Author Interviews, Brain Injury, Brigham & Women's - Harvard / 03.01.2021 Interview with: Nitin Joshi, Ph.D. Engineering in Medicine/Department of Medicine Brigham and Women's Hospital   Dr. Jeffrey M Karp Ph.D Principal Investigator Professor of Medicine at Brigham and Women’s Hospital Harvard Medical School What is the background for this study? Would you explain what is meant by the blood brain barrier? How will nanoparticles facilitate transport of drugs into the brain? Response: Over the past few decades, researchers have identified promising therapeutic agents that can target the biological pathways involved in brain diseases. Unfortunately, clinical translation of these therapeutics is limited by their inability to cross the blood brain barrier (BBB) and enter the brain at therapeutically effective levels. The BBB is a highly selective semipermeable border of cells that prevents molecules in the circulating blood from non-selectively crossing into the brain tissue. We have developed a simple targeted nanoparticle platform that can stably encapsulate therapeutic agents and enable their therapeutically effective delivery into the brain. In this work, we have demonstrated the utility of this platform for the treatment of traumatic brain injury (TBI), which is a leading cause of death and disability in children and young adults, with millions of people suffering TBI each year in accidents, sports, and military conflicts. Following primary injury, which is a result of the mechanical impact to the brain, secondary injury gradually occurs over months to years and can lead to neurological dysfunctions, including Alzheimer’s and Parkinson’s diseases. After TBI, the BBB is physically breached for a short time and previous approaches to achieve therapeutically effective transport of drugs across the BBB have been severely limited to utilizing this very short window. However, the extent to which the BBB is physically breached in TBI varies greatly across the patient population. Therefore, current approaches are applicable to only a subset of injuries with substantially breached BBB. Moreover, BBB can self-repair within a few hours to weeks post-injury to restore its integrity. Hence, physical breaching of BBB offers a limited window for therapeutic interventions, which is not ideal as the secondary injury can last months to years and may require repeated dosing over long term. The nanoparticle platform developed in this work can enable therapeutically effective delivery of drugs into the brain, irrespective of the state of the BBB. We achieved this by precise engineering of the surface properties of nanoparticles, which maximized their transport across the BBB. The therapeutic used in this study was a small interfering RNA (siRNA) molecule designed to inhibit the expression of the tau protein, which is believed to play a key role in neurodegeneration. Poly(lactic-co-glycolic acid), or PLGA, a biodegradable and biocompatible polymer used in several existing products approved by the U.S. Food and Drug Administration was used as the base material for nanoparticles. We systematically engineered and studied the surface properties of the nanoparticles to maximize their penetration across the intact, undamaged BBB in healthy mice. This led to the identification of a unique nanoparticle design that maximized the transport of the encapsulated siRNA across the intact BBB and also significantly improved the uptake by the brain cells.  (more…)
Author Interviews / 17.11.2020 Interview with: Franco Vazza. PhD Associate Professor. Department of Physics and Astronomy University of Bologna, Italy What is the background for this study? Response: We are an astrophysicist and a neurosurgeon, and we realised we had access, from our disciplines, to quantitative datasets to test the (long lived) idea that the two systems are very similar. So we designed simple experiments in which we can analyse both systems in an homogenous way. What are the main findings? Response:  If this work has any value, this is probably to be searched into the way it exposes the way in which such different systems (indeed sitting at the opposite extremes of cosmic scales) may evolve according to similar “macro” laws , i.e. not newer physical laws in any sense, but complex ways in which physical laws combine to evolve macro objects, or in this case networks of event. We hope this will trigger new research in this sense in the near future!  (more…)
Author Interviews, Education, Memory, Pediatrics / 08.10.2020 Interview with: Leonie Margarita Kausel, PhD Postdoctoral Researcher Development University Santiago, Chile What is the background for this study? Response: As a violin teacher, I observed the positive impact on many levels that musical training has on children and as a scientist (Biochemist), I was intrigued to be able to show this with data. I thought this was very important, because in my experience childhood music education can give you so much joy and important skills for life, but it is often not considered to be important in educational settings. After attending a seminar on education and neuroscience, I discovered that this discipline could allow me to investigate this in a scientific manner. This inspired me to enter the