Neurology Commons^™

Multimodal Imaging Evidence For Axonal And Myelin Deterioration In Amnestic Mild Cognitive Impairment, Brian T. Gold, Yang Jiang, David K. Powell, Charles D. Smith

Neuroscience Faculty Publications

White matter (WM) microstructural declines have been demonstrated in Alzheimer's disease and amnestic mild cognitive impairment (aMCI). However, the pattern of WM microstructural changes in aMCI after controlling for WM atrophy is unknown. Here, we address this issue through joint consideration of aMCI alterations in fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity, as well as macrostructural volume in WM and gray matter compartments. Participants were 18 individuals with aMCI and 24 healthy seniors. Voxelwise analyses of diffusion tensor imaging data was carried out using tract-based spatial statistics (TBSS) and voxelwise analyses of high-resolution structural data was conducted using …

Mechanisms Of Neuronal Death Induced By Environmental Toxicants In Murine Cortical Culture, Travis Rush

Dissertations (1934 -)

This study was directed at examining the neurotoxic mechanisms of several classes of environmental toxicants implicated in neurodegenerative disease. Primary cortical cultures were exposed to organophosphorus pesticides, heavy metals and the cyanobacterial toxin, beta-N-methylamino-L-alanine (BMAA). Several components relating to neuronal injury were assessed in each study and novel aspects are described.

The main action of organophosphorous insecticides is generally believed to be the inhibition of acetylcholinesterase. However, these compounds are now recognized to inhibit many other enzymes and cause neuronal death through a variety of mechanisms. I found that exposure to chlorpyrifos or diazinon caused concentration-dependent neurotoxicity that could not …

Fuzzy Logic: A “Simple” Solution For Complexities In Neurosciences?, Saniya Siraj Godil, Muhammad Shahzad Shamim, Ather Enam, Uvais Qidwai

Medical College Documents

Background: Fuzzy logic is a multi-valued logic which is similar to human thinking and interpretation. It has the potential of combining human heuristics into computer-assisted decision making, which is applicable to individual patients as it takes into account all the factors and complexities of individuals. Fuzzy logic has been applied in all disciplines of medicine in some form and recently its applicability in neurosciences has also gained momentum.
Methods: This review focuses on the use of this concept in various branches of neurosciences including basic neuroscience, neurology, neurosurgery, psychiatry and psychology.
Results: The applicability of fuzzy logic is not limited …

Neural Coding And Decoding, Alexander Dimitrov

Systems Science Friday Noon Seminar Series

Methods based on Rate Distortion theory have been successfully used to cluster stimuli and neural responses in order to study neural codes at a level of detail supported by the amount of available data. They approximate the joint stimulus-response distribution by quantizing paired stimulus-response observations into smaller reproductions of the stimulus and response spaces. An optimal quantization is found by maximizing an information-theoretic cost function subject to both equality and inequality constraints, in hundreds to thousands of dimensions. This analytical approach has several advantages over other current approaches:

• it yields the most informative approximation of the encoding scheme given the …

Sleep Well To Stay Safe: Ready For Primetime?, Mihai C. Teodorescu, Mariana Szklo-Coxe

Community & Environmental Health Faculty Publications

Commentary on Kling et al. Sleep problems and workplace injuries in Canada. Sleep 2010;33:611-618.

Increased Dendrite Branching In Aβpp/Ps1 Mice And Elongation Of Dendrite Arbors By Fasudil Administration, Brian A. Couch, George J. Demarco, Shannon L. Gourley, Anthony J. Koleske

School of Biological Sciences: Faculty Publications

Amyloid-β (Aβ) overproduction and dendrite arbor atrophy are hallmarks of Alzheimer’s disease. The RhoA GTPase (Rho) signals through Rho kinase (ROCK) to control cytoskeletal dynamics and regulate neuron structure. Hyperactive Rho signaling destabilizes neurons leading to dendritic regression that can be rescued by genetic or pharmacological reduction of ROCK signaling. To understand what effect reduced ROCK signaling has on the dendrite arbors of mice that overproduce Aβ, we administered the ROCK inhibitor fasudil to AβPP/PS1 transgenic mice. We report that increased dendrite branching occurs in AβPP/PS1 mice and that fasudil promotes …

