“A limited number of slices yields comparable results to all slices in foot intrinsic muscle deterioration ratio on computed tomography and magnetic resonance imaging” (2021) Journal of Biomechanics
A limited number of slices yields comparable results to all slices in foot intrinsic muscle deterioration ratio on computed tomography and magnetic resonance imaging
(2021) Journal of Biomechanics, 129, art. no. 110750, .
Zellers, J.A.a , Commean, P.K.b , Chen, L.c , Mueller, M.J.a , Hastings, M.K.a
a Program in Physical Therapy, Washington University School of Medicine in St. Louis, United States
b Mallinckrodt Institute of Radiology, Washington University School of Medicine in St. Louis, United States
c Division of Biostatistics, Washington University School of Medicine in St. Louis, United States
Abstract
Diagnostic imaging modalities, like computed tomography (CT) and magnetic resonance imaging (MRI), can be used to assess in vivo muscle quality. Quantitative assessment using these techniques is time-intensive and costly due in part to extensive post-processing needs. The purpose of this study was to identify whether a subset of slices on CT and MRI would yield comparable results to the full number of slices for a measure of muscle quality (muscle deterioration ratio = fat volume/muscle volume) in the foot intrinsic muscles of people with diabetes and peripheral neuropathy. CT (0.6 mm slice thickness) and MRI (3.5 mm slice thickness) scans were obtained using previously described methods. The total number of slices acquired during the scan was compared to several conditions using a portion of slices. Bland-Altman plots and Lin’s concordance correlation coefficient were used to test agreement. Any condition using at least three slices yielded substantial to almost perfect agreement with the total number of slices on both CT and MRI (Range of Lin’s concordance correlation coefficient: 0.947–0.999). Using a single slice in the middle of the region of interest demonstrated poor to moderate agreement with the total number of slices. The findings of this study suggest that using a limited number of slices to quantify muscle deterioration ratio on CT or MRI is a viable way to balance the combined need for measurement accuracy with feasibility in research and clinical settings. © 2021 Elsevier Ltd
Author Keywords
Diabetes; Diagnostic imaging; Foot; Quantitative MRI
Funding details
National Institutes of HealthNIHF32 DK123916, R01 DK107809
National Institute of Diabetes and Digestive and Kidney DiseasesNIDDK
Document Type: Article
Publication Stage: Final
Source: Scopus
“Genetic counseling as preventive intervention: toward individual specification of transgenerational autism risk” (2021) Journal of Neurodevelopmental Disorders
Genetic counseling as preventive intervention: toward individual specification of transgenerational autism risk
(2021) Journal of Neurodevelopmental Disorders, 13 (1), art. no. 39, .
Marrus, N.a , Turner, T.N.b , Forsen, E.a , Bolster, D.a , Marvin, A.c , Whitehouse, A.d , Klinger, L.e , Gurnett, C.A.f , Constantino, J.N.a
a Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid Ave; Box 8504, St. Louis, MO 63110, United States
b Department of Genetics, Washington University School of Medicine, 660 S. Euclid Ave; Box 8108, St. Louis, MO 63110, United States
c Maryland Center for Developmental Disabilities, Kennedy Krieger Institute, PACT Building/Office 121B; 7000 Tudsbury Road, Baltimore, MD 21244, United States
d Telethon Kids Institute, Perth Children’s Hospital, 15 Hospital Avenue, Nedlands, WA 6009, United States
e TEACCH Autism Program, Department of Psychiatry, University of North Carolina at Chapel Hill, Campus Box #7180, Chapel Hill, NC 27599-7180, United States
f Department of Neurology, Washington University School of Medicine, 660 S. Euclid Ave; Box 8111, St. Louis, MO 63110, United States
Abstract
Background: Although autism spectrum disorders (ASD) are among the most heritable of all neuropsychiatric syndromes, most affected children are born to unaffected parents. Recently, we reported an average increase of 3–5% over general population risk of ASD among offspring of adults who have first-degree relatives with ASD in a large epidemiologic family sample. A next essential step is to investigate whether there are measurable characteristics of individual parents placing them at higher or lower recurrence risk, as this information could allow more personalized genetic counseling. Methods: We assembled what is to our knowledge the largest collection of data on the ability of four measurable characteristics of unaffected prospective parents to specify risk for autism among their offspring: (1) sub clinical autistic trait burden, (2) parental history of a sibling with ASD, (3) transmitted autosomal molecular genetic abnormalities, and (4) parental age. Leveraging phenotypic and genetic data in curated family cohorts, we evaluate the respective associations between these factors and child outcome when autism is present in the family in the parental generation. Results: All four characteristics were associated with elevation in offspring risk; however, the magnitude of their predictive power—with the exception of isolated rare inherited pathogenic variants —does not yet reach a threshold that would typically be considered actionable for reproductive decision-making. Conclusions: Individual specification of risk to offspring of adults in ASD-affected families is not straightforwardly improved by ascertainment of parental phenotype, and it is not yet clear whether genomic screening of prospective parents in families affected by idiopathic ASD is warranted as a clinical standard. Systematic screening of affected family members for heritable pathogenic variants, including rare sex-linked mutations, will identify a subset of families with substantially elevated transmission risk. Polygenic risk scores are only weakly predictive at this time but steadily improving and ultimately may enable more robust prediction either singly or when combined with the risk variables examined in this study. © 2021, The Author(s).
Author Keywords
Early detection; Family studies; Genetic counseling; Personalized medicine; Reproductive health planning
Funding details
National Institutes of HealthNIH
National Institute of Mental HealthNIMHK08 MH112891, R00MH117165
National Cancer InstituteNCI30 CA91842
National Institute of Child Health and Human DevelopmentNICHD1P50HD103525
National Center for Research ResourcesNCRR
Institute of Clinical and Translational SciencesICTS
Autism Science FoundationASF
Georgia Clinical and Translational Science AllianceGaCTSA1TR000448
Document Type: Article
Publication Stage: Final
Source: Scopus
“Current neurologic treatment and emerging therapies in CDKL5 deficiency disorder” (2021) Journal of Neurodevelopmental Disorders
Current neurologic treatment and emerging therapies in CDKL5 deficiency disorder
(2021) Journal of Neurodevelopmental Disorders, 13 (1), art. no. 40, .
Olson, H.E.a , Daniels, C.I.a , Haviland, I.a , Swanson, L.C.a , Greene, C.A.a , Denny, A.M.M.a b , Demarest, S.T.c d , Pestana-Knight, E.e , Zhang, X.e , Moosa, A.N.e , Fidell, A.c d , Weisenberg, J.L.f , Suter, B.g , Fu, C.h , Neul, J.L.h , Percy, A.K.i , Marsh, E.D.j , Benke, T.A.c d k , Poduri, A.a
a Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children’s Hospital, 300 Longwood Avenue, Mailstop 3063, Boston, MA 02115, United States
b Division of Pediatric Neurology, University of Saskatchewan, Saskatoon, SK, Canada
c Children’s Hospital Colorado, University of Colorado, School of Medicine, Aurora, CO, United States
d Department of Pediatrics, School of Medicine, University of Colorado, Aurora, CO, United States
e Epilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, OH, United States
f Department of Pediatric Neurology, Washington University School of Medicine, St. Louis, MO, United States
g Division of Child Neurology, Texas Children’s Hospital, Departments of Neurology and Pediatrics, Baylor College of Medicine, Houston, TX, United States
h Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, United States
i Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, United States
j Division of Child Neurology, Children’s Hospital of Philadelphia, Departments of Neurology and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
k Departments of Pharmacology, Neurology, and Otolaryngology, School of Medicine, University of Colorado, Aurora, CO, United States
Abstract
Background: CDKL5 deficiency disorder (CDD) is associated with refractory infantile onset epilepsy, global developmental delay, and variable features that include sleep, behavioral disturbances, and movement disorders. Current treatment is primarily symptom-based and informed by experience in caring for this population. Methods: We describe medication and non-medication approaches to treatment of epilepsy and additional key neurologic symptoms (sleep disturbances, behavioral issues, movement disorders, and swallowing dysfunction) in a cohort of 177 individuals meeting criteria for CDD, 154 evaluated at 4 CDKL5 Centers of Excellence in the USA and 40 identified through the NIH Natural History Study of Rett and Related Disorders. Results: The four most frequently prescribed anti-seizure medications were broad spectrum, prescribed in over 50% of individuals. While the goal was not to ascertain efficacy, we obtained data from 86 individuals regarding response to treatment, with 2-week response achieved in 14–48% and sustained 3-month response in 5–36%, of those with known response. Additional treatments for seizures included cannabis derivatives, tried in over one-third of individuals, and clinical trial medications. In combination with pharmacological treatment, 50% of individuals were treated with ketogenic diet for attempted seizure control. Surgical approaches included vagus nerve stimulators, functional hemispherectomy, and corpus callosotomy, but numbers were too limited to assess response. Nearly one-third of individuals received pharmacologic treatment for sleep disturbances, 13% for behavioral dysregulation and movement disorders, and 43% had gastrostomy tubes. Conclusions: Treatment for neurologic features of CDD is currently symptom-based and empiric rather than CDD-specific, though clinical trials for CDD are emerging. Epilepsy in this population is highly refractory, and no specific anti-seizure medication was associated with improved seizure control. Ketogenic diet is commonly used in patients with CDD. While behavioral interventions are commonly instituted, information on the use of medications for sleep, behavioral management, and movement disorders is sparse and would benefit from further characterization and optimization of treatment approaches. The heterogeneity in treatment approaches highlights the need for systematic review and guidelines for CDD. Additional disease-specific and disease-modifying treatments are in development. © 2021, The Author(s).
