Alzheimer's - Dementia, Author Interviews, Cognitive Issues, McGill, Neurology, Technology / 28.01.2020 Interview with: Yasser Iturria-Medina PhD Assistant Professor, Department of Neurology and Neurosurgery Associate member of the Ludmer Centre for Neuroinformatics and Mental Health McConnell Brain Imaging Centre McGill University What is the background for this study? Response: As background, two main points:
  • Almost all molecular (gene expression) analyses performed in neurodegeneration are based on snapshots data, taking at one or a few time points covering the disease's large evolution. Because neurodegenerative diseases take decades to develop, until now we didn't have a dynamical characterization of these diseases. Our study tries to overcome such limitation, proposing a data-driven methodology to study long term dynamical changes associated to disease.
Also, we still lacked robust minimally invasive and low-cost biomarkers of individual neuropathological progression. Our method is able to offer both in-vivo and post-mortem disease staging highly predictive of neuropathological and clinical alterations. (more…)
Aging, Alzheimer's - Dementia, Author Interviews, MRI, Technology / 23.12.2019 Interview with: Dr. Weidong Luo Principal Scientist CorTechs Labs What is the background for this study? Response: We were interested in whether or not we can predict the age of the brain accurately from T1 weighted MRI and/or fluorodeoxyglucose (FDG) PET scans using the brain volumetric and the relative metabolic activity. The uptake of FDG is a clinical marker used to measure the uptake of glucose and therefore metabolism. Also, we were interested in the patterns of the predicted ages for Alzheimer's disease (AD) and minor cognitive impairment (MCI) subjects when using their brain measurements for age prediction in the normal brain age model.   (more…)
Author Interviews, Cognitive Issues, Environmental Risks, OBGYNE, Pediatrics / 24.10.2019 Interview with: Eva Tanner, PhD, MPH, Postdoctoral Researcher Department of Environmental Medicine and Public Health Icahn School of Medicine at Mount Sinai Carl-Gustaf Bornehag, PhD Professor at Karlstad University What is the background for this study? Response: Most prior research on health risks from chemical exposure study one chemical at a time. However, we are exposed to a multitude of chemicals every day in the air we breathe, food and water we consume, and things we touch. This is supported by global biomonitoring data showing that humans in general have a high number of chemicals identified in their bodies, i.e., in blood, urine, breast milk, saliva, etc. Unfortunately, we don’t know how such single chemicals act in complicated mixtures and impact our health, or the health of future generations. We conducted this study to help understand how prenatal exposure to mixtures of proven or suspected endocrine disrupting chemicals - found in common consumer products - during the earliest part of life may impact a child’s brain development and cognition in school age. (more…)
AACR, Author Interviews, Melanoma / 20.10.2019 Interview with: Qing Chen, M.D., Ph.D. Assistant Professor, Immunology, Microenvironment & Metastasis Program Scientific Director, Imaging Facility The Wistar Institute What is the background for this study? Response: We are focusing on how a specific type of brain cells, astrocytes, helps the cancer cells from melanoma and breast cancer to form metastatic lesions.  (more…)
Author Interviews, Genetic Research / 09.09.2019 Interview with: Prof. Dominic Furniss, DM MA MBBCh FRCS Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Science University of Oxford What is the background for this study? Response: We knew that there was a genetic component to handedness. Twin studies estimated that around 25% of the variation in handedness seen in the human population is down to genetic factors. Genetic factors associated with left handedness had been shown in specific patient populations, but this study has found factors in the general population and correlated them with functional brain imaging to shed more light on this fascinating subject. We have used both genetic and imaging data from the UK Biobank study to discover genetic variants that are related to left handedness. We have correlated these variants with changes in brain imaging, in particular showing increased functional connectivity between the language processing areas of the brain in left handers. The genetic variants that are associated with left handedness are also near to genes involved in forming the internal skeleton of neurons, and important in brain development, suggesting that being left handed is in part caused by a difference in brain development. It is clear, however, that there are also many non-genetic influences on whether a person is left handed or not. In addition, we confirmed previous observations that being left handed is associated with other neurological problems, such as schizophrenia, and protective of others, such as Parkinson's disease, and showed that this is related to shared genetic factors, and likely reflects differences in brain development.  (more…)
Addiction, Author Interviews, OBGYNE, Pediatrics, Tobacco Research, UCSD / 25.05.2019 Interview with: Davide Dulcis, PhD Associate Professor Department of Psychiatry, UCSD School of Medicine University of California, San Diego La Jolla, CA 92093-0603 What is the background for this study? What are the main findings?  Response: Previous studies in humans have shown that pre-natal and early life exposure to nicotine can lead to altered children behavior and propensity for drug abuse, but the precise mechanisms involved are still unclear. In this pre-clinical study we showed how nicotine “primes” neurons of the mouse brain’s reward center for a fate they normally would not have taken, making them more susceptible to the effects of nicotine when the animals are again exposed to nicotine later in life, said Dr. Benedetto Romoli, first author of the research article.   (more…)
