Medicine and Health Sciences Commons^™

The Performance Of Plasma Amyloid Beta Measurements In Identifying Amyloid Plaques In Alzheimer's Disease: A Literature Review, Abby L Brand, Paige E Lawler, James G Bollinger, Yan Li, Suzanne E Schindler, Melody Li, Samir Lopez, Vitaliy Ovod, Akinori Nakamura, Leslie M Shaw, Henrik Zetterberg, Oskar Hansson, Randall J Bateman

2020-Current year OA Pubs

The extracellular buildup of amyloid beta (Aβ) plaques in the brain is a hallmark of Alzheimer's disease (AD). Detection of Aβ pathology is essential for AD diagnosis and for identifying and recruiting research participants for clinical trials evaluating disease-modifying therapies. Currently, AD diagnoses are usually made by clinical assessments, although detection of AD pathology with positron emission tomography (PET) scans or cerebrospinal fluid (CSF) analysis can be used by specialty clinics. These measures of Aβ aggregation, e.g. plaques, protofibrils, and oligomers, are medically invasive and often only available at specialized medical centers or not covered by medical insurance, and PET …

Trem2 Dependent And Independent Functions Of Microglia In Alzheimer's Disease, Jinchao Hou, Yun Chen, Gary Grajales-Reyes, Marco Colonna

2020-Current year OA Pubs

Microglia are central players in brain innate immunity and have been the subject of extensive research in Alzheimer's disease (AD). In this review, we aim to summarize the genetic and functional discoveries that have advanced our understanding of microglia reactivity to AD pathology. Given the heightened AD risk posed by rare variants of the microglial triggering receptor expressed on myeloid cells 2 (TREM2), we will focus on the studies addressing the impact of this receptor on microglia responses to amyloid plaques, tauopathy and demyelination pathologies in mouse and human. Finally, we will discuss the implications of recent discoveries on microglia …

Lecanemab In Patients With Early Alzheimer's Disease: Detailed Results On Biomarker, Cognitive, And Clinical Effects From The Randomized And Open-Label Extension Of The Phase 2 Proof-Of-Concept Study, Eric Mcdade, Jeffrey L Cummings, Shobha Dhadda, Chad J Swanson, Larisa Reyderman, Michio Kanekiyo, Akihiko Koyama, Michael Irizarry, Lynn D Kramer, Randall J Bateman

2020-Current year OA Pubs

BACKGROUND: Lecanemab, a humanized IgG1 monoclonal antibody that targets soluble aggregated Aβ species (protofibrils), has demonstrated robust brain fibrillar amyloid reduction and slowing of clinical decline in early AD. The objective of this analysis is to report results from study 201 blinded period (core), the open-label extension (OLE), and gap period (between core and OLE) supporting the effectiveness of lecanemab.

METHODS: The lecanemab study 201 core was a double-blind, randomized, placebo-controlled study of 856 patients randomized to one of five dose regimens or placebo. An OLE of study 201 was initiated to allow patients to receive open-label lecanemab 10mg/kg biweekly …

Defective Proteostasis In Induced Pluripotent Stem Cell Models Of Frontotemporal Lobar Degeneration, Sidhartha Mahali, Rita Martinez, Melvin King, Anthony Verbeck, Oscar Harari, Bruno A Benitez, Kanta Horie, Chihiro Sato, Sally Temple, Celeste M Karch

2020-Current year OA Pubs

Impaired proteostasis is associated with normal aging and is accelerated in neurodegeneration. This impairment may lead to the accumulation of protein, which can be toxic to cells and tissue. In a subset of frontotemporal lobar degeneration with tau pathology (FTLD-tau) cases, pathogenic mutations in the microtubule-associated protein tau (MAPT) gene are sufficient to cause tau accumulation and neurodegeneration. However, the pathogenic events triggered by the expression of the mutant tau protein remain poorly understood. Here, we show that molecular networks associated with lysosomal biogenesis and autophagic function are disrupted in brains from FTLD-tau patients carrying a MAPT p.R406W mutation. We …

The Zona Incerta In Control Of Novelty Seeking And Investigation Across Species, Ilya E Monosov, Takaya Ogasawara, Suzanne N Haber, J Alexander Heimel, Mehran Ahmadlou