Synaptic Clustering Of Psd-95 Is Regulated By C-Abl Through Tyrosine Phosphorylation, Karen Perez De Arce, Lorena Varela-Nallar, Olivia Farias, Alejandra Cifuentes, Paulina Bull, Brian A. Couch, Anthony J. Koleske, Nibaldo C. Inestrosa, Alejandra R. Alvarez

School of Biological Sciences: Faculty Publications

The c-Abl tyrosine kinase is present in mouse brain synapses, but its precise synaptic function is unknown. We found that c-Abl levels in the rat hippocampus increase postnatally, with expression peaking at the first postnatal week. In 14 d in vitro hippocampal neuron cultures, c-Abl localizes primarily to the postsynaptic compartment, in which it colocalizes with the postsynaptic scaffold protein postsynaptic density protein-95 (PSD-95) in apposition to presynaptic markers. c-Abl associates with PSD-95, and chemical or genetic inhibition of c-Abl kinase activity reduces PSD-95 tyrosine phosphorylation, leading to reduced PSD-95 clustering and reduced synapses in treated neurons. c-Abl can phosphorylate …

Impairments In Attention In Occasionally Snoring Children: An Event-Related Potential Study., Maria E. Barnes, Elizabeth A. Huss, Krista N. Garrod, Eric Van Ray, Ehab Dayyat, David Gozal, Dennis L. Molfese

Faculty and Staff Scholarship

Objective: To determine whether minimal snoring is benign in children. Procedure: 22 rarely snoring children (mean age = 6.9 years, 11 females) and age- and sex-matched controls participated in an auditory oddball task wearing 128-electrode nets. Parents completed the Conners Parent Rating Scales–Revised Long (CPRS–R:L). Results: Snorers scored significantly higher on four CPRS-R:L subscales. Stepwise regression indicated that two ERP variables from a region of the ERP that peaked at 844 msec post-stimulus onset predicted CPRS-R:L Attention Deficit Hyperactivity Disorder (ADHD) Index scores. Conclusions: Occasional snorers, according to parental report, do exhibit ADHD-like behaviors. Basic sensory processing is longer than …

Resting State Default-Mode Network Connectivity In Early Depression Using A Seed Region-Of-Interest Analysis: Decreased Connectivity With Caudate Nucleus, Robyn Bluhm, Peter Williamson, Ruth Lanius, Jean Théberge, Maria Densmore, Robert Bartha, Richard Neufeld, Elizabeth Osuch

Philosophy Faculty Publications

Aim: Reports on resting brain activity in healthy controls have described a default-mode network (DMN) and important differences in DMN connectivity have emerged for several psychiatric conditions. No study to date, however, has investigated resting-state DMN in relatively early depression before years of medication treatment. The objective of the present study was, therefore, to investigate the DMN in patients seeking help from specialized mental health services for the first time for symptoms of depression.

Methods: Fourteen depressed subjects and 15 matched controls were scanned using 4-T functional magnetic resonance imaging while resting with eyes closed. All but one subject was …

Self-Consistent Analyses For Potential Conduction Block In Nerves By An Ultrashort High-Intensity Electric Pulse, R. P. Joshi, A. Mishra, Q. Hu, K. H. Schoenbach, A. Pakhomov

Bioelectrics Publications

Simulation studies are presented that probe the possibility of using high-field (>100kV ∕ cm), short-duration (∼50ns) electrical pulses for nonthermal and reversible cessation of biological electrical signaling pathways. This would have obvious applications in neurophysiology, clinical research, neuromuscular stimulation therapies, and even nonlethal bioweapons development. The concept is based on the creation of a sufficiently high density of pores on the nerve membrane by an electric pulse. This modulates membrane conductance and presents an effective "electrical short" to an incident voltage wave traveling across a nerve. Net blocking of action potential propagation can then result. A continuum approach based …

