Neurosciences Commons^™

Iron Dysregulation And Inflammation In Alzheimer’S Disease, Shino D. Magaki

Loma Linda University Electronic Theses, Dissertations & Projects

Alzheimer’s disease (AD) is the most common form of senile dementia in the US and worldwide but the causes of its pathogenesis are currently unknown. In this study, we examined two processes that have been implicated in the early stages of AD and other forms of neurodegeneration, iron dysregulation and inflammation, both of which can promote the increased production of amyloid precursor protein (APP). We have measured different pools of brain iron in transgenic iron regulatory protein 2 knockout (IRP2-/-) mice in the early stages of neurodegeneration and in affected brain regions from AD patients at different stages of the …

Relevance To Self: A Brief Review And Framework Of Neural Systems Underlying Appraisal, Taylor W. Schmitz, Sterling C. Johnson

Brain and Mind Institute Researchers' Publications

We argue that many similar findings observed in cognitive, affective, and social neuroimaging research may compose larger processes central to generating self-relevance. In support of this, recent findings from these research domains were reviewed to identify common systemic activation patterns. Superimposition of these patterns revealed evidence for large-scale supramodal processes, which are argued to mediate appraisal of self-relevant content irrespective of specific stimulus types (e.g. words, pictures) and task domains (e.g. induction of reward, fear, pain, etc.). Furthermore, we distinguish between two top-down sub-systems involved in appraisal of self-relevance, one that orients pre-attentive biasing information (e.g. anticipatory or mnemonic) to …

Restraint-Induced Corticosterone Secretion And Hypothalamic Crh Mrna Expression Are Augmented During Acute Withdrawal From Chronic Cocaine Administration, John R. Mantsch, Sarah Taves, Tayyiba Khan, Eric S. Katz, Tanveer Sajan, Lee C. Tang, William E. Cullinan, Dana R. Ziegler

Biomedical Sciences Faculty Research and Publications

Stress responses during cocaine withdrawal likely contribute to drug relapse and may be intensified as a consequence of prior cocaine use. The present study examined changes in stressor-induced activation of the hypothalamic–pituitary–adrenal (HPA) axis during acute withdrawal from chronic cocaine administration. Adult male Sprague–Dawley rats received daily administration of cocaine (30 mg/kg, i.p.) or saline for 14 days. Twenty-four hours after the last injection, rats in each group were sacrificed under stress-free conditions or following 30 min of immobilization. Plasma corticosterone (CORT) was measured in trunk-blood using radioimmunoassay, corticotropin-releasing hormone (CRH) mRNA levels in the paraventricularnucleus (PVN) of the hypothalamus …

Perceptual Functions Of Perirhinal Cortex In Rats: Zero-Delay Object Recognition And Simultaneous Oddity Discriminations., Susan J Bartko, Boyer D Winters, Rosemary A Cowell, Lisa M Saksida, Timothy J Bussey

Brain and Mind Institute Researchers' Publications

The perirhinal cortex (PRh) is widely accepted as having an important role in object recognition memory in humans and animals. Contrary to claims that PRh mediates declarative memory exclusively, previous evidence suggests that PRh has a role in the perceptual processing of complex objects. In the present study, we conducted an examination of the possible role of PRh in perceptual function in rats. We examined whether bilateral excitotoxic lesions of PRh or PPRh (perirhinal plus postrhinal cortices) in the rat would cause deficits in a zero-delay object-recognition task and a simultaneous oddity discrimination task. Both of these tasks measured spontaneous …

Genetic Factors In Preschool Executive Control: Relations Between Serotonin Genotype, Working Memory, And Set Shifting, S. A. Wiebe, M. Y. Chang, A. R. Johnson, J. Huggenvik, T. Jameson, K. A. Espy

Developmental Cognitive Neuroscience Laboratory: Faculty Publications

No abstract provided.

Retroviral Vector And Cell-Based Assay For Measuring The Mutation Rate Of Retroviruses Employing Same, Dawn P. Wooley, Kelly Jo Huang

Neuroscience, Cell Biology & Physiology Faculty Publications

Lentiviral-based retrovirus vectors and an in vivo mutation rate assay employing them. More particularly, an assay for directly determining the in vivo mutation rate of HIV-1.

