Maternal prenatal stress modulates antibody levels in offspring
(2025) Clinical Immunology Communications, 7, pp. 27-33.
Yeramilli, V.a , Harper, M.b , Cheddadi, R.a , Martin, C.a
a Department of Surgery, Washington University School of Medicine, Saint Louis, MO, United States
b Departmentof Surgery, University of Alabama at Birmingham, Birmingham, AL, United States
Abstract
Maternal stress is a risk factor for preterm birth and is associated with adverse birth outcomes and immune adaptations in the baby. In this study, we used a murine model of prenatal stress and measured serum immunoglobulin levels in the dams and offspring following stress. We found a significant decrease in the levels of all IgG subclasses in dams following stress. In contrast, we observed an increase in the levels of IgG1, IgG2b and IgG3 in the offspring derived from stressed dams compared to unstressed controls. We made similar observations in offspring that were fed corticosterone in drinking water during gestation indicating that these changes in immunoglobulin (Ig) levels are mediated by excess cortisol. Overall, the results from these studies will help better understand the casual link between prenatal maternal stress and compromised neonatal immunity and will help develop optimal vaccination strategies to protect both the pregnant women and infant. © 2024
Author Keywords
Antibodies; Cortisol; HPA axis; Humoral immunity; Prenatal stress
Funding details
American Surgical Association FoundationASAF
Document Type: Article
Publication Stage: Final
Source: Scopus
Tramadol as a fentanyl adulterant: Prevalence and management in a ToxIC Fentalog study prospective cohort
(2025) American Journal of Emergency Medicine, 89, pp. 169-173.
Dicker, F.a , Lothet, E.a , Schwarz, E.b , Aldy, K.c d , Brent, J.e , Wax, P.c f , Culbreth, R.c , Campleman, S.c , Krotulski, A.g , Logan, B.g h , Amaducci, A.i , Judge, B.j , Levine, M.b , Calello, D.k , Shulman, J.l , Hughes, A.m , Hendrickson, R.G.m , Meaden, C.W.k , Manini, A.F.n , On behalf of the Toxicology Investigators Consortium Fentalog Study Groupo
a Washington University in St. Louis School of Medicine, St. Louis, MO, United States
b University of California-Los Angeles, Los Angeles, CA, United States
c American College of Medical Toxicology, Phoenix, AZ, United States
d Baylor University Medical Center, Dallas, TX, United States
e University of Colorado School of Medicine, Aurora, CO, United States
f University of Texas Southwestern Medical Center, Dallas, TX, United States
g Center for Forensic Science Research and Education at the Fredric Rieders Family Foundation, Willow Grove, PA, United States
h NMS Labs, Horsham, PA, United States
i Lehigh Valley Health Network/USF Morsani College of Medicine, Allentown, PA, United States
j Corewell Health, Michigan State University, Grand Rapids, MI, United States
k Rutgers New Jersey Medical School, Newark, NJ, United States
l University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
m Oregon Health and Science University, Portland, OR, United States
n Icahn School of Medicine at Mount Sinai, Center for Research on Emerging Substances, Poisoning, Overdose, New Discoveries (RESPOND), NYC Health + Hospitals/Elmhurst, New York, NY, United States
Abstract
Background: Tramadol is an adulterant of illicit opioids. As it is a serotonin-norepinephrine reuptake inhibitor as well as a μ-opioid agonist, tramadol adulteration may worsen overdose signs and symptoms or affect the amount of naloxone patients receive. Methods: This is a multicenter, prospective cohort of adult patients with suspected opioid overdoses who presented to one of eight United States emergency departments and were included in the Toxicology Investigators Consortium’s Fentalog Study. Patient serum was analyzed via liquid chromatography quadrupole time-of-flight mass spectroscopy to detect opioids, novel psychoactive substances, and adulterants. Patients were separated into groups of those with tramadol detected versus no tramadol detected. Differences in naloxone administration, intubation, performance of cardiopulmonary resuscitation (CPR), or death between those exposed or not exposed to tramadol were evaluated. Results: From September 21, 2020 – October 31, 2021; 2298 patients were screened and 537 met inclusion criteria. Eighty-one patients (15 %) tested positive for tramadol. There was no significant difference found between those who reported chronic prescription opioid use (p = 0.81) or reported chronic pain (p = 0.27). Additionally, no difference was found between groups in the number of patients receiving a single, second, or third dose of naloxone (p = 0.25; 0.92; 0.59) or the proportion initiated on a naloxone infusion (p = 0.84). Similarly, there was no difference in outcomes of intubation, CPR, or death (p = 0.26; 0.75; 0.29). Conclusions: Tramadol was identified in a subset of patients presenting to the Emergency Department with opioid overdoses suggesting adulteration of illicitly manufactured fentanyl with tramadol. Its presence was not associated with a lack of treatment response, difference in severity of overdose, or increased risk of complications. © 2024 Elsevier Inc.
Author Keywords
Adulterant; Fentanyl; Opioid; Tramadol
Funding details
National Institute on Drug AbuseNIDA
National Institutes of HealthNIHR01DA048009
National Institutes of HealthNIH
Centers for Disease Control and PreventionCDC3R01DA048009-04S1
Centers for Disease Control and PreventionCDC
Document Type: Article
Publication Stage: Final
Source: Scopus
Synthesis and in vitro evaluation of novel compounds and discovery of a promising iodine-125 radioligand for purinergic P2X7 receptor (P2X7R)
(2025) Bioorganic and Medicinal Chemistry, 118, art. no. 118054, .