Optimization Of Biomathematical Model Predictions For Cognitive Performance Impairment In Individuals: Accounting For Unknown Traits And Uncertain States In Homeostatic And Circadian Processes, Hans P. A. Van Dongen, Christopher G. Mott, Jen-Kuang Huang, Daniel J. Mollicone, Frederic D. Mckenzie, David F. Dinges

Mechanical & Aerospace Engineering Faculty Publications

Current biomathematical models of fatigue and performance do not accurately predict cognitive performance for individuals with a priori unknown degrees of trait vulnerability to sleep loss, do not predict performance reliably when initial conditions are uncertain, and do not yield statistically valid estimates of prediction accuracy, These limitations diminish their usefulness for predicting the performance of individuals in operational environments. To overcome these 3 limitations, a novel modeling approach was developed, based on the expansion of a statistical technique called Bayesian forecasting. The expanded Bayesian forecasting procedure was implemented in the two-process model of sleep regulation, which has been used …

Confidence Intervals For Individualized Performance Models, Hans P. A. Van Dongen, Christopher G. Mott, Jen-Kuang Huang, Daniel J. Millicone, Frederic D. Mckenzie, David F. Dinges

Mechanical & Aerospace Engineering Faculty Publications

Commentary on Reifman J; Rajaraman S; Gribok AV. Moving Towards Individualized Performance Models. Sleep 2007;30(9):1081-82.

Brain Tumor Stem Cells: Role In Neuro-Oncogenesis And Therapeutic Implications, Muhammad Zeeshan Ozair, Adil Hameed Khan, Ather Enam

Department of Biological & Biomedical Sciences

Malignant brain tumors are notorious for high morbidity and mortality. Our deficient understanding of brain tumor pathogenesis is reflected in our inability to cure this disease. Treatment remains palliative at best. The cancer stem cell hypothesis of brain tumors promises to consolidate many observations which have previously eluded neuroscientists and may reveal why aberrations in developmental programs are among the commonest findings in brain tumors. It is ironic that brain ontogeny and cancer - two processes with very different outcomes - exploit similar mechanisms to multiply, migrate,and survive. Implications of this hypothesis extend beyond mere academic interest. It may explain …

Dissociation Of Automatic And Strategic Lexical-Semantics: Functional Magnetic Resonance Imaging Evidence For Differing Roles Of Multiple Frontotemporal Regions, Brian T. Gold, David A. Balota, Sara J. Jones, David K. Powell, Charles D. Smith, Anders H. Andersen

Neuroscience Faculty Publications

Behavioral research has demonstrated three major components of the lexical-semantic processing system: automatic activation of semantic representations, strategic retrieval of semantic representations, and inhibition of competitors. However, these component processes are inherently conflated in explicit lexical-semantic decision tasks typically used in functional magnetic resonance imaging (fMRI) research. Here, we combine the logic of behavioral priming studies and the neurophysiological phenomenon of fMRI priming to dissociate the neural bases of automatic and strategic lexical-semantic processes across a series of three studies. A single lexical decision task was used in all studies, with stimulus onset asynchrony or linguistic relationship between prime and …

The Ultrastructure Of The Olfactory System In Two Species Of Short-Tailed Shrews, Blarina Brevicauda And Blarina Carolinensis, Lisa Johnson Byrum

Theses and Dissertations in Biomedical Sciences

Several studies of the fine structure of the olfactory system of rodents have been conducted, but very little research has been done on members of the Insectivora. The olfactory systems of the northern short-tailed shrew, Blarina brevicauda, and the southern short-tailed shrew, Blarina carolinensis, were examined by light and electron microscopy. These shrews were live trapped in the vicinity of Norfolk, Virginia throughout all months of the year. Olfactory tissues were processed following standard transmission and scanning electron microscopy protocols. The olfactory system structures investigated included the olfactory epitheliumlmucosa (OEM), main olfactory bulb (MOB), accessory olfactory bulb (AOB), …