Is Gene Therapy A Good Therapeutic Approach For Hiv-Positive Patients?, Jai G. Marathe, Dawn P. Wooley

Neuroscience, Cell Biology & Physiology Faculty Publications

Despite advances and options available in gene therapy for HIV-1 infection, its application in the clinical setting has been challenging. Although published data from HIV-1 clinical trials show safety and proof of principle for gene therapy, positive clinical outcomes for infected patients have yet to be demonstrated. The cause for this slow progress may arise from the fact that HIV is a complex multi-organ system infection. There is uncertainty regarding the types of cells to target by gene therapy and there are issues regarding insufficient transduction of cells and long-term expression. This paper discusses state-of-the-art molecular approaches against HIV-1 and …

Genes And Behavior In Preschool Children: The Relation Between Dopamine Genotype And Latent Executive Control, S. A. Wiebe, M. J. Moehr, A. R. Johnson, M. Y. Chang, J. Huggenvik, T. Jameson, K. A. Espy

Developmental Cognitive Neuroscience Laboratory: Faculty Publications

Objective: Dopaminergic neurotransmission is implicated in the executive control of cognition and behavior (Braver & Cohen, 2000). Presence or absence of particular dopamine gene alleles relates to executive control performance (Casey, 2002; Roesch-Ely, 2005) and to attention problems and ADHD (Durston, 2005; Schmidt, 2001). The present study examined the relation between dopamine genotype and executive control in normally-developing preschool children. Participants and Methods: The sample included 133 children (66 girls; mean age 4 years, range 2;2-6 years). Children completed a battery of executive control tasks, and were genotyped for 4 dopamine genes: the dopamine receptors DRD2 and DRD4, the dopamine …

Β-N-Methylamino-L-Alanine Enhances Neurotoxicity Through Multiple Mechanisms, Doug Lobner, Peachy Mae T. Piana, Abed K. Salous, Robert W. Peoples

Biomedical Sciences Faculty Research and Publications

The idea that the environmental toxin β-N-methylamino-l-alanine (BMAA) is involved in neurodegenerative diseases on Guam has risen and fallen over the years. The theory has gained greater interest with recent reports that BMAA is biomagnified, is widely distributed around the planet, and is present in the brains of Alzheimer's patients in Canada. We provide two important new findings. First, we show that BMAA at concentrations as low as 10 μM can potentiate neuronal injury induced by other insults. This is the first evidence that BMAA at concentrations below the mM range can enhance death of cortical neurons and …

Anosognosia In Mild Cognitive Impairment: Relationship To Activation Of Cortical Midline Structures Involved In Self-Appraisal, Michele L. Ries, Britta M. Jabbar, Taylor W. Schmitz, Mehul A. Trivedi, Carey E. Gleason, Cynthia M. Carlsson, Howard A. Rowley, Sanjay Asthana, Sterling C. Johnson

Brain and Mind Institute Researchers' Publications

Awareness of cognitive dysfunction shown by individuals with Mild Cognitive Impairment (MCI), a condition conferring risk for Alzheimer's disease (AD), is variable. Anosognosia, or unawareness of loss of function, is beginning to be recognized as an important clinical symptom of MCI. However, little is known about the brain substrates underlying this symptom. We hypothesized that MCI participants' activation of cortical midline structures (CMS) during self-appraisal would covary with level of insight into cognitive difficulties (indexed by a discrepancy score between patient and informant ratings of cognitive decline in each MCI participant). To address this hypothesis, we first compared 16 MCI …

Atypical Antipsychotics And Cognitive Enhancement In Schizophrenia: The Current Status, Amresh Srivastava

Psychiatry Presentations

No abstract provided.

Cognition As An Outcome Measure In Schizophrenia, Amresh Srivastava

Psychiatry Presentations

No abstract provided.

Exploration Of Computational Methods For Classification Of Movement Intention During Human Voluntary Movement From Single Trial Eeg, Ou Bai, Peter Lin, Sherry Vorbach, Jiang Li, Steve Furlani, Mark Hallett

Electrical & Computer Engineering Faculty Publications

Objective: To explore effective combinations of computational methods for the prediction of movement intention preceding the production of self-paced right and left hand movements from single trial scalp electroencephalogram (EEG).