2020-Current year OA Pubs

Many organisms rely on a capacity to rapidly replicate, disperse, and evolve when faced with uncertainty and novelty. But mammals do not evolve and replicate quickly. They rely on a sophisticated nervous system to generate predictions and select responses when confronted with these challenges. An important component of their behavioral repertoire is the adaptive context-dependent seeking or avoiding of perceptually novel objects, even when their values have not yet been learned. Here, we outline recent cross-species breakthroughs that shed light on how the zona incerta (ZI), a relatively evolutionarily conserved brain area, supports novelty-seeking and novelty-related investigations. We then conjecture …

A Novel, Likely Pathogenic Variant In Ubtf-Related Neurodegeneration With Brain Atrophy Is Associated With A Severe Divergent Neurodevelopmental Phenotype, Rory J Tinker, Tiffany Guess, David C Rinker, Jonathan H Sheehan, Daniel Lubarsky, Binu Porath, Mackenzie Mosera, Ping Mayo, Emily Solem, Laura A Lee, Asha Sharam, Jennifer Brault

2020-Current year OA Pubs

BACKGROUND: A de novo, pathogenic, missense variant in UBTF, c.628G>A p.Glu210Lys, has been described as the cause of an emerging neurodegenerative disorder, Childhood-Onset Neurodegeneration with Brain Atrophy (CONDBA). The p.Glu210Lys alteration yields a positively charged stretch of three lysine residues. Functional studies confirmed this change results in a stronger interaction with negatively charged DNA and gain-of-function activity when compared to the wild-type sequence. The CONDBA phenotype reported in association with p.Glu210Lys consists of normal early-neurodevelopment followed by progressive motor, cognitive, and behavioral regression in early-to-middle childhood.

METHODS AND RESULTS: The current proband presented at 9 months of age with …

Mild Hypoxic-Ischemic Encephalopathy (Hie): Timing And Pattern Of Mri Brain Injury, Yi Li, Jessica L Wisnowski, Lina Chalak, Amit M Mathur, Robert C Mckinstry, Genesis Licona, Dennis E Mayock, Taeun Chang, Krisa P Van Meurs, Tai-Wei Wu, Kaashif A Ahmad, Marie-Coralie Cornet, Rakesh Rao, Aaron Scheffler, Yvonne W Wu

2020-Current year OA Pubs

BACKGROUND: Mild hypoxic-ischemic encephalopathy (HIE) is increasingly recognized as a risk factor for neonatal brain injury. We examined the timing and pattern of brain injury in mild HIE.

METHODS: This retrospective cohort study includes infants with mild HIE treated at 9 hospitals. Neonatal brain MRIs were scored by 2 reviewers using a validated classification system, with discrepancies resolved by consensus. Severity and timing of MRI brain injury (i.e., acute, subacute, chronic) was scored on the subset of MRIs that were performed at or before 8 days of age.

RESULTS: Of 142 infants with mild HIE, 87 (61%) had injury on …

Relationship Of Neurite Architecture To Brain Activity During Task-Based Fmri, Christin Schifani, Colin Hawco, Arash Nazeri, Aristotle N Voineskos

2020-Current year OA Pubs

Functional MRI (fMRI) has been widely used to examine changes in neuronal activity during cognitive tasks. Commonly used measures of gray matter macrostructure (e.g., cortical thickness, surface area, volume) do not consistently appear to serve as structural correlates of brain function. In contrast, gray matter microstructure, measured using neurite orientation dispersion and density imaging (NODDI), enables the estimation of indices of neurite density (neurite density index; NDI) and organization (orientation dispersion index; ODI) in gray matter. Our study explored the relationship among neurite architecture, BOLD (blood-oxygen-level-dependent) fMRI, and cognition, using a large sample (n = 750) of young adults of …

High-Throughput Analysis Of Tissue Microarrays Using Automated Desorption Electrospray Ionization Mass Spectrometry, Nicolás M Morato, Hannah Marie Brown, Diogo Garcia, Erik H Middlebrooks, Mark Jentoft, Kaisorn Chaichana, Alfredo Quiñones-Hinojosa, R Graham Cooks

