Author Interviews, Neurological Disorders, Technology / 29.06.2017

MedicalResearch.com Interview with: Howard Jay Chizeck ScD Professor, Electrical Engineering Adjunct Professor, Bioengineering Co-Director UW Biorobotics Laboratory Graduate Program in Neuroscience UW CoMotion Presidential Innovation Fellow Research Thrust Testbed Co-Leader MedicalResearch.com: What is the background for this study? What are the main findings? Response: Essential Tremor is treated using Deep Brain Stimulation (DBS) in some patients. Current clinical practice involves Deep Brain Stimulation with an "always on" stimulation. This causes extra battery drain, because stimulation is applied when not needed. Also excessive stimulation is not necessarily a good thing, Our work is aimed at adjusting the stimulation, so that it comes on and turns off only when needed to suppress tremor symptoms. (more…)
Author Interviews, JAMA, Parkinson's / 15.06.2017

MedicalResearch.com Interview with: Rajesh Pahwa MD Department of Neurology University of Kansas Medical Center, Kansas City, KS, MedicalResearch.com: What is the background for this study? What are the main findings? Response: Dyskinesia are one of the major unmet needs in Parkinson Disease patients. At the present time there are no approved medication for dyskinesia, however immediate release amantadine is used in PD patients with dyskinesia. ADS-5102 is a long acting, extended release capsule formulation of amantadine HCl administered once daily at bedtime. This study investigated the safety, efficacy and tolerability of ADS-5102 in Parkinson’s disease (PD) patients with levodopa-induced dyskinesia. This was a randomized, double-blind, placebo-controlled study of Parkinson’s disease patients with levodopa-induced dyskinesia. In total, 126 patients were randomized to placebo or 274 mg ADS-5102 administered orally at bedtime. ADS-5102 was associated with a significant reduction in dyskinesia at 12 weeks compared with placebo, as measured by the mean change in Unified Dyskinesia Rating Scale (treatment difference, –7.9; P =.0009). OFF time was significantly reduced in ADS-5102 patients compared to placebo (treatment difference -0.9 hours, p=.017). (more…)
Author Interviews, Neurological Disorders, PNAS / 17.04.2017

MedicalResearch.com Interview with: Zhiyong Zhao, Ph.D. Associate Professor Department of Obstetrics, Gynecology & Reproductive Sciences University of Maryland School of Medicine Baltimore, MD MedicalResearch.com: What is the background for this study? What are the main findings? Response: Diabetes in early pregnancy can cause neural tube defects in fetus. The defects are a result of failure in neural tube closure, due to excess cell death. The aim of this study was to delineate molecular processes that induce cell death. The main findings of this study are: (1) Hyperglycemia disrupts protein folding. The misfolded proteins, including the ones that are associated with neurodegenerative diseases, form aggregates, indicating similar molecular processes in both fetal neural tube defects and adult neurodegenerative diseases. (2) Protein aggregation leads to formation of a neurodegenerative disease-related cell death inducting mechanism. (more…)
Author Interviews, Neurological Disorders, Stem Cells / 12.04.2017

MedicalResearch.com Interview with: Dr. Darwin J. Prockop, M.D., Ph.D. Professor and Director Institute for Regenerative Medicine Texas A&M Health Science Center College of Medicine Temple, TX MedicalResearch.com: What is the background for this study? What are the main findings? Response: We and many others have been trying for many years to develop therapies with adult stem cells that might rescue the brain from the injuries and disease. Recently many of found that small vesicles secreted by adult stem cells have many of the beneficial effects of the cells themselves. The paper shows that a nasal spray of the vesicles can rescue mice from the long-term effects of severe epilepsy. (more…)
Author Interviews, Brain Injury, Neurological Disorders, Pediatrics / 06.04.2017

MedicalResearch.com Interview with: Emily Dennis PhD Postdoctoral Scholar Imaging Genetics Center Mark and Mary Stevens Neuroimaging and Informatics Institute USC MedicalResearch.com: What is the background for this study? What are the main findings? Response: We know that there is heterogeneity in outcome post-traumatic brain injury (TBI), but we generally think of this as a continuous variable - with most patients falling in the middle and only a few at the extremes in terms of recovery process and outcome. Our main finding was that interhemispheric transfer time (IHTT - the time it takes for information to move from one hemisphere of the brain to the other) identified 2 subgroups of TBI patients - those with slow IHTT and those with normal IHTT. These two groups show differences in cognitive function and brain structure, with the IHTT slow group showing structural disruptions that become progressively worse while the IHTT normal group seems to be recovering from the injury. (more…)
Author Interviews, Neurological Disorders / 23.03.2017

