Medical Sciences Commons^™

Magneto-Electric Nano-Particles For Non-Invasive Brain Stimulation, Kun Yue, Rakesh Guduru, Jeongmin Hong, Ping Liang, Madhavan Nair, Sakhrat Khizroev

Sakhrat Khizroev

This paper for the first time discusses a computational study of using magneto-electric (ME) nanoparticles to artificially stimulate the neural activity deep in the brain. The new technology provides a unique way to couple electric signals in the neural network to the magnetic dipoles in the nanoparticles with the purpose to enable a non-invasive approach. Simulations of the effect of ME nanoparticles for non-invasively stimulating the brain of a patient with Parkinson’s Disease to bring the pulsed sequences of the electric field to the levels comparable to those of healthy people show that the optimized values for the concentration of …

Brain Structure In Pediatric Tourette Syndrome, Alton C. Williams, Kevin J. Black

Kevin J. Black, MD

Mechanisms Of Action Of Antiseizure Drugs And The Ketogenic Diet., Michael Rogawski, Jong Rho, Wolfgang Löscher

Michael A. Rogawski

Cetaceans And Primates: Convergence In Intelligence And Self-Awareness, Lori Marino

Lori Marino, PhD

Cetaceans (dolphins, porpoises and whales) have been of greatest interest to the astrobiology community and to those interested in consciousness and selfawareness in animals. This interest has grown primarily from knowledge of the intelligence, language and large complex brains that many cetaceans possess. The study of cetacean and primate brain evolution and cognition can inform us about the contingencies and parameters associated with the evolution of complex intelligence in general, and, the evolution of consciousness. Striking differences in cortical organization in the brains of cetaceans and primates along with shared cognitive capacities such as self-awareness, culture, and symbolic concept comprehension, …

Therapeutic Medical Hypothermia--A Multispecialty Approach, Sudip Nanda, Nainesh Patel, Surya Bhatt, Claranne Mathiesen, John Castaldo, Shree Sharma, Santo Longo

Nainesh C Patel MD

No abstract provided.

A Pilot Study Of Basal Ganglia And Thalamus Structure By High Dimensional Mapping In Children With Tourette Syndrome, Alton C. Williams, Marie E. Mcneely, Deanna J. Greene, Jessica A. Church, Stacie L. Warren, Johanna M. Hartlein, Bradley L. Schlaggar, Kevin J. Black, Lei Wang

Kevin J. Black, MD

No abstract provided.

Hippocampal Functional Connectivity Patterns During Spatial Working Memory Differ In Right Versus Left Temporal Lobe Epilepsy., Gaelle Eve Doucet, Karol Osipowicz, Ashwini Sharan Md, Michael R Sperling, Joseph I Tracy

Gaelle Eve Doucet

Temporal lobe epilepsy (TLE), affecting the medial temporal lobe, is a disorder that affects not just episodic memory but also working memory (WM). However, the exact nature of hippocampal-related network activity in visuospatial WM remains unclear. To clarify this, we utilized a functional connectivity (FC) methodology to investigate hippocampal network involvement during the encoding phase of a functional magnetic resonance imaging (fMRI) visuospatial WM task in right and left TLE patients. Specifically, we assessed the relation between FC within right and left hippocampus-seeded networks, and patient performance (rate of correct responses) during the encoding phase of a block span WM …

Perampanel Inhibition Of Ampa Receptor Currents In Cultured Hippocampal Neurons, Chao-Yin Chen, Lucas Matt, Johannes Hell, Michael Rogawski

Michael A. Rogawski

Perampanel is an aryl substituted 2-pyridone AMPA receptor antagonist that was recently approved as a treatment for epilepsy. The drug potently inhibits AMPA receptor responses but the mode of block has not been characterized. Here the action of perampanel on AMPA receptors was investigated by whole-cell voltage-clamp recording in cultured rat hippocampal neurons. Perampanel caused a slow (τ~1 s at 3 µM), concentration-dependent inhibition of AMPA receptor currents evoked by AMPA and kainate. The rates of block and unblock of AMPA receptor currents were 1.5×105 M−1 s−1 and 0.58 s−1, respectively. Perampanel did not affect NMDA receptor currents. The extent …

Ihome: Ipad Application For Stoke Rehab At Home, Gustavo Saposnik

Gustavo Saposnik

No abstract provided.

