Network Modulation Following Sham Surgery In Parkinson's Disease,
2014
Northwell Health
Network Modulation Following Sham Surgery In Parkinson's Disease, J. H. Ko, A. Feigin, P. Mattis, C. C. Tang, Y. L. Ma, V. Dhawan, M. J. During, M. G. Kaplitt, D. Eidelberg
Journal Articles
Patient responses to placebo and sham effects are a major obstacle to the development of therapies for brain disorders, including Parkinson's disease (PD). Here, we used functional brain imaging and network analysis to study the circuitry underlying placebo effects in PD subjects randomized to sham surgery as part of a double-blind gene therapy trial. Metabolic imaging was performed prior to randomization, then again at 6 and 12 months after sham surgery. In this cohort, the sham response was associated with the expression of a distinct cerebello-limbic circuit. The expression of this network increased consistently in patients blinded to treatment and …
Quantifying Significance Of Topographical Similarities Of Disease-Related Brain Metabolic Patterns,
2014
Northwell Health
Quantifying Significance Of Topographical Similarities Of Disease-Related Brain Metabolic Patterns, J. H. Ko, P. Spetsieris, Y. L. Ma, V. Dhawan, D. Eidelberg
Journal Articles
Multivariate analytical routines have become increasingly popular in the study of cerebral function in health and in disease states. Spatial covariance analysis of functional neuroimaging data has been used to identify and validate characteristic topographies associated with specific brain disorders. Voxel-wise correlations can be used to assess similarities and differences that exist between covariance topographies. While the magnitude of the resulting topographical correlations is critical, statistical significance can be difficult to determine in the setting of large data vectors (comprised of over 100,000 voxel weights) and substantial autocorrelation effects. Here, we propose a novel method to determine the p-value of …
Characterization Of Disease-Related Covariance Topographies With Ssmpca Toolbox: Effects Of Spatial Normalization And Pet Scanners,
2014
Northwell Health
Characterization Of Disease-Related Covariance Topographies With Ssmpca Toolbox: Effects Of Spatial Normalization And Pet Scanners, S. C. Peng, Y. L. Ma, P. G. Spetsieris, P. Mattis, Andrew Feigin, V. Dhawan, D. Eidelberg
Journal Articles
To generate imaging biomarkers from disease-specific brain networks, we have implemented a general toolbox to rapidly perform scaled subprofile modeling (SSM) based on principal component analysis (PCA) on brain images of patients and normals. This SSMPCA toolbox can define spatial covariance patterns whose expression in individual subjects can discriminate patients from controls or predict behavioral measures. The technique may depend on differences in spatial normalization algorithms and brain imaging systems. We have evaluated the reproducibility of characteristic metabolic patterns generated by SSMPCA in patients with Parkinson's disease (PD). We used [F-18]fluorodeoxyglucose PET scans from patients with PD and normal controls. …
Thalamocortical Connectivity Correlates With Phenotypic Variability In Dystonia,
2014
Hofstra Northwell School of Medicine
Thalamocortical Connectivity Correlates With Phenotypic Variability In Dystonia, An Vo, W. Sako, M. Niethammer, M. Carbon, S. B. Bressman, A. M. Ulug, D. Eidelberg
Journal Articles
Dystonia is a brain disorder characterized by abnormal involuntary movements without defining neuropathological changes. The disease is often inherited as an autosomal-dominant trait with incomplete penetrance. Individuals with dystonia, whether inherited or sporadic, exhibit striking phenotypic variability, with marked differences in the somatic distribution and severity of clinical manifestations. In the current study, we used magnetic resonance diffusion tensor imaging to identify microstructural changes associated with specific limb manifestations. Functional MRI was used to localize specific limb regions within the somatosensory cortex. Microstructural integrity was preserved when assessed in subrolandic white matter regions somatotopically related to the clinically involved limbs, …
