Weakening Neural Connections Can Eliminate Fearful Memories

MedicalResearch.com Interview with:

Jun-Hyeong Cho MD PhD Department of Molecular, Cell and Systems Biology University of California, Riverside Riverside, CA 92521

Dr. Jun-Hyeong Cho

Jun-Hyeong Cho MD PhD
Department of Molecular, Cell and Systems Biology
University of California, Riverside
Riverside, CA 92521

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: To survive in a dynamic environment, animals develop fear responses to dangerous situations. For these adaptive fear responses to be developed, the brain must discriminate between different sensory cues and associate only relevant stimuli with aversive events.

In our current study, we investigated the neural mechanism how the brain does this, using a mouse model of fear learning and memory. Our study demonstrates that the formation of fear memory associated with an auditory cue requires selective synaptic strengthening in neural pathways that convey the auditory signals to the amygdala, an essential brain area for fear learning and memory.

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Refined Deep Brain Stimulation Turns On ‘As Needed’ To Treat Tremors

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

Prof. Chizeck

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.

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Extended-Release Amantadine Reduces Dyskinesia in Parkinson’s Disease

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).

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Neural Tube Defects in Infants Share Molecular Processes With Neurodegenerative Diseases

MedicalResearch.com Interview with:

Zhiyong Zhao, Ph.D. Associate Professor Department of Obstetrics, Gynecology & Reproductive Sciences University of Maryland School of Medicine Baltimore, MD

Dr. Zhiyong Zhao

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.

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Nasal Spray of Stem Cell Vesicles First Step Toward Treating Brain Diseases

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

Dr. Prockop

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.

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White Matter Trajectories Diverge In Children After Traumatic Brain Injury

MedicalResearch.com Interview with:

Emily Dennis Postdoctoral Scholar Imaging Genetics Center Mark and Mary Stevens Neuroimaging and Informatics Institute USC

Emily Dennis

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.

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Reward Circuit in Brain Localized To Central Amygdala

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.

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Excessive Sleeping May Be Early Marker of Dementia

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

Dr. Matthew Pase

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.
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Human Genetics Contributes To Zika-Induced Brain Damage

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

Dr. Ping Wu

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.

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Brain-Reward Circuit Both Under and Over Responsive in Addiction and Gambling

MedicalResearch.com Interview with:

Guillaume Sescousse, PhD Senior post-doc Donders Centre for Cognitive Neuroimaging The Netherlands

Dr. Guillaume Sescousse

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.

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Stuttering Linked To Decreased Blood Flow to Broca’s Area in Brain

MedicalResearch.com Interview with:

Jay Desai, M.D. Neurologist, Children’s Hospital Los Angeles Assistant Professor, Keck School of Medicine of USC

Dr. Jay Desai

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.

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Non-Invasive Interface Allows Subjects To Control Objects With Just Thoughts

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

Dr. Bin He

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.

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Neuroactive Steroids Evoke Inhibition Through Protein Kinase C Mechanism

MedicalResearch.com Interview with:

Dr. Paul Davies PhD Tufts University School of Medicine Department of Neuroscience Boston, MA 02111

Dr. Paul Davies

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.

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God Activates Reward Centers In Brain

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

Dr. Jeffrey S. Anderson

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.
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New Imaging Technology Can Measure Potential for Vision Loss in Neurofibromatosis

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

Dr. Marius George Linguraru

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.

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Deep Brain Stimulation Improves Parkinson’s Symptoms In Some Patients With SPG 11 Mutations

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

Dr. Adolfo Ramirez Zamora

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.

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Brain Network Connected To Consciousness and Awareness Identified

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

Dr. Michael Fox

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.

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How Does Consciousness Emerge From Brain’s Neural Network?

MedicalResearch.com Interview with:

Researchers suggest that there are unique areas in the brain’s neuronal network that can serve as the conscious complex of the brain, enabling conscious activity

Researchers suggest that there are unique areas in the brain’s neuronal network that can serve as the conscious complex of the brain, enabling conscious activity. Credit: Nir Lahav,     Eti Ben Simon

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.

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Missing Hand Persists in Brain Decades After Amputation

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.
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Thymectomy A Rational Choice For Some Patients With Myasthenia Gravis

MedicalResearch.com Interview with:

Photograph: Douglas Levere

Dr. Gil Wolfe

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.

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Human Brains, Because of Size, More Prone to Disconnection Syndromes

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 --

Dr. Zoltan Toroczkai

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.

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Small Molecule Shows Therapeutic Potential in Huntington’s Disease Model

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

Dr. Aleksey Kazantsev

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.

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Prolonged Antibiotic Therapy May Impact Brain Function

MedicalResearch.com Interview with:

Susanne Asu Wolf PhD Max-Delbrueck-Center for Molecular Medicine Berlin, Germany

Dr. Susanne Asu Wolf

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.

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Does the Brain Generate or Passively Transmit Thoughts?

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

Dr. Ezequiel Morsella

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.

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Rather Than Inhibiting Regrowth, Spinal Cord Scars May Support Nerve Healing

MedicalResearch.com Interview with:

Dr. Michael V. Sofroniew, MD PhD Professor of Neurobiology David Geffen School of Medicine UCLA

Dr. Michael Sofroniew

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.  Continue reading