2020-Current year OA Pubs

Tissue microarrays (TMAs) are commonly used for the rapid analysis of large numbers of tissue samples, often in morphological assessments but increasingly in spectroscopic analysis, where specific molecular markers are targeted via immunostaining. Here we report the use of an automated high-throughput system based on desorption electrospray ionization (DESI) mass spectrometry (MS) for the rapid generation and online analysis of high-density (6144 samples/array) TMAs, at rates better than 1 sample/second. Direct open-air analysis of tissue samples (hundreds of nanograms) not subjected to prior preparation, plus the ability to provide molecular characterization by tandem mass spectrometry (MS/MS), make this experiment versatile …

Differential Expression And Activities Of Cytochrome P450 3a In The Rat Brain Microsomes And Mitochondria, Nouf Alshammari, Devaraj Venkatapura Chandrashekar, Mamunur Rashid, Reza Mehvar

Pharmacy Faculty Articles and Research

Midazolam (MDZ), a benzodiazepine derivative, is metabolized to 1′- and 4-hydroxylated metabolites (1′-OH-MDZ and 4-OH-MDZ, respectively) by cytochrome P450 3A (CYP3A). The purpose of this study was to investigate the CYP3A-mediated hydroxylation of MDZ in the rat brain mitochondria (MT). Brain microsomes (MC) and MT fractions were prepared from rats (n = 8) using differential and density gradient centrifugations, and the purity of the fractions was evaluated using VDAC1 and calreticulin as markers of MT and MC, respectively. The formation rates of 1′-OH-MDZ and 4-OH-MDZ in the rat brain MC and MT samples were determined using an LC–MS/MS method …

Association Of Pediatric Buccal Epigenetic Age Acceleration With Adverse Neonatal Brain Growth And Neurodevelopmental Outcomes Among Children Born Very Preterm With A Neonatal Infection., Noha Gomaa, Chaini Konwar, Nicole Gladish, Stephanie H Au-Young, Ting Guo, Min Sheng, Sarah M Merrill, Edmond Kelly, Vann Chau, Helen M Branson, Linh G Ly, Emma G Duerden, Ruth E Grunau, Michael S Kobor, Steven P Miller

Department of Medicine Publications

IMPORTANCE: Very preterm neonates (24-32 weeks' gestation) remain at a higher risk of morbidity and neurodevelopmental adversity throughout their lifespan. Because the extent of prematurity alone does not fully explain the risk of adverse neonatal brain growth or neurodevelopmental outcomes, there is a need for neonatal biomarkers to help estimate these risks in this population.

OBJECTIVES: To characterize the pediatric buccal epigenetic (PedBE) clock-a recently developed tool to measure biological aging-among very preterm neonates and to assess its association with the extent of prematurity, neonatal comorbidities, neonatal brain growth, and neurodevelopmental outcomes at 18 months of age.

DESIGN, SETTING, AND …

Genome-Wide Meta-Analyses Reveal Novel Loci For Verbal Short-Term Memory And Learning., Jari Lahti, Samuli Tuominen, Qiong Yang, Giulio Pergola, Shahzad Ahmad, Najaf Amin, Nicola J Armstrong, Alexa Beiser, Katharina Bey, Joshua C Bis, Eric Boerwinkle, Jan Bressler, Archie Campbell, Harry Campbell, Qiang Chen, Janie Corley, Simon R Cox, Gail Davies, Philip L De Jager, Eske M Derks, Jessica D Faul, Annette L Fitzpatrick, Alison E Fohner, Ian Ford, Myriam Fornage, Zachary Gerring, Hans J Grabe, Francine Grodstein, Vilmundur Gudnason, Eleanor Simonsick, Elizabeth G Holliday, Peter K Joshi, Eero Kajantie, Jaakko Kaprio, Pauliina Karell, Luca Kleineidam, Maria J Knol, Nicole A Kochan, John B Kwok, Markus Leber, Max Lam, Teresa Lee, Shuo Li, Anu Loukola, Tobias Luck, Riccardo E Marioni, Karen A Mather, Sarah Medland, Saira S Mirza, Mike A Nalls, Kwangsik Nho, Adrienne O'Donnell, Christopher Oldmeadow, Jodie Painter, Alison Pattie, Simone Reppermund, Shannon L Risacher, Richard J Rose, Vijay Sadashivaiah, Markus Scholz, Claudia L Satizabal, Peter W Schofield, Katharina E Schraut, Rodney J Scott, Jeannette Simino, Albert V Smith, Jennifer A Smith, David J Stott, Ida Surakka, Alexander Teumer, Anbupalam Thalamuthu, Stella Trompet, Stephen T Turner, Sven J Van Der Lee, Arno Villringer, Uwe Völker, Robert S Wilson, Katharina Wittfeld, Eero Vuoksimaa, Rui Xia, Kristine Yaffe, Lei Yu, Habil Zare, Wei Zhao, David Ames, John Attia, David A Bennett, Henry Brodaty, Daniel I Chasman, Aaron L Goldman, Caroline Hayward, M Arfan Ikram, J Wouter Jukema, Sharon L R Kardia, Todd Lencz, Markus Loeffler, Venkata S Mattay, Aarno Palotie, Bruce M Psaty, Alfredo Ramirez, Paul M Ridker, Steffi G Riedel-Heller, Perminder S Sachdev, Andrew J Saykin, Martin Scherer, Peter R Schofield, Stephen Sidney, John M Starr, Julian Trollor, William Ulrich, Michael Wagner, David R Weir, James F Wilson, Margaret J Wright, Daniel R Weinberger, Stephanie Debette, Johan G Eriksson, Thomas H Mosley, Lenore J Launer, Cornelia M Van Duijn, Ian J Deary, Sudha Seshadri, Katri Räikkönen