MedicalResearch.com Interview with: Joshua Kim, researcher RIKEN-MIT Center for Neural Circuit Genetics at The Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA Howard Hughes Medical Institute, Massachusetts Institute of Technology Cambridge, MA 02139 MedicalResearch.com: What is the background for this study? Response: We previously identified to populations of neurons in a structure known as the basolateral amygdala, one that is capable of mediated fear-related behaviors and the other reward-related behaviors. Both of these basolateral amygdala populations send projections to a structure known as the central amygdala. For this study, we wanted to examine the function of 7 different populations of central amygdala neurons in regard to fear-related and reward-related function and how each of these 7 populations are connected to the 2 basolateral amygdala populations. (more…)
Alzheimer's - Dementia, Author Interviews, Neurology, Sleep Disorders / 25.02.2017

MedicalResearch.com Interview with: Dr. Matthew P. Pase Sidney Sax NHMRC Fellow, Department of Neurology Boston University School of Medicine Investigator, Framingham Heart Study; Senior Research Fellow, Swinburne University of Technology. Boston MA 02118 MedicalResearch.com: What is the background for this study? Response: Sleep disturbances are common in dementia. However, most studies have focused on patients who already have dementia and so it is unclear whether disturbed sleep is a symptom or a cause of dementia. We studied 2,457 older participants enrolled in the Framingham Heart Study, a large group of adults sampled from the community in Framingham, Massachusetts. We asked participants to indicate how long they typically slept each night. Participants were then observed for the following 10-years to determine who developed dementia, including dementia due to Alzheimer’s disease. Over the 10 years, we observed 234 cases of dementia. Information on sleep duration was then examined with respect to the risk of developing dementia. (more…)
Author Interviews, Neurological Disorders, Zika / 19.02.2017

MedicalResearch.com Interview with: Ping Wu, MD, PhD John S. Dunn Distinguished Chair in Neurological Recovery Professor, Department of Neuroscience & Cell Biology University of Texas Medical Branch Galveston, TX 77555-0620 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Zika viral infection poses a major global public health threat, evidenced by recent outbreaks in America with many cases of microcephaly in newborns and other neurological impairments. A critical knowledge gap in our understanding is the role of host determinants of Zika-mediated fetal malformation. For example, not all infants born to Zika-infected women develop microcephaly, and there is a wide range of Zika-induced brain damage. To begin to fill the gap, we infected brain stem cells that were derived from three human donors, and found that only two of them exhibited severer deficits in nerve cell production along with aberrant alterations in gene expression. (more…)
Addiction, Author Interviews, JAMA / 06.02.2017

MedicalResearch.com Interview with: Guillaume Sescousse, PhD Senior post-doc Donders Centre for Cognitive Neuroimaging The Netherlands with collaborators Maartje Luijten, PhD, and Arnt Schellekens, MD PhD MedicalResearch.com: What is the background for this study? What are the main findings? Response: People with an addiction process rewards in their brain differently from people who are not addicted. However, whether this is associated with “too much” or “too little” brain activity is an open question. Indeed, past research has produced conflicting findings. In order to get a reliable answer, we have combined 25 studies investigating brain reward sensitivity in more than 1200 individuals with and without addiction to various substances such as alcohol, nicotine or cocaine but also gambling. By analyzing the brain images from these studies, we have discovered an important difference in brain activity between expecting a reward and receiving a reward. Compared with non-addicted individuals, individuals with substance or gambling addiction showed a weaker brain response to anticipating monetary rewards. This weaker response was observed in the striatum, a core region of the brain reward circuit, possibly indicating that individuals with an addiction have relatively low expectations about rewards. In contrast, this same region showed a relatively stronger response to receiving a reward in individuals with substance addiction compared with non-addicted individuals. Many addiction rehab centres, such as Avante, offer targeted addiction relief strategies to help a specific person with their addiction. This stronger response possibly indicates a stronger surprise to getting the reward, and is consistent with low expectations. This same effect was not found among people addicted to gambling. (more…)
Author Interviews, Neurological Disorders, Radiology / 06.01.2017

MedicalResearch.com Interview with: Jay Desai, M.D. Neurologist, Children’s Hospital Los Angeles Assistant Professor, Keck School of Medicine of USC MedicalResearch.com: What is the background for this study? What are the main findings? Response: We obtained measures of blood flow at rest from all regions of brain using an MRI technique called pulsed arterial spin labeling in 26 participants (children and adults) with stuttering. We compared these blood flow measures with those from 36 fluent controls. We found decreased blood flow in Broca’s region in participants with stuttering when compared to the fluent controls. The amount of blood flow correlated inversely with the severity of stuttering and these findings extended into other portions of the language loop. We also detected alterations in blood flow in other brain regions including superior frontal gyrus, cerebellar nuclei and parietal cortex. (more…)
Author Interviews, Nature, Neurological Disorders, Technology / 16.12.2016

