Neuroscience and Neurobiology Commons^™

Novel Ubiquitin Neuropathology In Frontotemporal Dementia With Valosin-Containing Protein Gene Mutations, Mark Forman, Ian Mackenzie, Nigel Cairns, Eric Swanson, Philip Boyer, David Drachman, Bharati Jhaveri, Jason Karlawish, Alan Pestronk, Thomas Smith, Pang-Hsien Tu, Giles Watts, William Markesbery, Charles Smith, Virginia Kimonis

Jason Karlawish

Frontotemporal dementia (FTD) with inclusion body myopathy and Paget disease of bone (IBMPFD) is a rare, autosomal-dominant disorder caused by mutations in the valosin-containing protein (VCP) gene, a member of the AAA-ATPase gene superfamily. The neuropathology associated with sporadic FTD is heterogeneous and includes tauopathies and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). However, there is limited information on the neuropathology in IBMPFD. We performed a detailed, systematic analysis of the neuropathologic changes in 8 patients with VCP mutations. A novel pattern of ubiquitin pathology was identified in IBMPFD that was distinct from sporadic and familial FTLD-U without VCP gene …

Measuring Decision-Making Capacity In Cognitively Impaired Individuals, Jason Karlawish

Jason Karlawish

Cognitive and functional losses are only part of the spectrum of disability experienced by persons with Alzheimer's disease and related dementias. They also experience losses in the ability to make decisions, known as decision-making capacity. Researchers have made substantial progress in developing a model of capacity assessment that rests upon the concept of the 4 decision-making abilities: understanding, appreciation, choice and reasoning. Empirical research has increased our understanding of the effects of late-life cognitive impairment on a person's ability to make decisions. This review examines studies of the capacity to consent to treatment, research and the management of everyday functional …

The Capacity To Vote Of Persons With Alzheimer’S Disease, Paul S. Appelbaum, Richard S. Bonnie, Jason Karlawish

Jason Karlawish

OBJECTIVE: The right to vote can be abrogated when persons become incompetent to cast a ballot. This applies particularly to people with Alzheimer’s disease, who at some point will lose capacity. A 2001 federal court decision offered the first clear criteria (“Doe voting capacity standard”) for determining voting competence, focused on understanding the nature and effect of voting and on the ability to choose. This article explores how persons with Alzheimer’s disease perform on these criteria. METHOD: The Doe standard was operationalized in a brief questionnaire, along with measures of appreciation and reasoning about voting choices. Performance was assessed in …

Keynote Speaker Presentations: 5th Annual Umass Center For Clinical And Translational Research Retreat (Video), Robert H. Brown Jr., Thomas Grisso

Thomas Grisso

This video features the full keynote presentations from the 5th Annual UMass Center for Clinical and Translational Science Research Retreat at the University of Massachusetts Medical School (UMMS) in Worcester, MA, on May 20, 2014.

Beginning at 12:40

1st Keynote Speaker: Robert H. Brown, Jr., MD, D.Phil, Chair, Department of Neurology, UMMS. “Lou Gehrig Disease: From Mapping to Medicines”

Beginning at 1:22:19

2nd Keynote Speaker: Thomas Grisso, PhD, Director, Law and Psychiatry Program and Professor, Department of Psychiatry, UMMS. Recipient, Chancellor’s Medal for Distinguished Scholarship. “Translational Research in Law and Psychiatry”

Also included is a brief introductory presentation with updates …

Neurogenic Stem Cells Have The Capacity To Disperse Widely And Fuse With Host Neurons In Adult Rats, Kerry Thompson, Emily Kimes, Michele Kanemori, Daniella Amri, Ashley Noone, Jerika Barron, Ashley Saito, Omar Cortez-Toledo, Ellie Cortez-Toledo, David Arrizon, Johanna Quist, Yohualli Balderas, Melissa Miranda, Tina Tran, Frances Kim

Kerry Thompson

No abstract provided.