Author Keywords
CDKL5 deficiency disorder; Clinical trials; Developmental encephalopathy; Emerging therapies; Epileptic encephalopathy; Ketogenic diet; Movement disorders; Vagus nerve stimulator
Funding details
National Institute of Neurological Disorders and StrokeNINDS1K23NS107646
HHT Foundation InternationalU54 HD061222
Document Type: Article
Publication Stage: Final
Source: Scopus
“Upper Limb Performance in Daily Life Approaches Plateau Around Three to Six Weeks Post-stroke” (2021) Neurorehabilitation and Neural Repair
Upper Limb Performance in Daily Life Approaches Plateau Around Three to Six Weeks Post-stroke
(2021) Neurorehabilitation and Neural Repair, 35 (10), pp. 903-914.
Lang, C.E.a b c , Waddell, K.J.a , Barth, J.a , Holleran, C.L.a c , Strube, M.J.d , Bland, M.D.a b c
a Program in Physical Therapy, Washington University School of Medicine, St LouisMO, United States
b Program in Occupational Therapy, Washington University School of Medicine, St LouisMO, United States
c Department of Neurology, Washington University School of Medicine, St LouisMO, United States
d Department of Psychological and Brain Sciences, Washington University, St Louis, MO, United States
Abstract
Background. Wearable sensors allow for direct measurement of upper limb (UL) performance in daily life. Objective. To map the trajectory of UL performance and its relationships to other factors post-stroke. Methods. Participants (n = 67) with first stroke and UL paresis were assessed at 2, 4, 6, 8, 12, 16, 20, and 24 weeks after stroke. Assessments captured UL impairment (Fugl-Meyer), capacity for activity (Action Research Arm Test), and performance of activity in daily life (accelerometer variables of use ratio and hours of paretic limb activity), along with other potential modifying factors. We modeled individual trajectories of change for each measurement level and the moderating effects on UL performance trajectories. Results. Individual trajectories were best fit with a 3-parameter logistic model, capturing the rapid growth early after stroke within the longer data collection period. Plateaus (90% of asymptote) in impairment (bootstrap mean ± SE: 32 ± 4 days post-stroke) preceded those in capacity (41 ± 4 days). Plateau in performance, as measured by the use ratio (24 ± 5 days), tended to precede plateaus in impairment and capacity. Plateau in performance, as measured by hours of paretic activity (41 ± 6 days), occurred at a similar time to that of capacity and slightly lagged impairment. Modifiers of performance trajectories were capacity, concordance, UL rehabilitation, depressive symptomatology, and cognition. Conclusions. Upper limb performance in daily life approached plateau 3 to 6 weeks post-stroke. Individuals with stroke started to achieve a stable pattern of UL use in daily life early, often before neurological impairments and functional capacity started to stabilize. © The Author(s) 2021.
Author Keywords
outcome assessment; recovery; rehabilitation; stroke; upper extremity
Funding details
Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNICHDR01 HD068290, T32 HD007434, TR002344
Document Type: Article
Publication Stage: Final
Source: Scopus
“Generation of two induced pluripotent stem cell lines with heterozygous and homozygous GAG deletion in TOR1A gene from a healthy hiPSC line” (2021) Stem Cell Research
Generation of two induced pluripotent stem cell lines with heterozygous and homozygous GAG deletion in TOR1A gene from a healthy hiPSC line
(2021) Stem Cell Research, 56, art. no. 102536, .
Akter, M.a , Cui, H.a , Chen, Y.-H.b , Ding, B.a
a Department of Biology, University of Louisiana at Lafayette, 410 East Saint Mary Boulevard, Lafayette, LA 70503, United States
b Genome Engineering and iPSC Center (GEiC), Washington University at St LouisMO 63110, United States
Abstract
A typical DYT1 dystonia is caused by a heterozygous GAG deletion (c.907–909) in the TOR1A gene (ΔE, p.Glu303del) and the pathogenesis is not clear. In this study, human induced pluripotent stem cell (hiPSC) lines carrying the heterozygous or homozygous GAG deletion in TOR1A gene were generated by genetic modification of a healthy hiPSC line (WTC11, UCSFi001-A). These hiPSC lines showed the normal stem cell morphology and karyotype, expressed the same pluripotency markers as their parental line, and had the capacity to differentiate into three germ layers, providing a valuable resource in determining the pathogenesis of human DYT1 dystonia. © 2021 The Author(s)
Funding details
National Institutes of HealthNIH
U.S. Department of DefenseDODW81XWH2010186
National Institute of Neurological Disorders and StrokeNINDSNS112910
Document Type: Article
Publication Stage: Final
Source: Scopus
“Falls: A marker of preclinical Alzheimer disease: A cohort study protocol” (2021) BMJ Open
Falls: A marker of preclinical Alzheimer disease: A cohort study protocol
(2021) BMJ Open, 11 (9), art. no. e050820, .
Bollinger, R.M.a , Keleman, A.a , Thompson, R.b , Westerhaus, E.b , Fagan, A.M.b , Benzinger, T.L.S.c , Schindler, S.E.b , Xiong, C.d , Balota, D.b e , Morris, J.C.b , Ances, B.M.b , Stark, S.L.a
a Program in Occupational Therapy, Washington University, School of Medicine, St. Louis, MO, United States
b Department of Neurology, Washington University, School of Medicine, St. Louis, MO, United States
c Department of Radiology, Washington University, School of Medicine, St. Louis, MO, United States
d Division of Biostatistics, Washington University, School of Medicine, St. Louis, MO, United States
e Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO, United States
Abstract
Introduction Progression to symptomatic Alzheimer disease (AD) occurs slowly over a series of preclinical stages. Declining functional mobility may be an early indicator of loss of brain network integration and may lead to an increased risk of experiencing falls. It is unknown whether measures of functional mobility and falls are preclinical markers of AD. The purpose of this study is to examine (1) the relationship between falls and functional mobility with AD biomarkers to determine when falls occur within the temporal progression to symptomatic Alzheimer disease, and (2) the attentional compared with perceptual/motor systems that underlie falls and functional mobility changes seen with AD. Methods and analysis This longitudinal cohort study will be conducted at the Knight Alzheimer Disease Research Center. Approximately 350 cognitively normal participants (with and without preclinical AD) will complete an in-home visit every year for 4 years. During each yearly assessment, functional mobility will be assessed using the Performance Oriented Mobility Assessment, Timed Up and Go, and Timed Up and Go dual task. Data regarding falls (including number and severity) will be collected monthly by self-report and confirmed through interviews. This study will leverage ongoing neuropsychological assessments and neuroimaging (including molecular imaging using positron emission tomography and MRI) performed by the Knight Alzheimer Disease Research Center. Relationships between falls and biomarkers of amyloid, tau and neurodegeneration will be evaluated. Ethics and dissemination This study was approved by the Washington University in St. Louis Institutional Review Board (reference number 201807135). Written informed consent will be obtained in the home prior to the collection of any study data. Results will be published in peer-reviewed publications and presented at national and international conferences. Trial registration number NCT04949529; Pre-results. © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Author Keywords
adult neurology; dementia; neurological injury; neuropathology; neurophysiology
Funding details
P01 AG03991
P01 AG026276, P30 AG066444
National Institute on AgingNIA1 R01 AG057680-01A1
Document Type: Article
Publication Stage: Final
Source: Scopus
“Effect of Urate-Elevating Inosine on Early Parkinson Disease Progression: The SURE-PD3 Randomized Clinical Trial” (2021) JAMA – Journal of the American Medical Association
Effect of Urate-Elevating Inosine on Early Parkinson Disease Progression: The SURE-PD3 Randomized Clinical Trial
(2021) JAMA – Journal of the American Medical Association, 326 (10), pp. 926-939.
