Neurology Commons^™

Human Verbal Memory Encoding Is Hierarchically Distributed In A Continuous Processing Stream., Michal T. Kucewicz, Krishnakant Saboo, Brent M. Berry, Vaclav Kremen, Laura R. Miller, Fatemeh Khadjevand, Cory S. Inman, Paul Wanda, Michael R. Sperling, Richard Gorniak, Kathryn A. Davis, Barbara C. Jobst, Bradley Lega, Sameer A. Sheth, Daniel S. Rizzuto, Ravishankar K. Iyer, Michael J. Kahana, Gregory A. Worrell

Department of Neurology Faculty Papers

Processing of memory is supported by coordinated activity in a network of sensory, association, and motor brain regions. It remains a major challenge to determine where memory is encoded for later retrieval. Here, we used direct intracranial brain recordings from epilepsy patients performing free recall tasks to determine the temporal pattern and anatomical distribution of verbal memory encoding across the entire human cortex. High γ frequency activity (65-115 Hz) showed consistent power responses during encoding of subsequently recalled and forgotten words on a subset of electrodes localized in 16 distinct cortical areas activated in the tasks. More of the high …

Evaluating Trajectories Of Episodic Memory In Normal Cognition And Mild Cognitive Impairment: Results From Adni, Xiuhua Ding, Richard J. Charnigo, Frederick A. Schmitt, Richard J. Kryscio, Erin L. Abner, Alzheimer’S Disease Neuroimaging Initiative

Statistics Faculty Publications

BACKGROUND: Memory assessment is a key factor for the diagnosis of cognitive impairment. However, memory performance over time may be quite heterogeneous within diagnostic groups.

METHOD: To identify latent trajectories in memory performance and their associated risk factors, we analyzed data from Alzheimer's Disease Neuroimaging Initiative (ADNI) participants who were classified either as cognitively normal or as Mild Cognitive Impairment (MCI) at baseline and were administered the Rey Auditory Verbal Learning test (RAVLT) for up to 9 years. Group-based trajectory modeling on the 30-minute RAVLT delayed recall score was applied separately to the two baseline diagnostic groups.

RESULTS: There were …

Concussion In Student Athletes: Prevention, Assessment, And Recovery, Miriam A. Carroll-Alfano

Dissertations

The research presented in this study examines concussion among athletes from the perspectives of prevention, assessment, and recovery. The first study examines concussion education for high school athletes by surveying 157 collegiate athletes, who primarily attended high school in Illinois and Indiana, about the previous concussion education, including whether they received mandated education, the methods and providers of education, and their ability to name a variety of concussion symptoms. This study finds that despite legislative mandates in these states, 20% of student-athletes continue to report not receiving concussion education in high school, with females more likely to report not receiving …

Distinct Neuropsychological Profile And Associated Neurochemical Changes In Individuals With Mitochondrial Encephalomyopathy, Lactic Acidosis, And Stroke-Like Episodes (Melas), Emily B. Leaffer

Dissertations, Theses, and Capstone Projects

Background: Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS) is a maternally inherited progressive multisystemic disorder. Occurrence of seizure and/or stroke-like episode, as well as classic biomarkers (i.e., cerebral lactic acidosis, depleted N-acetylaspartate (NAA)), have been linked to neuropsychological deficit and trigger the developmental cascade of neurodegeneration affecting posterior prior to anterior brain regions. While a pattern of global deterioration has been reported, systematic examination in a large MELAS cohort has not been conducted.

Objective: First, we examined verbal and visual memory function and its relationship to brain metabolites (lactate, NAA) in individuals with MELAS. Second, we hypothesized that MELAS …

Fasudil In Combination With Bone Marrow Stromal Cells (Bmscs) Attenuates Alzheimer's Disease-Related Changes Through The Regulation Of The Peripheral Immune System., Jiezhong Yu, Yuqing Yan, Qingfang Gu, Gajendra Kumar, Hongqiang Yu, Yijin Zhao, Chunyun Liu, Ye Gao, Zhi Chai, Jasleen Chumber, Bao-Guo Xiao, Guang-Xian Zhang, Han-Ting Zhang, Yuqiang Jiang, Cun-Gen Ma