Regional Brain Metabolism In A Murine Systemic Lupus Erythematosus Model,
2014
Hofstra Northwell School of Medicine
Regional Brain Metabolism In A Murine Systemic Lupus Erythematosus Model, An Vo, B. T. Volpe, C. C. Tang, W. K. Schiffer, C. Kowal, P. T. Huerta, A. M. Ulug, S. L. Dewey, D. Eidelberg, B. Diamond
Journal Articles
Systemic lupus erythematosus (SLE) is characterized by multiorgan inflammation, neuropsychiatric disorders (NPSLE), and antinuclear antibodies. We previously identified a subset of anti-DNA antibodies (DNRAb) cross-reactive with the N-methyl-D-aspartate receptor, present in 30% to 40% of patients, able to enhance excitatory post-synaptic potentials and trigger neuronal apoptosis. DNRAb + mice exhibit memory impairment or altered fear response, depending on whether the antibody penetrates the hippocampus or amygdala. Here, we used 18F-fluorodeoxyglucose (FDG) microPET to plot changes in brain metabolism after regional blood-brain barrier (BBB) breach. In DNRAb + mice, metabolism declined at the site of BBB breach in the first 2 …
Consistent Abnormalities In Metabolic Network Activity In Idiopathic Rapid Eye Movement Sleep Behaviour Disorder,
2014
Northwell Health
Consistent Abnormalities In Metabolic Network Activity In Idiopathic Rapid Eye Movement Sleep Behaviour Disorder, P. Wu, H. Yu, S. C. Peng, Y. Dauvilliers, J. Wang, J. J. Ge, H. W. Zhang, D. Eidelberg, Y. L. Ma, C. T. Zuo
Journal Articles
Rapid eye movement sleep behaviour disorder has been evaluated using Parkinson's disease-related metabolic network. It is unknown whether this disorder is itself associated with a unique metabolic network. F-18-fluorodeoxyglucose positron emission tomography was performed in 21 patients (age 65.0 +/- 5.6 years) with idiopathic rapid eye movement sleep behaviour disorder and 21 age/gender-matched healthy control subjects (age 62.5 +/- 7.5 years) to identify a disease-related pattern and examine its evolution in 21 hemi-parkinsonian patients (age 62.6 +/- 5.0 years) and 16 moderate parkinsonian patients (age 56.9 +/- 12.2 years). We identified a rapid eye movement sleep behaviour disorder-related metabolic network …
Internal Maxillary Artery-Middle Cerebral Artery Bypass: Infratemporal Approach For Subcranial-Intracranial (Sc-Ic) Bypass,
2014
Hofstra Northwell School of Medicine
Internal Maxillary Artery-Middle Cerebral Artery Bypass: Infratemporal Approach For Subcranial-Intracranial (Sc-Ic) Bypass, E. Nossek, P. Costantino, M. Eisenberg, A. R. Dehdashti, A. Setton, D. J. Chalif, R. A. Ortiz, D. J. Langer
Journal Articles
BACKGROUND:Internal maxillary artery (IMax)-middle cerebral artery (MCA) bypass has been recently described as an alternative to cervical extracranial-intracranial bypass. This technique uses a keyhole craniectomy in the temporal fossa that requires a technically challenging end-to-side anastomosis.OBJECTIVE:To describe a lateral subtemporal craniectomy of the middle cranial fossa floor to facilitate wide exposure of the IMax to facilitate bypass.METHODS:Orbitozygomatic osteotomy is used followed by frontotemporal craniotomy and subsequently laterotemporal fossa craniectomy, reaching its medial border at a virtual line connecting the foramen rotundum and foramen ovale. The IMax was identified by using established anatomic landmarks, neuronavigation, and micro Doppler probe (Mizuho Inc. …
Intracellular Hmgb1 Inhibits Inflammatory Nucleosome Release And Limits Acute Pancreatitis In Mice,
2014
Hofstra Northwell School of Medicine