Schwarzschild, M.A.a b , Ascherio, A.c , Casaceli, C.d , Curhan, G.C.e , Fitzgerald, R.f , Kamp, C.d , Lungu, C.g , Macklin, E.A.b h , Marek, K.i , Mozaffarian, D.j k , Oakes, D.d , Rudolph, A.d , Shoulson, I.l , Videnovic, A.b , Scott, B.m , Gauger, L.n , Aldred, J.o p , Bixby, M.o , Ciccarello, J.o , Gunzler, S.A.q , Henchcliffe, C.r s , Brodsky, M.t , Keith, K.t , Hauser, R.A.u , Goetz, C.v , Ledoux, M.S.w , Hinson, V.x , Kumar, R.y , Espay, A.J.z , Jimenez-Shahed, J.aa , Hunter, C.ab , Christine, C.ac , Daley, A.ac , Leehey, M.ad , De Marcaida, J.A.ae , Friedman, J.H.af , Hung, A.b , Bwala, G.b , Litvan, I.ag , Simon, D.K.ah , Simuni, T.ai , Poon, C.ai , Schiess, M.C.aj , Chou, K.ak , Park, A.al , Bhatti, D.am , Peterson, C.am , Criswell, S.R.an , Rosenthal, L.ao , Durphy, J.ap , Shill, H.A.aq ar , Mehta, S.H.as , Ahmed, A.at , Deik, A.F.au , Fang, J.Y.av , Stover, N.aw , Zhang, L.ax , Dewey, R.B., Jray , Gerald, A.ay , Boyd, J.T.az , Houston, E.ba , Suski, V.bb , Mosovsky, S.bb , Cloud, L.bc , Shah, B.B.bd , Saint-Hilaire, M.be , James, R.bf , Zauber, S.E.bg , Reich, S.bh , Shprecher, D.aq ar , Pahwa, R.bi , Langhammer, A.bi , Lafaver, K.ai , Lewitt, P.A.bj , Kaminski, P.bj , Goudreau, J.bk , Russell, D.bk , Houghton, D.J.bl , Laroche, A.bm , Thomas, K.bn , McGraw, M.bo , Mari, Z.bp , Serrano, C.bq , Blindauer, K.br , Rabin, M.bs , Kurlan, R.bs , Morgan, J.C.bt , Soileau, M.bu bv , Ainslie, M.bw , Bodis-Wollner, I.bx , Schneider, R.B.d , Waters, C.by , Ratel, A.S.by , Beck, C.A.bz , Bolger, P.d , Callahan, K.F.b , Crotty, G.F.b , Klements, D.b , Kostrzebski, M.d , McMahon, G.M.e , Pothier, L.b , Waikar, S.S.be bf , Lang, A.ca cb , Mestre, T.cc
a Mass General Institute for Neurodegenerative Disease, Boston, MA, United States
b Department of Neurology, Massachusetts General Hospital, Mass General Institute for Neurodegenerative Disease, 114 16th St, Boston, MA 02129, United States
c Harvard School of Public Health, Boston, MA, United States
d University of Rochester, Rochester, NY, United States
e Brigham and Women’s Hospital, Boston, MA, United States
f Parkinson’s Foundation Research Advocates, Parkinson’s Foundation, New York, NY, United States
g Division of Clinical Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD, United States
h Harvard Medical School, Boston, MA, United States
i Institute for Neurodegenerative Disorders, New Haven, CT, United States
j Tufts School of Medicine and Division of Cardiology, Tufts Medical Center, Boston, MA, United States
k Friedman School of Nutrition Science and Policy, Boston, MA, United States
l Department of Neurology, University of Rochester Medical Center, Rochester, NY, United States
m Duke University, Durham, NC, United States
n Duke Medical Center, Durham, NC, United States
o Inland Northwest Research, Spokane, WA, United States
p Selkirk Neurology, Spokane, WA, United States
q University Hospitals Cleveland Medical Center, Cleveland, OH, United States
r University of California, Irvine, United States
s Weill Cornell Medical College, New York, NY, United States
t Oregon Health and Science University, Portland, United States
u University of South Florida, Tampa, United States
v Rush University Medical Center, Chicago, IL, United States
w Veracity Neuroscience LLC, Memphis, TN, United States
x Medical University of South Carolina, Charleston, United States
y Rocky Mountain Movement Disorders Center, Englewood, CO, United States
z University of Cincinnati, Cincinnati, OH, United States
aa Icahn School of Medicine at Mount Sinai, New York, NY, United States
ab Baylor College of Medicine, Houston, TX, United States
ac University of California, San Francisco, United States
ad University of Colorado, Denver, United States
ae Ayer Neuroscience Institute, Hartford HealthCare, Hartford, CT, United States
af Butler Hospital, Providence, RI, United States
ag University of California, San Diego, United States
ah Beth Israel Deaconess Medical Center, Boston, MA, United States
ai Northwestern University Feinberg School of Medicine, Chicago, IL, United States
aj University of Texas Health Science Center, Houston McGovern Medical School, Houston, United States
ak University of Michigan, Ann Arbor, United States
al Ohio State University Wexner Medical Center, Columbus, United States
am University of Nebraska Medical Center, Omaha, United States
an Washington University School of Medicine in St Louis, St Louis, MO, United States
ao Johns Hopkins School of Medicine, Baltimore, MD, United States
ap Albany Medical College, Albany, NY, United States
aq Banner Sun Health Research Institute, Sun City, AZ, United States
ar University of Arizona School of Medicine-Phoenix, United States
as Mayo Clinic Arizona, Scottsdale, United States
at Cleveland Clinic, Cleveland, OH, United States
au University of Pennsylvania, Philadelphia, United States
av Vanderbilt University Medical Center, Nashville, TN, United States
aw University of Alabama at Birmingham, United States
ax UC Davis, Davis, CA, United States
ay University of Texas Southwestern Medical Center, Dallas, United States
az University of Vermont, Burlington, United States
ba University of Vermont Medical Center, Burlington, United States
bb University of Pittsburgh, Pittsburgh, PA, United States
bc VCU Parkinson’s and Movement Disorders Center, Richmond, VA, United States
bd University of Virginia, Charlottesville, United States
be Boston University School of Medicine, Boston, MA, United States
bf Boston Medical Center, Boston, MA, United States
bg Indiana University, Bloomington, United States
bh University of Maryland School of Medicine, Baltimore, United States
bi University of Kansas Medical Center, Kansas City, United States
bj Henry Ford Hospital-West Bloomfield, West Bloomfield Township, MI, United States
bk Michigan State University, East Lansing, United States
bl Ochsner Medical Center, Jefferson, LA, United States
bm Ochsner Health System, Jefferson, LA, United States
bn Sentara Neurology Specialists, Norfolk, VA, United States
bo Center for Movement Disorders and Neurodegenerative Disease, Northwestern Medicine/Central DuPage Hospital, Winfield, IL, United States
bp Cleveland Clinic-Las Vegas, Las Vegas, NV, United States
bq University of Puerto Rico, San Juan, Puerto Rico
br Medical College of Wisconsin, Milwaukee, United States
bs Atlantic Neuroscience Institute, Summit, NJ, United States
bt Augusta University, Augusta, GA, United States
bu Texas Movement Disorder Specialists, Georgetown, United States
bv Scott and White Healthcare, Texas A and M University, Temple, United States
bw Baylor Scott and White Health, Temple, TX, United States
bx State University of New York Downstate Medical Center, Brooklyn, United States
by Columbia University, New York, NY, United States
bz University of Rochester Medical Center, Rochester, NY, United States
ca University of Toronto, Toronto, ON, Canada
cb Edmond J. Safra Program in Parkinson’s Disease, Toronto Western Hospital, Toronto, ON, Canada
cc University of Ottawa, Ottawa, ON, Canada
Abstract
Importance: Urate elevation, despite associations with crystallopathic, cardiovascular, and metabolic disorders, has been pursued as a potential disease-modifying strategy for Parkinson disease (PD) based on convergent biological, epidemiological, and clinical data. Objective: To determine whether sustained urate-elevating treatment with the urate precursor inosine slows early PD progression. Design, Participants, and Setting: Randomized, double-blind, placebo-controlled, phase 3 trial of oral inosine treatment in early PD. A total of 587 individuals consented, and 298 with PD not yet requiring dopaminergic medication, striatal dopamine transporter deficiency, and serum urate below the population median concentration (<5.8 mg/dL) were randomized between August 2016 and December 2017 at 58 US sites, and were followed up through June 2019. Interventions: Inosine, dosed by blinded titration to increase serum urate concentrations to 7.1-8.0 mg/dL (n = 149) or matching placebo (n = 149) for up to 2 years. Main Outcomes and Measures: The primary outcome was rate of change in the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS; parts I-III) total score (range, 0-236; higher scores indicate greater disability; minimum clinically important difference of 6.3 points) prior to dopaminergic drug therapy initiation. Secondary outcomes included serum urate to measure target engagement, adverse events to measure safety, and 29 efficacy measures of disability, quality of life, cognition, mood, autonomic function, and striatal dopamine transporter binding as a biomarker of neuronal integrity. Results: Based on a prespecified interim futility analysis, the study closed early, with 273 (92%) of the randomized participants (49% women; mean age, 63 years) completing the study. Clinical progression rates were not significantly different between participants randomized to inosine (MDS-UPDRS score, 11.1 [95% CI, 9.7-12.6] points per year) and placebo (MDS-UPDRS score, 9.9 [95% CI, 8.4-11.3] points per year; difference, 1.26 [95% CI, -0.59 to 3.11] points per year; P =.18). Sustained elevation of serum urate by 2.03 mg/dL (from a baseline level of 4.6 mg/dL; 44% increase) occurred in the inosine group vs a 0.01-mg/dL change in serum urate in the placebo group (difference, 2.02 mg/dL [95% CI, 1.85-2.19 mg/dL]; P<.001). There were no significant differences for secondary efficacy outcomes including dopamine transporter binding loss. Participants randomized to inosine, compared with placebo, experienced fewer serious adverse events (7.4 vs 13.1 per 100 patient-years) but more kidney stones (7.0 vs 1.4 stones per 100 patient-years). Conclusions and Relevance: Among patients recently diagnosed as having PD, treatment with inosine, compared with placebo, did not result in a significant difference in the rate of clinical disease progression. The findings do not support the use of inosine as a treatment for early PD. Trial Registration: ClinicalTrials.gov Identifier: NCT02642393. © 2021 American Medical Association. All rights reserved.