Signaling Mechanisms For Muscarinic Receptor-Mediated Coronary Vasoconstriction In Isolated Rat Hearts, Yi Zhang

Electronic Theses and Dissertations

The signaling mechanisms for muscarinic receptor-mediated vasoconstriction in coronary resistance arteries were studied in KCl-arrested isolated rat hearts perfused at a constant flow rate. The cholinergic agonists acetylcholine and bethanechol were given by bolus injection or constant infusion. The coronary vascular resistance was monitored by measuring the changes in perfusion pressure. The selective muscarinic agonist bethanechol caused a similar vasoconstrictor response as ACh, but with less potency and efficacy. Bolus injection of bethanechol evoked a phasic vasoconstriction in a dose-dependent manner, while infusion of bethanechol evoked a tonic vasoconstriction without producing tachyphylaxis. Coronary vascular responses to bethanechol were further examined …

Mouse Embryo Development In The Presence Of Capsaicin, Carlos Santiago Villar-Gosalvez

Theses and Dissertations in Biomedical Sciences

Capsaicin is the pungent agent found in hot peppers of the Capsicum genus. It is a potent neurotoxin that stimulates the degranulation and degeneration of C-afferent neurons. Capsaicin is widely used as a food condiment and medicine. Human exposure of capsaicin can exceed levels shown to be neurotoxic in laboratory animals. Additionally, capsaicin can cross the blood/placenta barrier and affect an embryo in utero. In order to assay the potential for toxicity to human embryos, mouse embryos were exposed to capsaicin and the effect of the capsaicin on embryo development was measured. Embryos were co-cultured in Krebs medium with 1% …

Gross And Histological Features Of A Myofascial Trigger Point In The Upper Trapezius, Kathryn E. Levee

Electronic Theses and Dissertations

The purpose of this study was to precisely locate, in living humans, a myofascial trigger point associated with the upper portion of the trapezius muscle (TrP1) that refers pain to the head and neck and to determine if this point is associated with anatomical structures. This study is descriptive and utilizes data from measurements of the location of TrP1 in relation to anatomical landmarks, of pressure sensitivity overlying the trigger point and electromyography recordings in localizing the trigger point. Information obtained from living humans was used to determine anatomical correlation to structures in cadavers. Results indicated there is little variability …

Lead Activation Of A Developmentally Regulated Calcium Channel In Rat Hippocampal Nerve Terminals, Troy E. Rhodes

Theses and Dissertations in Biomedical Sciences

Low level lead (Pb²⁺) exposure may produce lasting deficits in learning and memory by altering calcium (Ca²⁺) dependent processes. Isolated presynaptic nerve terminals from rat hippocampus were loaded with the intracellular (Ca²⁺) indicator Fura-2. The changes in cytoplasmic free calcium ([Ca²⁺]_i) were measured by stopped-flow fluorescence spectroscopy following depolarization with elevated potassium on a millisecond time scale (Lentzner et al., 1992). Depolarization promoted a rapid increase in Ca²⁺_i which occured in two kinetically distinguishable phases: a fast component, representing the activity of rapidly inactivating Ca²⁺ channels (τ …

Neuronal Toxicity Of Humoral Factors From Patients With Diabetic Neuropathy And Mechanism Of Neuronal Death On Cultured Adrenergic Neurons: Studies Of Autoimmune Pathogenesis In Diabetic Neuropathy, Dong Liu

Theses and Dissertations in Biomedical Sciences

Diabetic neuropathy is an extremely common medical problem because of the high frequency of diabetes and its complications. Diabetic neuropathy consists of not one, but many patterns of nerve injury, each potentially with its own discrete pathogenic mechanisms. Evidence is accumulating that indicates autoimmunity plays a role in diabetic peripheral neuropathy. However, the significance of immunopathogenesis of diabetic neuropathy is as yet unclear.