Intracellular Hmgb1 Inhibits Inflammatory Nucleosome Release And Limits Acute Pancreatitis In Mice, R. Kang, Q. Zhang, W. Hou, Z. Yan, R. Chen, J. Bonaroti, P. Bansal, T. R. Billiar, A. Tsung, Q. Wang, D. L. Bartlett, D. C. Whitcomb, E. B. Chang, X. Zhu, H. Wang, B. Lu, K. J. Tracey, L. Cao, X. G. Fan, M. T. Lotze, H. J., 3rd Zeh, D. Tang
Journal Articles
BACKGROUND & AIMS: High mobility group box 1 (HMGB1) is an abundant protein that regulates chromosome architecture and also functions as a damage-associated molecular pattern molecule. Little is known about its intracellular roles in response to tissue injury or during subsequent local and systemic inflammatory responses. We investigated the function of Hmgb1 in mice after induction of acute pancreatitis. METHODS: We utilized a Cre/LoxP system to create mice with pancreas-specific disruption in Hmbg1 (Pdx1-Cre; HMGB1(flox/flox) mice). Acute pancreatitis was induced in these mice (HMGB1(flox/flox) mice served as controls) after injection of l-arginine or cerulein. Pancreatic tissues and acinar cells were …
Gene-Based Therapies In Parkinson's Disease,
2014
Northwell Health
Gene-Based Therapies In Parkinson's Disease, P. J. Allen, A. Feigin
Journal Articles
Parkinson's disease (PD) is a progressive neurological disorder characterized primarily by the degeneration of nigrostriatal dopaminergic neurons and diminution of the neurotransmitter dopamine. Though dopamine replacement therapies such as levodopa can improve the symptoms of PD, the benefits may be overshadowed by side effects and the onset of symptoms not responsive to dopaminergic treatments (e.g., autonomic symptoms, gait and balance problems, and cognitive impairment). Furthermore, no therapies have proven to slow the neurodegenerative process. Novel approaches to address these difficult problems, and others, are being sought. Over the last decade, several innovative gene therapies for PD have entered human clinical …
Mitochondrial Dna Copy Numbers In Pyramidal Neurons Are Decreased And Mitochondrial Biogenesis Transcriptome Signaling Is Disrupted In Alzheimer’S Disease Hippocampi,
2014
Virginia Commonwealth University
Mitochondrial Dna Copy Numbers In Pyramidal Neurons Are Decreased And Mitochondrial Biogenesis Transcriptome Signaling Is Disrupted In Alzheimer’S Disease Hippocampi, Ann C. Rice, Paula M. Keeney, Norah K. Algarzae, Amy C. Ladd, Ravindar R. Thomas, James P. Bennett
Neurology Publications
Alzheimer's disease (AD) is the major cause of adult-onset dementia and is characterized in its pre-diagnostic stage by reduced cerebral cortical glucose metabolism and in later stages by reduced cortical oxygen uptake, implying reduced mitochondrial respiration. Using quantitative PCR we determined the mitochondrial DNA (mtDNA) gene copy numbers from multiple groups of 15 or 20 pyramidal neurons, GFAP(+) astrocytes and dentate granule neurons isolated using laser capture microdissection, and the relative expression of mitochondrial biogenesis (mitobiogenesis) genes in hippocampi from 10 AD and 9 control (CTL) cases. AD pyramidal but not dentate granule neurons had significantly reduced mtDNA copy numbers …
Clinical, Laboratory And Health-Related Quality Of Life Correlates Of Systemic Lupus Erythematosus Responder Index Response: A Post Hoc Analysis Of The Phase 3 Belimumab Trials,
2014
Zucker School of Medicine at Hofstra/Northwell
Clinical, Laboratory And Health-Related Quality Of Life Correlates Of Systemic Lupus Erythematosus Responder Index Response: A Post Hoc Analysis Of The Phase 3 Belimumab Trials, R. Furie, M. A. Petri, V. Strand, D. D. Gladman, Z. J. Zhong, W. W. Freimuth
Journal Articles
