“Filtering respiratory motion artifact from resting state fMRI data in infant and toddler populations” (2022) NeuroImage
Filtering respiratory motion artifact from resting state fMRI data in infant and toddler populations(2022) NeuroImage, 247, art. no. 118838, .
Kaplan, S.a , Meyer, D.a , Miranda-Dominguez, O.g h , Perrone, A.f j , Earl, E.h j , Alexopoulos, D.a , Barch, D.M.b d e , Day, T.K.M.f , Dust, J.a , Eggebrecht, A.T.b , Feczko, E.g h , Kardan, O.k , Kenley, J.K.a , Rogers, C.E.c d , Wheelock, M.D.b , Yacoub, E.i , Rosenberg, M.k , Elison, J.T.f g h , Fair, D.A.f g h i , Smyser, C.D.a b c
a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United Statesb Department of Radiology, Washington University School of Medicine, St. Louis, MO, United Statesc Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United Statesd Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United Statese Department of Psychological and Brain Sciences, Washington University School of Medicine, St. Louis, MO, United Statesf Institute of Child Development, University of Minnesota, Minneapolis, MN, United Statesg Department of Pediatrics, University of Minnesota, Minneapolis, MN, United Statesh Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, United Statesi Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota, Minneapolis, MN, United Statesj Department of Psychiatry, Oregon Health and Science University, Portland, OR, United Statesk Department of Psychology, University of Chicago, Chicago, IL, United States
AbstractThe importance of motion correction when processing resting state functional magnetic resonance imaging (rs-fMRI) data is well-established in adult cohorts. This includes adjustments based on self-limited, large amplitude subject head motion, as well as factitious rhythmic motion induced by respiration. In adults, such respiration artifact can be effectively removed by applying a notch filter to the motion trace, resulting in higher amounts of data retained after frame censoring (e.g., “scrubbing”) and more reliable correlation values. Due to the unique physiological and behavioral characteristics of infants and toddlers, rs-fMRI processing pipelines, including methods to identify and remove colored noise due to subject motion, must be appropriately modified to accurately reflect true neuronal signal. These younger cohorts are characterized by higher respiration rates and lower-amplitude head movements than adults; thus, the presence and significance of comparable respiratory artifact and the subsequent necessity of applying similar techniques remain unknown. Herein, we identify and characterize the consistent presence of respiratory artifact in rs-fMRI data collected during natural sleep in infants and toddlers across two independent cohorts (aged 8–24 months) analyzed using different pipelines. We further demonstrate how removing this artifact using an age-specific notch filter allows for both improved data quality and data retention in measured results. Importantly, this work reveals the critical need to identify and address respiratory-driven head motion in fMRI data acquired in young populations through the use of age-specific motion filters as a mechanism to optimize the accuracy of measured results in this population. © 2021
Author KeywordsNeurodevelopment; Neuroimaging, infant; Respiratory filtering; Resting-state fMRI
Funding detailsNational Institutes of HealthNIHP50 HD103525, R01 MH104324, R01 MH105538, R01 MH113883, R01 MH115357, R34 DA050291, U01 MH110274, UG3 OD023349Bill and Melinda Gates FoundationBMGFINV-015711, OPP1184813March of Dimes Foundation
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Relationships between correlated spikes, oxygen and LFP in the resting-state primate” (2022) NeuroImage
Relationships between correlated spikes, oxygen and LFP in the resting-state primate(2022) NeuroImage, 247, art. no. 118728, .
Li, J.M.a , Acland, B.T.a , Brenner, A.S.b , Bentley, W.J.a , Snyder, L.H.a b
a Department of Neuroscience, Washington University School of Medicine, 660 S Euclid Ave, Box 8108, St Louis, MO 63110, United Statesb Department of Biomedical Engineering, Washington University, St Louis, MO 63130, United States
AbstractResting-state functional MRI (rsfMRI) provides a view of human brain organization based on correlation patterns of blood oxygen level dependent (BOLD) signals recorded across the whole brain. The neural basis of resting-state BOLD fluctuations and their correlation remains poorly understood. We simultaneously recorded oxygen level, spikes, and local field potential (LFP) at multiple sites in awake, resting monkeys. Following a spike, the average local oxygen and LFP voltage responses each resemble a task-driven BOLD response, with LFP preceding oxygen by 0.5 s. Between sites, features of the long-range correlation patterns of oxygen, LFP, and spikes are similar to features seen in rsfMRI. Most of the variance shared between sites lies in the infraslow frequency band (0.01–0.1 Hz) and in the infraslow envelope of higher-frequency bands (e.g. gamma LFP). While gamma LFP and infraslow LFP are both strong correlates of local oxygen, infraslow LFP explains significantly more of the variance shared between correlated oxygen signals than any other electrophysiological signal. Together these findings are consistent with a causal relationship between infraslow LFP and long-range oxygen correlations in the resting state. © 2021
Author KeywordsDefault mode network; Functional connectivity; Magnetic resonance imaging; Neurohemodynamic coupling; Oxygen polarography
Funding detailsNational Institutes of HealthNIHR01MH102471National Institute of Mental HealthNIMHNational Institute of General Medical SciencesNIGMST32GM008151National Institute of Neurological Disorders and StrokeNINDSR21NS105090, R34NS118618
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Estimation of the mechanical properties of a transversely isotropic material from shear wave fields via artificial neural networks” (2022) Journal of the Mechanical Behavior of Biomedical Materials
Estimation of the mechanical properties of a transversely isotropic material from shear wave fields via artificial neural networks(2022) Journal of the Mechanical Behavior of Biomedical Materials, 126, art. no. 105046, .