Funding details
National Institutes of HealthNIH
U.S. Department of DefenseDOD
U.S. Food and Drug AdministrationFDA
National Institute of Neurological Disorders and StrokeNINDSU01NS089666, U01NS090259
Michael J. Fox Foundation for Parkinson’s ResearchMJFF11942, 14489
Bill and Melinda Gates FoundationBMGF
Rockefeller Foundation
American Orthopaedic Foot and Ankle SocietyAOFAS
Pfizer
AstraZeneca
Roche
Medtronic
American Academy of NeurologyAAN
Biogen
CHDI FoundationCHDI
Patient-Centered Outcomes Research InstitutePCORI
Teva Pharmaceutical Industries
St. Jude MedicalSJM
AbbVie
University of Nebraska Medical CenterUNMC
GE Healthcare
University of Chicago
Cleveland Clinic FoundationCCF
Takeda Pharmaceuticals U.S.A.TPUSA
International Parkinson and Movement Disorder SocietyMDS
Parkinsonfonden
Boston Scientific CorporationBSC
Fondation Brain Canada
Sunovion
School of Public Health, University of California BerkeleyUCB
Ontario Research FoundationORF
Abeona Therapeutics
Astex Pharmaceuticals
Parkinson Study GroupPSG
ACADIA PharmaceuticalsACADIA
Acorda Therapeutics
Neurocrine Biosciences
Arizona Alzheimer’s ConsortiumAAC
Kyowa Kirin Pharmaceutical DevelopmentKKD
Canadian Institutes of Health ResearchCIHR
Physicians’ Services Incorporated FoundationPSI
Parkinson Canada
Mitsubishi Tanabe Pharma CorporationMTPC
H. Lundbeck A/S
Document Type: Article
Publication Stage: Final
Source: Scopus
“Brain white matter structure and amyloid deposition in black and white older adults: The aric-pet study” (2021) Journal of the American Heart Association
Brain white matter structure and amyloid deposition in black and white older adults: The aric-pet study
(2021) Journal of the American Heart Association, 10 (17), art. no. e022087, . Cited 1 time.
Walker, K.A.a , Silverstein, N.b , Zhou, Y.c d , Hughes, T.M.e , Jack, C.R.f , Knopman, D.S.g , Sharrett, A.R.h , Wong, D.F.c , Mosley, T.H.i , Gottesman, R.F.j
a Laboratory of Behavioral Neuroscience, National Institute on Aging, Intramural Research Program, Baltimore, MD, United States
b Department of Medicine, SUNY Downstate Health Sciences University, Brooklyn, NY, United States
c Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States
d United Technologies, Shanghai, China
e Department of Internal Medicine, Section on Gerontology and Geriatrics Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States
f Department of Radiology, Rochester, MN, United States
g Department of Neurology, Mayo Clinic, Rochester, MN, United States
h Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
i Department of Medicine, Division of Geriatrics, University of Mississippi Medical Center, Jackson, MS, United States
j Stroke Branch, National Institute of Neurological Disorders and Stroke Intramural Research Program, NIH, Bethesda, MD, United States
Abstract
BACKGROUND: White matter abnormalities are a common feature of aging and Alzheimer disease, and tend to be more severe among Black individuals. However, the extent to which white matter abnormalities relate to amyloid deposition, a marker of Alzheimer pathology, remains unclear. This cross-sectional study examined the association of white matter abnormalities with cortical amyloid in a community sample of older adults without dementia and examined the moderating effect of race. METHODS AND RESULTS: Participants from the ARIC-PET (Atherosclerosis Risk in Communities-Positron Emission Tomography) study underwent brain magnetic resonance imaging, which quantified white matter hyperintensity volume and microstructural integrity using diffusion tensor imaging. Participants received florbetapir positron emission tomography imaging to measure brain amyloid. Associations between measures of white matter structure and elevated amyloid status were examined using multivariable logistic regression. Among 322 participants (43% Black), each SD increase in white matter hyperintensity volume was associated with a greater odds of elevated amyloid (odds ratio [OR], 1.37; 95% CI, 1.03–1.83) after adjusting for demo-graphic and cardiovascular risk factors. In race-stratified analyses, a greater white matter hyperintensity volume was more strongly associated with elevated amyloid among Black participants (OR, 2.00; 95% CI, 1.15–3.50), compared with White participants (OR, 1.29; 95% CI, 0.89–1.89). However, the race interaction was not statistically significant (P interaction=0.09). We found no association between white matter microstructure and elevated amyloid. CONCLUSIONS: The results suggest a modest positive relationship between white matter hyperintensity and elevated amyloid in older adults without dementia. Although the results indicate that this association is nonsignificantly stronger among Black participants, these findings will need to be confirmed or refuted using larger multiracial cohorts. © 2021 The Authors.
Author Keywords
Alzheimer disease; Amyloid; Cerebral microbleeds; Dementia; White matter disease
Funding details
National Institutes of HealthNIH
National Institute on AgingNIA
National Heart, Lung, and Blood InstituteNHLBI096812, 2U01HL096814, 2U01HL096899, 2U01HL096902, 2U01HL096917, HHSN268201700001I, U01 2U01HL 096812
National Institute on Deafness and Other Communication DisordersNIDCDK23 AG064122, K24 AG052573, R01-HL70825, R01AG040282, UL1RR025005
National Institute of Neurological Disorders and StrokeNINDS
Mayo Clinic
Document Type: Article
Publication Stage: Final
Source: Scopus
“Slow manifolds within network dynamics encode working memory efficiently and robustly” (2021) PLoS Computational Biology
Slow manifolds within network dynamics encode working memory efficiently and robustly
(2021) PLoS Computational Biology, 17 (9), art. no. e1009366, .
Ghazizadeh, E.a , Ching, S.a b c
a Electrical and Systems Engineering, Washington University in St. Louis, St. Louis, MO, United States
b Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States
c Division of Biology and Biomedical Sciences, Washington University in St. Louis, St. Louis, MO, United States
Abstract
Working memory is a cognitive function involving the storage and manipulation of latent information over brief intervals of time, thus making it crucial for context-dependent computation. Here, we use a top-down modeling approach to examine network-level mechanisms of working memory, an enigmatic issue and central topic of study in neuroscience. We optimize thousands of recurrent rate-based neural networks on a working memory task and then perform dynamical systems analysis on the ensuing optimized networks, wherein we find that four distinct dynamical mechanisms can emerge. In particular, we show the prevalence of a mechanism in which memories are encoded along slow stable manifolds in the network state space, leading to a phasic neuronal activation profile during memory periods. In contrast to mechanisms in which memories are directly encoded at stable attractors, these networks naturally forget stimuli over time. Despite this seeming functional disadvantage, they are more efficient in terms of how they leverage their attractor landscape and paradoxically, are considerably more robust to noise. Our results provide new hypotheses regarding how working memory function may be encoded within the dynamics of neural circuits. Copyright: © 2021 Ghazizadeh, Ching. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Is left-behind a real reason for children’s social cognition deficit? An fNIRS study on the effect of social interaction on left-behind preschooler’s prefrontal activation” (2021) PLoS ONE
Is left-behind a real reason for children’s social cognition deficit? An fNIRS study on the effect of social interaction on left-behind preschooler’s prefrontal activation
(2021) PLoS ONE, 16 (9 September 2021), art. no. e0254010, .
Ding, K.a b , Li, C.c , Jia, H.d , Zhang, M.e , Yu, D.a f
a Key Laboratory of Child Development and Learning Science of Ministry of Education, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China
b Division of Child and Adolescent Psychiatry, Washington University in St. Louis, St. Louis, MO, United States
c Hangzhou College of Early Childhood Teacher’s Education, Zhejiang Normal University, Hangzhou, China
d School of Psychology, Henan University, Kaifeng, China
e School of Psychology, Shanghai Normal University, Shanghai, China
f The Third Affiliated Hospital of Zhengzhou University, Henan, Zhengzhou, China
Abstract
The left-behind phenomenon, caused by parent out-migration, has become a common social issue and might lead to long-term and potential risks for children in rural areas of China. It is important to investigate the effect of social interaction on prefrontal activation of left-behind children in China because of possible effects of parent out-migration on children’s social cognition. We recruited 81 rural Chinese preschoolers aged 52–76 months (mean = 64.98 ± 6.321 months) preschoolers with three different statuses of parental out-migration (including non-, partially, and completely left-behind children). Using functional Near-Infrared Spectroscopy (fNIRS), we compared behavior and brain activation and in three groups (non-, partially-, completely-left-behind children) under two different social interaction conditions (child-teacher and child-stranger situation). Results revealed that initiating joint attention (IJA) may evoke higher brain activation than responding to joint attention (RJA) in the prefrontal cortex (PFC), especially in the case of initiating joint attention with the stranger. In addition, the activation of joint attention was positively correlated with children’s language score, cognitive flexibility, and facial expression recognition. More importantly, partially-left-behind children evoked higher brain activation in the IJA condition and presented a higher language level than completely/non-left-behind children. The current study provides insight into the neural basis of left-behind children’s development and revealed for the first time that family economic level and left-behind status may contribute to the lower social cognition. Copyright: © 2021 Ding et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding details
National Natural Science Foundation of ChinaNSFC61673113, 62073077
China Scholarship CouncilCSC201906090155
Document Type: Article
Publication Stage: Final
Source: Scopus
“Autism spectrum disorder in pediatric idiopathic intracranial hypertension” (2021) Life
Autism spectrum disorder in pediatric idiopathic intracranial hypertension
(2021) Life, 11 (9), art. no. 972, .