Using the N1E-115 mouse neuroblastoma cell line (NB) as a model of the adrenergic autonomic neuron, we found that sera of IDDM patients with neuropathy inhibit growth and differentiation of adrenergic neurons in culture (Pittenger et al, …

Identification And Characterization Of Mitochondrial Dna Variants In Alzheimer's Disease, Natasha Singh Hamblet

Theses and Dissertations in Biomedical Sciences

Alzheimer's Disease (AD) is a complex neurodegenerative disorder that affects a significant portion of the human population regardless of ethnicity or gender. A mitochondrial hypothesis of AD has been proposed based on a number of studies which establish altered oxidative phosphorylation (OXPHOS) and ATP synthesis in AD tissue. ATP demand is most prevalent in the brain; damage to OXPHOS could severely impair brain metabolism, thereby leading to a decline in cognitive function. Four out of five complexes in the OXPHOS pathway are partly encoded by mitochondrial DNA (mtDNA); thus, this may be a crucial site of lesions that alter brain …

Persistent Oral Dyskinesias Induced By Long-Term Haloperidol Treatment Is Dissociated From Changes In Neostriatal B(Max) And Mrna Content For Dopamine D(2) Receptors, Nuoyu Huang

Electronic Theses and Dissertations

Due to the presumed associations of dopamine (DA) receptor supersensitivity phenomena in both long-term neuroleptic-treated tardive dyskinetic rats and neonatal 6-hydroxydopamine (n6-OHDA)-lesioned rats, we studied the influence of haloperidol on n6-OHDA-lesioned rats. At 3 days after birth rats received 6-OHDA-HBr (200 $\mu$g, bilateral intracerebroventricularly; desipramine pretreatment, 20 mg/kg, 1h) or vehicle. Two months later haloperidol (1.5/kg/day $\times$ 2 days/week for 4 weeks, then 1.5 mg/kg/day, every day for 10 months) was added to the drinking water. Spontaneous oral activity of intact and n6-OHDA-lesioned rats receiving haloperidol was reached and maintained at significantly higher levels after 15 weeks of haloperidol treatment. …

Localisation Of The Gene For A Novel Form Of Charcot-Marie-Tooth Disease In An Isolated Population, Kaite Honeyman

Theses : Honours

Localising the gene for a previously undescribed autosomal recessive form of CMT involved the use of a relatively new approach to rapid genome screening based on the identification of segments which are inherited identical by descent (IBD) from common founding ancestors. It is most feasible for populations which have been founded relatively recently (say less than 25 generations) and which have remained relatively isolated either geographically or culturally. The method is not suitable for highly inbred populations, that is with first and second cousin matings, as many segments will be inherited by chance. It appears to be a suitable screening …

An Analysis Of Mitochondrial Dna In Rett Syndrome And Other Neurodegenerative Disorders, Catherine Erickson Burgess

Theses and Dissertations in Biomedical Sciences

Mitochondrial dysfunction resulting from mutations on mitochondrial DNA (mtDNA) is being recognized in a growing spectrum of diseases. These diseases, resulting from single base mutations, large deletions, or insertions, have been largely neuromuscular in origin. However, as an understanding of the effects of mtDNA mutations progresses, attention is now focusing on neurodegenerative diseases. Rett Syndrome (RS), a progressive neurodegenerative disease with predominantly female cases, demonstrates morphologic mitochondrial changes, mitochondrial enzyme deficiencies and maternal inheritance (characteristic of mtDNA diseases). No investigation of mtDNA involvement has been previously conducted and, to date, no biological marker exists for this disorder.