Methods: Twelve naïve subjects performed self-paced movements consisting of three key strokes with either hand. EEG was recorded from 128 channels. The exploration was performed offline on single trial EEG data. We proposed that a successful computational procedure for classification would consist of spatial filtering, temporal filtering, feature selection, and pattern classification. A systematic investigation was performed with combinations of spatial filtering using principal component analysis (PCA), independent component analysis …

Adenoviral Mediated Gene Transfer Into The Dog Brain In Vivo, Marianela Candolfi, Kurt Kroeger, Elizabeth Pluhar, Chunyan Liu, Carlos Barcia, Josee Bergeron, Mariana Puntel, James Curtin, Elizabeth Mcniel, Andrew Freese, John Ohlfest, Peter Moore, William Kuoy, Pedro Lowenstein, Maria Castro

Articles

OBJECTIVE: Glioblastoma multiforme (GBM) is a devastating brain tumor for which there is no cure. Adenoviral-mediated transfer of conditional cytotoxic (herpes simplex virus [HSV] 1-derived thymidine kinase [TK]) and immunostimulatory (Fms-like tyrosine kinase 3 ligand [Flt3L]) transgenes elicited immune-mediated long-term survival in a syngeneic intracranial GBM model in rodents. However, the lack of a large GBM animal model makes it difficult to predict the outcome of therapies in humans. Dogs develop spontaneous GBM that closely resemble the human disease; therefore, they constitute an excellent large animal model. We assayed the transduction efficiency of adenoviral vectors (Ads) encoding beta-galactosidase (betaGal), TK, …

Hormone Effects On Fmri And Cognitive Measures Of Encoding: Importance Of Hormone Preparation, C. E. Gleason, T. W. Schmitz, T. Hess, R. L. Koscik, M. A. Trivedi, M. L. Ries, C. M. Carlsson, M. A. Sager, S. Asthana, S. C. Johnson

Brain and Mind Institute Researchers' Publications

We compared fMRI and cognitive data from nine hormone therapy (HT)-naive women with data from women exposed to either opposed conjugated equine estrogens (CEE) (n = 10) or opposed estradiol (n = 4). Exposure to either form of HT was associated with healthier fMRI response; however, CEE-exposed women exhibited poorer memory performance than either HT-naive or estradiol-exposed subjects. These preliminary findings emphasize the need to characterize differential neural effects of various HTs. ©2006AAN Enterprises, Inc.

Narcotic Analgesics For Acute Migraine In The Emergency Room: Are We Meeting Headache Societies' Guidelines?, Mohammad Wasay, Khawaja Slaman Zaki, Saqib Uddin Khan, Rifat Rehmani

Department of Emergency Medicine

We analysed 161 patients with acute migraine in our emergency room (ER) to identify the use of narcotic analgesics as first-line treatment. Twenty-four percent of patients were treated with opioid analgesics and 76% patients were treated with non-opioid analgesics. Pain was completely relieved in 100 (62%) patients, partially relieved in 50 (31%) patients and was not relieved in 11 (7%) patients at the time of discharge. Pain relief was not related to the use of opioids vs. non-opioids. The treatment of acute migraine in our ER is in line with the guidelines of the Headache Societies and needs further improvement.

Soluble Amyloid Oligomers Increase Bilayer Conductance By Altering Dielectric Structure, Yuri Sokolov, J. Ashot Kozak, Rakez Kayed, Alexandr Chanturiya, Charles G. Glabe, James E. Hall

Neuroscience, Cell Biology & Physiology Faculty Publications

The amyloid hypothesis of Alzheimer's toxicity has undergone a resurgence with increasing evidence that it is not amyloid fibrils but a smaller oligomeric species that produces the deleterious results. In this paper we address the mechanism of this toxicity. Only oligomers increase the conductance of lipid bilayers and patch-clamped mammalian cells, producing almost identical current-voltage curves in both preparations. Oligomers increase the conductance of the bare bilayer, the cation conductance induced by nonactin, and the anion conductance induced by tetraphenyl borate. Negative charge reduces the sensitivity of the membrane to amyloid, but cholesterol has little effect. In contrast, the area …

Working Memory, Executive Functioning, And Children's Mathematics, R. Bull, K. A. Espy

Developmental Cognitive Neuroscience Laboratory: Faculty Publications

Approximately 3-6% of school-age children are estimated to have mathematics difficulties (Badian, 1983; Gross-Tsur, Manor, & Shalev, 1996; Kosc, 1974, Lewis, Hitch, & Walker, 1994). There are many more children in regular school classrooms who struggle with mathematics but whose performance is not considered sufficiently poor to be classified as meriting a specific disability in mathematics. Specific mathematic learning disability (MLD) is defined in psychiatric and educational venues as a large discrepancy between mathematics ability compared to reading and general intellectual ability, although the size of the discrepancy required varies. To further complicate matters, mathematic difficulties are associated with other …

Measuring The Development Of Executive Control With The Shape School, K. A. Espy, R. B. Bull, J Martin, W. Stroup

