Neurosciences Commons^™

Fornix Lesions Can Facilitate Acquisition Of The Transverse Patterning Task: A Challenge For "Configural" Theories Of Hippocampal Function., T J Bussey, E Clea Warburton, J P Aggleton, J L Muir

Brain and Mind Institute Researchers' Publications

Configural theories of hippocampal function predict that hippocampal dysfunction should impair acquisition of the transverse patterning task, which involves the concurrent solution of three discrimination problems: A+ versus B-; B+ versus C-; and C+ versus A-. The present study tested this prediction in rats using computer-graphic stimuli presented on a touchscreen. Experiment 1 assessed the effects of fornix lesions when the three problems were introduced sequentially (phase 1: A+ vs B-; phase 2: A+ vs B-, B+ vs C-; phase 3: A+ vs B-, B+ vs C-, C+ vs A-). Fornix lesions significantly facilitated acquisition of the complete transverse patterning …

Identifying Global Anatomical Differences: Deformation-Based Morphometry, J Ashburner, C Hutton, R Frackowiak, Ingrid Johnsrude, C Price, K Friston

Brain and Mind Institute Researchers' Publications

The aim of this paper is to illustrate a method for identifying macroscopic anatomical differences among the brains of different populations of subjects. The method involves spatially normalizing the structural MR images of a number of subjects so that they all conform to the same stereotactic space. Multivariate statistics are then applied to the parameters describing the estimated nonlinear deformations that ensue. To illustrate the method, we compared the gross morphometry of male and female subjects. We also assessed brain asymmetry, the effect of handedness, and interactions among these effects.

In Vivo And In Vitro Nuclear Magnetic Resonance Imaging And Spectroscopy Of Psychoactive Drugs In Rat Brain, Diana M. Lindquist

Theses and Dissertations

Four psychoactive drugs were studied using various in vivo nuclear magnetic resonance (NMR) techniques. Trifluoperazine (TFP) was given to several normal rats, whose brains were then studied using in vivo fluorine-19 NMR. Three peaks were detected in the in vivo fluorine spectra: one at -62 ppm, which was due to TFP, and two others at -55 and -75 ppm, which are due to unknown metabolites of TFP. Samples of skin, skull, muscle, and brain were obtained from these rats and extracted for in vitro analysis. The metabolites responsible for the in vivo peak at -75 ppm also appeared in the …

Direct Demonstration Of Retroviral Recombination In A Rhesus Monkey, Dawn P. Wooley, Randall A. Smith, Susan Czajak, Ronald C. Desrosiers

Neuroscience, Cell Biology & Physiology Faculty Publications

Recombination may be an important mechanism for increasing variation in retroviral populations. Retroviral recombination has been demonstrated in tissue culture systems by artificially creating doubly infected cells. Evidence for retroviral recombination in vivo is indirect and is based principally on the identification of apparently mosaic human immunodeficiency virus type 1 genomes from phylogenetic analyses of viral sequences. We infected a rhesus monkey with two different molecularly cloned strains of simian immunodeficiency virus. One strain of virus had a deletion in vpx and vpr, and the other strain had a deletion in nef. Each strain on its own induced low virus …

Neurobehavior In Preterm Neonates Exposed To Cocaine, Alcohol, And Tobacco, K. A. Espy, M. L. Riese, D. J. Francis

Developmental Cognitive Neuroscience Laboratory: Faculty Publications

Neonatal neurobehavioral development was investigated in a sample of 20 hospitalized, prenatally cocaine-exposed preterm infants and 20 matched non-exposed controls. Prenatal cocaine exposure was related to reductions in attention performance that remained apparent at 36 wks conceptional age. There was no impact of prenatal cocaine exposure on the rate of change in attention proficiency. In utero alcohol exposure was associated with increased rates of age-related change in motor skill. Alcohol-related performance deficits were transient; alcohol-exposed infants reached an equivalent level of motor performance exhibited by the non-exposed infants by 36 wks conceptional age. These findings highlight the importance of considering …

