Neurosciences Commons^™

The Effect Of Rare Variants In Trem2 And Pld3 On Longitudinal Cognitive Function In The Wisconsin Registry For Alzheimer's Prevention, Corinne D. Engelman, Burcu F. Darst, Murat Bilgel, Eva Vasiljevic, Rebecca L. Koscik, Bruno M. Jedynak, Sterling C. Johnson

Mathematics and Statistics Faculty Publications and Presentations

Recent studies have found an association between functional variants in TREM2 and PLD3 and Alzheimer's disease (AD), but their effect on cognitive function is unknown. We examined the effect of these variants on cognitive function in 1449 participants from the Wisconsin Registry for Alzheimer's Prevention, a longitudinal study of initially asymptomatic adults, aged 36–73 years at baseline, enriched for a parental history of AD. A comprehensive cognitive test battery was performed at up to 5 visits. A factor analysis resulted in 6 cognitive factors that were standardized into z scores (∼N [0, 1]); the mean of these z scores was …

Possible Breakdown Of Dopamine Receptor Synergism In A Mouse Model Of Huntington's Disease, Samantha F. Kennedy

LSU New Orleans Theses and Dissertations

The model of basal ganglia function proposed by Albin, Young and Penney (1989) describes two anatomically independent motor pathways, the direct and indirect. However, under normal conditions striatal dopamine (DA) is required for the expression of motor behavior, and DAergic control of the two pathways (via D1 and D2 receptors, respectively) is dependent on co-activation. We tested for a possible breakdown of D1/D2 synergism using transgenic R6/1 mice bearing the human huntingtin allele (Htt). Motor stereotypy, observed prior to the onset of HD-related symptoms, was rated on a 5-point scale following activation of: A) D1 receptors alone, B) D2 receptors …

Virtual Reality As A Training Tool To Treat Physical Inactivity In Children, Adam W. Kiefer, David Pincus, Michael J. Richardson, Gregory D. Myer

Psychology Faculty Articles and Research

Lack of adequate physical activity in children is an epidemic that can result in obesity and other poor health outcomes across the lifespan. Physical activity interventions focused on motor skill competence continue to be developed, but some interventions, such as neuromuscular training (NMT), may be limited in how early they can be implemented due to dependence on the child’s level of cognitive and perceptual-motor development. Early implementation of motor-rich activities that support motor skill development in children is critical for the development of healthy levels of physical activity that carry through into adulthood. Virtual reality (VR) training may be beneficial …

Novel Therapeutic Approaches For Juvenile Neuronal Ceroid Lipofuscinosis (Cln3), Megan Elizabeth Bosch

Theses & Dissertations

Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) is a lysosomal storage disease caused by autosomal recessive mutations in CLN3. Neuronal loss is thought to occur via glutamate excitotoxicity; however, little is known about neuron-astrocyte glutamate regulation in JNCL. We discovered that Cln3^Δex7/8 astrocytes have significantly lower basal spontaneous Ca²⁺ oscillations and decreased responses to glutamate, indicating a disrupted signaling network. Cln3^Δex7/8 astrocytes also displayed significantly lower basal mitochondrial respiration and ATP production, suggesting impaired metabolic functions. Concurrent with diminished astrocyte metabolism and Ca²⁺ signaling, Cln3^Δex7/8 neurons were hyper-responsive to glutamate stimulation. These studies suggest that CLN3 …