Qiu, L.a , Wang, J.a , Tewari, M.b , Rensing, D.T.a , Egan, T.M.b , Perlmutter, J.S.a c , Tu, Z.a
a Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, United States
b Department of Pharmacology and Physiology, Saint Louis University School of Medicine, St. Louis, MO 63104, United States
c Neurology, Neuroscience, Physical Therapy and Occupational Therapy, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
The purinergic P2X ligand-gated ion channel 7 receptor (P2X7R) plays a critical role in various inflammatory processes and other diseases. Fast determination of compounds P2X7R binding potency and discovery of a promise PET radiotracer for imaging P2X7R require a P2X7R suitable radioligand for radioactive competitive binding assay. Herein, we designed and synthesized thirteen new P2X7R ligands and determined the in vitro binding potency. The fluorescence screening assay identified the iodide compound 1c with high potency and specificity toward P2X7R with an IC50 of 0.25 ± 0.05 nM. Therefore, 1c was 125I-labeled to afford [125I]1c with a good radiochemical yield (44 ± 12 %, n = 3) and high radiochemical purity (>95 %). Radioligand saturation binding assay showed that [125I]1c specifically bound to human P2X7R with high affinity (Kd = 1.68 nM and Bmax = 94 fmol/mg). A radioactive high throughput binding assay using [125I]1c for our new compounds demonstrated that the imidazole compounds 1b, 1c, and 1d exhibited high inhibition for >70 %, while the analogues of GSK314181A exhibited low inhibition for <35 %. In addition, our radioligand competitive binding assays using [125I]1c demonstrated that 1b, 1c, and 1d have high potency with IC50 values of 7.91 ± 0.22, 7.06 ± 1.68, and 7.16 ± 0.41 nM toward P2X7R, respectively.Together, compounds 1b, 1c, and 1d are highly potent for P2X7R, and [125I]1c has great potential to be a radioligand for screening P2X7R binding potency of the new compounds and investigating the P2X7R expression in animal models of human disease. © 2024 The Author(s)
Author Keywords
Fluorescence assay; I-125 radiotracer; Purinergic P2X7 receptor; Radioligand competitive binding assay; Radioligand saturation binding assay
Funding details
American Parkinson Disease AssociationAPDA
National Institute of Neurological Disorders and StrokeNINDS
National Institutes of HealthNIH
Foundation for Barnes-Jewish HospitalFBJH
National Institute of Biomedical Imaging and BioengineeringNIBIBEB025815, 1R01GM112188
National Institute on AgingNIANS075527, NS103988, NS061025, NS134586, NS107281
National Institute of Mental HealthNIMHMH092797
Document Type: Article
Publication Stage: Final
Source: Scopus
Factor analysis and clustering of motor and psychiatric dimensions in idiopathic blepharospasm
(2025) Parkinsonism and Related Disorders, 131, art. no. 107241, .
Gigante, A.F.a , Hallett, M.b , Jinnah, H.A.c , Berardelli, A.d e , Perlmutter, J.S.f , Berman, B.D.g , Jankovic, J.h , Bäumer, T.i , Comella, C.j , Ercoli, T.k , Belvisi, D.d , Fox, S.H.l , Kim, H.-J.m , Moukheiber, E.S.n , Richardson, S.P.o , Weissbach, A.p , Muroni, A.q , Defazio, G.e r
a Section of Neurology, San Paolo Hospital, Bari, Italy
b National Institute of Neurological Disorders and Stroke, NIH, Bethesda, United States
c Department of Neurology and Human Genetics, Emory University School of Medicine, Atlanta, GA, United States
d Department of Human Neurosciences, Sapienza University of Rome, Italy
e IRCCS NEUROMED, Pozzilli, Italy
f Department of Neurology, Radiology, Neuroscience, Physical Therapy and Occupational Therapy, Washington University School of Medicine, St Louis, MO, United States
g Department of Neurology, Virginia Commonwealth University, Richmond, VA, United States
h Parkinson’s Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, United States
i Institute of Systems Motor Science, University of Lübeck, Germany
j Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, United States
k Department of Medical Sciences and Public Health, University of Cagliari, Italy
l Movement Disorder Clinic, Krembil Brain Institute, University Health Network, Toronto, ON, Canada
m Department of Neurology and Movement Disorder Centre, Seoul National University Hospital, Seoul, South Korea
n Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
o Department of Neurology, University of New Mexico/New Mexico VA Healthcare System, Albuquerque, NM, United States
p Institute of Systems Motor Science and Institute of Neurogenetics, University of Lübeck, Germany
q Neurology Unit, Azienda Ospedaliero-Universitaria of Cagliari, Italy
r Department of Translational Biomedicine and Neuroscience, Aldo Moro University of Bari, Italy
Abstract
Introduction: Idiopathic blepharospasm is a clinically heterogeneous form of focal dystonia, also associated with psychiatric symptoms. The identification of the most relevant sets of motor and psychiatric manifestations may help better understand the specific phenomenology of the condition and delineate blepharospasm subtypes more accurately. Methods: Patients with idiopathic blepharospasm were from the Dystonia Coalition project. Factor analysis of several motor and psychiatric scales was performed to identify the relevant determinants of blepharospasm severity. The selected items were then used in a data-driven cluster analysis to subtype blepharospasm individuals. Results: Factor analysis reduced the many variables in the motor and psychiatric scales to 13 variables distributed in four factors. When the four sets were used as clustering variables, three blepharospasm clusters were identified: cluster 1 was characterized by low levels of motor and psychiatric factors; cluster 2 showed high levels of both motor and psychiatric factors; and cluster 3 showed high levels of psychiatric factors (similar to cluster 2) but low level of motor factors (similar to that of cluster 1). Conclusions: Factor analysis enabled the identification of key motor and psychiatric determinants of blepharospasm severity. The derived factor sets provide a streamlined tool for predicting and measuring these dimensions. This approach also facilitated more precise cluster analysis and improved recognition of clinical subtypes. © 2024 Elsevier Ltd
Document Type: Article
Publication Stage: Final
Source: Scopus
” (2025) Neurosurgery
Diffusion MRI Metrics Characterize Postoperative Clinical Outcomes After Surgery for Cervical Spondylotic Myelopathy
(2025) Neurosurgery, 96 (1), pp. 69-77.