Hou, Z.a , Guertler, C.A.a , Okamoto, R.J.a , Chen, H.b c , Garbow, J.R.d , Kamilov, U.S.e , Bayly, P.V.a
a Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis, MO 63130, United Statesb Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, United Statesc Department of Radiation Oncology, Washington University School of Medicine, Saint Louis, MO 63108, United Statesd Biomedical Magnetic Resonance Laboratory, Washington University School of Medicine, 4525 Scott Avenue, CB 8227, St. Louis, MO 63110, United Statese Department of Electrical and Systems Engineering and Computer Science and Engineering, Washington University in St. Louis, St. Louis, MO 63130, United States
AbstractArtificial neural networks (ANN), established tools in machine learning, are applied to the problem of estimating parameters of a transversely isotropic (TI) material model using data from magnetic resonance elastography (MRE) and diffusion tensor imaging (DTI). We use neural networks to estimate parameters from experimental measurements of ultrasound-induced shear waves after training on analogous data from simulations of a computer model with similar loading, geometry, and boundary conditions. Strain ratios and shear-wave speeds (from MRE) and fiber direction (the direction of maximum diffusivity from diffusion tensor imaging (DTI)) are used as inputs to neural networks trained to estimate the parameters of a TI material (baseline shear modulus μ, shear anisotropy φ, and tensile anisotropy ζ). Ensembles of neural networks are applied to obtain distributions of parameter estimates. The robustness of this approach is assessed by quantifying the sensitivity of property estimates to assumptions in modeling (such as assumed loss factor) and choices in fitting (such as the size of the neural network). This study demonstrates the successful application of simulation-trained neural networks to estimate anisotropic material parameters from complementary MRE and DTI imaging data. © 2021 Elsevier Ltd
Author KeywordsAnisotropy; Artificial neural network; Focused ultrasound; Machine learning; MR elastography
Funding detailsNational Science FoundationNSFCMMI-17274212National Institutes of HealthNIHR01 EB027577
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Insulin-like growth factor II prevents MPP+ and glucocorticoid mitochondrial-oxidative and neuronal damage in dopaminergic neurons” (2022) Antioxidants
Insulin-like growth factor II prevents MPP+ and glucocorticoid mitochondrial-oxidative and neuronal damage in dopaminergic neurons(2022) Antioxidants, 11 (1), art. no. 41, .
Claros, S.a , Cabrera, P.b , Valverde, N.b , Romero-Zerbo, S.Y.a , López-González, M.V.a , Shumilov, K.c d , Rivera, A.c , Pavia, J.b , Martín-Montañez, E.b , Garcia-Fernandez, M.a
a Department of Human Physiology, Faculty of Medicine, Biomedical Research Institute of Malaga, Malaga University, Malaga, 29010, Spainb Department of Pharmacology and Paediatrics, Faculty of Medicine, Biomedical Research Institute of Malaga, Malaga University, Malaga, 29010, Spainc Department of Cell Biology, Faculty of Science, Biomedical Research Institute of Malaga, Malaga University, Malaga, 29010, Spaind School of Medicine, Washington University in St. Louis, St. Louis, MO 63101, United States
AbstractStress seems to contribute to Parkinson’s disease (PD) neuropathology, probably by dysregulation of the hypothalamic–pituitary–adrenal axis. Key factors in this pathophysiology are oxidative stress and mitochondrial dysfunction and neuronal glucocorticoid-induced toxicity. The insulin-like growth factor II (IGF-II), a pleiotropic hormone, has shown antioxidant and neuroprotective effects in some neurodegenerative disorders. Our aim was to examine the protective effect of IGF-II on a dopaminergic cellular combined model of PD and mild to moderate stress measuring oxidative stress parameters, mitochondrial and neuronal markers, and signalling pathways. IGF-II counteracts the mitochondrial-oxidative damage produced by the toxic synergistic effect of corticosterone and 1-methyl-4-phenylpyridinium, protecting dopaminergic neurons from death and neurodegeneration. IGF-II promotes PKC activation and nuclear factor (erythroid-derived 2)-like 2 antioxidant response in a glucocorticoid receptor-dependent pathway, preventing oxidative cell damage and maintaining mitochondrial function. Thus, IGF-II is a potential therapeutic tool for treatment and prevention of disease progression in PD patients suffering mild to moderate emotional stress. © 2021 by the author. Licensee MDPI, Basel, Switzerland.