Interhospital Transfer Before Thrombectomy Is Associated With Delayed Treatment And Worse Outcome In The Stratis Registry (Systematic Evaluation Of Patients Treated With Neurothrombectomy Devices For Acute Ischemic Stroke)., Michael T Froehler, Jeffrey L Saver, Osama O Zaidat, Reza Jahan, Mohammad Ali Aziz-Sultan, Richard P Klucznik, Diogo C Haussen, Frank R Hellinger, Dileep R Yavagal, Tom L Yao, David S Liebeskind, Ashutosh P Jadhav, Rishi Gupta, Ameer E Hassan, Coleman O Martin, Hormozd Bozorgchami, Ritesh Kaushal, Raul G Nogueira, Ravi H Gandhi, Eric C Peterson, Shervin R Dashti, Curtis A Given, Brijesh P Mehta, Vivek Deshmukh, Sidney Starkman, Italo Linfante, Scott H Mcpherson, Peter Kvamme, Thomas J Grobelny, Muhammad S Hussain, Ike Thacker, Nirav Vora, Peng Roc Chen, Stephen J Monteith, Robert D Ecker, Clemens M Schirmer, Eric Sauvageau, Alex Abou-Chebl, Colin P Derdeyn, Lucian Maidan, Aamir Badruddin, Adnan H Siddiqui, Travis M Dumont, Abdulnasser Alhajeri, M Asif Taqi, Khaled Asi, Jeffrey Carpenter, Alan Boulos, Gaurav Jindal, Ajit S Puri, Rohan Chitale, Eric M Deshaies, David H Robinson, David F Kallmes, Blaise W Baxter, Mouhammad A Jumaa, Peter Sunenshine, Aniel Majjhoo, Joey D English, Shuichi Suzuki, Richard D Fessler, Josser E Delgado Almandoz, Jerry C Martin, Nils H Mueller-Kronast, Stratis Investigators

Neuroscience Articles

BACKGROUND: Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation.

METHODS: STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or …

Ran Translation At C9orf72-Associated Repeat Expansions Is Selectively Enhanced By The Integrated Stress Response, Katelyn M. Green, M. Rebecca Glineburg, Michael G. Kearse, Brittany N. Flores, Alexander E. Linsalata, Stephen J. Fedak, Aaron C. Goldstrohm, Sami J. Barmada, Peter K. Todd

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Repeat-associated non-AUG (RAN) translation allows for unconventional initiation at disease-causing repeat expansions. As RAN translation contributes to pathogenesis in multiple neurodegenerative disorders, determining its mechanistic underpinnings may inform therapeutic development. Here we analyze RAN translation at G₄C₂ repeat expansions that cause C9orf72-associated amyotrophic lateral sclerosis and frontotemporal dementia (C9RAN) and at CGG repeats that cause fragile X-associated tremor/ataxia syndrome. We find that C9RAN translation initiates through a cap- and eIF4A-dependent mechanism that utilizes a CUG start codon. C9RAN and CGG RAN are both selectively enhanced by integrated stress response (ISR) activation. ISR-enhanced RAN translation requires an …

Structural Insights Into The Potency Of Sk Channel Positive Modulators, Young-Woo Nam, Razan Orfali, Tingting Liu, Kunqian Yu, Meng Cui, Heike Wulff, Miao Zhang

Pharmacy Faculty Articles and Research

Small-conductance Ca2+-activated K+ (SK) channels play essential roles in the regulation of cellular excitability and have been implicated in neurological and cardiovascular diseases through both animal model studies and human genetic association studies. Over the past two decades, positive modulators of SK channels such as NS309 and 1-EBIO have been developed. Our previous structural studies have identified the binding pocket of 1-EBIO and NS309 that is located at the interface between the channel and calmodulin. In this study, we took advantage of four compounds with potencies varying over three orders of magnitude, including 1-EBIO, NS309, SKS-11 (6-bromo-5-methyl-1H-indole-2,3-dione-3-oxime) and …

Validation Of Minimally-Invasive Sample Collection Methods For Measurement Of Telomere Length, Stephanie A. Stout, Jue Lin, Natalie Hernandez, Elyssia Poggi Davis, Judith E. Carroll, Laura M. Glynn

Psychology Faculty Articles and Research

Objective: The discovery of telomere length (TL) as a biomarker of cellular aging and correlate of age-related disease has generated a new field of research in the biology of healthy aging. Although the most common method of sample collection for TL is venous blood draw, less-invasive DNA collection methods are becoming more widely used. However, how TL relates across tissues derived from these sample collection methods is poorly understood. The current study is the first to characterize the associations in TL across three sample collection methods: venous whole blood, finger prick dried blood spot and saliva.