Department of Neurology Faculty Papers

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disease. Its mechanism is still not clear. Majority of research focused on the central nervous system (CNS) changes, while few studies emphasize on peripheral immune system modulation. Our study aimed to investigate the regulation of the peripheral immune system and its relationship to the severity of the disease after treatment in an AD model of APPswe/PSEN1dE9 transgenic (APP/PS1 Tg) mice. APP/PS1 Tg mice (8 months old) were treated with the ROCK-II inhibitor 1-(5-isoquinolinesulfonyl)-homo-piperazine (Fasudil) (intraperitoneal (i.p.) injections, 25 mg/kg/day), bone marrow stromal cells (BMSCs; caudal vein injections, 1 × 10

Effect Of Minor Surgery Under Propofol Anaesthesia On Brain Bdnf And Cognition, Muhammad Rafiq, Zahid Mahmood, Sajed Ali, Laure Pain

Pakistan Journal of Neurological Sciences (PJNS)

Brain Derived Neurotrophic Factor (BDNF) is a brain protein implicated in learning, memory and other cognitive functions. Changes in cellular brain functions as well as cognitive defects have been observed the days following anaesthesia, even for short-duration anaesthesia with/without surgery. Despites the role of neurotrophic factors in cognition, no data are still available on brain effects after anaesthesia. Purpose: To study the effect of minor surgery under short duration anaesthesia on cognition by investigating BDNF levels in plasma, hippocampus and cortex. METHODS: Male rats received an intra-peritoneal injection of either 120 mg/kg of propofol or intralipids solution or minor surgery …

Fasudil In Combination With Bone Marrow Stromal Cells (Bmscs) Attenuates Alzheimer’S Disease-Related Changes Through The Regulation Of The Peripheral Immune System, Jiezhong Yu, Yuqing Yan, Qingfang Gu, Gajendra Kumar, Hongqiang Yu, Yijin Zhao, Chunyun Liu, Ye Gao, Zhi Chai, Jasleen Chumber, Bao-Guo Xiao, Guang-Xian Zhang, Han-Ting Zhang, Yuqiang Jiang, Cun-Gen Ma

Faculty & Staff Scholarship

Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease. Its mechanism is still not clear. Majority of research focused on the central nervous system (CNS) changes, while few studies emphasize on peripheral immune system modulation. Our study aimed to investigate the regulation of the peripheral immune system and its relationship to the severity of the disease after treatment in an AD model of APPswe/PSEN1dE9 transgenic (APP/PS1 Tg) mice. APP/PS1 Tg mice (8 months old) were treated with the ROCK-II inhibitor 1-(5-isoquinolinesulfonyl)- homo-piperazine (Fasudil) (intraperitoneal (i.p.) injections, 25 mg/kg/day), bone marrow stromal cells (BMSCs; caudal vein injections, 1 × 106 BMSCs …

Baseline White Matter Hyperintensities And Hippocampal Volume Are Associated With Conversion From Normal Cognition To Mild Cognitive Impairment In The Framingham Offspring Study., Katherine J Bangen, Sarah R Preis, Lisa Delano-Wood, Philip A Wolf, David J Libon, Mark W Bondi, Rhoda Au, Charles Decarli, Adam M Brickman

Rowan-Virtua School of Osteopathic Medicine Departmental Research

INTRODUCTION: We examined associations between magnetic resonance imaging (MRI) markers of cerebrovascular disease and neurodegeneration with mild cognitive impairment (MCI) diagnosis at baseline and conversion from normal cognition to MCI at follow-up.

METHODS: Framingham Offspring participants underwent brain MRI and neuropsychological assessment at baseline (n=1049) and follow-up (n=561). Participants were classified at baseline and at follow-up as cognitively normal or MCI using sensitive neuropsychological criteria. White matter hyperintensity (WMH) volume, covert brain infarcts, hippocampal volume, and total cerebral brain volume were quantified.

RESULTS: Baseline measures of WMH and hippocampal volume were associated with MCI status cross-sectionally and also with conversion …

Cognitive Trajectory Changes Over 20 Years Before Dementia Diagnosis: A Large Cohort Study., Ge Li, Eric B Larson, Jane B Shofer, Paul K Crane, Laura E Gibbons, Wayne Mccormick, J D Bowen, Mary Lou Thompson

Articles, Abstracts, and Reports

BACKGROUND/OBJECTIVES: Longitudinal studies have shown an increase in cognitive decline many years before clinical diagnosis of dementia. We sought to estimate changes, relative to "normal" aging, in the trajectory of scores on a global cognitive function test-the Cognitive Abilities Screening Instrument (CASI).