OBJECTIVE: Correlates of systemic lupus erythematosus (SLE) Responder Index (SRI) response with clinical trial end points were examined using pooled data from the Study of Belimumab in Subjects with SLE (BLISS) trials (N=1684). METHODS: Changes in clinical, laboratory and health-related quality of life measures from baseline at 52 weeks were compared between SRI responders (n=761) and non-responders (n=923). RESULTS: More SRI responders than non-responders had >/=4-point (100% vs 3.8%) and >/=7-point (40.3% vs 1.3%) Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index reductions, no new British Isles Lupus Assessment Group (BILAG) A and7.5 mg/d to7.5 …
Approaching The Next Revolution? Evolutionary Integration Of Neural And Immune Pathogen Sensing And Response,
2014
Hofstra Northwell School of Medicine
Approaching The Next Revolution? Evolutionary Integration Of Neural And Immune Pathogen Sensing And Response, K. J. Tracey
Journal Articles
Mammalian immunity evolved by the process of natural selection that produced differential survival and reproduction advantages through combinations of hereditary traits underlying the response to pathogens. Primitive animals sense the presence of microbial pathogens through recognition of pathogen-derived molecules in their rudimentary immune and nervous systems. No molecular biological mechanism assigns primacy of pathogen sensing mechanisms to immune cells over neurons. Rather, in animals as diverse as Caenorhabditis elegans to mammals, neural reflexes are activated by the presence of pathogens and transduce neural mechanisms that control the development of immunity. A coming revolution in immunological thinking will require immunologists to …
Central Cholinergic Activation Of A Vagus Nerve-To-Spleen Circuit Alleviates Experimental Colitis,
2014
Hofstra Northwell School of Medicine
Central Cholinergic Activation Of A Vagus Nerve-To-Spleen Circuit Alleviates Experimental Colitis, H. Ji, M. F. Rabbi, B. Labis, V. A. Pavlov, K. J. Tracey, J. E. Ghia
Journal Articles
The cholinergic anti-inflammatory pathway is an efferent vagus nerve-based mechanism that regulates immune responses and cytokine production through alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) signaling. Decreased efferent vagus nerve activity is observed in inflammatory bowel disease. We determined whether central activation of this pathway alters inflammation in mice with colitis and the mediating role of a vagus nerve-to-spleen circuit and alpha 7nAChR signaling. Two experimental models of colitis were used in C57BL/6 mice. Central cholinergic activation induced by the acetylcholinesterase inhibitor galantamine or a muscarinic acetylcholine receptor agonist treatments resulted in reduced mucosal inflammation associated with decreased major histocompatibility …
High-Mobility Group Box 1 Protein Initiates Postoperative Cognitive Decline By Engaging Bone Marrow-Derived Macrophages,
2014
Hofstra Northwell School of Medicine
High-Mobility Group Box 1 Protein Initiates Postoperative Cognitive Decline By Engaging Bone Marrow-Derived Macrophages, S. Vacas, V. Degos, K. J. Tracey, M. Maze
Journal Articles
Background: Aseptic trauma engages the innate immune response to trigger a neuroinflammatory reaction that results in postoperative cognitive decline. The authors sought to determine whether high-mobility group box 1 protein (HMGB1), an ubiquitous nucleosomal protein, initiates this process through activation and trafficking of circulating bone marrow-derived macrophages to the brain. Methods: The effects of HMGB1 on memory (using trace fear conditioning) were tested in adult C57BL/6J male mice; separate cohorts were tested after bone marrow-derived macrophages were depleted by clodrolip. The effect of anti-HMGB1 neutralizing antibody on the inflammatory and behavioral responses to tibial surgery were investigated. Results: A single …
Lymphocyte Called Home: Beta2-Adreneric Neurotransmission Confines T Cells To Lymph Nodes To Suppress Inflammation,
2014
Hofstra Northwell School of Medicine
Lymphocyte Called Home: Beta2-Adreneric Neurotransmission Confines T Cells To Lymph Nodes To Suppress Inflammation, K J. Tracey
Journal Articles
No abstract provided.