Zhang, J.K.a b , Javeed, S.a , Greenberg, J.K.a , Yakdan, S.a , Kaleem, M.I.a , Botterbush, K.S.a , Benedict, B.a , Dibble, C.F.a , Sun, P.c , Sherrod, B.b , Dailey, A.T.b , Bisson, E.F.b , Mahan, M.b , Mazur, M.b , Song, S.-K.a , Ray, W.Z.a
a Department of Neurological Surgery, Washington University School of Medicine, Saint Louis , Missouri , USA
b Department of Neurological Surgery, University of Utah, Salt Lake City, UT, United States
c Department of Imaging Physics, UT MD Anderson Cancer Center, Houston, TX, United States
Abstract
BACKGROUND AND OBJECTIVES: Advanced diffusion-weighted MRI (DWI) modeling, such as diffusion tensor imaging (DTI) and diffusion basis spectrum imaging (DBSI), may help guide rehabilitation strategies after surgical decompression for cervical spondylotic myelopathy (CSM). Currently, however, postoperative DWI is difficult to interpret, owing to signal distortions from spinal instrumentation. Therefore, we examined the relationship between postoperative DTI/DBSI-extracted from the rostral C3 spinal level-and clinical outcome measures at 2-year follow-up after decompressive surgery for CSM. METHODS: Fifty patients with CSM underwent complete clinical and DWI evaluation-followed by DTI/DBSI analysis-at baseline and 2-year follow-up. Clinical outcomes included the modified Japanese Orthopedic Association score and comprehensive patient-reported outcomes. DTI metrics included apparent diffusion coefficient, fractional anisotropy, axial diffusivity, and radial diffusivity. DBSI metrics evaluated white matter tracts through fractional anisotropy, fiber fraction, axial diffusivity, and radial diffusivity as well as extra-axonal pathology through restricted and nonrestricted fraction. Cross-sectional Spearman’s correlations were used to compare postoperative DTI/DBSI metrics with clinical outcomes. RESULTS: Twenty-seven patients with CSM, including 15, 7, and 5 with mild, moderate, and severe disease, respectively, possessed complete baseline and postoperative DWI scans. At 2-year follow-up, there were 10 significant correlations among postoperative DBSI metrics and postoperative clinical outcomes compared with 3 among postoperative DTI metrics. Of the 13 significant correlations, 7 involved the neck disability index (NDI). The strongest relationships were between DBSI axial diffusivity and NDI (r = 0.60, P < .001), DBSI fiber fraction and NDI (r s = -0.58, P < .001), and DBSI restricted fraction and NDI (r s = 0.56, P < .001). The weakest correlation was between DTI apparent diffusion coefficient and NDI (r = 0.35, P = .02). CONCLUSION: Quantitative measures of spinal cord microstructure after surgery correlate with postoperative neurofunctional status, quality of life, and pain/disability at 2 years after decompressive surgery for CSM. In particular, DBSI metrics may serve as meaningful biomarkers for postoperative disease severity for patients with CSM. Copyright © Congress of Neurological Surgeons 2024. All rights reserved.
Document Type: Article
Publication Stage: Final
Source: Scopus
Arousal effects on oscillatory dynamics in the non-human primate brain
(2024) Cerebral Cortex (New York, N.Y. : 1991), 34 (12), .
Anand, S.A.a b , Sogukpinar, F.b , Monosov, I.E.a b c
a School of Medicine, Washington University in St. Louis, Fort Neuroscience Research Building, St. Louis, MO 63110, United States
b McKelvey School of Engineering, Washington University in St. Louis, One Brookings Drive., St. Louis, MO 63130, United States
c Department of Neuroscience, Washington University in St. Louis, Fort Neuroscience Research Building, St. Louis, MO 63110, United States
Abstract
Arousal states are thought to influence many aspects of cognition and behavior by broadly modulating neural activity. Many studies have observed arousal-related modulations of alpha (~8 to 15 Hz) and gamma (~30 to 50 Hz) power and coherence in local field potentials across relatively small groups of brain regions. However, the global pattern of arousal-related oscillatory modulation in local field potentials is yet to be fully elucidated. We simultaneously recorded local field potentials in numerous cortical and subcortical regions in the primate brain and assessed oscillatory activity and inter-regional coherence associated with arousal state. In high arousal states, we found a uniquely strong and coherent gamma oscillation between the amygdala and basal forebrain. In low arousal rest-like states, a relative increase in coherence at alpha frequencies was present across sampled brain regions, with the notable exception of the medial temporal lobe. We consider how these patterns of activity may index arousal-related brain states that support the processing of incoming sensory stimuli during high arousal states and memory-related functions during rest. © The Author(s) 2024. Published by Oxford University Press.