Neuroscience PhD program at the Pontificia Universidad Católica de Chile where I was lucky to work with Dr. Francisco Aboitiz, who has vast experience in attention research (ADHD) and is an international expert in language and evolution. At that time Dr. Mary Elizabeth Sutherland was making her postdoc at the lab, and she had worked with Dr. Robert Zatorre, one of the leading researchers in music and the brain. Also, I was lucky to work with Dr. Francisco Zamorano, a pioneer of fMRI research in Chile. So together we designed the research. :)  Also, I am very grateful that I could make a research stay at the Lab of Dr. Gottfried Schalug, who is also a pioneer in the research of music and the brain, and who inspired me to do this research since he wrote the first papers that I read about this subject.  (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…)
Addiction, Author Interviews, Education, Mental Health Research / 16.04.2019 Interview with: Lina Begdache, PhD, RDN, CDN, CNS-S, FAND Assistant Professor Health and Wellness Studies Department GW 15 Decker School of Nursing Binghamton University What is the background for this study? What are the main findings?  Response: College students engage in activities such as binge drinking, abuse of ADHD medications as "study drugs" or use of illicit drugs during a critical brain developmental window that supports maturation of the brain (the prefrontal cortex) necessary for emotional control, cognitive functions and regulation of impulsive behaviors. These activities not only affect brain function, thus mental health and cognitive functions, but may dampen brain development with potential long-lasting effects. As for findings, we were able to identify neurobehavioral patterns that associate with mental wellbeing and mental distress in young adults. Based on evidence from the literature, we constructed conceptual models that describe how one behavior may lead to another until virtuous or vicious cycles set-in.  (more…)
Author Interviews, Cannabis, Cognitive Issues, OBGYNE / 05.11.2018 Interview with: Ryan J. McLaughlin, PhD Assistant Professor Department of Integrative Physiology & Neuroscience College of Veterinary Medicine Washington State University Pullman, WA 99164-7620 What is the background for this study? What are the main findings?  Response: The use of cannabis during pregnancy is a growing health concern, yet the long-term cognitive ramifications for developing offspring remain largely unknown. Human studies exploring the long-term effects of maternal cannabis use have been sparse for several reasons, including the length and cost of such studies, as well as the fact that experimentally assigning mothers to smoke cannabis during pregnancy is obviously ethically impractical. Animal models of maternal cannabis use have been advantageous in this respect, but they have been limited by the drugs used (synthetic cannabinoids vs. THC vs. cannabis plant) and the way that they are administered. In our study, we used a more translationally relevant animal model of maternal cannabis use that exposes pregnant rat dams to whole plant cannabis extracts using the intra-pulmonary route of administration that is most common to human users. Our preliminary data indicate that twice-daily exposure to a high-dose cannabis extract during pregnancy may produce deficits in cognitive flexibility in adult rat offspring. Importantly, these rats did not experience general learning deficits, as they performed comparably to non-exposed offspring when required to follow a cue in their environment that dictate reinforcer delivery. Instead, deficits were observed only when rats were required to disregard this previous cue-based strategy and adopt a new egocentric spatial strategy in order to continue receiving the sugar reinforcers. (more…)
Author Interviews, Neurology / 15.08.2018 Interview with: Dr. Bojana Kuzmanovic PhD Max Planck Institute for Metabolism Research Translational Neurocircuitry Group Cologne, Germany What is the background for this study? What are the main findings? Response: Do our beliefs depend on what we want to believe? Until now, researchers failed to show how interactions between brain regions mediate the influence of motivation to adopt desirable notions on ongoing reasoning. Our study used optimized design and analyses to rule out alternative explanations and to identify underlying neurocircuitry mechanisms. What are the main findings? Response: First, we demonstrated that people’s belief formation behavior depends on their preferences. When people were asked to reconsider their beliefs about their future outcomes, they tended to rely more strongly on good news and to disregard bad news. Second, we showed that favorable belief updating activated the brain valuation system known to be responsive to rewards such as food or money (ventromedial prefrontal cortex, vmPFC). That is, the valuation system was activated when participants incorporated good news to improve their risk estimates, and when they disregarded bad news to avoid a worsening of their risk estimates. And third, the valuation system influenced other brain regions that are involved in deriving conclusions about oneself (dorsomedial prefrontal cortex, dmPFC). Importantly, the more participants were biased in their belief formation behavior, the stronger was the engagement and the influence of the valuation system. The influence of the valuation system on the reasoning system helps to understand how motivation can affect reasoning. It supports the idea that memories and knowledge we recall to form our beliefs are selected in such a way as to yield the desired conclusions. For example, when we wish to convince ourselves that our risk of having a heart attack is low although federal statistics indicate a higher risk, we might recall our healthy life style but not our family history of heart-related diseases, or neglect the fact that the federal population may have a comparable life style. (more…)