Our preliminary studies …

Co-Sensitization Of Dopamine And Serotonin Receptors Occurs In The Absence Of A Change In The Dopamine D1 Receptor Complex After A Neonatal 6-Ohda Lesion, Li Gong

Electronic Theses and Dissertations

To test whether SKF 38393 could ontogenetically sensitize dopamine (DA) D$\sb1$ receptors and whether this sensitization would be associated with biochemical changes, intact and neonatal 6-hydroxydopamine (6-OHDA)-lesioned rats (200 $\mu$g i.c.v.) were treated daily from birth with SKF 38393 (3.0 mg/kg i.p. x 28 days) or its vehicle. In DA D$\sb1$ neonatally sensitized 6-OHDA rats, enhanced locomotor responses were observed with the first SKF 38393 challenge dose (3.0 mg/kg i.p.) at 6 weeks. This response increased further with weekly SKF 38393 treatments. Enhanced stereotyped behaviors were seen in both lesioned and sensitized rats at 8 weeks. There was no change …

The Effect Of Trimethyltin On The Cholinergic System Of The Rat Hippocampus, Richard L. Cannon

Electronic Theses and Dissertations

Trimethyltin (TMT) is a neurotoxin occurring in the environment. Exposure to (TMT) is known to destroy specific neuronal components of the hippocampus in the rat and to cause clinical symptoms in exposed humans, including mnemonic deficits, that indicate hippocampal involvement. In addition to hippocampal cell loss TMT causes significant increases in cholinergic markers such as acetylcholinesterase (AChE) stain density and choline acetyltransferase (ChAT) activity in the hippocampus of rats. However, despite these observations the effect of TMT on hippocampal cholinergic system has not been investigated in detail. The purpose of the present study was to elucidate more fully the consequences …

Identification And Characterization Of Possible Multiple Binding Sites For ((3)H)8-Oh-Dpat In The Hippocampus, Dawna Lea Evans

Masters Theses

No abstract provided.

Fixed-Ratio Size As A Determinant Of The Development Of Tolerance To Morphine, Mark J. Nickel

Masters Theses

The acute and chronic effects of morphine were examined in pigeons exposed to a multiple schedule with fixed ratio 5, 25, and 125 components. Acute exposure to morphine (0.56-10.0 mg/kg) resulted in rate reductions under each component when the dose was 1 mg/kg or higher. With chronic exposure to 5.6 mg/kg, tolerance to the rate-reducing effects of morphine was evident under each fixed ratio component. The development of tolerance was determined to some extent by fixed-ratio size, a result similar to earlier findings with cocaine.

The Role Of Gaba In Reproductive Neuroendocrine Systems, Robert Carter Mcree

Theses and Dissertations in Biomedical Sciences

Local gamma-amino butyric acid (GABA) neurons in the hypothalamus can modulate the luteinizing hormone releasing hormone (LHRH) pulse generating system.

Two animal models (intact and ovariectomized rats) were used to determine the nature of modulation of LHRH release by GABA. The experiment determined the release of LHRH, serotonin (5-HT), and 5-hydroxyindole acetic acid (5-HIAA) during two hormonal states with each model. In the intact rat the proestrus and estrus states were examined, and in the ovariectomized rat in-vitro release was determined with (OVX₂) and without (OVX) estradiol treatment.

In-vivo experiments studied the effect of stimulation of GABA receptors …

Morphological And Physiological Examination Of A Demyelinating And Remyelinating Lesion, Paul Anson Felts

Theses and Dissertations in Biomedical Sciences

Multiple sclerosis causes demyelination of central nerve fibers, and it is this pathology which results in most of the symptoms of the disease. The repair of the fibers by remyelination has been advanced as a potential symptomatic therapy, but at present the conduction properties of remyelinated central fibers are not well understood. In this study the conduction properties of Schwannian or oligodendrocyte remyelinated central nerve fibers have been determined. In addition, the status of the blood-brain barrier has been examined in lesions characterized by Schwann cell remyelination. These lesions chronically lack astrocytes, a cell believed to be involved in the …