DESIGN: A prospective cohort study.

SETTING: Community-dwelling members of a U.S. health maintenance organization.

PARTICIPANTS: Individuals aged 65 and older who had no dementia diagnosis at baseline and had at least two visits with valid CASI test score (N = 4,315).

MEASUREMENTS: Average longitudinal trajectories, including changes in trajectory before clinical diagnosis in those who would be diagnosed …

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, …

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 …

Acute Treatment With Doxorubicin Affects Glutamate Neurotransmission In The Mouse Frontal Cortex And Hippocampus, Theresa Currier Thomas, Joshua A. Beitchman, Francois Pomerleau, Teresa Noel, Paiboon Jungsuwadee, D. Allan Butterfield, Daret K. St. Clair, Mary Vore, Greg A. Gerhardt

Spinal Cord and Brain Injury Research Center Faculty Publications

Doxorubicin (DOX) is a potent chemotherapeutic agent known to cause acute and long-term cognitive impairments in cancer patients. Cognitive function is presumed to be primarily mediated by neuronal circuitry in the frontal cortex (FC) and hippocampus, where glutamate is the primary excitatory neurotransmitter. Mice treated with DOX (25 mg/kg i.p.) were subjected to in vivo recordings under urethane anesthesia at 24h post-DOX injection or 5 consecutive days of cognitive testing (Morris Water Maze; MWM). Using novel glutamate-selective microelectrode arrays, amperometric recordings measured parameters of extracellular glutamate clearance and potassium-evoked release of glutamate within the medial FC and dentate gyrus (DG) …

Delirium Reduction Strategies For The Critically Ill, June Chaves, Sam Canonico, Will Cheney, Tammy Corey, Gil Fraser, Alex Kowalewski, Jen Low, Cardiac Intensive Care Unit, Haley Pelletier, Cathy Palleschi, Stephen Tyzik, Suneela Nayak, Ruth Hanselman

MaineHealth Maine Medical Center

Delirium, an acute and fluctuating disturbance of consciousness and cognition, is a common manifestation of acute brain dysfunction in critically ill patients. Patients with delirium have longer hospital stays and a lower 6-month survival rate than do patients without delirium. Preliminary research suggests that delirium may be associated with cognitive impairment that persists months to years after discharge.

In a large acute care hospital, the cardiac intensive care staff became interested in mitigating their unit’s high delirium rate of ventilated patients. At baseline, many members of the healthcare team did not believe that delirium could be prevented and the predominant …

Caloric Restriction Preserves Memory And Reduces Anxiety Of Aging Mice With Early Enhancement Of Neurovascular Functions, Ishita Parikh, Janet Guo, Kai-Hsiang Chuang, Yu Zhong, Ralf G. Rempe, Jared D. Hoffman, Rachel Armstrong, Björn Bauer, Anika M. S. Hartz, Ai-Ling Lin

Sanders-Brown Center on Aging Faculty Publications

Neurovascular integrity plays an important role in protecting cognitive and mental health in aging. Lifestyle interventions that sustain neurovascular integrity may thus be critical on preserving brain functions in aging and reducing the risk for age-related neurodegenerative disorders. Here we show that caloric restriction (CR) had an early effect on neurovascular enhancements, and played a critical role in preserving vascular, cognitive and mental health in aging. In particular, we found that CR significantly enhanced cerebral blood flow (CBF) and blood-brain barrier function in young mice at 5-6 months of age. The neurovascular enhancements were associated with reduced mammalian target of …

Diabetes Is Associated With Cerebrovascular But Not Alzheimer's Disease Neuropathology, Erin L. Abner, Peter T. Nelson, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Randall L. Woltjer, Nigel J. Cairns, Lei Yu, Hiroko H. Dodge, Chengjie Xiong, Kamal Masaki, Suzanne L. Tyas, David A. Bennett, Julie A. Schneider, Zoe Arvanitakis

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: The relationship of diabetes to specific neuropathologic causes of dementia is incompletely understood.