The Shape School: Assessing Executive Function In Preschool Children, K. A. Espy

Developmental Cognitive Neuroscience Laboratory: Faculty Publications

Age-related changes in executive function were examined on a new task, the Shape School, in 70 preschool children (32-68 months old). The Shape School is a colorful storybook designed to examine inhibition and switching processes in young children. Results confirmed that task efficiency varied significantly with age, with older age groups outperforming younger groups. Furthermore, inhibition efficiency improved significantly between 3 to 4 years of age, whereas switching skills showed developmental improvement from 4 to 5 years of age. These results suggest that the Shape School is sensitive to maturational effects and that performance can be parsed into inhibition and …

Right Medial Temporal-Lobe Contribution To Object-Location Memory, B Milner, Ingrid Johnsrude, J Crane

Brain and Mind Institute Researchers' Publications

An important aspect of normal human memory, and one humans share with many other species, is the ability to remember the location of objects in their environment. There is by now strong evidence from the study of epileptic patients undergoing brain surgery that right temporal-lobe lesions that encroach extensively upon the hippocampal and parahippocampal gyrus impair the delayed, but not the immediate, recall of the location of objects within a random array. These findings have now been extended to a multiple-trial, spatial-array learning task; by including not only patients tested after unilateral anterior temporal lobectomy but also those with a …

Triple Dissociation Of Anterior Cingulate, Posterior Cingulate, And Medial Frontal Cortices On Visual Discrimination Tasks Using A Touchscreen Testing Procedure For The Rat., T J Bussey, J L Muir, B J Everitt, T W Robbins

Brain and Mind Institute Researchers' Publications

Four experiments examined effects of quinolinic acid-induced lesions of the anterior cingulate, posterior cingulate, and medial frontal cortices on tests of visual discrimination learning, using a new "touchscreen" testing method for rats. Anterior cingulate cortex lesions impaired acquisition of an 8-pair concurrent discrimination task, whereas posterior cingulate cortex lesions facilitated learning but selectively impaired the late stages of acquisition of a visuospatial conditional discrimination. Medial frontal cortex lesions selectively impaired reversal learning when stimuli were difficult to discriminate; lesions of anterior and posterior cingulate cortex had no effect. These results suggest roles for the anterior cingulate, posterior cingulate, and medial …

Transcranial Magnetic Stimulation Of The Prefrontal Cortex Delays Contralateral Endogenous Saccades, Tony Ro, Avishai Henik, Liana Machado, Robert D. Rafal

Publications and Research

The contributions of the superior prefrontal cortex (SPFC) and the superior parietal lobule (SPL) in generating voluntary endogenous and reflexive visually guided saccades were investigated using transcranial magnetic stimulation (TMS). Subjects made choice saccades to the left or right visual field in response to a central arrowhead (endogenous go signal) or a peripheral asterisk (exogenous go signal) that were presented along with a single TMS pulse at varying temporal intervals. TMS over the SPFC increased latencies for saccades made in response to an endogenous go signal toward the contralateral hemifield. No effects were observed when the go signal was exogenous …

Hallucinations, Peter J. Whitehouse, Marian B. Patterson, Milton E. Strauss, David S. Geldmacher, James L. Mack, Grover C. Gilmore, Elizabeth Koss

Faculty Scholarship

No abstract provided.

Identification And Characterization Of The Thrombin Binding Sites On Fibrin, David A. Meh, Kevin R. Siebenlist, Michael W. Mosesson

Biomedical Sciences Faculty Research and Publications

Thrombin binds to fibrin at two classes of non-substrate sites, one of high affinity and the other of low affinity. We investigated the location of these thrombin binding sites by assessing the binding of thrombin to fibrin lacking or containing γ′ chains, which are fibrinogen γ chain variants that contain a highly anionic carboxyl-terminal sequence. We found the high affinity thrombin binding site to be located exclusively in D domains on γ′ chains (K_a, 4.9 × 10⁶⁻¹; n, 1.05 per γ′ chain), whereas the low affinity thrombin binding site was in the fibrin E …

Plasma Factor Xiii Binds Specifically To Fibrinogen Molecules Containing Γ‘ Chains, Kevin R. Siebenlist, David A. Meh, Michael W. Mosesson