Journal Articles

Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during …

Brain Volume In Chronic Ketamine Users - Relationship To Sub-Threshold Psychotic Symptoms And Relevance To Schizophrenia, Robert A Chesters, Fiona Pepper, Celia Morgan, Jonathan D Cooper, Oliver D Howes, Anthony C Vernon, James M Stone

2020-Current year OA Pubs

RATIONALE: Ketamine may model aspects of schizophrenia arising through NMDA receptor activity deficits. Although acute ketamine can induce effects resembling both positive and negative psychotic symptoms, chronic use may be a closer model of idiopathic psychosis.

OBJECTIVES: We tested the hypotheses that ketamine users had lower brain volumes, as measured using MRI, and greater sub-threshold psychotic symptoms relative to a poly-drug user control group.

METHODS: Ketamine users (n = 17) and poly-drug using controls (n = 19) were included in the study. All underwent volumetric MRI imaging and measurement of sub-threshold psychotic symptoms using the Comprehensive Assessment of At-Risk Mental …

Brain-Wide Versus Genome-Wide Vulnerability Biomarkers For Severe Mental Illnesses, Peter Kochunov, Aris Sotiras, Et Al.

2020-Current year OA Pubs

Severe mental illnesses (SMI), including major depressive (MDD), bipolar (BD), and schizophrenia spectrum (SSD) disorders have multifactorial risk factors and capturing their complex etiopathophysiology in an individual remains challenging. Regional vulnerability index (RVI) was used to measure individual's brain-wide similarity to the expected SMI patterns derived from meta-analytical studies. It is analogous to polygenic risk scores (PRS) that measure individual's similarity to genome-wide patterns in SMI. We hypothesized that RVI is an intermediary phenotype between genome and symptoms and is sensitive to both genetic and environmental risks for SMI. UK Biobank sample of N = 17,053/19,265 M/F (age = 64.8 …

Herpes Simplex Virus And Rates Of Cognitive Decline Or Whole Brain Atrophy In The Dominantly Inherited Alzheimer Network, Charlotte Warren-Gash, Brian A Gordon, Eric Mcdade, Randall J Bateman, John C Morris, Et Al.

2020-Current year OA Pubs

OBJECTIVE: To investigate whether herpes simplex virus type 1 (HSV-1) infection was associated with rates of cognitive decline or whole brain atrophy among individuals from the Dominantly Inherited Alzheimer Network (DIAN).

METHODS: Among two subsets of the DIAN cohort (age range 19.6-66.6 years; median follow-up 3.0 years) we examined (i) rate of cognitive decline (N = 164) using change in mini-mental state examination (MMSE) score, (ii) rate of whole brain atrophy (N = 149), derived from serial MR imaging, calculated using the boundary shift integral (BSI) method. HSV-1 antibodies were assayed in baseline sera collected from 2009-2015. Linear mixed-effects models …

Amyloid-Β And Tau Deposition Influences Cognitive And Functional Decline In Down Syndrome, Monika Grigorova, Beau Ances, Et Al.