Author Keywords
arousal; coherence; local field potentials
Document Type: Article
Publication Stage: Final
Source: Scopus
Experimental Pain Sensitivity and Parental Pain Catastrophizing
(2024) Children, 11 (12), art. no. 1528, .
Banerjee, G.a b , Brown, J.a b , McMichael, A.a b , Ben Abdallah, A.a b , Buday, S.a , Barch, D.M.c , Baranski, T.d , Haroutounian, S.a b , AuBuchon, J.a b , Nahman-Averbuch, H.a b
a Washington University Pain Center, Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, United States
b Division of Clinical and Translational Research, Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, United States
c Department of Psychological and Brain Sciences, Washington University School of Medicine, St. Louis, MO 63110, United States
d Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
Background/Objectives: Variability in biopsychosocial factors can explain the interindividual variability in pain. One factor that can impact pain is the pain catastrophizing level. Interestingly, parental pain catastrophizing is related to the severity of the clinical pain of their children. This study explored whether parental pain catastrophizing is also associated with their children’s experimental pain sensitivity. Methods: Forty-five healthy girls (mean age 12.07 ± 1.47 years) and one of their parents participated in this study. Parents completed the Pain Catastrophizing Scale (PCS) about their child’s pain (PCS-Parentchild) as well as their pain (PCS-Parent). Children completed the PCS about their pain (PCS-Child) and the Pubertal Developmental Scale (PDS). Children underwent psychophysical tests, including paradigms of temporal summation, heat- and pressure-conditioned pain modulation, offset analgesia, and cold pain tolerance. Correlations and regression models were conducted to assess the relationships between parental pain catastrophizing scales (separately for PCS-Parentchild and PCS-Parent) and experimental pain sensitivity with and without controlling for PCS-Child and PDS. T-tests were used to compare pain sensitivity between participants with vs. without a family history of psychiatric disorder. Results: No significant relationships were found between the experimental pain sensitivity measures and either PCS-Parentchild or PCS-Parent with and without controlling for PCS-Child and PDS. No differences were found in experimental pain sensitivity between participants with and without a family history of psychiatric disorder. Conclusions: Parental pain catastrophizing may contribute minimally to the individual variability in experimental pain sensitivity of healthy adolescent girls. © 2024 by the authors.
Author Keywords
pain catastrophizing; pain modulation; parental worrying; parent–child relations; quantitative sensory testing
Funding details
International Association for the Study of PainIASP
International Headache SocietyIHS
National Institutes of HealthNIHR01NS129742
National Institutes of HealthNIH
Document Type: Article
Publication Stage: Final
Source: Scopus
CCR2 restricts IFN-γ production by hippocampal CD8 TRM cells that impair learning and memory during recovery from WNV encephalitis
(2024) Journal of Neuroinflammation, 21 (1), art. no. 330, .
Ai, S.a b , Arutyunov, A.a b , Liu, J.b , Hill, J.D.a b e , Jiang, X.a b , Klein, R.S.c d
a Center for Neuroimmunology and Neuroinfectious Diseases, Washington University School of Medicine, St. Louis, MO, United States
b Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
c Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
d Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
e Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, Canada
Abstract
Central nervous system (CNS) resident memory CD8 T cells (TRM) that express IFN-γ contribute to neurodegenerative processes, including synapse loss, leading to memory impairment. Here, we show that CCR2 signaling in CD8 TRM that persist within the hippocampus after recovery from CNS infection with West Nile virus (WNV) significantly prevents the development of memory impairments. Using CCR2-deficient mice, we determined that CCR2 expression is not essential for CNS T cell recruitment or virologic control during acute WNV infection. However, transcriptomic analyses of forebrain CCR2+ versus CCR2− CD8 TRM during WNV recovery reveal that CCR2 signaling significantly regulates hippocampal CD8 TRM phenotype and function via extrinsic and intrinsic effects, limiting expression of CD103, granzyme A and IFN-γ, respectively, and increasing the percentages of virus-specific CD8 T cells. Consistent with this, WNV-recovered Cd8acreCcr2fl/fl mice exhibit decreased recognition memory. Overall, these data implicate CCR2 signaling in the regulation of CD8 TRM phenotype, including antiviral specificity and IFN-γ expression, highlighing a neuroprotective role for CCR2 in limiting CD8 T cell-mediated neuroinflammation and cognitive deficits, providing insights into potential therapeutic targets for CNS infections. © The Author(s) 2024.
Funding details
Universität zu KölnUoCR35NS122310
Universität zu KölnUoC
Document Type: Article
Publication Stage: Final
Source: Scopus
Multimodal oculomotor assessment reveals prodromal markers of Parkinson’s disease in non-manifesting LRRK2 G2019S mutation carriers
(2024) NPI Parkinson’s Disease, 10 (1), art. no. 234, .