Methods: TL …

The Climate Of Neurofeedback: Scientific Rigour And The Perils Of Ideology, Robert T. Thibault, Michael Lifshitz, Amir Raz

Psychology Faculty Articles and Research

Over the last six decades, an in-group with ideological and financial stakes has been conducting sub-par research to develop an ostensibly effective clinical intervention: EEG-neurofeedback. More recently, however, a string of independent studies featuring increased scientific rigour and tighter experimental controls has challenged the foundation on which EEG-neurofeedback stands. Earlier this year, Brain published one of the most robust EEG-neurofeedback experiments to date (Schabus et al., 2017), which sparked a flurry of correspondence concerning the therapeutic value of neurofeedback (Fovet et al., 2017; Schabus, 2017); notably, a parallel discussion continues in Lancet Psychiatry …

Validation Of Minimally-Invasive Sample Collection Methods For Measurement Of Telomere Length, Stephanie A. Stout, Jue Lin, Natalie Hernandez, Elysia Poggi Davis, Elizabeth Blackburn, Judith E. Carroll, Laura M. Glynn

Psychology: Faculty Scholarship

Objective: The discovery of telomere length (TL) as a biomarker of cellular aging and correlate of age-related disease has generated a new field of research in the biology of healthy aging. Although the most common method of sample collection for TL is venous blood draw, less-invasive DNA collection methods are becoming more widely used. However, how TL relates across tissues derived from these sample collection methods is poorly understood. The current study is the first to characterize the associations in TL across three sample collection methods: venous whole blood, finger prick dried blood spot and saliva.

Methods: TL …

Analysis Of Diagnostic, Preventive, And Disease-Modifying Therapeutic Measures Of Alzheimer’S Disease, Ghazal Habib Havoutis

HCNSO Student Capstones

Alzheimer’s disease (AD) is the most common late-onset neurodegenerative disorder and cause of dementia, characterized by the formation of neurofibrillary tangles and senile plaque deposits. The heterogeneous nature of the disease (both genetically and environmentally) makes it difficult to prevent or cure. Without prevention, the prevalence of AD is expected to triple by 2050. However, because the diagnosis of AD is usually preceded by years of cognitive impairment, early detection may aid in reducing prevalence. Thus, there is a need for validated diagnostic measures for early and improved diagnosis and prevention. In this review, current and ongoing classifiers of early …

Higher And Lower Order Factor Analyses Of The Temperament In Middle Childhood Questionnaire., Yuliya Kotelnikova, Thomas M Olino, Daniel N Klein, Sarah V M Mackrell, Elizabeth P Hayden

Brain and Mind Institute Researchers' Publications

The Temperament in Middle Childhood Questionnaire (TMCQ) is a widely used parent-report measure of temperament. However, neither its lower nor higher order structures has been tested via a bottom-up, empirically based approach. We conducted higher and lower order exploratory factor analyses (EFAs) of the TMCQ in a large ( N = 654) sample of 9-year-olds. Item-level EFAs identified 92 items as suitable (i.e., with loadings ≥.40) for constructing lower order factors, only half of which resembled a TMCQ scale posited by the measure's authors. Higher order EFAs of the lower order factors showed that a three-factor structure (Impulsivity/Negative Affectivity, Negative …

Hippocampal Gaba Enables Inhibitory Control Over Unwanted Thoughts, Taylor W. Schmitz, Marta M. Correia, Catarina S. Ferreira, Andrew P. Prescot, Michael C. Anderson

Brain and Mind Institute Researchers' Publications

© 2017 The Author(s). Intrusive memories, images, and hallucinations are hallmark symptoms of psychiatric disorders. Although often attributed to deficient inhibitory control by the prefrontal cortex, difficulty in controlling intrusive thoughts is also associated with hippocampal hyperactivity, arising from dysfunctional GABAergic interneurons. How hippocampal GABA contributes to stopping unwanted thoughts is unknown. Here we show that GABAergic inhibition of hippocampal retrieval activity forms a key link in a fronto-hippocampal inhibitory control pathway underlying thought suppression. Subjects viewed reminders of unwanted thoughts and tried to suppress retrieval while being scanned with functional magnetic resonance imaging. Suppression reduced hippocampal activity and memory …