2020-Current year OA Pubs

This study investigates whether tau has (i) an independent effect from amyloid-β on changes in cognitive and functional performance and (ii) a synergistic relationship with amyloid-β in the exacerbation of decline in aging Down syndrome (DS). 105 participants with DS underwent baseline PET [

Covariance-Based Vs. Correlation-Based Functional Connectivity Dissociates Healthy Aging From Alzheimer Disease, Jeremy F. Strain, Matthew R. Brier, Aaron Tanenbaum, Brian A. Gordon, John E. Mccarthy, Aylin Dincer, Daniel S. Marcus, Richard J. Perrin, John C. Morris, Tammie L. S. Benzinger, Randall J. Bateman, Beau M. Ances, Abraham Z. Snyder, Et Al.

2020-Current year OA Pubs

Prior studies of aging and Alzheimer disease have evaluated resting state functional connectivity (FC) using either seed-based correlation (SBC) or independent component analysis (ICA), with a focus on particular functional systems. SBC and ICA both are insensitive to differences in signal amplitude. At the same time, accumulating evidence indicates that the amplitude of spontaneous BOLD signal fluctuations is physiologically meaningful. We systematically compared covariance-based FC, which is sensitive to amplitude, vs. correlation-based FC, which is not, in affected individuals and controls drawn from two cohorts of participants including autosomal dominant Alzheimer disease (ADAD), late onset Alzheimer disease (LOAD), and age-matched …

Prenatal Exposure To Maternal Social Disadvantage And Psychosocial Stress And Neonatal White Matter Connectivity At Birth, Rachel E Lean, Christopher D Smyser, Rebecca G Brady, Regina L Triplett, Sydney Kaplan, Jeanette K Kenley, Joshua S Shimony, Tara A Smyser, J Phillip Miller, Deanna M Barch, Joan L Luby, Barbara B Warner, Cynthia E Rogers

2020-Current year OA Pubs

Early life adversity (social disadvantage and psychosocial stressors) is associated with altered microstructure in fronto-limbic pathways important for socioemotional development. Understanding when these associations begin to emerge may inform the timing and design of preventative interventions. In this longitudinal study, 399 mothers were oversampled for low income and completed social background measures during pregnancy. Measures were analyzed with structural equation analysis resulting in two latent factors: social disadvantage (education, insurance status, income-to-needs ratio [INR], neighborhood deprivation, and nutrition) and psychosocial stress (depression, stress, life events, and racial discrimination). At birth, 289 healthy term-born neonates underwent a diffusion MRI (dMRI) scan. …

Bold Cofluctuation 'Events' Are Predicted From Static Functional Connectivity, Zach Ladwig, Benjamin A. Seitzman, Ally Dworetsky, Yuhua Yu, Babatunde Adeyemo, Derek M. Smith, Steven E. Petersen, Caterina Gratton

2020-Current year OA Pubs

Recent work identified single time points ("events") of high regional cofluctuation in functional Magnetic Resonance Imaging (fMRI) which contain more large-scale brain network information than other, low cofluctuation time points. This suggested that events might be a discrete, temporally sparse signal which drives functional connectivity (FC) over the timeseries. However, a different, not yet explored possibility is that network information differences between time points are driven by sampling variability on a constant, static, noisy signal. Using a combination of real and simulated data, we examined the relationship between cofluctuation and network structure and asked if this relationship was unique, or …

Shared Brain And Genetic Architectures Between Mental Health And Physical Activity, Wei Zhang, Sarah E Paul, Anderson Winkler, Ryan Bogdan, Janine D Bijsterbosch

2020-Current year OA Pubs

Physical activity is correlated with, and effectively treats various forms of psychopathology. However, whether biological correlates of physical activity and psychopathology are shared remains unclear. Here, we examined the extent to which the neural and genetic architecture of physical activity and mental health are shared. Using data from the UK Biobank (N = 6389), we applied canonical correlation analysis to estimate associations between the amplitude and connectivity strength of subnetworks of three major neurocognitive networks (default mode, DMN; salience, SN; central executive networks, CEN) with accelerometer-derived measures of physical activity and self-reported mental health measures (primarily of depression, anxiety disorders, …

Incisionless Targeted Adeno-Associated Viral Vector Delivery To The Brain By Focused Ultrasound-Mediated Intranasal Administration, Dezhuang Ye, Jinyun Yuan, Yaoheng Yang, Yimei Yue, Zhongtao Hu, Siaka Fadera, Hong Chen

2020-Current year OA Pubs

BACKGROUND: Adeno-associated viral (AAV) vectors are currently the leading platform for gene therapy with the potential to treat a variety of central nervous system (CNS) diseases. There are numerous methods for delivering AAVs to the CNS, such as direct intracranial injection (DI), intranasal delivery (IN), and intravenous injection with focused ultrasound-induced blood-brain barrier disruption (FUS-BBBD). However, non-invasive and efficient delivery of AAVs to the brain with minimal systemic toxicity remain the major challenge. This study aims to investigate the potential of focused ultrasound-mediated intranasal delivery (FUSIN) in AAV delivery to brain.