Author Interviews, Nature, Neurological Disorders, Nursing / 18.04.2019 Interview with: Elsa F. Fouragnan PhD School of Psychology (Faculty of Health and Human Sciences) University of Plymouth What is the background for this study? What are the main findings?  Response: Counterfactual thinking is a psychological process that involves the tendency to create possible alternatives to life events that are currently happening. It is very important because it gives us the ability to switch away from uninteresting activities if better ones become available. For example, if you are working or doing the housework, you may be thinking about gardening or watching a movie later. As soon as your duties are finished, you may engage in these more exciting activities. In our study, macaque monkeys were tasked to find treats under several colored cups (on a screen). Some of these cups were better than others but were not always available, thus the animals had to retain what they had learnt about the good cups in case they became available again. We found that a frontal part of the brain called the anterior cingulate cortex was responsible for tracking which cups were the best in order to efficiently switch to them if the opportunity arose. If this part of the brain was not functioning properly, then animals were stuck in non-optimal choices. To reveal the causal role of the anterior cingulate cortex, we used a new neurostimulation method called low-intensity repetitive ultrasound to modulates activity in this part of the brain with millimetre accuracy. (more…)
Author Interviews, Cognitive Issues, Memory, University Texas / 16.04.2019 Interview with: Dr. Sandra Bond Chapman PhD Founder and Chief Director, Center for BrainHealth, Co-Leader, The BrainHealth Project University of Texas, Dallas What is the background for this study? Response: Finding effective treatments to reverse or slow rates of cognitive decline for those at risk for developing dementia is one of the most important and urgent challenges of the 21st century. Brain stimulation is gaining attention as a viable intervention to increase neuroplasticity when used in isolation or when combined with cognitive training regimens. Given the growing evidence that certain cognitive training protocols, such as SMART, benefit people with Mild Cognitive Impairment (MCI), a population that is vulnerable to Alzheimer’s disease, we were interested in exploring whether we could further increase the gains from cognitive training (i.e., SMART) when the training was preceded by brain stimulation using tDCS.  (more…)
ADHD, Author Interviews, Genetic Research, Mental Health Research, Pediatrics, Schizophrenia / 31.01.2019 Interview with: Silvia Alemany, PhD first author Barcelona Institute for Global Health (ISGlobal), a centre supported by "la Caixa". In collaboration with co-authors: Philip Jansen,MD, MSc and Tonya White, MD, PhD Erasmus University Medical Center, Rotterdam What is the background for this study? Response: Individuals affected by psychiatric disorders can demonstrate morphological brain abnormalities when compared to healthy controls. Although both genetic and environmental factors can account for these brain abnormalities, we expect that genetic susceptibility for psychiatric disorders has the greatest influence on the development of the brain. Genetic susceptibility for psychiatric disorders can be estimated at the individual level by generating polygenic risk scores. Using this methodology, genetic susceptibility to psychiatric disorders and cognition has been associated with behavior problems in childhood. These findings suggest that heritable neurobiological mechanisms are at play in very early in the course of the illnesses. (more…)
Author Interviews, Pediatrics / 10.01.2019 Interview with: PHILIPPE P. HUJOEL PhD, DDS, MSD, MS Professor, Oral Health Sciences Adjunct Professor, Epidemiology Adjunct Professor, Periodontics Dental Public Health Sciences, School of Dentistry University of Washington What is the background for this study? Response: In 2012, an economist, Kevin Denny, identified an association between breastfeeding and handedness.  The newly published study attempted to refute this association in a larger population, and with more control for potential confounding variables. (more…)
Author Interviews, Cognitive Issues, Mental Health Research / 16.05.2018 Interview with: Dr. Eero Vuoksimaa PhD Institute for Molecular Medicine University of Helsinski Finland What is the background for this study? What are the main findings? Response: There are many previous reports indicating a positive association between height and cognitive ability but the underlying mechanisms behind this correlation are not well known. We used a mediation model to test if this association is explained by brain size as measured with cortical grey matter size. We found that total cortical surface mediated the relationship between height and cognitive ability. (more…)