Buildings With Brain Power: Library Architecture In Neural Terms., Hannah Bennett

Hannah Bennett

The connection between neuroscience and the built environment is a fairly new interdisciplinary field and one in which both fields, in their respective pursuits, have worked to understand the relationship between design choices, human behavior, and biological processes. Taken together and applied in tandem, these two activities have potential to vastly improve the effectiveness of buildings designed with the healthcare facilities, laboratories, or elementary schools, all of which share objectives of healing and intellectual cultivation. This paper will extend the dialogue to library design, perhaps the most representationally loaded expression of “mental space.” The library has seen profound changes in …

Similarities Between Human And Animal Spatial Memory: Item And Order Information, Robert H.I. Dale

Robert H. I. Dale

Human subjects, sitting at the center of a circle of eight lights, were tested on analogues of radial-maze item-recognition (Roberts & Smythe, 1979) and order-recognition (Kesner & Novak, 1982) tasks. Subjects in the item-recognition condition saw a list of seven lights, and then the nonlist (eighth) light was tested against the first, fourth, or seventh light from the list. The sub- jects were required to point toward the non list light. Subjects in the order-recognition condition saw a series of eight lights, followed by a test of the first and second, fourth and fifth, or seventh and eighth serial positions. …

Spatial And Temporal Response Patterns On The Eight-Arm Radial Maze, Robert H.I. Dale

Robert H. I. Dale

Six maze-experienced hooded rats were timed during five trials on which they collected water from all arms of an eight-arm radial maze, then made five more choices. All subjects frequently exhibited a “task-completion pause:” The subjects rarely spent more than 1 sec in the center of the maze between choices until they had entered all eight arms, then stopped in the center of the maze. In contrast, the time spent in each arm gradually increased until all of the water had been obtained, then decreased slightly. Four subjects began every trial by choosing eight consecutive adjacent arms. The task-completion pause …

The Relative Attenuation Of Self-Stimulation, Eating And Drinking Produced By Dopamine-Receptor Blockade, E. T. Rolls, B. J. Rolls, P. H. Kelly, S. G. Shaw, R. J. Wood, Robert H.I. Dale

Robert H. I. Dale

Spiroperidol, which blocks dopamine (DA) receptors, attenuated self-stimulation of the nucleus accumbens, septal area, hippocampus, anterior hypothalamus and ventral tegmental area. Dopamine is thus involved in self-stimulation of many sites (in addition to the lateral hypothalamus). The attenuation was not a simple motor impairment of the speed of bar-pressing in that the nucleus accumbens and septal self-stimulation rates were lower than those in treated animals self-stimulating at other sites (Experiment 1). Feeding was partly attenuated, and drinking was much less attenuated by the spiroperidol. Since the rats bar-pressed for brain- stimulation reward, chewed pellets to eat, and licked a tube …

Limitations On Spatial Memory In Mice, Robert H.I. Dale, Martin Bedard

Robert H. I. Dale

Rats have an impressive ability to remember locations they have visited. Two experiments used an eight-arm radial maze to determine whether mice showed two important characteristics of this spatial memory: its durability, and its dependence on stimuli outside the maze (extreme stimuli). In Experiment 1, food-deprived mice were allowed to eat from four of the eight arms of the maze then, after delays of 5 sec, 1 min, or 5 min, they were permitted to choose the remaining arms. Choice accuracy declined significantly with the longer delays, but always remained above chance. In Experiment 2, the maze was rotated 180° …

The Hippocampus As Episodic Encoder: Does It Play Tag?, Robert H.I. Dale

Robert H. I. Dale

Rawlins’s characterization of the hippocampus as a “high-capacity, immediate-term memory store” captures the essential idea in a number of previous models. For example, Gaffan (1974), Gray (1984), Hirsh (1980), Kesner (Bierley, Kesner & Novak 1983), Olton (Olton, Becker & Handelmann 1979), Solomon (1980), and Winocur (1980) all agree that hippocampal animals show memory deficits when required to identify, for whatever reason, one specific event out of a list of recent events. Although these authors disagree on a number of details, Rawlins has identified their models common ground, the core of each model. (It is only fair to note that Gaffan …