Jensen, A.K.a b , Sheldon, C.A.a c , Paley, G.L.a d , Szperka, C.L.b e , Liu, G.W.e , Liu, G.T.a b , McCormack, S.E.b f
a Division of Ophthalmology, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, United States
b Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, United States
c Department of Ophthalmology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
d Department of Ophthalmology, Washington University, St. Louis, MO 63110, United States
e Division of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, United States
f Division of Endocrinology and Diabetes, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, United States
Abstract
In recent years, the substantial burden of medical comorbidities in autism spectrum disorder (ASD) populations has been described. We report a retrospective observational case series of pediatric patients with suspected idiopathic intracranial hypertension (IIH) and concurrent ASD. Pediatric subjects with suspected IIH aged 2–18 years were identified by review of a pediatric neuro-ophthalmologist’s database spanning from July 1993 to April 2013. ASD diagnoses were identified within this cohort by an ICD-9 diagnosis code search and database review. Three subjects had concurrent ASD diagnoses; all were non-obese males. Since the retrospective observational case series was performed in April 2013, we identified three additional IIH cases in boys with ASD. Our experience suggests that IIH may be a comorbidity of ASD, particularly in non-obese boys. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Author Keywords
Autism; Idiopathic intracranial hypertension; IIH; Pseudotumor cerebri syndrome
Funding details
Children’s Hospital of PhiladelphiaCHOP
Document Type: Article
Publication Stage: Final
Source: Scopus
“Emotion Differentiation in Current and Remitted Major Depressive Disorder” (2021) Frontiers in Psychology
Emotion Differentiation in Current and Remitted Major Depressive Disorder
(2021) Frontiers in Psychology, 12, art. no. 685851, .
Thompson, R.J.a , Liu, D.Y.a , Sudit, E.a , Boden, M.b
a Emotion and Mental Health Lab, Department of Psychological Brain Sciences, Washington University in St. Louis, St. Louis, MO, United States
b VA Palo Alto Health Care System, Palo Alto, CA, United States
Abstract
People with current major depressive disorder (MDD) experience diminished emotion differentiation. We tested the hypothesis that this emotional disturbance is chronic and also characterizes those whose MDD has remitted. As our main aim, we examined emotion differentiation in conjunction with elevated negative and diminished positive emotional intensity, which are both cardinal symptoms of MDD. As an exploratory aim, we examined the predominant theoretical conceptualization that people low in emotion differentiation use more general state terms (e.g., bad) and fewer emotion terms (e.g., anger) to describe their emotional experience. Participants (assessed via diagnostic interview) included individuals who had current MDD (current depressed; n = 48), individuals whose MDD was in full remission (remitted depressed; n = 80), and healthy controls (n = 87). Participants also completed two self-report measures of depressive symptoms and reported momentary emotion repeatedly for 14 days via experience sampling, from which we computed emotion differentiation (i.e., intraclass correlation coefficient) and emotional intensity (i.e., average of the mean emotion ratings across surveys). Finally, participants described a momentary emotional experience via an open-response format, which was coded for the use of general state and emotion terms. Compared to the healthy control group, the current and remitted depressed groups showed similarly low levels of negative and positive emotion differentiation. These findings suggest that diminished emotion differentiation may be a stable characteristic of depressive disorders and a possible target for future prevention efforts. Diminished negative emotion differentiation was significantly associated with higher depressive symptoms as assessed by only one of the depression measures, though this finding did not hold after adjusting for negative emotional intensity. Finally, participants’ emotion differentiation was not associated with use of general state and emotion terms, and groups did not use general state and emotion terms in ways that were consistent with the predominant theoretical conceptualization of emotion differentiation, suggesting the need for clarification in this research domain. © Copyright © 2021 Thompson, Liu, Sudit and Boden.
Author Keywords
emotion differentiation; emotional granularity; experience sampling; major depressive disorder; remitted depression
Funding details
Washington University in St. LouisWUSTL
Document Type: Article
Publication Stage: Final
Source: Scopus
“COVID-19 in Patients With Neuromyelitis Optica Spectrum Disorders and Myelin Oligodendrocyte Glycoprotein Antibody Disease in North America: From the COViMS Registry” (2021) Neurology(R) Neuroimmunology & Neuroinflammation
COVID-19 in Patients With Neuromyelitis Optica Spectrum Disorders and Myelin Oligodendrocyte Glycoprotein Antibody Disease in North America: From the COViMS Registry
(2021) Neurology(R) Neuroimmunology & Neuroinflammation, 8 (5), .
Newsome, S.D.a , Cross, A.H.b , Fox, R.J.b , Halper, J.b , Kanellis, P.b , Bebo, B.b , Li, D.b , Cutter, G.R.b , Rammohan, K.W.b , Salter, A.b
a From the Johns Hopkins University School of Medicine (S.D.N.), Baltimore, MD; Washington University in St. Louis School of Medicine (A.H.C., A.S.), MO; Mellen Center for MS (R.J.F.), Cleveland Clinic, OH; Consortium of MS Centers (J.H.), Hackensack, NJ; MS Society of Canada (P.K.), Toronto, Ontario, Canada; National Multiple Sclerosis Society (B.B.) New York, NY; University of British Columbia (D.L.), Vancouver, British Columbia, Canada; The University of Alabama at Birmingham (G.R.C.); and University of Miami School of Medicine (K.W.R.), FL. snewsom2@jhmi.edu
b From the Johns Hopkins University School of Medicine (S.D.N.), Baltimore, MD; Washington University in St. Louis School of Medicine (A.H.C., A.S.), MO; Mellen Center for MS (R.J.F.), Cleveland Clinic, OH; Consortium of MS Centers (J.H.), Hackensack, NJ; MS Society of Canada (P.K.), Toronto, Ontario, Canada; National Multiple Sclerosis Society (B.B.) New York, NY; University of British Columbia (D.L.), Vancouver, British Columbia, Canada; The University of Alabama at Birmingham (G.R.C.); and University of Miami School of Medicine (K.W.R.), FL
Abstract
BACKGROUND AND OBJECTIVE: To describe the impact of coronavirus disease 2019 (COVID-19) on people with neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD). METHODS: The COVID-19 Infections in Multiple Sclerosis (MS) and Related Diseases (COViMS) Registry collected data on North American patients with MS and related diseases with laboratory-positive or highly suspected SARS-CoV-2 infection. Deidentified data were entered into a web-based registry by health care providers. Data were analyzed using t-tests, Pearson χ2 tests, or Fisher exact tests for categorical variables. Univariate logistic regression models examined effects of risk factors and COVID-19 clinical severity. RESULTS: As of June 7, 2021, 77 patients with NMOSD and 20 patients with MOGAD were reported in the COViMS Registry. Most patients with NMOSD were laboratory positive for SARS-CoV-2 and taking rituximab at the time of COVID-19 diagnosis. Most patients with NMOSD were not hospitalized (64.9% [95% CI: 53.2%-75.5%]), whereas 15.6% (95% CI: 8.3%-25.6%) were hospitalized only, 9.1% (95% CI: 3.7%-17.8%) were admitted to the ICU and/or ventilated, and 10.4% (95% CI: 4.6%-19.5%) died. In patients with NMOSD, having a comorbidity was the sole factor identified for poorer COVID-19 outcome (OR = 6.0, 95% CI: 1.79-19.98). Most patients with MOGAD were laboratory positive for SARS-CoV-2, and almost half were taking rituximab. Among patients with MOGAD, 75.0% were not hospitalized, and no deaths were recorded; no factors were different between those not hospitalized and those hospitalized, admitted to the ICU, or ventilated. DISCUSSION: Among the reported patients with NMOSD, a high mortality rate was observed, and the presence of comorbid conditions was associated with worse COVID-19 outcome. There were no deaths reported in the patients with MOGAD, although these observations are limited due to small sample size. Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Glucose-mediated de novo lipogenesis in photoreceptors drives early diabetic retinopathy” (2021) Journal of Biological Chemistry
Glucose-mediated de novo lipogenesis in photoreceptors drives early diabetic retinopathy
(2021) Journal of Biological Chemistry, 297 (3), art. no. 101104, .