Riek, H.C.a , Visanji, N.P.b c d e f , Pitigoi, I.C.a , Di Luca, D.G.b g , Armengou-Garcia, L.b , Ahmed, N.b , Perkins, J.E.a , Brien, D.C.a , Huang, J.a , Coe, B.C.a , Huang, J.b , Ghate, T.b , Lang, A.E.b c e f , Marras, C.b e , Munoz, D.P.a h
a Centre for Neuroscience Studies, Queen’s University, ON, Kingston, Bangladesh
b Edmond J. Safra Program in Parkinson’s Disease and the Morton and Gloria Shulman Movement Disorders Clinic, University Health Network, Toronto, ON, Canada
c Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada
d Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
e Krembil Brain Institute, University Health Network, Toronto, ON, Canada
f Rossy PSP Centre, University Health Network, Toronto, ON, Canada
g Department of Neurology, Washington University in St. Louis, St. Louis, MO, United States
h Department of Biomedical and Molecular Sciences, Queen’s University, ON, Kingston, Bangladesh
Abstract
Oculomotor behaviour changes in patients with Parkinson’s disease (PD) are a promising source of prodromal disease markers. Capitalizing on this phenomenon to facilitate early diagnosis requires oculomotor assessment in prodromal cohorts. We examined oculomotor behaviour in non-manifesting LRRK2 G2019S mutation carriers (LRRK2-NM), who have heightened PD risk. Seventeen LRRK2-NM participants, 47 patients with idiopathic PD, and 63 healthy age-matched control participants completed an interleaved pro- and antisaccade task while undergoing video-based eye-tracking. We analyzed between-group differences in saccade, pupil, blink, and fixation acquisition behaviour. Patients with PD showed previously demonstrated abnormalities (saccade hypometria, antisaccade errors). Relative to controls, LRRK2-NM participants and patients with PD both displayed increased short-latency prosaccades and reduced pupil velocity, plus altered fixation acquisition—less preemptive returning of gaze to the future fixation point location. Interestingly, the effect on blink probability was opposite—higher than controls in LRRK2-NM participants but lower in patients with PD. Future longitudinal studies must confirm the viability of these features as prodromal PD markers. © The Author(s) 2024.
Funding details
Parkinson Canada
Ontario Brain InstituteOBI
Canadian Institutes of Health ResearchCIHRPJT-190028
Canadian Institutes of Health ResearchCIHR
Michael J. Fox Foundation for Parkinson’s ResearchMJFFMOP-FDN-148418
Michael J. Fox Foundation for Parkinson’s ResearchMJFF
Document Type: Article
Publication Stage: Final
Source: Scopus
Disentangling the impact of motion artifact correction algorithms on functional near-infrared spectroscopy-based brain network analysis
(2024) Neurophotonics, 11 (4), art. no. 045006, .
Guan, S.a b , Li, Y.a b , Luo, Y.c , Niu, H.d , Gao, Y.e , Yang, D.f , Li, R.a g
a University of Macau, Institute of Collaborative Innovation, Center for Cognitive and Brain Sciences, Taipa, Macau
b University of Macau, Department of Psychology, Faculty of Social Science, Taipa, Macau
c Sun Yat-Sen University, School of Biomedical Engineering, Shenzhen, China
d Beijing Normal University, IDG/McGovern Institute for Brain Research, State Key Laboratory of Cognitive Neuroscience and Learning, Beijing, China
e Stanford University, Center for Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, Stanford, CA, United States
f Washington University School of Medicine, Mallinckrodt Institute of Radiology, St. Louis, MO, United States
g University of Macau, Department of Electrical and Computer Engineering, Faculty of Science and Technology, Taipa, Macau
Abstract
Significance: Functional near-infrared spectroscopy (fNIRS) has been widely used to assess brain functional networks due to its superior ecological validity. Generally, fNIRS signals are sensitive to motion artifacts (MA), which can be removed by various MA correction algorithms. Yet, fNIRS signals may also undergo varying degrees of distortion due to MA correction, leading to notable alternation in functional connectivity (FC) analysis results. Aim: We aimed to investigate the effect of different MA correction algorithms on the performance of brain FC and topology analyses. Approach: We evaluated various MA correction algorithms on simulated and experimental datasets, including principal component analysis, spline interpolation, correlation-based signal improvement, Kalman filtering, wavelet filtering, and temporal derivative distribution repair (TDDR). The mean FC of each pre-defined network, receiver operating characteristic (ROC), and graph theory metrics were investigated to assess the performance of different algorithms. Results: Although most algorithms did not differ significantly from each other, the TDDR and wavelet filtering turned out to be the most effective methods for FC and topological analysis, as evidenced by their superior denoising ability, the best ROC, and an enhanced ability to recover the original FC pattern. Conclusions: The findings of our study elucidate the varying impact of MA correction algorithms on brain FC analysis, which could serve as a reference for choosing the most appropriate method for future FC research. As guidance, we recommend using TDDR or wavelet filtering to minimize the impact of MA correction in brain network analysis. © The Authors. Published by SPIE under a Creative Commons Attribution 4.0 International License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.
Author Keywords
brain network; functional connectivity; functional near-infrared spectroscopy; motion artifact
Funding details
National Natural Science Foundation of ChinaNSFC82301743
National Natural Science Foundation of ChinaNSFC
Fundo para o Desenvolvimento das Ciências e da TecnologiaFDCT0010/2023/ITP1
Fundo para o Desenvolvimento das Ciências e da TecnologiaFDCT
Universidade de MacauUMSRG2023-00015-ICI
Universidade de MacauUM
Document Type: Article
Publication Stage: Final
Source: Scopus
Dorsal Root Ganglion Stimulation for Chronic Pelvic Pain Secondary to Endometriosis
(2024) Neuromodulation, .