Biomedical Sciences Faculty Research and Publications

The difference between peak 1 and peak 2 fibrinogen lies in their γ chains. Peak 1 molecules contain 2 γA chains; peak 2 molecules contain 1 γA and 1 γ‘ chain, the latter of which contains a 20 amino acid extension (γ‘ 408−427) replacing the carboxyl-terminal 4 amino acids of the γA chain (γA 408−411). While the existence of γ‘ chains in plasma fibrinogen molecules has been known for many years, their function remains unknown. When fibrinogen is purified from plasma, the factor XIII zymogen (A₂B₂) copurifies with it and is found only in the peak …

Evidence For Intramolecular Cross-Linked Aα·Γ Chain Heterodimers In Plasma Fibrinogen, Kevin R. Siebenlist, Michael W. Mosesson

Biomedical Sciences Faculty Research and Publications

A peptide band of ∼105 kDa migrating near the γ dimer position of disulfide bond reduced human plasma fibrinogen prepared from fresh single donor or outdated plasma was identified by SDS−PAGE. The band, amounting to ∼2% of the total Aα/γ chain population, was thrombin and plasmin sensitive and reacted with antibodies to Aα or γ chains but not with antibodies to Bβ chains, plasminogen, or factor XIII. Amino acid sequencing revealed a double sequence corresponding to that of Aα and γ chains, indicating that the band consists of covalently cross-linked Aα·γ chain heterodimers. Aα·γ heterodimers were identified as a component …

The Relationship Between The Fibrinogen D Domain Self-Association/Cross-Linking Site (Gammaxl) And The Fibrinogen Dusart Abnormality (Aalpha R554c-Albumin): Clues To Thrombophilia In The "Dusart Syndrome", Michael W. Mosesson, Kevin R. Siebenlist, James F. Hainfeld, J. S. Wall, C. Soria, J. P. Caen

Biomedical Sciences Faculty Research and Publications

Cross-linking of fibrinogen at its COOH-terminal gamma chain cross-linking site occurs in the presence of factor XIIIa due to self-association at a constitutive D domain site ("gammaXL"). We investigated the contribution of COOH-terminal regions of fibrinogen Aalpha chains to the gammaXL site by comparing the gamma chain cross-linking rate of intact fibrinogen (fraction I-2) with that of plasma fraction I-9, plasmic fraction I-9D, and plasmic fragment D1, which lack COOH-terminal Aalpha chain regions comprising approximately 100, approximately 390, and 413 residues, respectively. The cross-linking rates were I-2 > I-9 > 1-9D = D1, and indicated that the terminal 100 or more Aalpha …

A Recombinant Inwardly Rectifying Potassium Channel Coupled To Gtp-Binding Proteins, Kim W. Chan, M. Noelle Langan, Jin Liang Sui, J. Ashot Kozak, Amanda Pabon, John A. A. Ladias, Diomedes E. Logothetis

Neuroscience, Cell Biology & Physiology Faculty Publications

GTP-binding (G) proteins have been shown to mediate activation of inwardly rectifying potassium (K+) channels in cardiac, neuronal and neuroendocrine cells. Here, we report functional expression of a recombinant inwardly rectifying channel which we call KGP (or hpKir3.4), to signify that it is K+ selective, G-protein-gated and isolated from human pancreas. KGP expression in Xenopus oocytes resulted in sizeable basal (or agonist-independent) currents while coexpression with a G-protein-linked receptor, yielded additional agonist-induced currents. Coexpression of KGP and hGIRK1 (a human brain homolog of GIRK1/Kir3.1) produced much larger basal currents than those observed with KGP or hGIRK1 alone, and upon coexpression …

Neonatal Cranial Ultrasound Abnormalities In Lbw Infants: Relation To Cognitive Outcomes At Age Six, Agnes H. Whitaker, Judy F. Feldman, Ronan Van Rossem, Irvin Sam Schonfeld, Jennifer A. Pinto-Martin, Carolyn Torre, Suzannah R. Blumenthal, Nigel S. Paneth

Publications and Research

bjective: To assess the independent relation of neonatal cranial ultrasound (US) abnormalities in low birth weight (LBW) infants to cognitive outcomes at 6 years of age.
Design: Prospective cohort study.
Sample and Methods: Six-year follow-up data were obtained on a regional birth cohort of LBW infants (< 2 kg) systematically screened as neonates with serial US. US abnormalities were dichotomized into isolated germinal matrix/intraventricular hemorrhage (GM/IVH) and parenchymal lesions/ventricular enlargement (PL/VE). Global cognitive outcomes (mental retardation, borderline intelligence, and normal intelligence) and selected specific cognitive abilities were assessed at 6 years of age with standardized instruments. Multivariate techniques were used to assess the effects of US independent of maternal social …

Effect Of Neurotrophic Factors On Cholinergic Neurons In The Septo-Hippocampal Pathway Of Normal And Af64a Treated Rats, Christopher Andrew Willson

Dissertations

No abstract provided.