METHODS: Mice were intranasally administered with AAV5 encoding enhanced …

Alterations In Cerebral Glucose Metabolism Measured By Fdg Pet In Subjects Performing A Meditation Practice Based On Clitoral Stimulation, Andrew B. Newberg, Nancy A. Wintering, Chloe Hriso, Faezeh Vedaei, Feroze B. Mohamed, Sara E. Gottfried, Reneita Ross

Institute of Emerging Health Professions Faculty Papers

Background: The relationship between sexuality, or the libido, and spirituality or religion has long been debated in psychiatry. Recent studies have explored the neurophysiology of both sexual experiences and spiritual practices such as meditation or prayer. In the present study, we report changes in cerebral glucose metabolism in a unique meditation practice augmented by clitoral stimulation called, Orgasmic Meditation, in which a spiritual state is described to be attained by both male and female participants engaged in the practice as a pair.

Methods: Male (N=20) and female (N=20) subjects had an intravenous catheter connected to a bag of normal saline …

Planning System For The Optimization Of Electric Field Delivery Using Implanted Electrodes For Brain Tumor Control, Erin Iredale, Brynn Voigt, Adam Rankin, Kyungho W Kim, Jeff Z Chen, Susanne Schmid, Matthew O Hebb, Terry M Peters, Eugene Wong

Anatomy and Cell Biology Publications

BACKGROUND: The use of non-ionizing electric fields from low-intensity voltage sources (< 10 V) to control malignant tumor growth is showing increasing potential as a cancer treatment modality. A method of applying these low-intensity electric fields using multiple implanted electrodes within or adjacent to tumor volumes has been termed as intratumoral modulation therapy (IMT).

PURPOSE: This study explores advancements in the previously established IMT optimization algorithm, and the development of a custom treatment planning system for patient-specific IMT. The practicality of the treatment planning system is demonstrated by implementing the full optimization pipeline on a brain phantom with robotic electrode implantation, postoperative imaging, and treatment stimulation.

METHODS: The integrated planning pipeline in 3D Slicer begins with importing and segmenting patient magnetic resonance images (MRI) or computed tomography (CT) images. The segmentation process is manual, followed by a semi-automatic smoothing step that allows …

Disease Burden Affects Aging Brain Function, Lori L Beason-Held, Danielle Fournier, Andrea T Shafer, Elisa Fabbri, Yang An, Chiung-Wei Huang, Murat Bilgel, Dean F Wong, Luigi Ferrucci, Susan M Resnick

2020-Current year OA Pubs

BACKGROUND: Most older adults live with multiple chronic disease conditions, yet the effect of multiple diseases on brain function remains unclear.

METHODS: We examine the relationship between disease multimorbidity and brain activity using regional cerebral blood flow (rCBF) 15O-water PET scans from 97 cognitively normal participants (mean baseline age 76.5) in the Baltimore Longitudinal Study of Aging (BLSA). Multimorbidity index scores, generated from the presence of 13 health conditions, were correlated with PET data at baseline and in longitudinal change (n = 74) over 5.05 (2.74 SD) years.