Author Interviews, JAMA, Mental Health Research, OBGYNE, Pediatrics / 11.04.2018 Interview with: Jiook Cha, PhD Assistant Professor Division of Child and Adolescent Psychiatry Columbia University Medical Center New York, NY 10032 What did we already know about the connection between maternal SSRI use during pregnancy and infant brain development, and how do the current study findings add to our understanding? What’s new/surprising here and why does it matter for mothers and babies? Response: Prior studies have shown mixed results in terms of the associations between maternal SRI use during pregnancy and offspring’s brain and cognitive development. Neurobiological studies with animal models suggest that SSRI use perturbs serotonin signaling and that this has important effects on cognitive development (a study conducted an author of this paper, Jay Gingrich, MD, PhD: Ansorge et al., 2004, Science). The human literature has been more mixed in terms of the associations of prenatal exposure to SSRI with brain and cognitive development. In our study, we used neonatal brain imaging because this is a direct, non-invasive method to test associations between SSRI use and brain development at an early developmental stage, limiting the effects of the post-natal environment. In our study, we had two different control groups, that is, a non-depressed SSRI-free group (healthy controls), and depressed but SSRI-free (SSRI controls) group. Also, in our study we used rigorous imaging analytics that significantly improve the quantitative nature of MR-derived signals from the brain structure using two of the nation’s fastest supercomputers (Argonne National Laboratory and Texas Advanced Computing Center) and allows robust reconstruction of brain’s grey and white matter structure in the infants’ brains. We report a significant association of prenatal exposure to SSRI with a volume increases within many brain areas, including the amygdala and insula cortex, and an increase in white matter connection strength between the amygdala and insular cortex. We were surprised by the magnitude of the effects (or the statistical effect size), compared with other brain imaging studies in psychiatry with children or adults’ brains. Importantly, it should be noted that our estimates of brain structure are still experimental and for research-purpose only. This means that our data need to be replicated and rigorously tested against confounders in order to make a firm conclusion. While our study suggests a “potential” association between prenatal exposure to SSRI and a change in fetal or infant brain development, we still need more research.  tracts_in_the_brain (more…)
Author Interviews, Neurology / 05.04.2018 Interview with: “Mother and Child” by Mary Cassatt (American, Pittsburgh, Pennsylvania 1844–1926 Le Mesnil-Théribus, Oise) via The Metropolitan Museum of Art is licensed under CC0 1.0Yi-Ya Fang NYU School of Medicine Dayu Lin, PhD Neuroscience Institute, New York University Langone School of Medicine,  Department of Psychiatry, Center for Neural Science New York, NY Response: Maternal behaviors are essential for survival of offspring across mammalian species. In rodents, mothers show several characteristic pup caring behaviors including grooming pups, crouching over pups and approaching and retrieving pups. Decades of research has been trying to understand how the neural circuit is wired to generate these elaborate maternal behaviors. Medial preoptic area (MPOA), which is located at anterior part of hypothalamus, has been indicated to be important for maternal behaviors. Many studies consistently found deficits in maternal behaviors after damaging the MPOA. To dissect the maternal circuits in the brain, we looked into the properties of the Esr1+ cells. In this study, we identify estrogen receptor α (Esr1) expressing cells in MPOA as key mediators of pup approach and retrieval. We focused on Esr1 (Esr1) expressing cells in the MPOA since estrogen has been shown to facilitate maternal behaviors, presumably through its action of estrogen sensing cells. We found that reversible inactivation of MPOA Esr1+ cells impairs maternal behaviors whereas optogenetic activation of MPOA Esr1+ cells induces immediate pup retrieval. Additionally, we found that MPOA Esr1+ cells are preferentially activated during maternal behaviors, and the cell responses changed across reproductive states. Tracing studies revealed that MPOA Esr1+ cells project strongly to ventral tegmental area (VTA), a region that has been indicated in motivation and reward. Specifically, MPOA Esr1+ cells provide strong inhibitory inputs preferentially to the GABAergic cells in the VTA, which in turn could disinhibit the dopaminergic cells.  VTA dopaminergic cells are highly activated during maternal behaviors. Altogether, our study provides new insight into the neural circuit that generates maternal behaviors. (more…)
Author Interviews, PLoS / 30.03.2018 Interview with: Ksenija Marinkovic and Lauren Beaton Psychology Department - College of Sciences Spatio-Temporal Brain Imaging Lab Center for Clinical and Cognitive Neuroscience San Diego State University San Diego CA What is the background for this study? What are the main findings? Response: In general, we subjectively perceive our actions to be under our deliberate and voluntary control. However, our results are consistent with other accruing evidence suggesting that a large portion of our behavior is automatic and not accessible to conscious experience. The automatic processing primarily underlies predictable daily routines when we seem to be on an “auto-pilot”. In contrast, situations that are ambiguous or that evoke incompatible response tendencies engage cognitive control which allows conscious override of the preplanned actions and results in flexible behavior. Our