MedicalResearch.com 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 MedicalResearch.com: 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, Neurological Disorders / 07.12.2016

MedicalResearch.com Interview with: Dr. Paul Davies PhD Tufts University School of Medicine Department of Neuroscience Boston, MA 02111 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Inhibition in the brain regulates neuronal action potential generation, too little inhibition can directly cause conditions such as epileptic seizures, neurodevelopment disorders, and neurodegenerative disorders. The main type of inhibition in the mammalian brain occurs when the neurotransmitter γ-aminobutyric acid (GABA) binds to the GABA type A receptors (GABAARs), a ligand-gated ion channel. Once bound with GABA, the receptor changes shape to open the ion channel allowing negative charged chloride ions to flow through into the cell and inhibiting excitation steaming from positive charged ions flowing through opposing excitatory ion channels. GABAARs mediate both synaptic (phasic) and extrasynaptic (tonic) inhibitory neurotransmission in the CNS and are the sites of action of benzodiazepines, barbiturates, general anesthetics and neuro-active steroids. We have been focused on the extrasynaptic GABAARs that mediate tonic inhibition. In the dentate gyrus of the hippocampus, neocortex, striatum and the thalamus tonic inhibition is largely dependent on GABAARs composed of α4, β2/3, and δ subunits. Neuro-active steroids play a central role in regulating behavior via their ability to allosterically enhance GABAARs, particularly extrasynaptic α4-containing GABAARs. Allosteric enhancement means that neuro-active steroids bind to GABAARs and cause a further change in the structure of the ion channel allowing it to remain open for longer. For the last few decades, allosteric enhancement of GABAARs by neuro-active steroids has been the prevailing explanation for how the steroids increase inhibition in the brain. However, recently we described a new mechanism where the neuro-active steroid, THDOC, increased the association of protein kinase C (PKC) with extrasynaptic α4β3 subunit-containing GABAARs. The increase in PKC-mediated phosphorylation of α4 and β3 subunits leads to an increase in membrane insertion from intracellular stores, an increase in GABAAR stability in the membrane, and a prolonged increase of tonic inhibition, even after when the neuro-active steroids have been removed. For this present study we asked whether other neuro-active steroids demonstrated the same metabotropic activity. We tested another endogenous neuro-active steroid, allopregnanolone (ALLO), and the synthetic neuro-active steroid, ganaxolone. In collaboration with SAGE Therapeutics, we also tested another synthetic neuro-active steroid, SGE-516. We found that all the neuro-active steroids tested were able to allosterically potentiate both synaptic and, to a lesser degree, extrasynaptic GABAARs. Short 15-minute exposures to neuro-active steroids resulted in significantly increase in phosphorylation of β3 subunits, and long lasting enhancement of tonic current. These increases were metabotropic in nature, being dependent upon PKC mediated phosphorylation. Following this short 15-minute exposure we saw a change in synaptic currents only with SGE-516 suggesting a selectivity of this metabotropic pathway to extrasynaptic GABAARs. Although ganaxolone was an effective allosteric modulator, it did not produce a metabotropic enhancement of tonic current suggesting that not all neuroactive steroids work through this pathway. (more…)
Author Interviews, MRI, Psychological Science / 02.12.2016

MedicalResearch.com Interview with: Jeffrey S. Anderson, MD, PhD Director the fMRI Neurosurgical Mapping Service Principal Investigator for the Utah Functional Neuroimaging Laboratory University of Utah MedicalResearch.com: 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, Ophthalmology, Pediatrics / 23.11.2016