RESULTS: At baseline, voxel-based analysis showed that higher multimorbidity scores were associated …

Mild Hypothermia Fails To Protect Infant Macaques From Brain Injury Caused By Prolonged Exposure To Antiseizure Drugs, Chrysanthy Ikonomidou, Sophie H Wang, Nicole A Fuhler, Shreya Larson, Saverio Capuano 3rd, Kevin R Brunner, Kristin Crosno, Heather A Simmons, Andres F Mejia, Kevin K Noguchi

2020-Current year OA Pubs

Barbiturates and benzodiazepines are GABA

Minimal Change Prion Retinopathy: Morphometric Comparison Of Retinal And Brain Prion Deposits In Creutzfeldt-Jakob Disease, Vanessa S Goodwill, Ian Dryden, Jihee Choi, Chiara De Lillo, Katrin Soldau, Jorge Llibre-Guerra, Henry Sanchez, Christina J Sigurdson, Jonathan H Lin

2020-Current year OA Pubs

Sporadic Creutzfeldt-Jakob disease (sCJD) is the most commonly diagnosed human prion disease caused by the abnormal misfolding of the 'cellular' prion protein (PrP

Rapidplan Hippocampal Sparing Whole Brain Model Version 2-How Far Can We Reduce The Dose?, Hefei Liu, Ryan Clark, Anthony Magliari, Robert Foster, Francisco Reynoso, Matthew Schmidt, Vinai Gondi, Christopher Abraham, Heather Curry, Patrick Kupelian, Deepak Khuntia, Sushil Beriwal

2020-Current year OA Pubs

Whole-brain radiotherapy has been the standard palliative treatment for patients with brain metastases due to its effectiveness, availability, and ease of administration. Recent clinical trials have shown that limiting radiation dose to the hippocampus is associated with decreased cognitive toxicity. In this study, we updated an existing Knowledge Based Planning model to further reduce dose to the hippocampus and improve other dosimetric plan quality characteristics. Forty-two clinical cases were contoured according to guidelines. A new dosimetric scorecard was created as an objective measure for plan quality. The new Hippocampal Sparing Whole Brain Version 2 (HSWBv2) model adopted a complex recursive …

Multimodal Magnetic Resonance Neuroimaging Measures Characteristic Of Early Cart-Treated Pediatric Hiv: A Feature Selection Approach, Isaac L Khobo, Marcin Jankiewicz, Martha J Holmes, Francesca Little, Mark F Cotton, Barbara Laughton, Andre J W Van Der Kouwe, Allison Moreau, Emmanuel Nwosu, Ernesta M Meintjes, Frances C Robertson

2020-Current year OA Pubs

Children with perinatally acquired HIV (CPHIV) have poor cognitive outcomes despite early combination antiretroviral therapy (cART). While CPHIV-related brain alterations can be investigated separately using proton magnetic resonance spectroscopy (

Subcortical-Cortical Dynamical States Of The Human Brain And Their Breakdown In Stroke, Chiara Favaretto, Michele Allegra, Gustavo Deco, Nicholas V Metcalf, Joseph C Griffis, Gordon L Shulman, Andrea Brovelli, Maurizio Corbetta

2020-Current year OA Pubs

The mechanisms controlling dynamical patterns in spontaneous brain activity are poorly understood. Here, we provide evidence that cortical dynamics in the ultra-slow frequency range (<0.01-0.1 Hz) requires intact cortical-subcortical communication. Using functional magnetic resonance imaging (fMRI) at rest, we identify Dynamic Functional States (DFSs), transient but recurrent clusters of cortical and subcortical regions synchronizing at ultra-slow frequencies. We observe that shifts in cortical clusters are temporally coincident with shifts in subcortical clusters, with cortical regions flexibly synchronizing with either limbic regions (hippocampus/amygdala), or subcortical nuclei (thalamus/basal ganglia). Focal lesions induced by stroke, especially those damaging white matter connections between basal ganglia/thalamus and cortex, provoke anomalies in the fraction times, dwell times, and transitions between DFSs, causing a bias toward abnormal network integration. Dynamical anomalies observed 2 weeks after stroke recover in time and contribute to explaining neurological impairment and long-term outcome.

Precision Dynamical Mapping Using Topological Data Analysis Reveals A Hub-Like Transition State At Rest, Manish Saggar, James M Shine, Raphaël Liégeois, Nico U F Dosenbach, Damien Fair

2020-Current year OA Pubs

In the absence of external stimuli, neural activity continuously evolves from one configuration to another. Whether these transitions or explorations follow some underlying arrangement or lack a predictable ordered plan remains to be determined. Here, using fMRI data from highly sampled individuals (~5 hours of resting-state data per individual), we aimed to reveal the rules that govern transitions in brain activity at rest. Our Topological Data Analysis based Mapper approach characterized a highly visited transition state of the brain that acts as a switch between different neural configurations to organize the spontaneous brain activity. Further, while the transition state was …