study used a multimodal imaging approach that combines perfect time sensitivity of magnetoencephalography (MEG) with structural magnetic resonance imaging (MRI) to investigate spatio-temporal stages of the seamless interplay between automatic and controlled processing. MEG is a highly sensitive method that records magnetic fields generated by the brain’s neural activity in real time. Young, healthy, participants performed a version of the Eriksen Flanker task, which presents two colored squares on either side of a centrally presented target square that appears after a short delay. Participants are instructed to press a button corresponding to the color of the target square in the middle and to pay no attention to the flankers. Although participants know that the flankers are irrelevant, they are unable to disregard them deliberately. Instead, flankers trigger an automatic preparation to respond. This is particularly apparent on mismatch trials on which the flanker color is misleading and it activates the wrong hand. Target appearance overrides the initial automatic response as the response plan is switched to the other hand to make a correct response. This process reflects recruitment of cognitive control or the decision-making capacity which includes a range of functions such monitoring contextual demands, selecting the correct response, and suppressing an automatic but irrelevant action. Our multimodal MEG imaging method has allowed us to track the neural response as the brain prepares an incorrect response to flankers and then “switches” motor preparation between hemispheres. This approach makes it possible to investigate the interplay between automatic and controlled processing and dissect decision making as it unfolds. The addition of a moderate dose of alcohol dysregulates this frontal network involved in motor decision making, which decreases accuracy when response conflict is present and lowers neural activity reflecting cognitive control. Related to this overall decrease, and of clinical importance, is the reduced ability to employ cognitive control to refrain from drinking excessively. However, the underlying patterns of response-switching were preserved under alcohol, suggesting that alcohol primarily induces deficits upstream during decision making and not during executing motor commands.  (more…)
Author Interviews, Psychological Science, Vanderbilt / 29.11.2017 Interview with: Alex Maier, PhD Assistant Professor of Psychology Assistant Professor of Ophthalmology and Visual Science Vanderbilt University What is the background for this study? What are the main findings? Response: We were interested in finding out about how the brain shifts attention from one location to another. We knew that when we attend a certain location, brain activity increases in a specific way. This increase in activity is how we perform better when we use attention. What we knew less about is what happens when attention moves between locations. To our surprise, we found that there is a brief moment in between these attentional enhancements, while attention moves from one location to another, where the brain does the complete opposite and decreases its activity. Shifting attention thus has a brief negative effect on our brain’s ability to process information about the world around us. (more…)
Author Interviews, Cognitive Issues, Compliance, HIV, JAMA / 16.11.2017 Interview with: Ryan Sanford, MEng Department of Neurology and Neurosurgery Montreal Neurological Institute McGill University, Montréal, Québec, Canada What is the background for this study? What are the main findings? Response: With the introduction of combination antiretroviral therapy (cART) the outlook for HIV+ individuals has dramatically shifted from a fatal disease to a chronic manageable condition. However, HIV-associated neurocognitive disorders are still prevalent. The etiology of this dysfunction remains unknown. Previous work has reported progressive brain atrophy in HIV+ individuals with advanced disease and poor viral suppression, but it is unclear whether stable treatment and effective viral suppression can mitigate the progression of brain atrophy. To examine this issue, we followed well-treated HIV+ individuals with good viral suppression and well-matched controls, and assessed whether ongoing brain atrophy occurs over time. The main finding in this study was the HIV+ participants had reduced brain volumes and poorer cognitive performance compared to the control group, but the changes in brain volumes and cognitive performance were similar between the groups. (more…)
Author Interviews / 27.01.2017 Interview with: DR. Y. (YAÏR) PINTO Faculty of Social and Behavioural Sciences Programme group Brain and Cognition UvA What is the background for this study? Response: I've done research into patients in whom the corpus callosum was entirely removed surgically, at an adult age, to relieve epileptic seizures. The removal of the corpus callosum all but eliminates communication between both cerebral hemispheres. Therefore these patients are referred to as split-brain patients. The canonical view of these patients is that their consciousness is split as well. That is, the notion, which is found in many textbooks and reviews, is that in a split-brain patient each hemisphere is an conscious agent, independent of the other hemisphere. This notion is mainly based on the following key observation. When an image is presented to the left visual field, the patient indicates verbally, and with his right hand, that he saw nothing. Yet, with his left hand he indicates that he did see the object! Conversely, if a stimulus appears in his right visual field, he will indicate awareness of this stimulus when he responds verbally or with his right, yet with his left hand he will report that he saw nothing. This exactly fits the notion that in a split-brain patient the two separated hemispheres each become an independent conscious agent. The left hemisphere perceives the right visual field, controls language and the right side of the body. The right hemisphere experiences the left visual field and controls the left hand. This, and other discoveries on split-brain patients, earned Roger Sperry the nobel-prize in Medicine in 1981. (more…)