Author Interviews, Pediatrics / 11.07.2018 Interview with: Andrew N. Meltzoff Ph.D. Job and Gertrud Tamaki Endowed Chair Co-Director, Institute for Learning & Brain Sciences (I-LABS) Professor of Psychology Elected member of the American Academy of Arts & Sciences. University of Washington, Box 357920 Seattle, WA 98195 What is the background for this study? What are the main findings?  Response: We are applying safe, noninvasive neuroscience techniques to examine the development of young children. We are especially interested in social-emotional learning and cognitive development. The way the body is represented in the brain is well-studied topic in cognitive neuroscience using adults, for example, the classical studies by W. Penfield on the ‘sensorimotor homunculus’ in the adult brain. The development of neural body map in human infants is, however, deeply understudied. We think that the way the body is represented in the brain will provide important information about infant learning prior to language. For example, one of the chief avenues of learning in human infants is through observation and imitation. Infants watch what adults do and imitate those behaviors, rapidly learning about people, things, and causal relations. The mechanisms of imitation themselves are interesting. In order to imitate, infants need to know what part of their body to move and how to move it. We wanted to explore the representations of the human body in the infant brain prior to language. (more…)
Author Interviews, Columbia, Neurology / 09.07.2018 Interview with: Andrew Goldman PhD Laboratory for Intelligent Imaging and Neural Computing Department of Biomedical Engineering, Columbia University Presidential Scholar in Society and Neuroscience, Columbia University Andrew Goldman PhD Laboratory for Intelligent Imaging and Neural Computing Department of Biomedical Engineering, Columbia University Presidential Scholar in Society and Neuroscience, Columbia University What is the background for this study? What are the main findings? Response: Many Western musicians have difficulty improvising, despite having extensive training and experience. These musicians learn about and use similar musical structures in their playing (like chords, scales, rhythmic patterns, etc.) as experienced improvisers, but they may know about them in different ways. In other words, different musicians have different ways of knowing and learning about similar musical structures. To understand which ways of knowing facilitate the ability to improvise contributes to an understanding of how people are able to use knowledge creatively. Western music provides an important opportunity to compare these different ways of knowing because in other improvisatory domains of behavior (like speaking), it is difficult to find people who know how to do it but cannot improvise with it (e.g., if you know a language, you can very likely improvise with that language). In order to advance our understanding of these improvisatory ways of knowing, we compared musicians with varying degrees of improvisation experience in a task that tested how they categorized musical chords. In Western music, different chords are theorized to have similar “functions.” For example, on a guitar, there are different ways to play a C chord, and you could often substitute one for the other. You might even play another chord in place of the C chord and have it sound similar, or lead to a similar subsequent harmony. Improvisers often use notation that specifies classes of chords rather than specific realizations (versions) of a chord whereas those who do not typically improvise use notation that specifies the full realization of the chord. By analogy, one chef might use a recipe that calls for “citrus” (in music, a class of musical chord) while another chef’s recipe might specifically call for “lemon” (in music, a specific realization of a functional class of chords). We tested whether improvisers categorize similar-functioning harmonies as more similar to each other than different-functioning harmonies, and compared how less experienced improvisers categorize the same harmonies. Our task required the musicians to listen to a series of repeating harmonies (the “standard” stimuli) and pick out occasional chords that were different in any way (the “deviant” stimuli). Some deviant stimuli were different versions of the standard chord (like limes in place of lemons) and some deviant stimuli were chords with different musical functions (like bananas instead of lemons). The more experienced improvisers were better at detecting the function deviants than the exemplar deviants whereas the less experienced improvisers showed little difference in their ability to detect the two types of deviants. In other words, because improvisers categorize the different versions of the same chord as similar, they have a relatively harder time picking out the similarly functioning harmonies. This was measured using behavioral data, and electroencephalography (EEG), which can be used to provide a neural measure of how different stimuli are perceived to be from each other. (more…)