Role Of Membrane Gm1 On Early Neuronal Membrane Actions Of Aβ During Onset Of Alzheimer's Disease, E. J. Fernandez-Perez, Fernando Sepulveda, Robert W. Peoples, Luis G. Aguayo

Biomedical Sciences Faculty Research and Publications

The ability of beta-amyloid peptide (Aβ) to disrupt the plasma membrane through formation of pores and membrane breakage has been previously described. However, the molecular determinants for these effects are largely unknown. In this study, we examined if the association and subsequent membrane perforation induced by Aβ was dependent on GM1levels. Pretreatment of hippocampal neurons with D-PDMP decreased GM1 and Aβ clustering at the membrane (Aβ fluorescent-punctas/20 μm, control = 16.2 ± 1.1 vs. D-PDMP = 6.4 ± 0.4, p < 0.001). Interestingly, membrane perforation with Aβ occurred with a slower time course when the GM1 content was diminished (time to establish perforated configuration (TEPC) (min): control = 7.8 ± 2 vs. low GM1 = 12.1 ± 0.5, p < 0.01), suggesting that the presence of GM1 in the membrane can modulate the distribution and the membrane perforation by Aβ. On the other hand, increasing GM1 facilitated the membrane perforation (TEPC: control = 7.8 ± 2 vs. GM1 = 6.2 ± 1 min, p < 0.05). Additionally, using Cholera Toxin Subunit-B (CTB) to block the interaction of Aβ with GM1 attenuated membrane perforation significantly. Furthermore, …

Cerebrovascular Pathology In Down Syndrome And Alzheimer Disease, Elizabeth Head, Michael J. Phelan, Eric Doran, Ronald C. Kim, Wayne W. Poon, Frederick A. Schmitt, Ira T. Lott

Sanders-Brown Center on Aging Faculty Publications

People with Down syndrome (DS) are at high risk for developing Alzheimer disease (AD) with age. Typically, by age 40 years, most people with DS have sufficient neuropathology for an AD diagnosis. Interestingly, atherosclerosis and hypertension are atypical in DS with age, suggesting the lack of these vascular risk factors may be associated with reduced cerebrovascular pathology. However, because the extra copy of APP leads to increased beta-amyloid peptide (Aβ) accumulation in DS, we hypothesized that there would be more extensive and widespread cerebral amyloid angiopathy (CAA) with age in DS relative to sporadic AD. To test this hypothesis CAA, …

Exercise, Learning And Emotional Health: Interdisciplinary Approaches To Translational Action, Tessa L. Koschel

UNLV Theses, Dissertations, Professional Papers, and Capstones

Exercise positively effects physical, psychological and neurological wellbeing. Though the population at large is becoming increasingly aware of the multi-faceted benefits of exercise, the majority of people fail to meet daily exercise recommendations. Largely, demands of everyday life such as work, school and family take priority over fitness. The issue therefore becomes a matter of time. In a world of media multi-tasking and immediate gratification, the challenge to health professionals becomes incorporation and manipulation of these consistencies to improve exercise uptake and adherence. Focus must shift from the idea of making additional time for exercise, to adding exercise to time …

A Customized Quantitative Pcr Microrna Panel Provides A Technically Robust Context For Studying Neurodegenerative Disease Biomarkers And Indicates A High Correlation Between Cerebrospinal Fluid And Choroid Plexus Microrna Expression, Wang-Xia Wang, David W. Fardo, Gregory A. Jicha, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNA (miRNA) expression varies in association with different tissue types and in diseases. Having been found in body fluids including blood and cerebrospinal fluid (CSF), miRNAs constitute potential biomarkers. CSF miRNAs have been proposed as biomarkers for neurodegenerative diseases; however, there is a lack of consensus about the best candidate miRNA biomarkers and there has been variability in results from different research centers, perhaps due to technical factors. Here, we sought to optimize technical parameters for CSF miRNA studies. We examined different RNA isolation methods and performed miRNA expression profiling with TaqMan® miRNA Arrays. More specifically, we developed a customized …