Rajagopal, R.a , Sylvester, B.a , Zhang, S.a , Adak, S.b , Wei, X.b , Bowers, M.c , Jessberger, S.c , Hsu, F.-F.b , Semenkovich, C.F.b d
a The Department of Ophthalmology and Visual Sciences, Washington University, School of Medicine, Saint Louis, MO, United States
b Division of Endocrinology, Metabolism, and Lipid Research, Washington University, School of Medicine, Saint Louis, MO, United States
c Laboratory of Neural Plasticity, Faculties of Medicine and Science, Brain Research Institute, University of Zurich, Zurich, Switzerland
d Department of Cell Biology and Physiology, Washington University, School of Medicine, Saint Louis, MO, United States
Abstract
Diabetic retinopathy (DR) is an increasingly frequent cause of blindness across populations; however, the events that initiate pathophysiology of DR remain elusive. Strong preclinical and clinical evidence suggests that abnormalities in retinal lipid metabolism caused by diabetes may account for the origin of this disease. A major arm of lipid metabolism, de novo biosynthesis, is driven by elevation in available glucose, a common thread binding all forms of vision loss in diabetes. Therefore, we hypothesized that aberrant retinal lipid biogenesis is an important promoter of early DR. In murine models, we observed elevations of diabetes-associated retinal de novo lipogenesis ~70% over control levels. This shift was primarily because of activation of fatty acid synthase (FAS), a rate-limiting enzyme in the biogenic pathway. Activation of FAS was driven by canonical glucose-mediated disinhibition of acetyl-CoA carboxylase, a major upstream regulatory enzyme. Mutant mice expressing gain-of-function FAS demonstrated increased vulnerability to DR, whereas those with FAS deletion in rod photoreceptors maintained preserved visual responses upon induction of diabetes. Excess retinal de novo lipogenesis -either because of diabetes or because of FAS gain of function -was associated with modestly increased levels of palmitate-containing phosphatidylcholine species in synaptic membranes, a finding with as yet uncertain significance. These findings implicate glucose-dependent increases in photoreceptor de novo lipogenesis in the early pathogenesis of DR, although the mechanism of deleterious action of this pathway remains unclear. © 2021 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Funding details
DK020579
National Institutes of HealthNIHDK101392, EY025269, P30EY002687, P60 DK20579
Research to Prevent BlindnessRPB
Horncrest Foundation
Document Type: Article
Publication Stage: Final
Source: Scopus
“Cell-free DNA ultra-low-pass whole genome sequencing to distinguish malignant peripheral nerve sheath tumor (MPNST) from its benign precursor lesion: A cross-sectional study” (2021) PLoS Medicine
Cell-free DNA ultra-low-pass whole genome sequencing to distinguish malignant peripheral nerve sheath tumor (MPNST) from its benign precursor lesion: A cross-sectional study
(2021) PLoS Medicine, 18 (8), art. no. e1003734, .
Szymanski, J.J.a , Sundby, R.T.b , Jones, P.A.a c , Srihari, D.d , Earland, N.a c , Harris, P.K.a , Feng, W.a , Qaium, F.a , Lei, H.b , Roberts, D.d , Landeau, M.d , Bell, J.d , Huang, Y.a , Hoffman, L.b , Spencer, M.b , Spraker, M.B.a e , Ding, L.d e f g , Widemann, B.C.b , Shern, J.F.b , Hirbe, A.C.c d e h , Chaudhuri, A.A.a c e i j
a Division of Cancer Biology, Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, United States
b Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States
c Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO, United States
d Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
e Siteman Cancer Center, Barnes Jewish Hospital, Washington University School of Medicine, St. Louis, MO, United States
f McDonnel Genome Institute, Washington University in, Saint Louis, MO, United States
g Department of Genetics, Washington University School of Medicine, St. Louis, MO, United States
h Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
i Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, MO, United States
j Department of Computer Science and Engineering, Washington University in St. Louis, St. Louis, MO, United States
Abstract
Background The leading cause of mortality for patients with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome is the development of malignant peripheral nerve sheath tumor (MPNST), an aggressive soft tissue sarcoma. In the setting of NF1, this cancer type frequently arises from within its common and benign precursor, plexiform neurofibroma (PN). Transformation from PN to MPNST is challenging to diagnose due to difficulties in distinguishing cross-sectional imaging results and intralesional heterogeneity resulting in biopsy sampling errors. Methods and findings This multi-institutional study from the National Cancer Institute and Washington University in St. Louis used fragment size analysis and ultra-low-pass whole genome sequencing (ULP-WGS) of plasma cell-free DNA (cfDNA) to distinguish between MPNST and PN in patients with NF1. Following in silico enrichment for short cfDNA fragments and copy number analysis to estimate the fraction of plasma cfDNA originating from tumor (tumor fraction), we developed a noninvasive classifier that differentiates MPNST from PN with 86% pretreatment accuracy (91% specificity, 75% sensitivity) and 89% accuracy on serial analysis (91% specificity, 83% sensitivity). Healthy controls without NF1 (participants = 16, plasma samples = 16), PN (participants = 23, plasma samples = 23), and MPNST (participants = 14, plasma samples = 46) cohorts showed significant differences in tumor fraction in plasma (P = 0.001) as well as cfDNA fragment length (P < 0.001) with MPNST samples harboring shorter fragments and being enriched for tumor-derived cfDNA relative to PN and healthy controls. No other covariates were significant on multivariate logistic regression. Mutational analysis demonstrated focal NF1 copy number loss in PN and MPNST patient plasma but not in healthy controls. Greater genomic instability including alterations associated with malignant transformation (focal copy number gains in chromosome arms 1q, 7p, 8q, 9q, and 17q; focal copy number losses in SUZ12, SMARCA2, CDKN2A/B, and chromosome arms 6p and 9p) was more prominently observed in MPNST plasma. Furthermore, the sum of longest tumor diameters (SLD) visualized by cross-sectional imaging correlated significantly with paired tumor fractions in plasma from MPNST patients (r = 0.39, P = 0.024). On serial analysis, tumor fraction levels in plasma dynamically correlated with treatment response to therapy and minimal residual disease (MRD) detection before relapse. Study limitations include a modest MPNST sample size despite accrual from 2 major referral centers for this rare malignancy, and lack of uniform treatment and imaging protocols representing a real-world cohort. Conclusions Tumor fraction levels derived from cfDNA fragment size and copy number alteration analysis of plasma cfDNA using ULP-WGS significantly correlated with MPNST tumor burden, accurately distinguished MPNST from its benign PN precursor, and dynamically correlated with treatment response. In the future, our findings could form the basis for improved early cancer detection and monitoring in high-risk cancer-predisposed populations. © 2021 Public Library of Science. All rights reserved.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Head-to-Head Comparison of 8 Plasma Amyloid-β 42/40 Assays in Alzheimer Disease” (2021) JAMA Neurology
Head-to-Head Comparison of 8 Plasma Amyloid-β 42/40 Assays in Alzheimer Disease
(2021) JAMA Neurology, .
Janelidze, S.a , Teunissen, C.E.b , Zetterberg, H.c d e f , Allué, J.A.g , Sarasa, L.g , Eichenlaub, U.h , Bittner, T.i , Ovod, V.j , Verberk, I.M.W.b , Toba, K.k l , Nakamura, A.m , Bateman, R.J.j , Blennow, K.d n , Hansson, O.a o
a Clinical Memory Research Unit, Department of Clinical Sciences Malmo, Lund University, Solvegatan 19, BMC B11, Lund, 221 84, Sweden
b Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam University Medical Center, Amsterdam, Netherlands
c Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden
d Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
e Department of Neurodegenerative Disease, University College London, Institute of Neurology, London, United Kingdom
f United Kingdom Dementia Research Institute, University College London, London, United Kingdom
g Mass Spectrometry Laboratory, Araclon Biotech, Zaragoza, Spain
h Roche Diagnostics, Penzberg, Germany
i F. Hoffmann-La Roche, Basel, Switzerland
j Department of Neurology, Washington University, School of Medicine, St Louis, MO, United States
k National Center for Geriatrics and Gerontology, Obu, Aichi, Japan
l Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
m Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan
n Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden
o Memory Clinic, Skåne University Hospital, S:t Johannesgatan 8, Malmö, SE-20502, Sweden
Abstract
Importance: Blood-based tests for brain amyloid-β (Aβ) pathology are needed for widespread implementation of Alzheimer disease (AD) biomarkers in clinical care and to facilitate patient screening and monitoring of treatment responses in clinical trials. Objective: To compare the performance of plasma Aβ42/40 measured using 8 different Aβ assays when detecting abnormal brain Aβ status in patients with early AD. Design, Setting, and Participants: This study included 182 cognitively unimpaired participants and 104 patients with mild cognitive impairment from the BioFINDER cohort who were enrolled at 3 different hospitals in Sweden and underwent Aβ positron emission tomography (PET) imaging and cerebrospinal fluid (CSF) and plasma collection from 2010 to 2014. Plasma Aβ42/40 was measured using an immunoprecipitation-coupled mass spectrometry developed at Washington University (IP-MS-WashU), antibody-free liquid chromatography MS developed by Araclon (LC-MS-Arc), and immunoassays from Roche Diagnostics (IA-Elc); Euroimmun (IA-EI); and Amsterdam University Medical Center, ADx Neurosciences, and Quanterix (IA-N4PE). Plasma Aβ42/40 was also measured using an IP-MS-based method from Shimadzu in 200 participants (IP-MS-Shim) and an IP-MS-based method from the University of Gothenburg (IP-MS-UGOT) and another immunoassay from Quanterix (IA-Quan) among 227 participants. For validation, 122 participants (51 cognitively normal, 51 with mild cognitive impairment, and 20 with AD dementia) were included from the Alzheimer Disease Neuroimaging Initiative who underwent Aβ-PET and plasma Aβ assessments using IP-MS-WashU, IP-MS-Shim, IP-MS-UGOT, IA-Elc, IA-N4PE, and IA-Quan assays. Main Outcomes and Measures: Discriminative accuracy of plasma Aβ42/40 quantified using 8 different assays for abnormal CSF Aβ42/40 and Aβ-PET status. Results: A total of 408 participants were included in this study. In the BioFINDER cohort, the mean (SD) age was 71.6 (5.6) years and 49.3% of the cohort were women. When identifying participants with abnormal CSF Aβ42/40 in the whole cohort, plasma IP-MS-WashU Aβ42/40 showed significantly higher accuracy (area under the receiver operating characteristic curve [AUC], 0.86; 95% CI, 0.81-0.90) than LC-MS-Arc Aβ42/40, IA-Elc Aβ42/40, IA-EI Aβ42/40, and IA-N4PE Aβ42/40 (AUC range, 0.69-0.78; P <.05). Plasma IP-MS-WashU Aβ42/40 performed significantly better than IP-MS-UGOT Aβ42/40 and IA-Quan Aβ42/40 (AUC, 0.84 vs 0.68 and 0.64, respectively; P <.001), while there was no difference in the AUCs between IP-MS-WashU Aβ42/40 and IP-MS-Shim Aβ42/40 (0.87 vs 0.83; P =.16) in the 2 subcohorts where these biomarkers were available. The results were similar when using Aβ-PET as outcome. Plasma IPMS-WashU Aβ42/40 and IPMS-Shim Aβ42/40 showed highest coefficients for correlations with CSF Aβ42/40 (r range, 0.56-0.65). The BioFINDER results were replicated in the Alzheimer Disease Neuroimaging Initiative cohort (mean [SD] age, 72.4 [5.4] years; 43.4% women), where the IP-MS-WashU assay performed significantly better than the IP-MS-UGOT, IA-Elc, IA-N4PE, and IA-Quan assays but not the IP-MS-Shim assay. Conclusions and Relevance: The results from 2 independent cohorts indicate that certain MS-based methods performed better than most of the immunoassays for plasma Aβ42/40 when detecting brain Aβ pathology. © 2021 American Medical Association. All rights reserved.