Aging, Author Interviews, Neurological Disorders, Yale / 22.12.2016 Interview with: Ifat Levy, PhD Associate Professor Comparative Med and Neuroscience Yale School of Medicine What is the background for this study? What are the main findings? Response: The proportion of older adults in the population is rapidly rising. These older adults need to make many important decisions, including medical and financial ones, and therefore understanding age-related changes in decision making is of high importance. Prior research has shown that older adults tend to be more risk averse than their younger counterparts when making choices between sure gains and lotteries. For example, asked to choose between receiving $5 for sure and playing a lottery with 50% of gaining $12 (but also 50% of gaining nothing), older adults are more likely than young adults to prefer the safe $5. We were interested in understanding the neurobiological mechanisms that are involved in these age-related shifts in preferences. An earlier study that we have conducted in young adults provided a clue. In that study, we measured the risk preference of each participant (based on a series of choices they made between safe and risky options), and also used MRI to obtain a 3D image of their brain. Comparing the behavioral and anatomical measures, we found an association between individual risk preferences and the gray-matter volume of a particular brain area, known as “right posterior parietal cortex” (rPPC), which is located at the back of the right side of the brain. Participants with more gray matter in that brain area were, on average, more tolerant of risk (or less risk averse). This suggested a very interesting possibility – that perhaps the increase in risk aversion observed in older adults is linked to the thinning of gray matter which is also observed in elders. In the current study we set out to test this hypothesis, by measuring risk preference and gray matter density in a group of 52 participants between the ages of 18 and 88. We found that, as expected, older participants were more risk averse than younger ones, and also had less gray matter in their rPPC. We also replicated our previous finding - that less gray matter was associated with higher risk aversion. The critical finding, however, was that the gray matter volume was a better predictor of increased risk aversion than age itself.  Essentially, if both age and the gray matter volume of rPPC were used in the same statistical model, rPPC volume predicted risk preferences, while age did not. Moreover, the predictive power was specific to the rPPC – when we added the total gray matter volume to the model, it did not show such predictive power. (more…)
Author Interviews, Nature, Neurological Disorders, Technology / 16.12.2016 Interview with: Bin He, Ph.D. Director, Institute for Engineering in Medicine Director, Center for Neuroengineering Distinguished McKnight University Professor of Biomedical Engineering Medtronic-Bakken Endowed Chair for Engineering in Medicine University of Minnesota, Minneapolis, MN 55455 What is the background for this study? What are the main findings? Response: This work is aimed at developing a noninvasive brains-computer interface to allow disabled patients to control their environment by just thinking about it. We found 8 human subjects were able to accomplish 3D reach and grasp tasks without using any muscle activities but just thinking about it. (more…)
Author Interviews, Memory, Sleep Disorders / 16.12.2016 Interview with: Roi Levy The Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, The Mina and Everard Goodman Faculty of Life Sciences Bar Ilan University Ramat Gan, Israel What is the background for this study? Response: Long-term memory after an experience takes many hours to be reach its final form. During the consolidation period, the nascent memory is labile: the consolidation can be interrupted by new experiences, or new experiences that are too insignificant to be remembered can capture the consolidation process, and thereby be remembered. To avoid potentially maladaptive interactions between a new experience and consolidation, a major portion of the consolidation is deferred to the time in which we sleep, when new experiences are unlikely. For over 100 years, studies have demonstrated that sleep improves memory formation. More recent studies have shown that consolidation occurs during sleep, and that consolidation depends on the synthesis of products that support memory formation. Consolidation is unlikely to be shut off immediately when we are awakened from sleep. At this time, even a transient experience could capture the consolidation, leading to a long-lasting memory of an event that should not be remembered, or could interfere with the consolidation. We have identified a mechanism that prevents long-term memories from being formed by experiences that occur when awakened from sleep. (more…)