Widespread Theta Synchrony And High-Frequency Desynchronization Underlies Enhanced Cognition., E. A. Solomon, J. E. Kragel, Michael R. Sperling, Ashwini Sharan, G. Worrell, M. Kucewicz, C. S. Inman, B. Lega, K. A. Davis, J. M. Stein, B. C. Jobst, K. A. Zaghloul, S. A. Sheth, D. S. Rizzuto, M. J. Kahana

Department of Neurology Faculty Papers

The idea that synchronous neural activity underlies cognition has driven an extensive body of research in human and animal neuroscience. Yet, insufficient data on intracranial electrical connectivity has precluded a direct test of this hypothesis in a whole-brain setting. Through the lens of memory encoding and retrieval processes, we construct whole-brain connectivity maps of fast gamma (30-100 Hz) and slow theta (3-8 Hz) spectral neural activity, based on data from 294 neurosurgical patients fitted with indwelling electrodes. Here we report that gamma networks desynchronize and theta networks synchronize during encoding and retrieval. Furthermore, for nearly all brain regions we studied, …

Modeling Post Stroke Respiratory Dysfunction, Apneas And Cognitive Decline, Anthony Patrizz

Dissertations and Theses (Open Access)

Modeling Post Stroke Respiratory Dysfunction,

Apneas and Cognitive Decline

Anthony Patrizz, B.A.

Advisory Professor: Louise McCullough M.D., Ph.D.

Stroke is a major cause of mortality and the leading cause of long-term disability in the US. More than 60% of individuals suffering a first time stroke develop respiratory dysfunction, prolonging recovery and increasing mortality. Post-stroke cognitive decline is a major contributor to disability and nursing home placement, therefore the cognitive consequences of Stroke Induced Respiratory Dysfunction (SIRD) need to be explored if we hope to enhance functional recovery. The first step towards treatment of the negative consequences of SIRD is the …

Astaxanthin Attenuates Mptp Induced Neurotoxicity And Modulates Cognitive Function In Aged Mice, Beth Grimmig

USF Tampa Graduate Theses and Dissertations

Parkinson’s disease is the second common neurodegenerative disease and is most frequently diagnosed in individuals over 60. There are no available medications that can prevent or restore the loss of neurons that correspond to motor impairments in patients. Identifying novel therapeutic compounds that are capable of slowing and reversing the extensive neurodegeneration that occurs in PD remains an important goal of the field. While basic research has identified potential therapeutic agents, studies often use young model organisms to demonstrate efficacy of the target compound. This approach ignores the impact of the aged CNS on the disease process, and likely contributes …

Habituation And Dishabituation In The Olfactory Bulb: From Neural Responses To Behavior, Mary Cameron Ogg

Theses and Dissertations (ETD)

Habituation and dishabituation modulate the neural resources and behavioral significance allocated to incoming stimuli across the sensory systems. The purpose of the research presented in this dissertation was to characterize these processes in the mouse olfactory bulb (OB) and to determine if OB acetylcholine (ACh) has a role in physiological and behavioral olfactory dishabituation. Calcium imaging was used to determine the timecourse and magnitude of habituation in different parts of the OB during and after a prolonged odor presentation. Widefield imaging of the dendritic, or glomerular, response of OB output cells demonstrated that prolonged odor input habituates glomerular responses during …

Changes In The Cholinergic, Catecholaminergic, Orexinergic And Serotonergic Structures Forming Part Of The Sleep Systems Of Adult Mice Exposed To Intrauterine Alcohol, Oladiran I. Olateju, Adhil Bhagwandin, Amadi O. Ihunwo, Paul R. Manger