da Silva Freitas, T.a b , Barbosa de Oliveira, A.J.a b , Golovac, S.c , Assumpcao de Monaco, B.d e
a Functional Neurosurgery – Syrian Lebanese Hospital, DF, Brasilia, Brazil
b Functional Neurosurgery, Base Hospital, DF, Brasilia, Brazil
c The Pain Institute, Lecanto, FL, United States
d Functional and Pain Clinic, SP, Sao Paulo, Brazil
e Pediatric Neurosurgery, Washington University in St. Louis, St Louis, MO, United States
Abstract
Introduction: Chronic pelvic pain (CPP) is a multifaceted condition that poses significant challenges in clinical management owing to its complex and varied pathophysiology, including neuropathic, somatic, visceral, and musculoskeletal components. Endometriosis is frequently associated with CPP, necessitating a comprehensive, multimodal treatment strategy. This approach typically includes physical and behavioral therapy, pharmacologic interventions, surgical management of endometriosis, and various pain-modulating procedures. Neuromodulation, particularly spinal cord stimulation (SCS), has been used in refractory cases; however, its use is often met with limited success and a notable rate of explants. This case series presents nine patients with intractable CPP secondary to endometriosis, unresponsive to conventional treatments, who were treated with dorsal root ganglion stimulation (DRG-S). Materials and Methods: Between 2022 and 2023, ten patients with severe CPP secondary to endometriosis, unresponsive to various multimodal treatments—including previous interventional pain procedures, gynecologic surgery, and in some cases, SCS—were recruited for this prospective study. Of these, nine patients underwent permanent DRG-S, with bilateral L1 and S2 DRG-S leads placed (four leads per patient). Patients were assessed for pain intensity using the visual analog scale (VAS), narcotic consumption, and quality of life (QoL) using the 12-item short-form (SF-12) survey, with a 12-month follow-up period. Nonparametric statistical analyses were conducted using SPSS. Results: One patient was excluded from the study owing to a lack of pain relief during the DRG-S trial. The remaining nine patients underwent permanent bilateral L1 and S2 DRG-S placement. Significant improvement in pain scores was observed and sustained throughout the follow-up period (VAS 9 ± 1.5–2 ± 2.0; p = 0.003), along with a marked reduction in opioid consumption, with four patients becoming completely free of narcotics (p = 0.046). SF-12 physical scores improved by 60.2 ± 7.8 (p = 0.006), and SF-12 mental scores improved by 45.9 ± 2.76 (p = 0.01). Conclusion: Bilateral L1 and S2 DRG-S yielded robust and sustained outcomes, including significant improvements in pain scores, reduced narcotic consumption, and enhanced QoL over a 12-month follow-up period. © 2024 The Authors
Author Keywords
Chronic pelvic pain (CPP); dorsal root ganglion stimulation (DRG-S); endometriosis; neuromodulation; pain management
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Psychotropic medication usage in sporadic versus genetic behavioral-variant frontotemporal dementia
(2024) Alzheimer’s and Dementia, .
Vargas-Gonzalez, J.-C.a b , Dimal, N.a b , Cortez, K.b , Heuer, H.c , Forsberg, L.K.d , Appleby, B.S.e , Barmada, S.f , Bozoki, A.g , Clark, D.h , Cobigo, Y.c , Darby, R.R.i , Dickerson, B.C.j , Domoto-Reilly, K.k , Galasko, D.R.l , Geschwind, D.H.m , Ghoshal, N.n , Graff-Radford, N.R.o , Grant, I.M.p , Irwin, D.q , Hsiung, G.-Y.R.r , Honig, L.S.s , Kantarci, K.d , Léger, G.C.l , Litvan, I.l , Mackenzie, I.R.r , Masdeu, J.C.t , Mendez, M.F.m , Onyike, C.U.u , Pascual, B.t , Pressman, P.v , Ramos, E.M.m , Roberson, E.D.w , Rogalski, E.x , Boeve, B.F.d , Boxer, A.L.c , Rosen, H.J.c , Tartaglia, M.C.a b y , ALLFTD Consortium Investigatorsz
a Division of Neurology, University of Toronto, Toronto, ON, Canada
b Memory Clinic, University Health Network, Toronto, ON, Canada
c Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, United States
d Department of Neurology, Mayo Clinic, Rochester, MN, United States
e Department of Neurology, Case Western Reserve University, Beachwood, OH, United States
f University of Michigan, Ann Arbor, MI, United States
g Department of Neurology, University of North Carolina, Chapel Hill, NC, United States
h Indiana University, Indianapolis, IN, United States
i Vanderbilt University, Nashville, TN, United States
j Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
k Department of Neurology, University of Washington, Seattle, WA, United States
l University of California San Diego, San Diego, CA, United States
m Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States
n Memory Diagnostic Center, Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
o Mayo Clinic, Jacksonville, FL, United States
p Department of Psychiatry and Behavioral Sciences, Mesulam Center for Cognitive Neurology and Alzheimer’s Disease, Northwestern Feinberg School of Medicine, Chicago, IL, United States
q Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
r University of British Columbia, Vancouver, BC, Canada
s Neurology Department and Taub Institute, Columbia University Irving Medical Center, New York, NY, United States
t Nantz National Alzheimer Center, Houston Methodist, Houston, TX, United States
u Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
v University of Colorado Denver, Denver, CO, United States
w Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, United States
x Healthy Aging & Alzheimer’s Research Care (HAARC) Center, Department of Neurology, University of Chicago, Chicago, IL, United States
y Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada
Abstract
INTRODUCTION: Psychotropic medication (PM) use in behavioral-variant frontotemporal dementia (bvFTD) is higher than in other dementias. However, no information exists on whether PM use differs between sporadic and genetic bvFTD. METHODS: We analyzed data from sporadic and genetic bvFTD participants with PM prescriptions in the Advancing Research and Treatment in Frontotemporal Lobar Degeneration/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects study. We estimated ordinal odds ratio (OOR) of having more PM comparing sporadic and genetic bvFTD. Finally, we explored the neuropsychiatric symptom (NPS) combinations using classification and regression trees (CART). RESULTS: We included 263 with sporadic and 193 with genetic bvFTD. The OOR for sporadic bvFTD to be on PM was 1.75 (95% confidence interval: 1.21 to 2.53) for the fully adjusted model. CART revealed the most common NPS combination was apathy + personality changes in 18% of participants. DISCUSSION: Participants with sporadic bvFTD were twice as likely to be on PM compared to genetic bvFTD. The reason for increased PM usage in sporadic bvFTD participants should be further investigated. Highlights: We report on patients with behavioral variant frontotemporal dementia (bvFTD). We evaluated the psychotropic medication (PM) prescription at baseline in the cohort. Patients with sporadic bvFTD had more prescriptions for PM than genetic patients. The frequency of symptoms combination was different in sporadic and genetic bvFTD. © 2024 The Author(s). Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association.
