to the total number of new brain lesions that appeared on brain scans, which is a marker of disease activity.
The researchers found that when B cells were reduced to below a threshold of 64 cells per microliter, disease activity, as measured by appearance of new brain lesions, was significantly reduced. On average, participants had an annualized rate of less than one new brain lesion per year when B cells were maintained below a threshold of 32 to 64 cells per microliter, compared with 16 lesions without treatment.
The most common side effects, defined as those occurring in at least five percent of participants and at a rate twice that of placebo for weeks zero to12, were injection-related reaction, dizziness, anxiety, fever, respiratory tract infection and nerve pain.
Study author Daren Austin, PhD, of GlaxoSmithKline in Uxbridge, United Kingdom, and a member of the American Academy of Neurology, said the study results also suggest that peripheral, rather than central, B cells may be the most relevant target for anti-B cell therapy.
“These results need to be validated, of course, but the findings are interesting,” Austin said. “They provide new insight into the mechanism of B cells in MS and present a possible new target threshold for exploring the potential benefit of anti-B cell therapy.” Ofatumumab is not approved anywhere in the world for use in the treatment of multiple sclerosis.
Filed under MS B cells immune system ofatumumab lesion activity neurology neuroscience science
Biologists discover a key regulator in the pacemakers of our brain and heart
Biologists have discovered how an outer shield over T-type channels change the electrochemical signaling of heart and brain cells. Understanding how these shields work will help researchers eventually develop a new class of drugs for treating epilepsy, cardiovascular disease and cancer.
The study from the University of Waterloo is published in the Journal of Biological Chemistry today and is featured as the “Paper of the Week” for its significance.
The researchers discovered T-type channels in the pond snail, Lymnaea stagnalis, can shift from using calcium ions to using sodium ions to generate the electrical signal because of an outer shield of amino acids called a turret situated above the channel’s entrance.
Low voltage T-type channels generate tiny pulses of current at regular intervals by selectively passing positively charged cations across the cell’s membrane through a gate-like channel. The channels are normally extremely selective, allowing just one sodium ion to pass for every 10,000 calcium ions.
The resulting rhythmic signals produced by this transfer of cations are what support the synchronous contraction of our heart muscles and neuronal firing in parts of the brain, like the thalamus, which helps regulate our sleep-wake cycle, or circadian rhythm.
In addition to their published findings, the researchers also found the shield-like turrets in pond snails restrict access of therapeutic drugs to the channel.
T-type channels in pond snails and other invertebrates are similar to those found in humans. Although pond snails reach only 7 cm in length, its simple neural network and physiology make it a popular model organism with neurobiologists.
Over-active T-type channels are linked to epilepsy, cardiac problems, neuropathic pain, as well as the spreading of several kinds of cancer. Drugs that could quench out-of-control T-type channel activity are unable to bind to the channels themselves.
“We wanted to understand the molecular structures of T-type channels,” said Spafford. “How they pass ionic currents to generate electrical activity, and to identify drug binding sites, and the drugs which may block these channels to treat neurological disease or heart complications.”
The group is currently investigating how dismantling this extracellular turret will improve drug access and binding in T-type channels.
Filed under sodium channels calcium channels T-type channels brain cells pond snail neuroscience science