MedicalResearch.com Interview with: Marius George Linguraru, DPhil, MA, MB Principal Investigator Associate Professor of Pediatrics and Radiology George Washington University School of Medicine and Health Sciences Children’s National Health System Washington, DC MedicalResearch.com: What is the background for this study? What are the main findings? Response: Neurofibromatosis type 1 (NF1) is the most common cancer predisposition syndrome affecting the central nervous with an incidence of one in 3,000 births. Nearly one in five children with NF1 develops an optic pathway glioma (OPG), a low-grade tumor of the anterior visual pathway (i.e., optic nerves, chiasm and tracts). These tumors are not amenable to surgical resection and can cause permanent vision loss ranging from a mild decline in visual acuity to complete blindness. Only half of children with NF1-OPGs will experience vision loss, typically between 1 to 6 years of age. The other half will never lose vision or require treatment. All previous studies have consistently demonstrated that the change in NF1-OPG size is not related to the clinical outcome. For example, the optic pathway glioma size may be stable or even decrease, yet the vision will decline. Alternatively, the OPG size may increase, yet the clinical outcome remains stable or even improves. As no imaging or clinical features can identify which children with NF1-OPGs will ultimately lose vision, clinicians struggle to follow these children and decide when to intervene. We used quantitative imaging technology to accurately assess in magnetic resonance imaging (MRI) the total volume of OPGs in NF1. We also determined the retinal nerve fiber layer thickness in these children, a measure of axonal degeneration and an established biomarker of visual impairment. The results were outstanding, as we showed for the first time that the volume of an optic pathway glioma is indeed correlated with the likelihood of vision loss in children with Neurofibromatosis type 1. (more…)
Author Interviews, JAMA, Neurological Disorders, Parkinson's / 21.11.2016

MedicalResearch.com Interview with: Adolfo Ramirez Zamora, MD Associate Professor of Neurology and Phyllis E. Dake Endowed Chair in Movement Disorders Department of Neurology Albany Medical College MedicalResearch.com: What is the background for this study? What are the main findings? Response: Patients with SPG 11 mutations can present with motor symptoms characterized by juvenile onset dystonia, Parkinsonism and lower extremity spasticity. Parkinsonism appears to be responsive to levodopa therapy early in the disease but treatment is complicated by the occurrence of motor fluctuations resembling parkinson disease. Patients have short duration of medication effects, unpredictable response to medications along with generalized, excessive involuntary movements known as dyskinesias. Deep Brain stimulation is a well-established treatment for movement disorders but it has never been used in this disease. We first report the clinical outcome obtained with globus pallidus internal deep brain stimulation in a patient with parkinsonism, dystonia, dyskinesias related to SPG 11. Additionally, we report for the first time the basal ganglia changes observed in the disease using intraoperative neuronal recordings. Patient had a sustained and remarkable response to stimulation over the next two years without side effects. Neurophysiologic changes revealed a unique pattern of neuronal firing despite of the resemblance to advance Parkinsons disease. (more…)
Author Interviews, Brigham & Women's - Harvard, Neurological Disorders / 17.11.2016

MedicalResearch.com Interview with: Michael D. Fox, MD, PhD Assistant Professor in Neurology Berenson-Allen Center for Noninvasive Brain Stimulation Division of Cognitive Neurology, Department of Neurology Beth Israel Deaconess Medical Center Boston, MA MedicalResearch.com: What is the background for this study? What are the main findings? Response: Consciousness is thought to be composed of arousal plus awareness, but no one knows where these processes live in the human brain. We took a unique approach to this question by studying human brain lesions that disrupt consciousness and cause coma. We found one small spot in the brainstem that was specific for coma (i.e. lesions that hit this spot caused coma while lesions that didn’t hit the spot did not cause coma). In other words, there was one spot in the human brainstem that, when lesioned, disrupted arousal and caused coma We then looked at the connectivity of that brainstem spot, and found that it was connected to two cortical regions previously implicated in awareness. These cortical regions also contained a unique type of brain cell thought only to be present in higher order mammals that are self-aware. To confirm our findings, we looked at the integrity of our network in patients with disorders of consciousness (e.g. persistent vegetative state) and found selective disruption of this network. (more…)
Author Interviews, Neurological Disorders / 04.11.2016

MedicalResearch.com Interview with: Nir Lahav Physics Department Bar-Ilan University in Israel MedicalResearch.com: 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, Neurological Disorders / 31.08.2016

MedicalResearch.com Interview with: Sanne Kikkert, DPhil student FMRIB Centre, University of Oxford Oxford, United Kingdom MedicalResearch.com: What is the background for this study? Response: One of the most mysterious questions about the brain’s ability to adaptively change to new circumstances is: what happens to the brain once a key input is lost (e.g. through amputation)? It has been thought that the hand representation in the brain, located in the primary somatosensory cortex, is maintained by regular sensory input from the hand. Indeed, textbooks teach that any sensory representation in the brain will be ‘overwritten’ if its primary input stops. Following this explanation, people who have undergone hand amputation would show extremely low or no activity related to its original focus in the brain area of the missing hand. However, we know that amputees often experience phantom sensations from their missing hand, such that when asked to move a phantom finger they can ‘feel’ that movement. We previously showed that we can trace some activity in the missing hand brain area when amputees move their phantom hand. In this study, we were interested in finding how the representation of a missing hand is stored in the brain. (more…)
Author Interviews, NEJM, Neurological Disorders, Surgical Research / 12.08.2016