Author Keywords
behavioral symptoms; frontotemporal dementia; frontotemporal lobar degeneration; medication usage; psychotropic drugs
Funding details
Centers for Disease Control and PreventionCDC
National Institutes of HealthNIH
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Examining objective and subjective sleep measures and neurocognition in older adults with HIV: A cross-sectional study in the deep South
(2024) Applied Neuropsychology: Adult, .
Cody, S.L.a , Bui, C.b , Gunn, H.c , Doudell, K.R.c , Foster, P.P.d , Nance, A.S.a , Goodin, B.R.e , Thomas, S.J.f , Vance, D.E.g
a Capstone College of Nursing, The University of Alabama, Tuscaloosa, AL, United States
b Alabama Life Research Institute, The University of Alabama, Tuscaloosa, AL, United States
c Department of Psychology, The University of Alabama, Tuscaloosa, AL, United States
d Department of Community Medicine Population Health, School of Medicine, The University of Alabama, Tuscaloosa, AL, United States
e Department of Anesthesiology, Washington University Pain Center, Washington University, St. Louis, MO, United States
f Department of Psychiatry & Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL, United States
g School of Nursing, University of Alabama at Birmingham, Birmingham, AL, United States
Abstract
As people live longer with HIV, reports of poor sleep and neurocognitive impairments are expected to increase. Poor sleep and neurocognitive impairments commonly occur in people living with HIV (PLWH) and some medications (e.g., anticholinergics) contribute to these problems. The association between sleep and neurocognition among PLWH taking such medications remains unclear. This study examined trend level associations between neurocognitive domains and subjective and objective sleep outcomes. Among 29 PLWH (Mage = 61 years old), the use of anticholinergics and/or antidepressants were examined as a moderator between neurocognition and sleep outcomes. For PLWH taking anticholinergics and/or antidepressants, the associations between insomnia and neurocognitive measures were counter-intuitive, and so were the associations between sleep time and neurocognitive measures. For these adults, objective longer sleep time was associated with poorer verbal learning (immediate, p =.005; delayed recall, p =.002) and visuospatial memory (delayed recall, p =.010). Greater sleep efficiency was associated with better visuospatial memory (immediate, p =.007; delayed recall p =.022). Despite sleep benefits, the use of anticholinergics and/or antidepressants may compromise neurocognitive function in older PLWH. Clinical implications include routine sleep and neurocognitive assessments along with medication monitoring to detect adverse neurocognitive effects of commonly prescribed medications. © 2024 Taylor & Francis Group, LLC.
Author Keywords
Aging; HIV; neurocognition; sleep quality
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Self-reported Hearing Quality of Life for Adolescent Cochlear Implant Recipients: A Longitudinal Study
(2024) Journal of the American Academy of Audiology, .
Davidson, L.S.a b , Geers, A.E.c , Uchanski, R.M.a , Siu, K.d
a Department of Otolaryngology, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
b Central Institute for the Deaf, St. Louis, MO, United States
c School of Behavioral and Brain Sciences, The University of Texas at Dallas, Dallas, TX, United States
d Program in Audiology and Communication Sciences, Department of Otolaryngology, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
Abstract
Background Clinicians are increasingly interested in self-reported hearing-specific quality of life (HQoL) for cochlear implant (CI) recipients, including pediatric CI recipients. Purpose (1) To compare HQoL of adolescent CI recipients to those of peers with typical hearing (TH); (2) to examine, longitudinally, HQoL for a set of CI recipients; and (3) to determine the effects of child, demographic, audiological, speech perception, and language variables on adolescent HQoL. Research Design Hearing Environments and Reflections on Quality of Life (HEARQL) questionnaires were completed by children with CIs at elementary (HEARQL-26) and adolescent (HEARQL-28) ages. Study Sample Eighty CI recipients and 21 children with TH. Data Collection and Analysis HEARQL-28 scores for the CI and TH groups were compared using nonparametric tests. Regression models were used to examine longitudinal results and to explore predictor variables for adolescent CI participants’ HEARQL-28 scores. Results HEARQL-28 scores for CI participants were lower than those of peers with TH. For both CI and TH adolescents, the HEARQL subscale with the lowest score is “Hearing Situations.” CI participants’ HEARQL scores at elementary age were not significantly correlated with scores at adolescence. Over 70% of unexplained variance remains even after inclusion of variables with established contributions to traditional CI benefit. Conclusions Self-reported HEARQL scores are largely unexplained for pediatric CI recipients; multidisciplinary explorations of other sources of variance, such as social, emotional, and psychosocial factors, should be pursued. © 2024. American Academy of Audiology. All rights reserved.