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Sex Differences in the Role of CNIH3 on Spatial Memory and Synaptic Plasticity” (2021) Biological Psychiatry
Sex Differences in the Role of CNIH3 on Spatial Memory and Synaptic Plasticity
(2021) Biological Psychiatry, .
Frye, H.E.a b h , Izumi, Y.c d e , Harris, A.N.f , Williams, S.B.a b , Trousdale, C.R.a b , Sun, M.-Y.c , Sauerbeck, A.D.g , Kummer, T.T.g , Mennerick, S.c d e , Zorumski, C.F.c d e , Nelson, E.C.c , Dougherty, J.D.c f , Morón, J.A.a b c d
a Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
b Pain Center, Washington University School of Medicine, St. Louis, MO, United States
c Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
d Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, United States
e Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, MO, United States
f Department of Genetics, Washington University School of Medicine, St. Louis, MO, United States
g Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
h Program in Neuroscience, Washington University in St. Louis, St. Louis, MO, United States
Abstract
Background: CNIH3 is an AMPA receptor (AMPAR) auxiliary protein prominently expressed in the dorsal hippocampus (dHPC), a region that plays a critical role in spatial memory and synaptic plasticity. However, the effects of CNIH3 on AMPAR-dependent synaptic function and behavior have not been investigated. Methods: We assessed a gain-of-function model of Cnih3 overexpression in the dHPC and generated and characterized a line of Cnih3−/− C57BL/6 mice. We assessed spatial memory through behavioral assays, protein levels of AMPAR subunits and synaptic proteins by immunoblotting, and long-term potentiation in electrophysiological recordings. We also utilized a super-resolution imaging workflow, SEQUIN (Synaptic Evaluation and Quantification by Imaging of Nanostructure), for analysis of nanoscale synaptic connectivity in the dHPC. Results: Overexpression of Cnih3 in the dHPC improved short-term spatial memory in female mice but not in male mice. Cnih3−/− female mice exhibited weakened short-term spatial memory, reduced dHPC synapse density, enhanced expression of calcium-impermeable AMPAR (GluA2-containing) subunits in synaptosomes, and attenuated long-term potentiation maintenance compared with Cnih3+/+ control mice; Cnih3−/− males were unaffected. Further investigation revealed that deficiencies in spatial memory and changes in AMPAR composition and synaptic plasticity were most pronounced during the metestrus phase of the estrous cycle in female Cnih3−/− mice. Conclusions: This study identified a novel effect of sex and estrous on CNIH3’s role in spatial memory and synaptic plasticity. Manipulation of CNIH3 unmasked sexually dimorphic effects on spatial memory, synaptic function, AMPAR composition, and hippocampal plasticity. These findings reinforce the importance of considering sex as a biological variable in studies of memory and hippocampal synaptic function. © 2021 Society of Biological Psychiatry
Author Keywords
AMPA receptors; Hippocampus; Memory; Sex differences; Super-resolution microscopy; Synaptic plasticity
Funding details
CDI-CORE-2015-505, CDI-CORE-2019-813
National Institutes of HealthNIHDA041781, DA041883, DA042499, DA042581, DA042620, DA045463, DA046436, GM008151, I01BX005204
Brain Research FoundationBRFBRFSG-2017-05
BrightFocus FoundationBFFA2017084S
Foundation for Barnes-Jewish Hospital3770, 4642
Washington University School of Medicine in St. LouisWUSM
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Getting in synch: Unpacking the role of parent-child synchrony in the development of internalizing and externalizing behaviors” (2021) Development and Psychopathology
Getting in synch: Unpacking the role of parent-child synchrony in the development of internalizing and externalizing behaviors
(2021) Development and Psychopathology, .
Quiñones-Camacho, L.E.a , Hoyniak, C.P.a , Wakschlag, L.S.b , Perlman, S.B.a
a Department of Psychiatry, Washington University in St. Louis, School of Medicine, St. Louis, MO, United States
b Department of Medical Social Sciences, Feinberg School of Medicine, Institute for Innovations in Developmental Sciences, Northwestern University, Evanston, IL, United States
Abstract
While substantial research supports the role of parent-child interactions on the emergence of psychiatric symptoms, few studies have explored biological mechanisms for this association. The current study explored behavioral and neural parent-child synchronization during frustration and play as predictors of internalizing and externalizing behaviors across a span of 1.5 years. Parent-child dyads first came to the laboratory when the child was 4-5 years old and completed the Disruptive Behavior Diagnostic Observation Schedule: Biological Synchrony (DB-DOS: BioSync) task while functional near-infrared spectroscopy (fNIRS) data were recorded. Parents reported on their child’s internalizing and externalizing behaviors using the Child Behavior Checklist (CBCL) four times over 1.5 years. Latent growth curve (LGC) modeling was conducted to assess neural and behavioral synchrony as predictors of internalizing and externalizing trajectories. Consistent with previous investigations in this age range, on average, internalizing and externalizing behaviors decreased over the four time points. Parent-child neural synchrony during a period of play predicted rate of change in internalizing but not externalizing behaviors such that higher parent-child neural synchrony was associated with a more rapid decrease in internalizing behaviors. Our results suggest that a parent-child dyad’s ability to coordinate neural activation during positive interactions might serve as a protective mechanism in the context of internalizing behaviors. © The Author(s), 2021. Published by Cambridge University Press.
Author Keywords
externalizing; internalizing; neural synchrony; parent-child synchrony; prefrontal cortex (PFC)
Funding details
National Institutes of HealthNIHR01-MH107540
National Institute of Mental HealthNIMHT32 MH100019-06
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Elevation of Pro-inflammatory and Anti-inflammatory Cytokines in Rat Serum after Acute Methamphetamine Treatment and Traumatic Brain Injury” (2021) Journal of Molecular Neuroscience
Elevation of Pro-inflammatory and Anti-inflammatory Cytokines in Rat Serum after Acute Methamphetamine Treatment and Traumatic Brain Injury
(2021) Journal of Molecular Neuroscience, .