The Role Of Fibrinogen D Domain Intermolecular Association Sites In The Polymerization Of Fibrin And Fibrinogen Tokyo Ii (Γ275 Arg→Cys), Michael W. Mosesson, Kevin R. Siebenlist, James P. Diorio, M. Matsuda, James F. Hainfeld, J. S. Wall

Biomedical Sciences Faculty Research and Publications

Intermolecular end-to-middle domain pairing between a thrombin-exposed 'A' polymerization site in the central 'E' domain of fibrin, and a constitutive complementary 'a' site in each outer 'D' domain ('D:E'), is necessary but not alone sufficient for normal fibrin assembly, as judged from previous studies of a congenital dysfibrinogen, Tokyo II (gamma 275 arg-->cys), which showed defective fibrin clot assembly and a normal D:E interaction (Matsuda, M., M. Baba, K. Morimoto, and C. Nakamikawa, 1983. J. Clin. Invest. 72:1034-1041). In addition to the 'a' polymerization site, two other constitutive intermolecular association sites on fibrinogen D domains have been defined: between …

Modulation Of Neutrophil Functions By Neurotransmitters Implicated In Stress, Chok Ping Wan

Loma Linda University Electronic Theses, Dissertations & Projects

Stress has long been implicated in immune modulation. People under chronic stress have no change in the circulating basal levels of catecholamines while plasma levels of neuropeptide Y (NPY) are significantly increased. Sympathetic nerve fibers with NPY have been found to innervate immune organs. It was hypothesized that NPY might be a mediator in immune modulation in people under chronic stress. Human neutrophils were used as a model to study the effects of NPY alone or together with norepinephrine on the immune system. We now report that NPY modulates oxidative burst (OB) triggered by zymosan in human neutrophils while it …

A Possible Genetic Defect In The Causes Of Brain Aneurysms, George Austin, Wouter Schievink, Delbert Dickson, Stephanie Richardson, Emily Hanford

The Dr. George M. Austin Neurology Research Collection

A Possible Genetic Defect in the Causes of Brain Aneurysms. George Austin, M.D, Wouter Schievink, M.D., Delbert Dickson, M.D., Stephanie Richardson, B.S., and Emily Handford, B.S. 1 pg. Handwritten note indicates presentation at The American Association of Neurological Surgeons, April 1995, Orland Florida.

A Genetic Defect In Brain Aneurysms, George Austin, Wouter Schievink, Delbert Dickson, Stephanie Richardson, Emily Hanford

The Dr. George M. Austin Neurology Research Collection

A Genetic Defect in Brain Aneurysms. George Austin, M.D., Woutler Schievink, M.D., Delbert Dickson, M.D., Stephanie Richardson, B.S. and Emily Hanford, B.S. 1 pg. Handwritten not indicates conference presentation, American College of Surgeons, Southern Chapter, January 20-22, 1995.

Characterization Of The On And Off Pathways In Human Vision, Luisa Roveri

Master's Theses

No abstract provided.

Progressive Cross-Linking Of Fibrin Gamma Chains Increases Resistance To Fibrinolysis, Kevin R. Siebenlist, Michael W. Mosesson

Biomedical Sciences Faculty Research and Publications

In the presence of plasma transglutaminase (factor XIIIa) fibrin first undergoes intermolecular covalent cross-linking between its gamma chains to create gamma dimers followed by slower cross-linking among its alpha chains to form alpha polymers. Progressive cross-linking of gamma chain dimers occurs at the slowest rate, resulting in gamma trimers and gamma tetramers (“gamma multimers”). Most studies indicate that cross-linked fibrin clots become resistant to fibrinolysis, but the basis for this event is not clear. In this study, we explored the role of gamma chain multimerization compared with alpha polymerization as causal factors in time-dependent development of resistance to fibrinolysis. Fibrin …