Pediatric Super-Refractory Status Epilepticus Treated With Allopregnanolone, Eileen Broomall, Joanne Natale, Michele Grimason, Joshua Goldstein, Craig Smith, Celia Chang, Stephen Kanes, Michael Rogawski, Mark Wainwright

Michael A. Rogawski

Super-refractory status epilepticus is a life-threatening condition. Resistance to benzodiazepine and barbiturate treatment for this disorder is thought to be due to internalization of synaptic GABA-A receptors, and withdrawal of benzodiazepines and barbiturates during treatment often triggers seizure recurrence. The neurosteroid allopregnanolone acts as a positive allosteric modulator of synaptic and extrasynaptic GABA-A receptors. Here we describe the use of allopregnanolone in two pediatric patients with super-refractory status epilepticus. This treatment allowed the general anesthetic infusions to be weaned with resolution of status epilepticus. This is the first report of allopregnanolone use to treat status epilepticus in children.

Anticonvulsant Potencies Of The Enantiomers Of The Neurosteroids Androsterone And Etiocholanolone Exceed Those Of The Natural Forms, Dorota Zolkowska, Ashish Dhir, Kathiresan Krishnan, Douglas F. Covey, Michael A. Rogawski

Michael A. Rogawski

RATIONALE: Androsterone [(3α,5α)-3-hydroxyandrostan-17-one; 5α,3α-A] and its 5β-epimer etiocholanolone [(3α,5β)-3-hydroxyandrostan-17-one; 5β,3α-A)], the major excreted metabolites of testosterone, are neurosteroid positive modulators of GABA-A receptors. Such neurosteroids typically show enantioselectivity in which the natural form is more potent than the corresponding unnatural enantiomer. For 5α,3α-A and 5β,3α-A, the unnatural enantiomers are more potent at GABA-A receptors than the natural forms. OBJECTIVES: The aim of this study was to compare the anticonvulsant potencies and time courses of 5α,3α-A and 5β,3α-A with their enantiomers in mouse seizure models. METHODS: Steroids were administered intraperitoneally to male NIH Swiss mice 15 min (or up to 6 …

Proconvulsant Actions Of Intrahippocampal Botulinum Neurotoxin B In The Rat, Sonja Bröer, Dorota Zolkowska, Manuela Gernert, Michael A. Rogawski

Michael A. Rogawski

Botulinum neurotoxins (BoNTs) may affect the excitability of brain circuits by inhibiting neurotransmitter release at central synapses. There is evidence that local delivery of BoNT serotypes A and E, which target synaptosomal-associated protein 25, a component of the release machinery specific to excitatory synapses, can inhibit seizure generation. BoNT serotype B (BoNT/B) targets VAMP2, which is expressed in both excitatory and inhibitory terminals. Here we assessed the effects of unilateral intrahippocampal infusion of BoNT/B in the rat on intravenous pentylenetetrazol (PTZ) seizure thresholds, and on the expression of spontaneous behavioral and electrographic seizures. Infusion of BoNT/B (500 and 1000 Unit) …

Plasma Apolipoprotein E And Alzheimer Disease Risk: The Aibl Study Of Aging, Veer Bala Gupta, Simon Laws, Victor Villemagne, David Ames, Ashley Bush, Kathryn Ellis, James Lui, Colin Masters, Christopher Rowe, Cassandra Szoeke, Kevin Taddei, Ralph Martins

Simon Laws

Objective: There is mounting evidence for the contribution of apoE to the pathophysiology of Alzheimer disease (AD). Studies also indicate that plasma apoE levels may reflect disease status, suggesting that apoE is a potential AD biomarker. However, while some studies of apoE levels in plasma have presented correlations with AD pathology, others have not. Thus, there is a lack of consensus as to the suitability of plasma apoE as an AD biomarker. The major objective of this cross-sectional study was to investigate total plasma apoE as well as levels of the apoE4 form in a large, highly characterized cohort which …