MedicalResearch.com Interview with: Gil I. Wolfe, MD, FAAN Irvin and Rosemary Smith Professor and Chair Dept. of Neurology/Jacobs Neurological Institute Univ. at Buffalo Jacobs School of Medicine and Biomedical Sciences/SUNY Buffalo General Medical Center Buffalo, NY 14203-1126 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Thymectomy has been used in myasthenia gravis (MG), in particular those patients who do not have a tumor of the thymus gland, known as a thymoma, for over 75 years without randomized data to support its use. A practice parameter in 2000 on behalf of the American Academy of Neurology stated that the benefits of thymectomy in this population of non-thymomatou smyasthenia gravis patients remained uncertain, classified thymectomy as a treatment option in this group, and called for rigorous, randomized studies. What we found is that compared to an identical prednisone protocol alone, that extended transsternal thymectomy confers significant benefits to non-thymomatous MG patients over a period of three years after the procedure. The benefits include better disease status, reduced prednisone requirements, fewer hospitalizations to manage  myasthenia gravis worsenings, and a lower symptom profile related to side effects from medications used to control the disease state. (more…)
Author Interviews, Neurological Disorders, PLoS / 21.07.2016

MedicalResearch.com Interview with: Zoltan Toroczkai, PhD, Professor of Physics Concurrent Professor of Computer Science and Engineering Physics Department University of Notre Dame, Notre Dame, IN, 46556 MedicalResearch.com: What is the background for this study? Response: The mammalian brain is arguably the most complex information processing network and with billions of neurons and trillions of connections it presents formidable challenges to deciphering its fundamental mechanisms for information processing. In the brain, information is encoded into the spatio-temporal firing patterns of groups of neurons (population coding), making the connectivity structure of the network crucial for brain function. Damages to this network have been associated with diseases such as Alzheimer’s, autism and schizophrenia, and thus understanding the cortical network would also help better understand certain diseases of the brain. An experimentally and computationally more feasible approach is to study the anatomical (physical connectivity) network between the functional areas of the cortex, a mosaic of brain patches, each associated with a specific function (e.g., visual, auditory, somatosensory). Based on phylogenic considerations one expects the existence of common fundamental network architectural (and implicitly, processing) principles to be present in all mammalian brains. However, the mammalian brain spans over five orders of variation in size and thus it is not clear at all what are this common architectural features and how would we find them. The challenge here is to compare networks of the same nature (information processing type) but of different orders, with different nodal identities, and of very different spatial embedding (geometrical size) properties. (more…)
Author Interviews, Brigham & Women's - Harvard, Neurological Disorders / 15.07.2016

MedicalResearch.com Interview with: Aleksey G. Kazantsev, PhD Associate Professor in Neurology, Harvard Medical School Drug Discovery Laboratory MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Response: There is no cure (disease modify therapy) for any neurodegenerative disorders (ND), most common Alzheimer’s and Parkinson’s or orphan like Huntington’s diseases. Numerous studies show that the pathologies of neurodegenerative diseases at molecular levels are similar but highly complex. No single neurodegenerative mechanism has emerged as predominant, slowing a development of efficient therapy. While gene and cell-based therapeutic approaches are still evolving, we relay on discovery of small molecule drugs as essentially the only strategy with approved track record in human subjects. However, so far a traditional approach of targeting single cellular pathway was unsuccessful for CNS drug development. The current study demonstrated a novel approach of using small molecule with multiple putative neuroprotective activities, which is essentially a combinatorial approach to use compound distinct activities to ameliorate/bock/prevent not one, but a few neurodegenerative pathways. (more…)
Author Interviews, Microbiome, Neurological Disorders / 22.05.2016

MedicalResearch.com Interview with: Susanne Asu Wolf PhD Max-Delbrueck-Center for Molecular Medicine Berlin, Germany MedicalResearch.com: What inspired you to research this link between Ly6Chi monocytes, antibiotics and neurogenesis? Dr. Wolf: As a neuroimmunologist I research the communication between the immune system and the brain. Amongst other research groups we found almost 10 years ago that T cells are needed to maintain brain homeostasis and plasticity, namely neurogenesis. Since only activated T cells enter the brain, we were looking for a mouse model, where immune cells are not activated. My former supervisor Polly Matzinger (NIH), a well-known immunologist, suggested to use germ free mice, born and raised in an isolator without any contact to a pathogen or any bacteria. I did a pilot experiment with the germ free mice, but wanted to get closer to possible applications in humans. Since humans are rarely born and raised in a sterile environment, I was looking for another model. By chance I met with the group of Bereswill and Heimesaat (Berlin, Charite) who provided me with a model, where due to prolonged treatment with an antibiotic cocktail, the microbiota are below detection level and the mice are also virtually germ free. They got me into contact with the second senior author of the paper Ildiko Dunay (University of Magdeburg). Her expertise is the function of Ly6Chi monocytes during infection with malaria or toxoplasmosis. Now we were ready to investigate the gut-immune-brain axis with the focus on neurogenesis and cognition. Meanwhile the impact of the microbiome on behavior was reported by several research groups using “sterile” germ free mice and I was also curious if we could see similar differences in our antibiotic treated mice. (more…)
Author Interviews, Neurological Disorders, Psychological Science / 19.04.2016