Addiction, Author Interviews, Mental Health Research / 13.06.2018 Interview with: Scott J. Russo PhD Fishberg Dept. of Neuroscience Friedman Brain Institute, and Center for Affective Neuroscience Icahn School of Medicine at Mount Sinai New York, NY What is the background for this study? What are the main findings?  Response: There is increasing evidence that aggressive behavior might share key features with addiction.  For example, aggressive mice develop positive associations with environmental cues associated with previous aggressive encounters (ie. they find aggression rewarding) and aggressive animals will work very hard to obtain access to a subordinate animal in order to attack them. Some of the same brain regions that are activated in response to addictive drugs, like cocaine and morphine, are also activated by aggressive experience.  Thus we hypothesized that there may be shared neurobiological mechanisms between addiction and aggression. Our study showed that there is accumulation of the addiction-related transcription factor, ΔFosB, in the nucleus accumbens, a brain region well know to regulate the rewarding and addictive properties of drugs of abuse. (more…)
Abuse and Neglect, Neurology / 14.03.2018 Interview with: Veljko Dubljević, Ph.D., D.Phil. Assistant Professor of Philosophy, Department of Philosophy and Religious Studies, and Science Technology and Society Program, North Carolina State University Raleigh, NC 27607 What is the background for this study? Response: There is considerable controversy about the interpretation of data of the neuroscientific studies done by Benjamin Libet. On the one hand, Libet claimed that his work disproves certain metaphysical conceptions of free will (Libertarianism), whereas it does not disprove others (e.g., Compatibilism). In a nutshell, the reason for these claims is that Libet found preparatory brain activity (Readiness Potentials or RPs) some 500ms before the conscious decision to act was felt by study participants. That seemed to exclude the possibility that mental causation was taking place. At the same time, the onset of movement left a time-window for a 'veto-decision'. This led Libet to conclude that there is no 'free will', but that there is a 'free won't'. On the other hand, there were many criticisms of the study - methodological or substantive. Most notably, Patrick Haggard argued that it is not RPs that are correlates of a decision to act, but Lateralized Readiness Potentials (LRPs). Haggard agreed with many critics of Libet in that RPs could be connected to a range of other phenomena, and that preparatory brain activity that is most important for a decision to act already has to be 'lateralized'. Namely, the decision to move the left or right arm is critical in this regard, and will lead to RP being focused in one or the other hemisphere, thus making LRPs the point of interest for any conscious decision to act. All in all, Haggard claimed to have replicated Libet's major findings, with the caveat that timing of LRPs excludes the time-frame for a 'veto-decision'. This Haggard claimed makes the evidence more in line with the metaphysical doctrine of 'hard determinism', which excludes agency and responsibility. Many other neuroscientists followed Libet's (and Haggard's) lead and these experiment became part of 'lore' in neuroscience education - many other labs performed similar experiments and claimed to basically replicate the findings. Our study was the first to review all available evidence. (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, Psychological Science / 17.10.2017 Interview with: Tamara Masters, PhD Marketing Marriott School of Management Brigham Young University What is the background for this study? What are the main findings? Response: As a marketing professor I have studied the disparity of what people are willing to sell items/products for and how much that differs from how much others are willing to pay. I do research in consumer decision making and find the neurophysiological aspects of consumers fascinating.  I read medical and neuroscience research for fun and see many ways individuals may be effected in the use of their limited resources.  We are all consumers – many make purchases of some type daily – even it if it is to play online games or where and how to get our next meal. The main findings relate to how a person is either attached to or feels an aversion to losing an object.  There has been debate as to which of these factors leads to a difference in buy and selling prices.  This research provides a new and unique look at how BOTH factors must be present for this disparity to emerge.  This research is unique because it uses combines the fields neuroscience, psychology and economics to explain something we all experience. (more…)