Author Interviews, MRI, Psychological Science / 02.12.2016 Interview with: Jeffrey S. Anderson, MD, PhD Director the fMRI Neurosurgical Mapping Service Principal Investigator for the Utah Functional Neuroimaging Laboratory University of Utah What is your study about? Response: Billions of people find meaning in life and make choices based on religious and spiritual experiences. These experiences range from epiphanies that change the lives of celebrated mystics to subtle feelings of peace and joy in the lives of neighbors, friends, or family members that are interpreted as spiritual, divine, or transcendent. Astonishingly, with all we understand about the brain, we still know very little about how the brain participates in these experiences. We set out to answer what brain networks are involved in representing spiritual feelings in one group of people, devout Mormons. (more…)
Author Interviews, Neurological Disorders / 04.11.2016 Interview with: Nir Lahav Physics Department Bar-Ilan University in Israel What is the background for this study? Response: Our brain is a very complex network, with approximately 100 billion neurons and 100 trillion synapses between the neurons. The question is how can we cope with this enormous complexity? Ultimately, scientists seek to understand how a global phenomenon such as consciousness can emerge from our neuronal network. We used network theory in order to cope with this complexity and to determine how the structure of the human cortical network can support complex data integration and conscious activity. Previous studies have shown that the human cortex is a network with small world properties, which means that it has many local structures and some shortcuts from global structures which connect faraway areas (similar to the difference between local buses and cross-country trains). The cortex also has many hubs, which are nodes that have a high number of links (like central stations), that are also strongly interconnected between themselves, making it easy to travel between the brain's information highways.But in order to examine how the structure of the network can support global emerging phenomena, like consciousness, we need to look not only in the different nodes. We need to check global areas with lots of nodes. That's why we applied a network analysis called k-shell decomposition. This analysis takes into account the connectivity profile of each node making it easy to uncover different neighborhoods of connections in the cortical network, we called shells. The most connected neighborhood in the network is termed the network's nucleus. until today scientists were only interested in the network's nucleus, but we found that these different shells can hold important information about how the brain integrates information from the local levels of each node to the entire global network. For the first time we can build a comprehensive topological model of our cortex. (more…)
Author Interviews, Cannabis, OBGYNE, Pediatrics / 21.06.2016 Interview with: Dr. Hanan El Marroun, PhD Assistant Professor Department of Child and Adolescent Psychiatry, Department of Epidemiology The Generation R Study Erasmus, The Netherlands What is the background for this study? What are the main findings? Response: The background for the study is that little is known about the potential long-term effects of cannabis exposure during pregnancy on child development. The main findings are the prenatal cannabis exposure was associated with differences in cortical thickness in childhood. What should readers take away from your report? Response: That our findings suggest an association between prenatal cannabis exposure and cortical thickness in children. However, the results must be carefully interpreted, as there may be other factors involved that we did not take into account. Therefore, further research is needed to explore the causal nature of this association. (more…)
ADHD, Author Interviews, Mental Health Research, Nature, NYU / 22.10.2015 Interview with: Michael M. Halassa, MD, PhD, Assistant professor Departments of Psychiatry and Neuroscience and Physiology The Neuroscience Institute Depts. of Psychitatry Langone Medical Center New York, NY 10016 Medical Research: What is the background for this study? What are the main findings? Dr. Halassa:  Attention is a vital aspect of our daily life and our minds are not merely a reflection of the outside world, but rather a result of careful selection of inputs that are relevant. In fact, if we indiscriminately open up our senses to what’s out there, we would be totally overwhelmed. Selecting relevant inputs and suppressing distractors is what we call attention, and as humans we are able to attend in a highly intentional manner. Meaning, we choose what to pay attention to, and we do so based on context. If you’re driving and getting directions from your GPS, you’ll be intentionally splitting your attention between your vision and hearing. Now, in one context, you might have just updated the GPS software, so you know it’s reliable; this would allow you to intentionally pay attention more to the voice coming from the GPS. In another context, the GPS software may be outdated making voice instructions unreliable. This context would prompt you to direct your attention more towards using visual navigation cues and less to the GPS voice. How the brain intentionally and dynamically directs attention based context is unknown. The main strength of our study is that we were able to study context-dependent attention in mice. Mice are unique models because they provide genetic tools to study brain circuits. Meaning, we can turn