METHODS: We used logistic regression to evaluate the association between diabetes and infarcts, Braak neurofibrillary tangle stage, and neuritic plaque score in 2365 autopsied persons. In a subset of >1300 persons with available cognitive data, we examined the association between diabetes and cognition using Poisson regression.

RESULTS: Diabetes increased odds of brain infarcts (odds ratio [OR] = 1.57, P < .0001), specifically lacunes (OR = 1.71, P < .0001), but not Alzheimer's disease neuropathology. Diabetes plus infarcts was associated with lower cognitive scores at end of life than infarcts or diabetes alone, and diabetes plus high level of Alzheimer's neuropathologic changes was associated with lower mini-mental state examination scores than the pathology alone.

DISCUSSION: This study supports the conclusions that diabetes increases the risk of cerebrovascular but not Alzheimer's disease pathology, and at least some of diabetes' relationship to …

Acth Prevents Deficits In Fear Extinction Associated With Early Life Seizures, Andrew T. Massey, David K. Lerner, Gregory L. Holmes, Rod C. Scott, Amanda Hernan

Dartmouth Scholarship

Objective: Early life seizures (ELS) are often associated with cognitive and psychiatric comorbidities that are detrimental to quality of life. In a rat model of ELS, we explored long-term cognitive outcomes in adult rats. Using ACTH, an endogeneous HPA-axis hormone given to children with severe epilepsy, we sought to prevent cognitive deficits. Through comparisons with dexamethasone, we sought to dissociate the corticosteroid effects of ACTH from other potential mechanisms of action.

Results: Although rats with a history of ELS were able to acquire a conditioned fear learning paradigm and controls, these rats had significant deficits in their ability to extinguish …

Ferritin Levels In The Cerebrospinal Fluid Predict Alzheimer's Disease Outcomes And Are Regulated By Apoe, Scott Ayton, Noel G. Faux, Ashley I. Bush, Charles D. Smith, Greg A. Jicha, Peter A. Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Alzheimer's Disease Neuroimaging Initiative

Neurology Faculty Publications

Brain iron elevation is implicated in Alzheimer's disease (AD) pathogenesis, but the impact of iron on disease outcomes has not been previously explored in a longitudinal study. Ferritin is the major iron storage protein of the body; by using cerebrospinal fluid (CSF) levels of ferritin as an index, we explored whether brain iron status impacts longitudinal outcomes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We show that baseline CSF ferritin levels were negatively associated with cognitive performance over 7 years in 91 cognitively normal, 144 mild cognitive impairment (MCI) and 67 AD subjects, and predicted MCI conversion to AD. …

Dopaminergic Modulation Of Memory And Affective Processing In Parkinson Depression, Lee X. Blonder, John T. Slevin, Richard J. Kryscio, Catherine A. Martin, Anders H. Andersen, Charles D Smith, Frederick A. Schmitt

Magnetic Resonance Imaging and Spectroscopy Center Faculty Publications

Depression is common in Parkinson's disease and is associated with cognitive impairment. Dopaminergic medications are effective in treating the motor symptoms of Parkinson's disease; however, little is known regarding the effects of dopaminergic pharmacotherapy on cognitive function in depressed Parkinson patients. This study examines the neuropsychological effects of dopaminergic pharmacotherapy in Parkinsonian depression. We compared cognitive function in depressed and non-depressed Parkinson patients at two time-points: following overnight withdrawal and after the usual morning regimen of dopaminergic medications. A total of 28 non-demented, right-handed patients with mild to moderate idiopathic Parkinson's disease participated. Ten of these patients were depressed according …

Pharmacological Studies Of Nicotine And Galantamine Effects On Age Associated Memory Impairment And The Neurotrophic System In Aged Female Rats, Kristen L. French

MUSC Theses and Dissertations

Nicotine and Galantamine were studied for their pharmacological effects on age associated memory impairment (AAMI) and the neurotrophin system in the aged female F344 rat. Nicotine was found to have dose dependent effects on cognition in the 24 month old rat. A low dose of nicotine improved both working and reference memory (WM, RM) performance on the water radial arm maze and also improved the ability of aged rats to handle an increasing WM load. A high dose did not improve WM and caused deficits in RM, and high cotinine levels in these subjects correlated with worse performance. Nicotine treatment …