Author Interviews, Pediatrics, Psychological Science / 24.08.2017 Interview with: Dan Romer PhD Research director, Annenberg Public Policy Center Director of its Adolescent Communication Institute University of Pennsylvania What is the background for this study? Response: In recent years, findings from research in developmental neuroscience indicate that the myelination of the prefrontal cortex (PFC) extends into the third decade of life, proceeding more slowly than in other brain regions. Because subcortical and sensory brain regions appear to mature earlier, this and other findings have been taken as evidence that adolescents may have less ability to control their behavior than children do. These findings spawned theories of “imbalanced” adolescent brain development that were proposed to explain heightened vulnerability to risky behavior and adverse health outcomes during adolescence. Although there is little doubt that as adolescents enter adulthood, they are at risk for many health outcomes that can accompany the initiation of such behaviors as driving, having sex, using drugs, and playing sports. But most adolescents make it through this period of development without serious health consequences. Thus, the argument that a brain deficit is responsible for such adverse health outcomes seemed to overgeneralize effects that only occur for a minority of adolescents. Furthermore, when my colleagues and I examined the evidence in support of imbalance theories, we found it unconvincing. Indeed, it seemed that findings from neuroscience were interpreted through the lens of stereotypes about adolescents that conflate exploration with impulsivity. That is, many of the risky behaviors that attract adolescents are novel activities that reflect lack of experience rather than lack of control over behavior.  (more…)
Author Interviews, Emory / 09.06.2017 Interview with: Dr. Robert Liu, PhD Silvio O. Conte Center for Oxytocin and Social Cognition Center for Translational Social Neuroscience Department of Biology Graduate Program in Neuroscience Emory University, Atlanta, Georgia What is the background for this study? What are the main findings? Response: This study describes for the first time some of the novel brain mechanisms underlying how social relationships are formed.  In this case we studied the formation of a pair bond in voles.  Pair bonding in voles is not exactly the same as love in humans, but we believe that pair bonding in voles likely shares many of the underlying neural mechanisms as falling in love in humans, such as developing a rewarding feeling towards your partner. Basically, we discovered that rhythmic oscillations of groups of neurons in the prefrontal cortex, an area of the brain that is involved in decision making and executive function, can control the strength of oscillations at a different frequency in populations of neurons in the nucleus accumbens, an area that is involved in pleasure and reward, as well as addiction.  We show that the strength of that PFC-NAc control predicted how quickly animals would begin to show affectionate behavior, analogous to people who may fall in love quicker than others.  But the most intriguing thing was that when animals mated for the first time, the strength of the control of the reward system by the decision making circuit increased, and the greater the increase in that control, the faster the animal started huddling or showing affection toward its partner.  We think that this cortical control of the reward system allows for the neural encoding of the partner’s features (odors, sounds) to become stamped into the reward system, so that the partner becomes rewarding themselves.  Indeed in studies in humans, parts of the striatum, to which the nucleus accumbens belongs, become activated when men look at images of their lovers or when mothers look at images of babies. We not only observed that during pair bond formation the cortex controls rhythmic activity within the reward system, but we actually recreated that communication using a highly innovative technique that allows us to control neural activity using light.  We expressed a light sensitive protein in the cortical neurons that project to the reward system, and then light stimulated those projections in the reward system in animals at the same frequency as normally happens during mating, but in this case the animals were not allowed to mate. By simply recreating the neural oscillatory control of the cortex of the reward area when the female was near the male, we biased how affectionately she acted towards him. We think that the implications for this is not restricted to forming bonds or falling in love, but tells us something fundamental about how certain brain circuits communicate with each other to build social relationships, to make us feel pleasure from being with others that we like.  We believe that by understanding how social cues get instantiated into the brain’ reward system, we may ultimately be able to use this information to help people with impairments in the forming strong social relationships, such as in autism or schizophrenia. (more…)