Associatioin Of Plasma Aβ Peptides With Blood Pressure In The Elderly, Jean-Charles Lambert, Jean Dallongeville, Kathryn A. Ellis, Susanna Schraen-Maschke, James Lui, Simon Laws, Julie Dumont, Florence Richard, Dominque Cottel, Claudine Berr, David Ames, Colin L. Masters, Christopher C. Rowe, Cassandra Szoeke, Christophe Tzourio, Jean-Francois Dartigues, Luc Buee, Ralph Martins, Philippe Amouyel

Simon Laws

Background Aß peptides are often considered as catabolic by-products of the amyloid ß protein precursor (APP), with unknown physiological functions. However, several biological properties have been tentatively attributed to these peptides, including a role in vasomotion. We assess whether plasma Aß peptide levels might be associated with systolic and diastolic blood pressure values (SBP and DBP, respectively). Methodology/Principal Findings Plasma Aß1-40 and Aß1-42 levels were measured using an xMAP-based assay in 1,972 individuals (none of whom were taking antihypertensive drugs) from 3 independent studies: the French population-based 3C and MONA-LISA (Lille) studies (n = 627 and n = 769, respectively) …

Epilepsy Therapy Development: Technical And Methodologic Issues In Studies With Animal Models, Aristea S. Galanopoulou, Merab Kokaia, Jeffrey A. Loeb, Astrid Nehlig, Asla Pitkanen, Michael A. Rogawski, Kevin J. Staley, Vicky H. Whittemore, F. Edward Dudek

Michael A. Rogawski

The search for new treatments for seizures, epilepsies, and their comorbidities faces considerable challenges. This is due in part to gaps in our understanding of the etiology and pathophysiology of most forms of epilepsy. An additional challenge is the difficulty in predicting the efficacy, tolerability, and impact of potential new treatments on epilepsies and comorbidities in humans, using the available resources. Herein we provide a summary of the discussions and proposals of the Working Group 2 as presented in the Joint American Epilepsy Society and International League Against Epilepsy Translational Workshop in London (September 2012). We propose methodologic and reporting …

Towards Objectively Quantifying Sensory Hypersensitivity: A Pilot Study Of The “Ariana Effect.”, Vassilis N. Panagopoulos, Deanna J. Greene, Meghan C. Campbell, Kevin J. Black

Kevin J. Black, MD

Background. Normally one habituates rapidly to steady, faint sensations. People with sensory hypersensitivity (SH), by contrast, continue to attend to such stimuli and find them noxious. SH is common in Tourette syndrome (TS) and autism, and methods to quantify SH may lead to better understanding of these disorders. In an attempt to objectively quantify SH severity, the authors tested whether a choice reaction time (CRT) task was a sensitive enough measure to detect significant distraction from a steady tactile stimulus, and to detect significantly greater distraction in subjects with more severe SH.

Methods. Nineteen ambulatory adult volunteers with varying scores …

Encephalopathy Caused By Bartonella Henselae Following Cat Scratch, Joseph L. Yozviak Do, Facp, John Margraf Md, Marcelo Gareca Md

Joseph L Yozviak DO, FACP

No abstract provided.

Neuroactive Steroids For The Treatment Of Status Epilepticus, Michael Rogawski, Carlos Loya, Kiran Reddy, Dorota Zolkowski, Christoph Lossin

Michael A. Rogawski

Benzodiazepines are the current first-line standard-of-care treatment for status epilepticus but fail to terminate seizures in about one third of cases. Synaptic GABA-A receptors, which mediate phasic inhibition in central circuits, are the molecular target of benzodiazepines. As status epilepticus progresses, these receptors are internalized and become functionally inactivated, conferring benzodiazepine resistance, which is believed to be a major cause of treatment failure. GABA-A receptor positive allosteric modulator neuroactive steroids, such as allopregnanolone, also potentiate synaptic GABA-A receptors, but in addition they enhance extrasynaptic GABA-A receptors that mediate tonic inhibition. Extrasynaptic GABA-A receptors are not internalized, and desensitization of these …