Author Keywords
adolescents; cochlear implants; hearing loss; self-reported hearing QoL
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Longitudinal cognitive performance of participants with sporadic early onset Alzheimer’s disease from LEADS
(2024) Alzheimer’s and Dementia, .
Hammers, D.B.ab , Eloyan, A.a , Taurone, A.a , Thangarajah, M.a , Gao, S.b , Beckett, L.c , Polsinelli, A.J.ab , Kirby, K.ab , Dage, J.L.ab , Nudelman, K.d , Aisen, P.e , Reman, R.e , La Joie, R.f , Lagarde, J.f , Atri, A.g , Clark, D.ab , Day, G.S.h , Duara, R.i , Graff-Radford, N.R.h , Grant, I.j , Honig, L.S.k , Johnson, E.C.B.l , Jones, D.T.m , Masdeu, J.C.n , Mendez, M.F.o , Womack, K.p , Musiek, E.p , Onyike, C.U.q , Riddle, M.r , Rogalski, E.s , Salloway, S.r , Sha, S.J.t , Turner, R.S.u , Wingo, T.S.v , Wolk, D.A.w , Carrillo, M.C.x , Rabinovici, G.D.f y , Dickerson, B.C.z , Apostolova, L.G.d ab aa ab , the LEADS Consortiumab
a Department of Biostatistics, Center for Statistical Sciences, Brown University, Providence, RI, United States
b Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN, United States
c Department of Public Health Sciences, University of California – Davis, Davis, CA, United States
d Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States
e Alzheimer’s Therapeutic Research Institute, University of Southern California, San Diego, CA, United States
f Department of Neurology, University of California – San Francisco, San Francisco, CA, United States
g Banner Sun Health Research Institute, Sun City, AZ, United States
h Department of Neurology, Mayo Clinic, Jacksonville, FL, United States
i Wien Center for Alzheimer’s Disease and Memory Disorders, Mount Sinai Medical Center, Miami, FL, United States
j Department of Psychiatry and Behavioral Sciences, Mesulam Center for Cognitive Neurology and Alzheimer’s Disease, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
k Taub Institute and Department of Neurology, Columbia University Irving Medical Center, New York, NY, United States
l Department of Neurology and Human Genetics, Emory University School of Medicine, Atlanta, GA, United States
m Department of Neurology, Mayo Clinic, Rochester, MN, United States
n Nantz National Alzheimer Center, Houston Methodist and Weill Cornell Medicine, Houston, TX, United States
o Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
p Department of Neurology, Washington University in St. Louis, St. Louis, MO, United States
q Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
r Department of Neurology, Alpert Medical School, Brown University, Providence, RI, United States
s Healthy Aging & Alzheimer’s Research Care Center, Department of Neurology, University of Chicago, Chicago, IL, United States
t Department of Neurology & Neurological Sciences, Stanford University, Palo Alto, CA, United States
u Department of Neurology, Georgetown University, Washington, DC, United States
v Department of Neurology, UC Davis Alzheimer’s Disease Research Center, University of California – Davis, Davis, CA, United States
w Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
x Medical & Scientific Relations Division, Alzheimer’s Association, Chicago, IL, United States
y Department of Radiology & Biomedical Imaging, University of California – San Francisco, San Francisco, CA, United States
z Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
aa Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine Indianapolis, Indianapolis, IN, United States
ab Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, United States
Abstract
INTRODUCTION: Early-onset Alzheimer’s disease (EOAD) manifests prior to the age of 65, and affects 4%–8% of patients with Alzheimer’s disease (AD). The current analyses sought to examine longitudinal cognitive trajectories of participants with early-onset dementia. METHODS: Data from 307 cognitively normal (CN) volunteer participants and those with amyloid-positive EOAD or amyloid-negative cognitive impairment (EOnonAD) were compared. Cognitive trajectories across a comprehensive cognitive battery spanning 42 months were examined using mixed-effects modeling. RESULTS: The EOAD group displayed worse cognition at baseline relative to EOnonAD and CN groups, and more aggressive declines in cognition over time. The largest effects were observed on measures of executive functioning domains, while memory declines were blunted in EOAD. DISCUSSION: EOAD declined 2–4× faster than EOnonAD, and EOAD pathology is not restricted to memory networks. Early identification of deficits is critical to ensure that individuals with sporadic EOAD can be considered for treatment using disease-modifying medications. Highlights: Represents the most comprehensive longitudinal characterization of sporadic EOAD to date. The trajectory of cognitive declines was steep for EOAD participants and worse than for other groups. Executive functioning measures exhibited the greatest declines over time in EOAD. © 2024 The Author(s). Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association.
Author Keywords
Alzheimer’s disease; amnestic; atypical variant; early-onset; longitudinal
Funding details
Fondation pour la Recherche sur Alzheimer
National Institute on AgingNIAU01 AG016976, P50 AG005146, P50 AG008702, P30 AG010124, P50 AG005681, P30 AG062422, U01AG6057195, P50AG047366, U24AG021886, P30 AG010133, P30AG066506, P50 AG025688, P30 AG062421, P30 AG013854, K23AG080071, R56 AG057195, P50 AG023501
National Institute on AgingNIA
Alzheimer’s AssociationAALDRFP‐21‐818464, AARG‐22‐926940
Alzheimer’s AssociationAA
Document Type: Article
Publication Stage: Article in Press
Source: Scopus