Kobeissy, F.H.a b c , Shakkour, Z.a , Hayek, S.E.d , Mohammad, W.e f , Gold, M.S.g , Wang, K.K.W.b c
a Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
b Program for Neurotrauma, Neuroproteomics, and Biomarkers Research, Gainesville, FL, United States
c Department of Emergency Medicine, University of Florida, Gainesville, FL, United States
d Department of Psychiatry, American University of Beirut, Beirut, Lebanon
e Clinical Pharmacology Department, Menoufia Medical School, Menoufia University, Al Minufya, Egypt
f Basic medical science department, Kulliyyah of Medicine, International Islamic University Malaysia, Kuantan, Pahang, Malaysia
g Washington University School of Medicine, Department of Psychiatry, and National Council, Washington University in St. Louis, Institute for Public Health, St. Louis, MO, United States
Abstract
The use of methamphetamine (METH) is a growing worldwide epidemic that bears grave societal implications. METH is known to exert its neurotoxic effects on the dopaminergic and serotonergic systems of the brain. In addition to this classical studied mechanism of damage, findings from our laboratory and others have shown that acute METH treatment and mechanical injury, i.e. traumatic brain injury (TBI), share common cell injury mechanism(s). Since neuro-inflammation is a signature event in TBI, we hypothesize that certain cytokine levels might also be altered in rat brain exposed to an acute METH insult. In this study, using a cytokine antibody array chip, we evaluated the serum levels of 19 cytokines in rats 24 h after exposure to a 40 mg/kg acute regimen of METH. Data were compared to rats subjected to experimental TBI using the controlled cortical impact (CCI) injury model and saline controls. Sandwich ELISA method was used to further validate some of the findings obtained from the antibody cytokine array. We confirmed that three major inflammatory-linked cytokines (IL-1β, IL-6, and IL-10) were elevated in the METH and TBI groups compared to the saline group. Such finding suggests the involvement of an inflammatory process in these brain insults, indicating that METH use is, in fact, a stressor to the immune system where systemic involvement of an altered cytokine profile may play a major role in mediating chemical brain injury after METH use. © 2021, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
Author Keywords
Drug use; IL-10; IL-1β; IL-6; Methamphetamine; Traumatic brain injury
Funding details
U.S. Department of DefenseDODDAMD17-03–1-0066
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Stroke-related alterations in inter-areal communication” (2021) NeuroImage: Clinical
Stroke-related alterations in inter-areal communication
(2021) NeuroImage: Clinical,
Allegra, M.a , Favaretto, C.b c , Metcalf, N.d , Corbetta, M.b c d , Brovelli, A.a
a Institut de Neurosciences de la Timone UMR 7289, Aix Marseille Université, CNRS, Marseille, 13005, France
b Department of Neuroscience, Neurological Clinic, University of Padua, Padua, Italy
c Padova Neuroscience Center, University of Padua, Padua, Italy
d Department of Neurology, Radiology, and Neuroscience, Washington University in St. Louis, St. Louis, MO, United States
Abstract
Beyond causing local ischemia and cell damage at the site of injury, stroke strongly affects long-range anatomical connections, perturbing the functional organization of brain networks. Several studies reported functional connectivity abnormalities parallelling both behavioral deficits and functional recovery across different cognitive domains. FC alterations suggest that long-range communication in the brain is altered after stroke. However, standard FC analyses cannot reveal the directionality and time scale of inter-areal information transfer. We used resting-state fMRI and covariance-based Granger causality analysis to quantify network-level information transfer and its alteration in stroke. Two main large-scale anomalies were observed in stroke patients. First, inter-hemispheric information transfer was significantly decreased with respect to healthy controls. Second, stroke caused inter-hemispheric asymmetries, as information transfer within the affected hemisphere and from the affected to the intact hemisphere was significantly reduced. Both anomalies were more prominent in resting-state networks related to attention and language, and they correlated with impaired performance in several behavioral domains. Overall, our findings support the hypothesis that stroke provokes asymmetries between the affected and spared hemisphere, with different functional consequences depending on which hemisphere is lesioned. © 2021 The Author(s)
Author Keywords
Granger causality; Resting state fMRI; Stroke
Funding details
945539
ANR-17-HBPR-0001
Document Type: Article
Publication Stage: Final
Source: Scopus
“Multimodal Artificial Neurological Sensory-Memory System Based on Flexible Carbon Nanotube Synaptic Transistor” (2021) ACS Nano
Multimodal Artificial Neurological Sensory-Memory System Based on Flexible Carbon Nanotube Synaptic Transistor
(2021) ACS Nano, .
Wan, H.a b , Zhao, J.a , Lo, L.-W.b , Cao, Y.c , Sepúlveda, N.d , Wang, C.a
a Electrical and Systems Engineering, Washington University in St. Louis, St. Louis, MI 63130, United States
b Institute of Materials Science and Engineering, Washington University in St. Louis, St. Louis, MI 63130, United States
c State Key Laboratory of Industrial Control Technology, College of Control Science and Engineering, Zhejiang University, Zhejiang, Hangzhou, 310027, China
d Electrical and Computer Engineering, Michigan State University, East Lansing, MN 48824, United States
Abstract
As the initial stage in the formation of human intelligence, the sensory-memory system plays a critical role for human being to perceive, interact, and evolve with the environment. Electronic implementation of such biological sensory-memory system empowers the development of environment-interactive artificial intelligence (AI) that can learn and evolve with diversified external information, which could potentially broaden the application of the AI technology in the field of human-computer interaction. Here, we report a multimodal artificial sensory-memory system consisting of sensors for generating biomimetic visual, auditory, tactile inputs, and flexible carbon nanotube synaptic transistor that possesses synapse-like signal processing and memorizing behaviors. The transduction of physical signals into information-containing, presynaptic action potentials and the synaptic plasticity of the transistor in response to single and long-term action potential excitations have been systematically characterized. The bioreceptor-like sensing and synapse-like memorizing behaviors have also been demonstrated. On the basis of the memory and learning characteristics of the sensory-memory system, the well-known psychological model describing human memory, the “multistore memory”model, and the classical conditioning experiment that demonstrates the associative learning of brain, “Pavlov’s dog’s experiment”, have both been implemented electronically using actual physical input signals as the sources of the stimuli. The biomimetic intelligence demonstrated in this neurological sensory-memory system shows its potential in promoting the advancement in multimodal, user-environment interactive AI. © 2021 American Chemical Society.
Author Keywords
artificial intelligence; biomimetic memory/learning; environment-interactive; multimodal sensing; synaptic transistor
Funding details
University of WashingtonUW
Michigan State University FoundationMSUF16-SPG-Full-3236
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Variations of the grid and place cells in the entorhinal cortex and dentate gyrus of 6 individuals aged 56 to 87 years (Variaciones de las células de cuadrícula y de posicionamiento de la corteza entorrinal y del giro dentado de 6 humanos de 56 a 87 años)” (2021) Neurologia
González-Marrero, I.a , Hernandez-Garcia, J.A.a , Gonzalez-Davila, E.b , Carmona-Calero, E.M.a c , Gonzalez-Toledo, J.M.a , Castañeyra-Ruiz, L.d , Hernandez-Abad, L.G.a c , Castañeyra-Perdomo, A.a c
a Unidad de Anatomía y Embriología Humana, Departamento de Ciencias Médicas Básicas, Facultad de Ciencias de la Salud, Universidad de La Laguna, Tenerife, Islas Canaria, Spain
b Departamento de Matemáticas, Estadística e Investigación Operativa, Universidad de La Laguna, Tenerife, Islas Canaria, Spain
c Instituto de Investigación y Ciencias, Puerto del Rosario, Fuerteventura, Islas Canarias, Spain
d Department of Neurological Surgery, Washington University School of Medicine and the St. Louis Children’s Hospital, St. Louis, MO, United States
Abstract
Introduction: The relationship between the entorhinal cortex and the hippocampus has been studied by different authors, who have highlighted the importance of grid cells, place cells, and the trisynaptic circuit in the processes that they regulate: the persistence of spatial, explicit, and recent memory and their possible impairment with ageing. Objective: We aimed to determine whether older age causes changes in the size and number of grid cells contained in layer III of the entorhinal cortex and in the granular layer of the dentate gyrus of the hippocampus. Methods: We conducted post-mortem studies of the brains of 6 individuals aged 56-87 years. The brain sections containing the dentate gyrus and the adjacent entorhinal cortex were stained according to the Klüver-Barrera method, then the Image J software was used to measure the individual neuronal area, the total neuronal area, and the number of neurons contained in rectangular areas in layer III of the entorhinal cortex and layer II of the dentate gyrus. Statistical analysis was subsequently performed. Results: We observed an age-related reduction in the cell population of the external pyramidal layer of the entorhinal cortex, and in the number of neurons in the granular layer of the dentate gyrus. Conclusion: Our results indicate that ageing causes a decrease in the size and density of grid cells of the entorhinal cortex and place cells of the dentate gyrus. © 2021 Sociedad Española de Neurología
Author Keywords
Ageing; Dentate gyrus; Entorhinal cortex; Grid cells; Place cells
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Mental imagery-based self-regulation: Effects on physical activity behaviour and its cognitive and affective precursors over time” (2021) British Journal of Health Psychology
Mental imagery-based self-regulation: Effects on physical activity behaviour and its cognitive and affective precursors over time
(2021) British Journal of Health Psychology, .
Ackermann, N.a , Cameron, L.D.b , Maki, J.a , Carter, C.R.a , Liu, Y.a , Dart, H.a , Bowen, D.J.c , Colditz, G.A.a , Waters, E.A.a
a Washington University in St. LouisMO, United States
b University of California at Merced, United States
c University of Washington, United States
Abstract
Objectives: (1) Test whether a mental imagery-based self-regulation intervention increases physical activity behaviour over 90 days; (2) Examine cognitive and affective precursors of change in physical activity behaviour. Design: A randomized control trial with participants (N = 500) randomized to one of six intervention conditions in a 3 (risk communication format: bulleted list, table, risk ladder) x 2 (mental imagery behaviour: physical activity, active control [sleep hygiene]) factorial design. Methods: After receiving personalized risk estimates via a website on a smartphone, participants listened to an audiorecording that guided them through a mental imagery activity related to improving physical activity (intervention group) or sleep hygiene behaviour (active control). Participants received text message reminders to complete the imagery for 3 weeks post-intervention, 4 weekly text surveys to assess behaviour and its cognitive and affective precursors, and a mailed survey 90 days post-baseline. Results: Physical activity increased over 90 days by 19.5 more minutes per week (95%CI: 2.0, 37.1) in the physical activity than the active control condition. This effect was driven by participants in the risk ladder condition, who exercised 54.8 more minutes (95%CI 15.6, 94.0) in the physical activity condition than participants in the active control sleep hygiene group. Goal planning positively predicted physical activity behaviour (b = 12.2 minutes per week, p = 0.002), but self-efficacy, image clarity, and affective attitudes towards behaviours did not (p > 0.05). Conclusions: Mental imagery-based self-regulation interventions can increase physical activity behaviour, particularly when supported by personalized disease risk information presented in an easy-to-understand format. © 2021 The British Psychological Society
Author Keywords
Intervention; Mental imagery; mHealth; Physical activity; Self-regulation
Funding details
National Institutes of HealthNIHR01CA190391
National Cancer InstituteNCI
National Center for Advancing Translational SciencesNCATS
Institute of Clinical and Translational SciencesICTSUL1TR002345
Document Type: Article
Publication Stage: Article in Press
Source: Scopus