The Intrinsic Severity Hypothesis Of Pharmacoresistance To Antiepileptic Drugs, Michael Rogawski

Michael A. Rogawski

Pharmacoresistance to antiepileptic drugs (AEDs) is a barrier to seizure freedom for many persons with epilepsy. For nearly two decades, pharmacoresistance has been framed in terms of factors affecting the access of AEDs to their molecular targets in the brain or the actions of the drugs on these targets. Shortcomings in this prevailing view led to the formulation of the intrinsic severity hypothesis of pharmacoresistance to AEDs, which is based on the recognition that there are neurobiologic factors that confer phenotypic variation among individuals with etiologically similar forms of epilepsy and postulates that more severe epilepsy is more difficult to …

Gene And Stem Cell Therapies For Treating Epilepsy., Janice Naegele, Xu Maisano

Janice R Naegele

No abstract provided.

Malignant Peripheral Nerve Sheath Tumor (Mpnst): An Overview With Emphasis On Pathology, Imaging And Management Strategies., Timothy C. Beer

Timothy C Beer

MPNSTs are rare malignancies that are classically associated with pre-existing plexiform neurofibromas in neurofibromatosis type 1 (NF-1) patients, but also occur in association with radiation as well as sporadically in patients with no known risk factors. The typical presentation of sporadic MPNST is a new painless enlarging mass. The typical presentation of MPNST in an NF-1 patient is rapid enlargement or new onset of pain associated with a pre-existing plexiform neurofibroma. Although both MPNST and benign neurofibromas share in common the absence of neurofibromin function due to loss of both NF-1 alleles, malignant transformation to MPNST requires several additional aberrations, …

Multi-Scale Modeling Of Angiotensin Ii Induced Neuronal Regulatory Mechanisms In The Brain, Rajanikanth Vadigepalli

Rajanikanth Vadigepalli

Poster Presentation.

Ab Deposition In Idiopathic And Dup15q11.2-Q13 Autism Spectrum Disorders, J Wegiel, Janusz Frackowiak, Bozena Mazur-Kolecka, N Carolyn Schanen, Edwin H. Cook Jr, Marian Sigman, Ted Brown, Izabela Kuchna, Jarek Wegiel, Krzysztof Nowicki, Humi Imaki, Shuang Yong Ma, Abha Chauhan, Ved Chauhan, David L. Miller, Pankaj D. Mehta, Michael Flory, Ira L. Cohen, Eric London, Barry Reisberg, Mony J. De Leon, Thomas Wisnieski

N C Schanen

Background: It has been shown that amyloid ß (Ab), a product of proteolytic cleavage of the amyloid b precursor protein (APP), accumulates in neuronal cytoplasm in non-affected individuals in a cell type–specific amount.

Methodology/Principal Findings: In the present study, we found that the percentage of amyloid-positive neurons increases in subjects diagnosed with idiopathic autism and subjects diagnosed with duplication 15q11.2-q13 (dup15) and autism spectrum disorder (ASD). In spite of interindividual differences within each examined group, levels of intraneuronal Ab load were significantly greater in the dup(15) autism group than in either the control or the idiopathic autism group in 11 …

Sudden Infant Death Syndrome: Postulated Role Of Impaired Vasoactive Neuropeptide-Related Inflammatory Modulation, Donald Staines, Ekua Brenu, Sonya Marshall-Gradisnik

Sonya Marshall-Gradisnik

Sudden infant death syndrome (SIDS) has been extensively investigated in the context of infection as a contributing factor in the death of otherwise apparently healthy infants. A number of infectious agents have been implicated suggesting the causal pathomechanism is related to infection, but not necessarily solely attributable to any one type of infection. An alternative provocative hypothesis is that of post-infection autoimmunity affecting critical novel neurotransmitters of the vasoactive neuropeptide family. Their role in respiratory and cardiac functioning together with novel hypotheses postulating their autoimmune compromise may suggest a role in SIDS etiology following infection. Animal models demonstrate their vital …

Learning From Mistakes: Improving Initial Fingertip Force Scaling By Observing Lifting Errors, Gavin Buckingham, Minnie Tang, Paul Gribble, Melvyn Goodale

Gavin Buckingham

• When lifting objects that are lighter or heaver than we expect them to be, individuals typically misapply forces in a way that reflects their prior expectations of heaviness.