circuits on and off very precisely in the mouse, and in a way we cannot do in other experimental animals. The inability to do these types of manipulations has been the major roadblock for progress in understanding what brain circuits mediate attention and its intentional allocation. Because we couldn’t train mice to drive and listen to the GPS, we decided to do something much simpler. Based on context (the type of background noise in the experimental enclosure), a mouse had to select between conflicting visual and auditory stimuli in order to retrieve a milk reward. Mice love milk; it turns out, and will work tirelessly to do well on getting it. Each trial, the mouse is told ‘you need to pick the light flash’ or ‘you need to pick the auditory sweep’; these stimuli appeared on either side of the mouse randomly so the animal really had to pay attention in order to get its reward. It also had to take the context into account. We found that mice did this task, and as humans would do, they were reliant on the prefrontal cortex for determining the appropriate context. The major finding was that the prefrontal cortex changed the sensitivity of the brain to incoming stimuli (meaning, made the visual stimulus brighter when the mouse cared about vision and made the auditory stimulus louder when the mouse cared about hearing), by influencing activity in the thalamus. The thalamus is the major early relay station in the brain. The prefrontal cortex does that by instructing the brain’s switchboard, known as the thalamic reticular nucleus (TRN) to control how much visual or auditory information the thalamus was letting through. So in a sense, we discovered that executive function, represented by the prefrontal cortex, can talk to ‘attentional filters’ in the thalamus to determine what ultimately is selected from the outside environment to build our internal world. (more…)
Author Interviews, Nutrition / 17.08.2015

Karen Hardy  ICREA, Catalan Institution for Research and Advanced Studies Departament de Prehistòria Facultat de Filosofia i Lletres Universitat Autònoma de Barcelona Barcelona, Interview with: Dr. Karen Hardy  ICREA, Catalan Institution for Research and Advanced Studies Departament de Prehistòria Facultat de Filosofia i Lletres Universitat Autònoma de Barcelona Barcelona, Spain   MedicalResearch: What is the background for this study? What are the main findings? Dr. Hardy: There continues to be little clear agreement on what quantitatively constitutes a healthy diet. The global increase in the incidence of obesity and diet-related metabolic diseases have intensified interest in ancestral or “Palaeolithic” diets as it is clear that to a first order of approximation our physiology should be optimized to the diet that we have experienced during our evolutionary past. However, reconstructing ancestral diets is very challenging, and exactly what was eaten during the Palaeolithic remains largely unknown. Until now, there has been a heavy focus on the role of animal fats and protein in the development of the human brain and there is little doubt that increases in meat consumption from around 3.4 million years ago, was a major driver. However, the role of carbohydrates, particularly in the form of starch-rich plant foods, has largely been overlooked. But the human brain today uses up to 25 % of the body’s energy budget and up to 60 % of blood glucose as a general rule, while pregnancy and lactation in particular, place additional demands on the body’s glucose budget. In this study we integrated multiple lines of evidence from human genetics, archaeology, anthropology, physiology, and nutrition, to hypothesise that cooked carbohydrates played an important part in the evolution of the body, and particularly the brain, over the last 800,000 years. Our results suggest that while meat was important, brain growth is less likely to have happened without the energy obtained from carbohydrates. While cooking has also been proposed as contributing to early brain development, it has a particularly profound effect on the digestibility of starch. Furthermore, humans are unusual among primates in that they have many copies of the salivary amylase gene (average of around six salivary amylase genes, other primates have only two) leading to more efficient starch digestion. This suggests that cooking starch-rich plants and having more amylase coevolved. We don’t know exactly when the number of amylase gene copies multiplied, but genetic data suggest it was in the last million years; a timeframe that brackets archaeological evidence for cooking and when our brain size increase accelerated (around 800,000 years ago). Salivary amylases are largely ineffective on raw crystalline starch, but cooking substantially increases both their energy-yielding potential and glycemia. (more…)
Alzheimer's - Dementia, Author Interviews, Sleep Disorders / 08.08.2015