Brain and Mind Institute

We examined the effect of chronic prenatal alcohol exposure on certain neuronal systems involved with the sleep-wake cycle of C57BL/6J mice exposed to prenatal alcohol once they had reached 56 days post-natal. Pregnant mice were exposed to alcohol, through oral gavage, on gestational days 7–16, with recorded blood alcohol concentration (BAC)s averaging 1.84 mg/ml (chronic alcohol group, CA). Two control groups, an oral gavage sucrose control group (chronic alcohol control group, CAc) and a non-treated control group (NTc), were also examined. At 56 days post-natal, the pups from each group were sacrificed and the whole brain sectioned in a coronal …

Multiparametric Mri Changes Persist Beyond Recovery In Concussed Adolescent Hockey Players, Kathryn Y. Manning, Amy Schranz, Robert Bartha, Gregory A. Dekaban, Christy Barreira, Arthur Brown, Lisa Fischer, Kevin Asem, Timothy J. Doherty, Douglas D. Fraser, Jeff Holmes, Ravi S. Menon

BrainsCAN Publications

Objective: To determine whether multiparametric MRI data can provide insight into the acute and long-lasting neuronal sequelae after a concussion in adolescent athletes.

Methods: Players were recruited from Bantam hockey leagues in which body checking is first introduced (male, age 11–14 years). Clinical measures, diffusion metrics, resting-state network and region-to-region functional connectivity patterns, and magnetic resonance spectroscopy absolute metabolite concentrations were analyzed from an independent, age-matched control group of hockey players (n 5 26) and longitudinally in concussed athletes within 24 to 72 hours (n 5 17) and 3 months (n 5 14) after a diagnosed concussion.

Results: There were …

Non-Fluent Speech Following Stroke Is Caused By Impaired Efference Copy, Lynda Feenaughty, Alexandra Basilakos, Leonardo Bonilha, Dirk B. Den Ouden, Chris Rorden, Brielle C. Stark, Julius Fridriksson

Communication Sciences and Disorders Faculty Articles and Research

Efference copy is a cognitive mechanism argued to be critical for initiating and monitoring speech: however, the extent to which breakdown of efference copy mechanisms impact speech production is unclear. This study examined the best mechanistic predictors of non-fluent speech among 88 stroke survivors. Objective speech fluency measures were subjected to a principal component analysis (PCA). The primary PCA factor was then entered into a multiple stepwise linear regression analysis as the dependent variable, with a set of independent mechanistic variables. Participants’ ability to mimic audio-visual speech (“speech entrainment response”) was the best independent predictor of non-fluent speech. We suggest …

Contributions Of Appetitive And Aversive Motivational Systems To Decision-Making, Heather E. Soder

USF Tampa Graduate Theses and Dissertations

Optimal decision-making entails outcome evaluation, comparing received costs and benefits with predicted costs and benefits. The anterior cingulate cortex (ACC), a brain area with major connections to the appetitive and aversive motivation systems, may provide the neural substrate of this evaluation process. One way to measure the relative contribution of these systems on decision-making is to measure individual differences in risk-taking behaviors. For individuals who make risky choices, this evaluation step may be biased: some show a preference for immediate, short-term rewards (increased appetitive system), while devaluing the long-term consequences of their choices (decreased aversive system). However, most studies supporting …

Family Income, Cumulative Risk Exposure, And White Matter Structure In Middle Childhood, Alexander J. Dufford, Pilyoung Kim

Psychology: Faculty Scholarship

Family income is associated with gray matter morphometry in children, but little is known about the relationship between family income and white matter structure. In this paper, using Tract-Based Spatial Statistics, a whole brain, voxel-wise approach, we examined the relationship between family income (assessed by income-to-needs ratio) and white matter organization in middle childhood (N = 27, M = 8.66 years). Results from a non-parametric, voxel-wise, multiple regression (threshold-free cluster enhancement, p < 0.05 FWE corrected) indicated that lower family income was associated with lower white matter organization [assessed by fractional anisotropy (FA)] for several clusters in white matter tracts involved in cognitive and emotional functions including fronto-limbic circuitry (uncinate fasciculus and cingulum bundle), association fibers (inferior longitudinal fasciculus, superior longitudinal fasciculus), and corticospinal tracts. Further, we examined the possibility that cumulative risk (CR) exposure might function as one of the potential pathways by which family income influences neural outcomes. Using multiple regressions, we found lower FA in portions of these tracts, including those found in the left cingulum bundle and left superior longitudinal fasciculus, was significantly related to greater exposure to CR (β = -0.47, p < 0.05 and β = -0.45, p < 0.05).