Radial-Maze Performance In The Rat Following Lesions Of Posterior Neocortex, Melvyn A. Goodale, Robert H.I. Dale

Robert H. I. Dale

The present experiment was designed to investigate the role of posterior neocortex (areas 17, 18 and 18a) in the maintenance of performance on the radial maze. Following training to criterion on the 8-arm radial maze, rats received either sham operations, bilateral eye enucleations, lesions of posterior neocortex, or combined enucleations and lesions of posterior neocortex. While the enucleated animals with intact brains showed a slight, but significant performance decrement relative to the sham-operated group, the other two groups, with lesions of areas 17, 18 and 18a, each showed a massive deficit. This large deficit was observed even in the group …

Parallel-Arm Maze Performance Of Sighted And Blind Rats: Spatial Memory And Maze Structure, Robert H.I. Dale

Robert H. I. Dale

Sighted and peripherally blinded groups of rats learned to obtain a small reward from each arm of an eight-arm parallel maze, and a sighted group was similarly trained on a radial maze. The parallel-sighted and parallel-blind groups were equally slow, and much slower than the radial-sighted group, to attain criterion performance. The three groups shared several response characteristics: selectively avoiding the most recently entered arms, frequently choosing adjacent arms, and an absence of 'spatial generalization' among the arms. The findings support a simple model proposing how subjects identify and choose among the maze-arms.

Role Of Gluk1 Kainate Receptors In Seizures, Epileptic Discharges, And Epileptogenesis, Brita Fritsch, Janine Reis, Maciej Gasior, Rafal M. Kaminski, Michael A. Rogawski

Michael A. Rogawski

Kainate receptors containing the GluK1 subunit have an impact on excitatory and inhibitory neurotransmission in brain regions, such as the amygdala and hippocampus, which are relevant to seizures and epilepsy. Here we used 2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA), a potent and selective agonist of kainate receptors that include the GluK1 subunit, in conjunction with mice deficient in GluK1 and GluK2 kainate receptor subunits to assess the role of GluK1 kainate receptors in provoking seizures and in kindling epileptogenesis. We found that systemic ATPA, acting specifically via GluK1 kainate receptors, causes locomotor arrest and forelimb extension (a unique behavioral characteristic of GluK1 …

Role Of Gluk1 Kainate Receptors In Seizures, Epileptic Discharges, And Epileptogenesis, Brita Fritsch, Janine Reis, Maciej Gasior, Rafal M. Kaminski, Michael A. Rogawski

Michael A. Rogawski

Kainate receptors containing the GluK1 subunit have an impact on excitatory and inhibitory neurotransmission in brain regions, such as the amygdala and hippocampus, which are relevant to seizures and epilepsy. Here we used 2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA), a potent and selective agonist of kainate receptors that include the GluK1 subunit, in conjunction with mice deficient in GluK1 and GluK2 kainate receptor subunits to assess the role of GluK1 kainate receptors in provoking seizures and in kindling epileptogenesis. We found that systemic ATPA, acting specifically via GluK1 kainate receptors, causes locomotor arrest and forelimb extension (a unique behavioral characteristic of GluK1 …

Painful Disparities, Painful Realities, Amanda C. Pustilnik

Amanda C Pustilnik

Legal doctrines and decisional norms treat chronic claims pain differently than other kinds of disability or damages claims because of bias and confusion about whether chronic pain is real. This is law’s painful disparity. Now, breakthrough neuroimaging can make pain visible, shedding light on these mysterious ills. Neuroimaging shows these conditions are, as sufferers have known all along, painfully real. This Article is about where law ought to change because of innovations in structural and functional imaging of the brain in pain. It describes cutting-edge scientific developments and the impact they should make on evidence law and disability law, and, …