MedicalResearch.com Interview with: Ezequiel Morsella, Ph.D. Associate Professor of Neuroscience Department of Psychology San Francisco State University Assistant Adjunct Professor Department of Neurology University of California, San Francisco Boardmember, Scientific Advisory Board Institute of Cognitive Neurology (INECO), Buenos Aires MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Morsella: The study is based on Passive Frame Theory, which I discuss below in brief, and on ironic processing, in which one is more likely to think about something (e.g., white bears) when instructed to not think about that thing.  Based on this research, the Reflexive Imagery Task (RIT) reveals that, following the activation of certain "action sets" (i.e., dispositions to act one way or another), conscious thoughts can arise involuntarily and systematically when one is presented with certain stimuli.  In the most basic version of the RIT, subjects are presented with visual objects and instructed to not think of the names of the objects, which is challenging.  In the new study, we show that the effect arises not only for automatic processes (e.g., forms of cued-memory retrieval) but also for processes involving more, in a sense, moving parts (e.g., symbol manipulation, in which symbols are mentally manipulated).  In the study, subjects were first trained to perform a word-manipulation task similar to the game of Pig Latin (e.g., “CAR” becomes “AR-CAY”). This task involves complex symbol manipulations.  After training, though participants were instructed to no longer transform stimulus words in this way, the RIT effect still arose on roughly 40% of the trials. The present experiment provides additional evidence for Passive Frame Theory, a new, comprehensive and internally coherent framework that illuminates the role of conscious processing in the brain. Click here for more information about Passive Frame Theory: https://www.psychologytoday.com/blog/consciousness-and-the-brain/201604/passive-frame-theory-new-synthesis Although consciousness is not "epiphenomenal" (meaning that it serves no function) or omnipresent (e.g., as in panpsychism, which states that consciousness is a property of all matter), in Passive Frame Theory, the role of consciousness is much more passive and less teleological (i.e., less purposeful) than that of other theoretical accounts. The framework reveals that consciousness has few moving parts and no memory, no reasoning, or symbol manipulation, which is relevant to the present study. Consciousness does the same thing, over and over, for various processes, making it seem that it does more than it does.  Hence, consciousness, over time, seems to be more flexible than it actually is. (more…)
Author Interviews, Nature / 12.04.2016

MedicalResearch.com Interview with: Dr. Michael V. Sofroniew, MD PhD Professor of Neurobiology David Geffen School of Medicine UCLA MedicalResearch.com: What is the background for this study? Dr. Sofroniew: For over seventy-five years, it has been thought that scars formed by cells called astrocytes actively prevent the regeneration of damaged nerve fibers (also known as axons) across injury sites in the brain and spinal cord. This view was based largely on two forms of circumstantial evidence: (1) after injury, damaged nerve fibers do not regrow past astrocyte scars and appear to be ‘stalled’ within them; (2) astrocytes (along with other cells) can produce molecules that inhibit nerve fiber growth in cell culture experiments. We also initially subscribed to this inhibitory view of astrocyte scars and about twenty years ago my lab began to develop experimental tools that allowed us to prevent astrocyte scar formation in mice. The hope was that preventing astrocyte scar formation would lead to nerve fiber regeneration across brain or spinal cord injuries. Unfortunately, although we were successful in preventing scar formation, we never saw any regrowth of nerve fibers in spite of multiple different attempts over many years of work. We were disappointed and held back from publishing those results, but kept thinking about the problem and looking for new ways to study it. Over the last five years, new tools and information became available that allowed us to return to this question and probe further. We kept getting similar kinds of results and eventually we collected enough different types of evidence to convince ourselves that the original view that astrocyte scars prevent nerve fiber regrowth was incorrect. MedicalResearch.com: What are the main findings? Dr. Sofroniew: We found that after preventing astrocyte scar formation, or after removing chronic astrocyte scars, there was no spontaneous regrowth of damaged nerve fibers and that instead, the nerve fibers retracted further back away from spinal cord injury sites. We found that both astrocytes and other cells in the injury sites produced numerous molecules that could support nerve fiber regrowth along with molecules that might repel or inhibit it. This suggested a complex molecular environment that needs to be studied more. We also found that when appropriate growth factors were applied locally into the injury site, nerve fibers could be stimulated to regrow in spite of astrocyte scar formation, and that this stimulated regrowth was significantly reduced, and not improved, when scar formation was prevented. Together, these findings show that rather than being major inhibitors of nerve fiber regrowth, scar-forming astrocytes can be supportive of such growth.  (more…)
Author Interviews, Neurological Disorders, NYU / 26.02.2016