Helene Benveniste, MD, PhD Professor of Anesthesiology and Radiology Vice Chair for Research, Department of Anesthesiology Stony Brook Medicine, Stony Brook Interview with: Helene Benveniste, MD, PhD Professor of Anesthesiology and Radiology Vice Chair for Research, Department of Anesthesiology Stony Brook Medicine, Stony Brook NY Medical Research: What is the background for this study? Dr. Benveniste: The ‘glymphatic’ pathway is a part of the brain and is responsible for removal of waste products and excess fluid that built up especially during wakefulness. The concept was introduced by Nedergaard’s team in 2012 from University of Rochester. Importantly it has been shown to remove waste products such as soluble amyloid beta and tau protein which build up excessively in the brain of subjects afflicted with Alzheimer’s disease. The glymphatic system has been studied in detail in animal models (not yet humans) and actually is a brain-wide pathway which runs along (i.e. on the outside) of all vessels in the brain and connects to the space around the brain cells (referred to as the interstitial fluid (ISF) space). The outer part of the glymphatic network ‘tube’ is bordered by a certain type of brain cells so-called ‘astroglial’ cells which are arranged in a special way so that their endfeet cover >97% of the surface of all brain vessels. One can think of this as if the astroglial cell’s ‘endfeet’ are arranged as a donut shaped tube around all the vessels. On the astroglial endfeet there are special water channels (aquaporin-4 water channels) which are critical for how efficiently the glymphatic system can get rid of waste because it allows water to move fast through the brain tissue so as to ‘flush’ waste products out efficiently. The small gap between the astroglial endfeet also act like a ‘sieve’ so that only waste products of a certain size can access the entire pathway. Cerebrospinal fluid (CSF) circulates into the glymphatic pathway from the surface of the brain along the arteries which dives directly from the surface into the deeper part of the brain; and ultimately enters the space around the brain cells; and sweeps through it and thereby mixes with the interstitial fluid of the brain which contains waste products. The CSF-ISF mix with the waste products is then flushed out on the other ‘side’ along the veins and ultimately ends up in lymph vessels in the body and then in the blood. It has been shown that the glymphatic pathway removes brain waste more efficiently in a state of ‘unconsciousness’ e.g. sleep or anesthesia when compared to wakefulness. Given this intriguing finding i.e. that sleeps seems to affect the waste clearance from the brain we thought that the next to look at was sleeping positions. We did these studies in anesthetized rodents. (more…)
Author Interviews, Emory, Neurological Disorders / 15.04.2015

Erwin G. Van Meir, PhD Professor, Departments of Neurosurgery and Hematology & Medical Oncology Leader, Winship Cancer Institute Cancer Cell Biology Program Founding Director, Graduate Program in Cancer Biology Director, Laboratory for Molecular Neuro-Oncology Emory University School of Medicine Atlanta GA Interview with: Erwin G. Van Meir, PhD Professor, Departments of Neurosurgery and Hematology & Medical Oncology Leader, Winship Cancer Institute Cancer Cell Biology Program Founding Director, Graduate Program in Cancer Biology Director, Laboratory for Molecular Neuro-Oncology Emory University School of Medicine Atlanta GA 30322 Medical Research: What is the background for this study? What are the main findings? Dr. Van Meir: In this study we queried the role of the BAI1 protein in normal physiology. To do this we generated a transgenic mouse, which lacks the expression of the Bai1 gene. The mice had no obvious anomalies and reproduced according to mendelian rules. Since BAI1 is strongly expressed in the brain, including in neurons, we wondered whether they might have some cognitive defect that would only be revealed under specific testing conditions. We had the mice perform in an experiment that tests their ability to orient themselves in space and memorize the location of a hidden platform in a water maze. This experiment clearly demonstrated that the Bai1 deficient mice had deficits in spatial learning and memory. We then further probed the electrophysiological, anatomical and biochemical basis of this abnormal physiologic behavior and showed that hippocampal neurons had abnormal synaptic plasticity, reduced thickness of the post synaptic density and that this was associated with an increased degradation of a key PSD protein called PSD-95. (more…)
Aging, Author Interviews / 20.03.2015

Kamen Tsvetanov, PhD Centre for Speech, Language and the Brain Department of Psychology University of Cambridge Downing Street Cambridge, United Interview with: Kamen Tsvetanov, PhD Centre for Speech, Language and the Brain Department of Psychology University of Cambridge Downing Street Cambridge, United Kingdom   Medical Research: What is the background for this study? What are the main findings? Dr. Tsvetanov: Older brains may be more similar to younger brains than previously thought! In our study we have shown that changes in the aging brain previously observed using functional magnetic resonance imaging (fMRI) – one of the standard ways of measuring brain activity – may be due to changes in our blood vessels, rather than changes in the activity of our nerve cells, our neurons. Given the large number of fMRI studies used to assess the aging brain, this has important consequences for understanding how the brain changes with age and it challenges current theories of ageing. (more…)
Alzheimer's - Dementia, Author Interviews / 05.02.2015 Interview with: V. Zlokovic, MD, PhD Professor and Chair Department of Physiology and Biophysics Keck School of Medicine of USC.V. Zlokovic, MD, PhD Professor and Chair Department of Physiology and Biophysics Keck School of Medicine of USC.   Medical Research: What is the background for this study? What are the main findings? Dr. Zlokovic: Our team used high-resolution imaging of the living human brain to show for the first time that the brain’s protective blood barrier becomes leaky with age, starting at the hippocampus, a critical learning and memory center that is damaged by Alzheimer’s disease. (more…)