Effects Of Light On Flight Crew Health And Alertness; Study Results Revealed, Lori Brown

Lori Brown

Portable bright light units, the Boeing Alertness Model (BAM) and Jeppessen Crew Alert application have been introduced in a field study with long haul pilots and cabin crew in ground breaking research – which may lead to improvements in aviation safety through the development of new preventive alertness strategies. Western Michigan University, Novair Airlines, Nature Bright, Jeppesen Crew Alert and leading sleep scientists collaborated to examine whether timed blue light integrated with the Boeing Alertness Model will improve alertness, and mitigate cognitive fatigue. The CrewAlert application and timed light puts innovative preventative fatigue strategies in the palm of the crew …

Jmu 4-Va Grant: Gene Expression Analysis In The Developing Vertebrate Retina Using Next Generation Sequencing, Raymond A. Enke

Ray Enke Ph.D.

Massively Parallel Nonparametric Regression, With An Application To Developmental Brain Mapping, Philip T. Reiss, Lei Huang, Yin-Hsiu Chen, Lan Huo, Thaddeus Tarpey, Maarten Mennes

Lei Huang

We propose a penalized spline approach to performing large numbers of parallel nonparametric analyses of either of two types: restricted likelihood ratio tests of a parametric regression model versus a general smooth alternative, and nonparametric regression. Compared with naively performing each analysis in turn, our techniques reduce computation time dramatically. Viewing the large collection of scatterplot smooths produced by our methods as functional data, we develop a clustering approach to summarize and visualize these results. Our approach is applicable to ultra-high-dimensional data, particularly data acquired by neuroimaging; we illustrate it with an analysis of developmental trajectories of functional connectivity at …

Effects Of Polychlorinated Biphenyl (Pcb) On Response Perseveration And Ultrasonic Vocalization Emission In Rat During Development, Howard Cromwell

Howard Casey Cromwell

The 3 major symptoms of autistic spectrum disorders include 1) social behavioral alterations, 2) problems in communication and 3) higher-order motoric deficits of perseveration and stereotyped movements. Previous work has shown that early developmental exposure to polychlorinated biphenyls (PCBs) alters rat pup social motivation and juvenile rat social recognition/investigation. The present work extends this previous research by examining how perinatal PCB exposure alters motoric functions and communication abilities at different stages of development. Action perseveration was examined using performance measures from a T-maze environment. Communication abilities were evaluated by monitoring ultrasound emission in rat pups during a brief isolation from …

Reportinfluence Of Emotional States On Inhibitory Gating: Animal Models To Clinical Neurophysiology, Howard Cromwell

Howard Casey Cromwell

tIntegrating research efforts using a cross-domain approach could redefine traditional constructs used inbehavioral and clinical neuroscience by demonstrating that behavior and mental processes arise not fromfunctional isolation but from integration. Our research group has been examining the interface betweencognitive and emotional processes by studying inhibitory gating. Inhibitory gating can be measured viachanges in behavior or neural signal processing. Sensorimotor gating of the startle response is a well-usedmeasure. To study how emotion and cognition interact during startle modulation in the animal model,we examined ultrasonic vocalization (USV) emissions during acoustic startle and prepulse inhibition. Wefound high rates of USV emission during the …

Stimulus Induced Reversal Of Information Flow Through A Cortical Network For Animacy Perception., Sarah Shultz, Rebecca Van Den Honert, Andrew Engell, Gregory Mccarthy

Andrew Engell

Neural And Genetic Degeneracy Underlies Caenorhabditis Elegans Feeding Behavior, Christopher Fang-Yen

Christopher Fang-Yen

Jmu 4-Va Grant: Characterizing Epigenetic Regulation Of Gene Experession During Development Of The Vertebrate Retina, Raymond A. Enke

Ray Enke Ph.D.