• Because we lift in this predictive way, large and small cubes elicit these characteristic errors even when they are adjusted to have equal mass. Lifters will apply too much force to a large cube and substantially less force to a small cube – errors that are rapidly corrected with repeated lifts (Flanagan & Beltzner, 2000).

• When watching others lift objects, an observer’s motor system automatically reacts in a way …

Lifting Without Seeing: The Role Of Vision In Perceiving And Acting Upon The Size‐Weight Illusion, Gavin Buckingham, Melvyn Goodale

Gavin Buckingham

Our expectations of an object’s heaviness not only drive our fingertip forces, but also our perception of heaviness. This effect is highlighted by the classic size-weight illusion (SWI), where different‐sized objects of identical mass feel different weights (Charpentier, 1891) long after any initial errors in the application of fingertip forces have been corrected (Flanagan & Beltzner, 2000).

Here, we examined whether our expectations about the weight of an upcoming lift are sufficient to induce the SWI in a single wooden cube when lifted without visual feedback, by varying the size of the object seen prior to the lift during a …

Laterality, Perception, And Action During The Size-Weight Illusion, Gavin Buckingham, Nathalie Ranger, Melvyn Goodale

Gavin Buckingham

In the classic size-weight illusion (SWI), a small object will feel heavier than an larger object of equal weight (Charpentier, 1891). Individuals continue to perceive this illusory difference in weight long after their gripping and lifting forces have scaled to the actual, identical, mass of the illusion-inducing stimuli (Flanagan & Beltzner, 2000).

The independence of our weight perception and fingertip force application has only been quantified in the right hand of right-handers. The immunity to this perceptual illusion may be affected by manual asymmetries (e.g., Gonzalez, Ganel & Goodale, 2006).

We examined perception of heaviness and fingertip force scaling in …

Modeling Brain Tumors Using Avian Retroviral Gene Transfer, Tod D. Holland, Eric C. Holland

Tod D Holland

RCAS/tv-a is a system for post-natal cell type specific gene transfer. It is used for the modeling of gliomas and medulloblastomas. This system provides a combination of lineage tracing from the cell origin with oncogenesis induced by mis-expression of specific genes. The genes that are most potent at inducing tumors are those that encode components of signal transduction and undifferentiated cells are most capable of serving as the cell of origin. The system effectively generates tumors with the histologic characteristics of human disease. Mice bearing RVAS/tv-a induced brain tumors are currently being used for preclinical trials to understand the biology …

Gender Differences In Presenting And Prodromal Stroke Symptoms, Eileen Stuart-Shor, Gregory A. Wellenius, Donna Dello Iacono, Murray A. Mittleman

Eileen Stuart-Shor

BACKGROUND AND PURPOSE: Prompt recognition of stroke symptoms is critical to timely treatment and women have increased delay to treatment. Women may be more likely to present with atypical symptoms, but this hypothesis has not been extensively evaluated.

METHODS: We examined gender differences in the prevalence of presenting and prodromal stroke symptoms among 1107 consecutive patients hospitalized with neurologist-confirmed acute ischemic stroke. Patient demographics, clinical variables, and stroke symptoms were abstracted from medical records by trained abstractors using standardized forms. Estimates were age-standardized to the age distribution of men and women combined. Presenting symptoms occurred within 24 hours of incident …

A Dissociation Between Perception And Action In The Material‐Weight Illusion, Gavin Buckingham, Jonathan Cant, Kai-Ling Kao, Melvyn Goodale

Gavin Buckingham

We examined what forces are applied to objects that elicit this illusion when they are lifted.We predicted that:

(1) Forces on early trials will scale to each participant’s expectations of how much a particular block will weigh ‐ excessive force will be applied to the metal block and insufficient force applied to the polystyrene block.

(2) Forces on later trials will scale to the real weight of each block ‐ identical levels of force applied to all the blocks.

(3) MWI will persist throughout ‐ polystyrene block will feel the heaviest, metal block will feel the lightest.