MedicalResearch.com Interview with: Michael A. Long, PhD New York University School of Medicine Assistant Professor New York Stem Cell Foundation Robertson Neuroscience Investigator Medical Research: What is the background for this study? Response: Speech is, of course, central to our everyday lives, and it is perhaps the most thoroughly studied human behavior.  That said, many aspects of how our brain produces speech are still poorly understood. Human brains are extremely complex, and many of the tools that are available to understand the function of the brain are quite limited.  Although we have a good idea of the brain regions involved in producing speech, our understanding of the roles that each area plays to enable us to produce words is much less clear. Medical Research: How did you become interested in this problem?  Response: I am a basic researcher focusing on the mechanisms that enable the brain to produce complex behaviors.  We primarily study the songbird brain, which contains several clearly defined areas that are dedicated to producing the song.  Through careful study, many research groups have discovered how these areas are working together to produce the song.  I realized that this kind of perspective may be useful to further our understanding of human speech production. Medical Research: How did you translate the findings from the songbird brain to the human brain? Response: Many years ago, when I was a postdoc with Michalel Fee at MIT, I used a small head-mounted cooling device to selectively lower the temperature of specific brain regions in the songbird by a few degrees.  To our surprise and delight, the cooling of a specific brain area – called HVC – resulted in a slowing of the tempo of that song.  From this finding, we realized that HVC was a key timing center for singing, and by cooling that ‘clock’, the song that was produced happened more slowly. When I established my own lab at NYU, I reached out Dr. Matthew Howard’s Neurosurgery group at the University of Iowa because of his impressive history of making fundamental discoveries about human brain function.  There I met Dr. Jeremy Greenlee, and we discussed using a cooling approach for understanding human speech.  Since 2011, we worked with 22 patients that were undergoing neurosurgery for either epilepsy or tumor removal.  Patients were asked to recite simple lists of words, like the days of the week, while a device with a footprint about the size of a quarter would cool different places along the surface of the brain.  (more…)
Author Interviews, Epilepsy, Neurological Disorders, Stroke / 20.02.2016

MedicalResearch.com Interview with: Alexander Merkler, MD Fellow in neuro critical care Weill Cornell Medical College and New York-Presbyterian Hospital, New York Medical Research: What is the background for this study? What are the main findings? Dr. Merkler:  Patients with stroke often ask about what type of problems they may expect in the future. As neurologists, we often warm our patients about the risk for recurrent stroke, infections, clots, eating difficulty, and depression. Although seizures are a well-known complication of stroke, there was little data regarding the long-term rate of seizures in patients who have a stroke. Therefore, we sought to evaluate the long-term risk of seizures following stroke in order to better advise physicians and patients on the likelihood of developing seizures after suffering a stroke. We identified over 600,000 patients with stroke and found that the rate of seizures after stroke is high – 15.3% of all patients with stroke will develop seizures. Patients who have hemorrhagic stroke face an even higher rate of seizures – 24% of patients with hemorrhagic type stroke will develop seizures. The rate of seizures after ischemic stroke was significantly higher than previous literature - 13.5% of patients with an ischemic stroke had a seizure in our study. (more…)
Author Interviews, Brigham & Women's - Harvard, Multiple Sclerosis, Neurological Disorders, Stem Cells / 26.01.2016

MedicalResearch.com Interview with: Zhigang He, PhD, BM Professor of Neurology  and Michela Fagiolini, PhD Assistant Professor of Neurology F.M. Kirby Neurobiology Center, Department of Neurology Children’s Hospital, Harvard Medical School Boston, MA 02115, USA