Effects Of Natural Sequence Variation On Recognition By Monoclonal Antibodies Neutralize Simian Immunodeficiency Virus Infectivity, Weon Sang Choi, Catherine Collignon, Clotilde Thiriart, Dawn P. Wooley, E. J. Scott, Karen A. Kent, Ronald C. Desrosiers

Neuroscience, Cell Biology & Physiology Faculty Publications

The determinants of immune recognition by five monoclonal antibodies (KK5, KK9, KK17, Senv7.1, and Senv101.1) that neutralize simian immunodeficiency virus infectivity were analyzed. These five neutralizing monoclonal antibodies were generated to native SIVmac251 envelope glycoprotein expressed by a vaccinia virus recombinant vector. All five recognize conformational or discontinuous epitopes and require native antigen for optimal recognition. These monoclonal antibodies also recognize SIVmac239 gp120, but they do not recognize gp120 of two natural variants of SIVmac239, 1-12 and 8-22, which evolved during the course of persistent infection in vivo (D.P.W. Burns and R.C. Desrosiers, J. Virol. 65:1843-1854, 1991). Recombinant viruses which …

Increased Brain Aneurysm Wall Strain: A Further Hazard For Rupture, George M. Austin, Wouter Schievink, Delbert Dickson, Stephanie Richardson, Emily Hanford

The Dr. George M. Austin Neurology Research Collection

Increased Aneurysm Wall Strain: A Potential for Rupture. George M. Austin, M.D., Wouter Schievink, M.D., Delbert Dickson, M.D., Stephanie Richardson, B.S. August 12,1994. Portland, Oregon, 3 pg. See also previously presented version in additional files.

High Rates Of Frameshift Mutations Within Homo-Oligomeric Runs During A Single Cycle Of Retroviral Replication, Dawn P. Wooley, H. M. Temin

Neuroscience, Cell Biology & Physiology Faculty Publications

Homo-oligomeric runs were inserted into a spleen necrosis virus-based retrovirus vector to determine the nature and rate of mutations within runs of 10 to 12 identical nucleotides during a single replication cycle. Clones of helper cells containing integrated copies of retroviral vectors were used to produce virus for infection of target (nonhelper) cells. Proviral sequences from target cell clones were compared with proviral sequences from helper cell clones to study mutations that occurred during a single cycle of replication. In addition to the internal region spanning the homo-oligomeric inserts, a naturally occurring run of 10 T's in the long terminal …

[George M. Austin Autobiography Drafts], George M. Austin, Society Of Neurological Surgeons Historian

The Dr. George M. Austin Neurology Research Collection

George M. Austin autobiography drafts.

1. Draft dated September 26, 1994.
2. “First Draft” dated September 21, 1994
3. Draft handwritten on lined yellow paper
4. Typed letter. To All members Society of Neurological Surgeons From Historian. Letter requests a biography and photograph.

Factors Altering Aneurysm Wall Strain, George M. Austin

The Dr. George M. Austin Neurology Research Collection

Factors Altering Aneurysm Wall Strain. George M. Austin, M.D. Poster presentation. American Association of Neurological Surgeons, San Diego Convention Center. April 9-14, 1994. 1 pg.

Brain Aneurysms And Aging, G. M. Austin, W. Schievink, D. Dickson

The Dr. George M. Austin Neurology Research Collection

Brain Aneurysms and Aging. G. M. Austin, M.D., W. Schievink, M.D., and D. Dickson, M.D., 1994. Presentation manuscript. 1 pg.

A Genetic Basis For Brain Aneurysms, G. Austin, W. Schievink, D. Dickson, S. Richardson

The Dr. George M. Austin Neurology Research Collection

A Genetic Basis for Brain Aneurysms. Austin, G., Schievenk, W., Dickson, D., and Richardson, S. Brain Aneurysm Research Laboratory, Neuroscience Institute, U.C.S.B., Santa Barbara, CA. A handwritten note indicates that this is an abstract presented at the Biophysical Society, February 12-16, 1995. 2 pg.