Developmental Cognitive Neuroscience Laboratory: Faculty Publications

Although several neurodevelopmental and psychiatric disorders can emerge during the preschool period, there are comparatively few instruments to assess executive control. Evidence for validity of the Shape School (K. A. Espy, 1997) was examined in a sample of 219 typically developing young children. There was good evidence for validity, as Shape School performance variables were interrelated and were associated to other criterion measures considered to measure aspects of executive control. Also suggesting validity, the Shape School variables varied as a function of whether the task demands (a) were executive, (b) required inhibition of a prepotent response or context-controlled selection among …

Activation Of Brain Regions Vulnerable To Alzheimer's Disease: The Effect Of Mild Cognitive Impairment, S. C. Johnson, T. W. Schmitz, C. H. Moritz, M. E. Meyerand, H. A. Rowley, A. L. Alexander, K. W. Hansen, C. E. Gleason, C. M. Carlsson, M. L. Ries, S. Asthana, K. Chen, E. M. Reiman, G. E. Alexander

Brain and Mind Institute Researchers' Publications

This study examined the functionality of the medial temporal lobe (MTL) and posterior cingulate (PC) in mild cognitive impairment amnestic type (MCI), a syndrome that puts patients at greater risk for developing Alzheimer disease (AD). Functional MRI (fMRI) was used to identify regions normally active during encoding of novel items and recognition of previously learned items in a reference group of 77 healthy young and middle-aged adults. The pattern of activation in this group guided further comparisons between 14 MCI subjects and 14 age-matched controls. The MCI patients exhibited less activity in the PC during recognition of previously learned items, …

Neuromechanics Of Multifunctionality During Rejection In Aplysia Californica, Hui Ye, Douglas W. Morton, Hillel J. Chiel

Faculty Scholarship

How are the same muscles and neurons used to generate qualitatively different behaviors? We studied this question by analyzing the biomechanical and neural mechanisms of rejection responses in the marine mollusk Aplysia californica and compared these mechanisms with those used to generate swallowing responses (Ye et al., 2006). During rejection, the central grasper of the feeding structure closes to push inedible food out of the buccal cavity. This contrasts with swallowing, during which the grasper is open as it moves toward the jaws (protracts). We examined how the shape change of the grasper during rejection mechanically reconfigured the surrounding musculature. …

Genetic Bases Of Executive Control In Preschool Children: Trails-P Performance Is Related To Drd2 Genotype, S. A. Wiebe, M. Y. Chang, J. Huggenvik, T. Jameson, K. A. Espy

Developmental Cognitive Neuroscience Laboratory: Faculty Publications

Several studies link the D2 dopamine receptor (DRD2) with executive control and the ability to adapt behavior to changing contextual contingencies in human adults (Roesch-Ely 2005; Rodriguez-Jimenez 2006) and in animal models (Kruzich 2004). The present study examined relations between DRD2 and executive control in human development. Recently, a version of the Trail-Making Task suitable for preschool children was developed, which does not require knowledge of letters or numbers (TRAILS-P; Espy 2004). The Trail-Making Test is a neuropsychological test sensitive to frontal or executive dysfunction (Reitan 1955) where subjects must connect stimuli on a page in sequence, connecting letters only …

Structural Mri Discriminates Individuals With Mild Cognitive Impairment From Age-Matched Controls: A Combined Neuropsychological And Voxel Based Morphometry Study, Mehul A. Trivedi, Allison K. Wichmann, Britta M. Torgerson, Michael A. Ward, Taylor W. Schmitz, Michele L. Ries, Rebecca L. Koscik, Sanjay Asthana, Sterling C. Johnson

Brain and Mind Institute Researchers' Publications

Background: Several previous studies have reported that amnestic mild cognitive impairment (aMCI), a significant risk factor for Alzheimer's disease (AD), is associated with greater atrophy in the medial temporal lobe (MTL) and posterior cingulate gyrus (PCG). Method: In the present study, we examined the cross-sectional accuracy (i.e., the sensitivity and specificity) of voxel-based morphometry (VBM) in discriminating individuals with MCI (n = 15) from healthy age-matched controls (n = 15). In addition, we also sought to determine whether baseline GM volume predicted aMCI patients that converted to AD from those that did not approximately 2 years after the baseline visit. …

Unlv Magazine, Cate Weeks, Shane Bevell, Erin O'Donnell, Eric Leake, Lori Bachand, David G. Schwartz, David Ashley

UNLV Magazine

No abstract provided.