Medical Research: What is the background for this study? Drs. Fagiolini and He: Brain or spinal cord injury is still a major medical problem and there is no effective treatment of promoting functional recovery. A key issue is the nerve fibers, or axons, connecting different brain regions are damaged and cannot be repaired. For example, the axons in the optic nerve are the only channels transmitting visual signals from eye to brain. If damaged, our brain will not be able to receive visual signals and be blinded. Thus, a logical therapy should be to stimulate damaged axons to regrow to the targets and reconnect the eyes and brain. Studies in the past from us and others revealed several approaches of promoting the regrowth of injured axons, but it was unknown whether these regenerated axons could form functional connections and mediate functional recovery. Medical Research: What are the main findings? Drs. Fagiolini and He:  What we discovered in this study is that these regenerated axons could form functional connections, synapses, in the brain targets, but surprisingly fail to mediate behavioral visual function recovery. In mammals, many long projecting axons are insulated by lipid-enriched myelin sheets which could significantly speed up nerve conduction and facilitate the functional coordination of different brain regions during behavior. Interestingly, we found that different from intact optic nerves, these regenerated axons fail to be myelinated and thus possess poor conductance. When we treat these mice with compounds that can improve nerve conduction, we do observe partial yet significant functional recovery. Thus, there are at least two pieces of information from this study:
  • First, axon regrowth might not enough for functional recovery, nerve conduction could be another hurdle;
  • Second, the combination of these manipulations could serve a proof-of-principle example for achieving functional recovery.
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Author Interviews, Neurological Disorders, Sleep Disorders / 19.01.2016

More on Sleep Research on MedicalResearch.com MedicalResearch.com Interview with: Dr. Andrew Lim MD, FRCPC Assistant Professor Neurology Sunnybrook Health Sciences Centre Toronto, ON Medical Research: What is the background for this study? What are the main findings? Dr. Lim: Our group had previously shown that sleep fragmentation is associated with an increased risk of dementia and cognitive decline.  However, there were gaps in what we knew about underlying brain changes that may link sleep fragmentation with these neurological outcomes.  Experiments in mice and other animals suggested that damage to blood vessels may be one potential mechanism. In this study of 315 older individuals who had their sleep measured using wrist-watch like accelerometers, we found that individuals who had the most fragmented sleep were also more likely to have more severe damage to brain blood vessels and blood-vessel related brain injury at death. (more…)
Author Interviews, JAMA, Mental Health Research, MRI, Neurological Disorders / 12.12.2015

MedicalResearch.com Interview with: Stephane De Brito, PhD Birmingham Fellow School of Psychology Robert Aitken Building, Room 337a University of Birmingham  UK Medical Research: What is the background for this study? What are the main findings? Dr. De Brito: In the last decade, an increasing number of neuroimaging studies have used structural magnetic resonance imaging (sMRI) to examine the brains of youths who show behavioural problems that include antisocial and aggressive behaviour. Those studies have mostly relied on a method called voxel-based morphometry (or VBM), which is a whole-brain and automated technique that allows researchers to objectively assess the local composition of brain tissue, such as grey matter volume. The main problem is that the findings from those sMRI studies have been quite disparate and few have been replicated, partly due to differences in sample sizes and characteristics across studies. Therefore, we set out to carry out a meta-analysis of the available data to provide a clearer account of the literature on this topic. A particular strength of our meta-analysis is that we used the original brain imaging maps (also referred to as statistical parametric maps) from 11 of the 13 studies, which makes our analysis more accurate and reliable. The final sample comprised of 394 youths with behavioural problems and 350 typically developing youths, making it the largest study on this topic to date. Our results showed that, compared to typically developing youths, those with behavioural problems show reduced grey matter volume in the amygdala, the insula, and the prefrontal cortex. These brain areas have been shown to be important for decision-making, empathic responses, processing facial expressions and emotion regulation; key cognitive and affective processes that are shown to be deficient in youths with behavioural problems. (more…)
Author Interviews, Genetic Research, Heart Disease, Neurological Disorders, NIH, Science / 05.12.2015

MedicalResearch.com Interview with: Jonathan Kaltman, MD Chief, Heart Development and Structural Diseases Branch Division of Cardiovascular Sciences National Heart, Lung, and Blood Institute Medical Research: What are the main findings? Dr. Kaltman:  Congenital heart disease (CHD) is the most common birth defect but the cause for most defects is unknown.  Surgery and clinical care of patients with congenital heart disease has improved survival but now we are learning that many patients have neurodevelopmental abnormalities, including learning disability and attention/behavioral issues. Medical Research:  What are the main findings?
  • Using exome sequencing we found that patients with  congenital heart disease have a substantial number of de novo mutations.  This finding is especially strong in patients with CHD and another structural birth defect and/or neurodevelopmental abnormalities.
  • Many of the genes identified are known to be expressed in both the heart and the brain, suggesting a single mutation may contribute to both congenital heart disease and neurodevelopmental abnormalities.
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