Mapping Human Brain Networks With Cortico-Cortical Evoked Potentials,
2014
Northwell Researcher
Mapping Human Brain Networks With Cortico-Cortical Evoked Potentials, C. J. Keller, C. J. Honey, P. Megevand, L. Entz, I. Ulbert, A. D. Mehta
Journal Articles
The cerebral cortex forms a sheet of neurons organized into a network of interconnected modules that is highly expanded in humans and presumably enables our most refined sensory and cognitive abilities. The links of this network form a fundamental aspect of its organization, and a great deal of research is focusing on understanding how information flows within and between different regions. However, an often-overlooked element of this connectivity regards a causal, hierarchical structure of regions, whereby certain nodes of the cortical network may exert greater influence over the others. While this is difficult to ascertain non-invasively, patients undergoing invasive electrode …
Nanocomposite Scaffold For Chondrocyte Growth And Cartilage Tissue Engineering: Effects Of Carbon Nanotube Surface Functionalization,
2014
Hofstra Northwell School of Medicine
Nanocomposite Scaffold For Chondrocyte Growth And Cartilage Tissue Engineering: Effects Of Carbon Nanotube Surface Functionalization, N. O. Chahine, N. M. Collette, C. B. Thomas, D. C. Genetos, G. G. Loots
Journal Articles
The goal of this study was to assess the long-term biocompatibility of single-wall carbon nanotubes (SWNTs) for tissue engineering of articular cartilage. We hypothesized that SWNT nanocomposite scaffolds in cartilage tissue engineering can provide an improved molecular-sized substrate for stimulation of chondrocyte growth, as well as structural reinforcement of the scaffold's mechanical properties. The effect of SWNT surface functionalization (-COOH or -PEG) on chondrocyte viability and biochemical matrix deposition was examined in two-dimensional cultures, in three-dimensional (3D) pellet cultures, and in a 3D nanocomposite scaffold consisting of hydrogels + SWNTs. Outcome measures included cell viability, histological and SEM evaluation, GAG …
Targeting A Heterogeneous Tumor: The Promise Of The Interleukin-13 Receptor Alpha2,
2014
Hofstra Northwell School of Medicine
Targeting A Heterogeneous Tumor: The Promise Of The Interleukin-13 Receptor Alpha2, I. Bodhinayake, M. Ottenhausen, J. A. Boockvar
Journal Articles
No abstract provided.
Transcranial Magnetic Stimulation Across The Menstrual Cycle: What Do Hormones Have To Do With It?,
2014
Hofstra Northwell School of Medicine
Transcranial Magnetic Stimulation Across The Menstrual Cycle: What Do Hormones Have To Do With It?, C. L. Harden
Journal Articles
No abstract provided.
Medical Management With Or Without Interventional Therapy For Unruptured Brain Arteriovenous Malformations (Aruba): A Multicentre, Non-Blinded, Randomised Trial,
2014
Hofstra Northwell School of Medicine
Medical Management With Or Without Interventional Therapy For Unruptured Brain Arteriovenous Malformations (Aruba): A Multicentre, Non-Blinded, Randomised Trial, J. P. Mohr, M. K. Parides, C. Stapf, E. Moquete, C. S. Moy, J. R. Overbey, R. A. S. Salman, E. Vicaut, R. Libman, Aruba Investigators Int, +12 Additional Authors
Journal Articles
Background The clinical benefit of preventive eradication of unruptured brain arteriovenous malformations remains uncertain. A Randomised trial of Unruptured Brain Arteriovenous malformations (ARUBA) aims to compare the risk of death and symptomatic stroke in patients with an unruptured brain arteriovenous malformation who are allocated to either medical management alone or medical management with interventional therapy. Methods Adult patients (>= 18 years) with an unruptured brain arteriovenous malformation were enrolled into this trial at 39 clinical sites in nine countries. Patients were randomised (by web-based system, in a 1: 1 ratio, with random permuted block design [block size 2, 4, …