Paradoxical Facilitation Of Object Recognition Memory After Infusion Of Scopolamine Into Perirhinal Cortex: Implications For Cholinergic System Function., Boyer D Winters, Lisa M Saksida, Timothy J Bussey

Brain and Mind Institute Researchers' Publications

The cholinergic system has long been implicated in learning and memory, yet its specific function remains unclear. In the present study, we investigated the role of cortical acetylcholine in a rodent model of declarative memory by infusing the cholinergic muscarinic receptor antagonist scopolamine into the rat perirhinal cortex during different stages (encoding, storage/consolidation, and retrieval) of the spontaneous object recognition task. Presample infusions of scopolamine significantly impaired object recognition compared with performance of the same group of rats on saline trials; this result is consistent with previous reports supporting a role for perirhinal acetylcholine in object information acquisition. Scopolamine infusions …

Combining An Autologous Peripheral Nervous System “Bridge” And Matrix Modification By Chondroitinase Allows Robust, Functional Regeneration Beyond A Hemisection Lesion Of The Adult Rat Spinal Cord, John D. Houle, Veronica J. Tom, Debra A. Mayes, Gail Wagoner, Napoleon Phillips, Jerry Silver

Neuroscience, Cell Biology & Physiology Faculty Publications

Chondroitinase-ABC (ChABC) was applied to a cervical level 5 (C5) dorsal quadrant aspiration cavity of the adult rat spinal cord to degrade the local accumulation of inhibitory chondroitin sulfate proteoglycans. The intent was to enhance the extension of regenerated axons from the distal end of a peripheral nerve (PN) graft back into the C5 spinal cord, having bypassed a hemisection lesion at C3. ChABC-treated rats showed (1) gradual improvement in the range of forelimb swing during locomotion, with some animals progressing to the point of raising their forelimb above the nose, (2) an enhanced ability to use the forelimb in …

Representation Of Head-Centric Flow In The Human Motion Complex., Jeroen Goossens, Sean P Dukelow, Ravi S Menon, Tutis Vilis, Albert V Van Den Berg

Brain and Mind Institute Researchers' Publications

Recent neuroimaging studies have identified putative homologs of macaque middle temporal area (area MT) and medial superior temporal area (area MST) in humans. Little is known about the integration of visual and nonvisual signals in human motion areas compared with monkeys. Through extra-retinal signals, the brain can factor out the components of visual flow on the retina that are induced by eye-in-head and head-in-space rotations and achieve a representation of flow relative to the head (head-centric flow) or body (body-centric flow). Here, we used functional magnetic resonance imaging to test whether extra-retinal eye-movement signals modulate responses to visual flow in …

Self-Appraisal Decisions Evoke Dissociated Dorsal-Ventral Ampfc Networks, Taylor W. Schmitz, Sterling C. Johnson

Brain and Mind Institute Researchers' Publications

The anterior medial prefrontal cortex (aMPFC) is consistently active during personally salient decisions, yet the differential contributory processes of this region along the dorsal-ventral axis are less understood. Using a self-appraisal decision-making task and functional magnetic resonance imaging, we demonstrated task-dependent connectivity of ventral aMPFC with amygdala, insula, and nucleus accumbens, and dorsal aMPFC connectivity with dorsolateral PFC and bilateral hippocampus. These aMPFC networks appear to subserve distinct contributory processes inherent to self-appraisal decisions, specifically a dorsally mediated cognitive and a ventrally mediated affective/self-relevance network. © 2005 Elsevier Inc. All rights reserved.

Fibrinogen-Containing Y Chains; Is The Assay Measuring What Farrell's Group Expects?, Kevin R. Siebenlist

Biomedical Sciences Faculty Research and Publications

No abstract provided.

Neuromechanics Of Coordination During Swallowing In Aplysia Californica, Hui Ye, Douglas W. Morton, Hillel J. Chiel

Faculty Scholarship

Bernstein (1967) hypothesized that preparation of the periphery was crucial for correct responses to motor output. To test this hypothesis in a behaving animal, we examined the roles of two identified motor neurons, B7 and B8, which contribute to feeding behavior in the marine mollusk Aplysia californica. Neuron B7 innervates a hinge muscle and has no overt behavioral effect during smaller-amplitude (type A) swallows, because the hinge muscle is too short to exert force. Neuron B8 activates a muscle (I4) that acts solely to grasp material during type A swallows. During larger-amplitude (type B) swallows, the behavioral actions of both …