Cortical Contribution To Linear, Non-Linear And Frequency Components Of Motor Variability Control During Standing, Niklas König Ignasiak

Physical Therapy Faculty Articles and Research

Motor variability is an inherent feature of all human movements and reflects the quality of functional task performance. Depending on the requirements of the motor task, the human sensory-motor system is thought to be able to flexibly govern the appropriate level of variability. However, it remains unclear which neurophysiological structures are responsible for the control of motor variability. In this study, we tested the contribution of cortical cognitive resources on the control of motor variability (in this case postural sway) using a dual-task paradigm and furthermore observed potential changes in control strategy by evaluating Ia-afferent integration (H-reflex). Twenty healthy subjects …

Volition And Action In The Human Brain: Processes, Pathologies, And Reasons, Itzhak Fried, Patrick Haggard, Biyu J. He, Aaron Schurger

Psychology Faculty Articles and Research

Humans seem to decide for themselves what to do, and when to do it. This distinctive capacity may emerge from an ability, shared with other animals, to make decisions for action that are related to future goals, or at least free from the constraints of immediate environmental inputs. Studying such volitional acts proves a major challenge for neuroscience. This review highlights key mechanisms in the generation of voluntary, as opposed to stimulus-driven actions, and highlights three issues. The first part focuses on the apparent spontaneity of voluntary action. The second part focuses on one of the most distinctive, but elusive, …

Epigenetic Suppression Of Hippocampal Calbindin-D28k By Δfosb Drives Seizure-Related Cognitive Deficits., Jason C. You, Kavitha Muralidharan, Jin W. Park, Iraklis Petrof, Mark S. Pyfer, Brian F. Corbett, John J. Lafrancois, Yi Zheng, Xiaohong Zhang, Carrie A. Mohila, Daniel Yoshor, Robert A. Rissman, Eric J. Nestler, Helen E. Scharfman, Jeannie Chin

Department of Neuroscience Faculty Papers

The calcium-binding protein calbindin-D28k is critical for hippocampal function and cognition, but its expression is markedly decreased in various neurological disorders associated with epileptiform activity and seizures. In Alzheimer's disease (AD) and epilepsy, both of which are accompanied by recurrent seizures, the severity of cognitive deficits reflects the degree of calbindin reduction in the hippocampal dentate gyrus (DG). However, despite the importance of calbindin in both neuronal physiology and pathology, the regulatory mechanisms that control its expression in the hippocampus are poorly understood. Here we report an epigenetic mechanism through which seizures chronically suppress hippocampal calbindin expression and impair cognition. …

Corticosterone Regulates Both Naturally Occurring And Cocaine‐Induced Dopamine Signaling By Selectively Decreasing Dopamine Uptake, Daniel S. Wheeler, Amanda L. Ebben, Beliz Kurtoglu, Marissa E. Lovell, Austin T. Bohn, Isabella A. Jasek, David A. Baker, John R. Mantsch, Paul J. Gasser, Robert A. Wheeler

Biomedical Sciences Faculty Research and Publications

Stressful and aversive events promote maladaptive reward‐seeking behaviors such as drug addiction by acting, in part, on the mesolimbic dopamine system. Using animal models, data from our laboratory and others show that stress and cocaine can interact to produce a synergistic effect on reward circuitry. This effect is also observed when the stress hormone corticosterone is administered directly into the nucleus accumbens (NAc), indicating that glucocorticoids act locally in dopamine terminal regions to enhance cocaine's effects on dopamine signaling. However, prior studies in behaving animals have not provided mechanistic insight. Using fast‐scan cyclic voltammetry, we examined the effect of systemic …