Author KeywordsHormonal stress; Insulin-like growth factor II; Mitochondria; Neuroprotection; Oxidative stress; Parkinson’s disease
Funding detailsUMA18-FEDERJA-004Junta de Andalucía
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Dopamine D4 receptor is a regulator of morphine-induced plasticity in the rat dorsal striatum” (2022) Cells
Dopamine D4 receptor is a regulator of morphine-induced plasticity in the rat dorsal striatum(2022) Cells, 11 (1), art. no. 31, .
Rivera, A.a , Suárez-Boomgaard, D.a , Miguelez, C.b , Valderrama-Carvajal, A.a , Baufreton, J.c d , Shumilov, K.a e , Taupignon, A.c d , Gago, B.f , Real, M.Á.a
a Facultad de Ciencias, Instituto de Investigación Biomédica, Universidad de Málaga, Málaga, 29071, Spainb Department of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, 48940, Spainc Institut des Maladies Neurodegeneratives, Université de Bordeaux, UMR 5293, Bordeaux, 33000, Franced Institut des Maladies Neurodegeneratives, CNRS, UMR 5293, Bordeaux, 33000, Francee School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, United Statesf Facultad de Medicina, Instituto de Investigación Biomédica, Universidad de Málaga, Málaga, 29071, Spain
AbstractLong-term exposition to morphine elicits structural and synaptic plasticity in reward-related regions of the brain, playing a critical role in addiction. However, morphine-induced neuroadaptations in the dorsal striatum have been poorly studied despite its key function in drug-related habit learning. Here, we show that prolonged treatment with morphine triggered the retraction of the dendritic arbor and the loss of dendritic spines in the dorsal striatal projection neurons (MSNs). In an attempt to extend previous findings, we also explored whether the dopamine D4 receptor (D4R) could modulate striatal morphine-induced plasticity. The combined treatment of morphine with the D4R agonist PD168,077 produced an expansion of the MSNs dendritic arbors and restored dendritic spine density. At the electrophysiological level, PD168,077 in combination with morphine altered the electrical properties of the MSNs and decreased their excitability. Finally, results from the sustantia nigra showed that PD168,077 counteracted morphine-induced upregulation of μ opioid receptors (MOR) in striatonigral projections and downregulation of G protein-gated inward rectifier K+ channels (GIRK1 and GIRK2) in dopaminergic cells. The present results highlight the key function of D4R modulating morphine-induced plasticity in the dorsal striatum. Thus, D4R could represent a valuable pharmacological target for the safety use of morphine in pain management. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Author KeywordsAddiction; Caudate putamen; Dopamine; Dopamine D4 receptor; Morphine; Plasticity; Receptor–receptor interaction
Funding detailsANR-10-LABX-43Agence Nationale de la RechercheANRANR-15-CE37-0006Eusko JaurlaritzaPUE21-03Euskal Herriko UnibertsitateaEHUCOLAB20/07Universitat Politècnica de ValènciaUPVCentre National de la Recherche ScientifiqueCNRSUniversité de BordeauxJunta de AndalucíaCTS-0161, P09-CVI-4702
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Superior Verbal Memory Outcome After Stereotactic Laser Amygdalohippocampotomy” (2021) Frontiers in Neurology
Superior Verbal Memory Outcome After Stereotactic Laser Amygdalohippocampotomy(2021) Frontiers in Neurology, 12, art. no. 779495, .
Drane, D.L.a b c , Willie, J.T.d , Pedersen, N.P.a e , Qiu, D.f , Voets, N.L.g , Millis, S.R.h , Soares, B.P.i , Saindane, A.M.f , Hu, R.f , Kim, M.S.c , Hewitt, K.C.a , Hakimian, S.c , Grabowski, T.c , Ojemann, J.G.j , Loring, D.W.a b , Meador, K.J.k , Faught, E., Jr.a b , Miller, J.W.c j , Gross, R.E.a e l
a Department of Neurology, Emory University School of Medicine, Atlanta, GA, United Statesb Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, United Statesc Department of Neurology, University of Washington School of Medicine, Seattle, WA, United Statesd Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO, United Statese Coulter Department of Biomedical Engineering, Emory University, Atlanta, GA, United Statesf Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, United Statesg Nuffield Department of Clinical Neurosciences, Oxford Centre for Functional MRI of the Brain, University of Oxford, Oxford, United Kingdomh Department of Physical Medicine and Rehabilitation, Wayne State University School of Medicine, Detroit, MI, United Statesi Department of Radiology, University of Vermont Medical Center, Burlington, VT, United Statesj Department of Neurological Surgery, University of Washington School of Medicine, Seattle, WA, United Statesk Department of Neurology, Stanford University School of Medicine, Stanford, CA, United Statesl Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, United States
AbstractObjective: To evaluate declarative memory outcomes in medically refractory epilepsy patients who underwent either a highly selective laser ablation of the amygdalohippocampal complex or a conventional open temporal lobe resection. Methods: Post-operative change scores were examined for verbal memory outcome in epilepsy patients who underwent stereotactic laser amygdalohippocampotomy (SLAH: n = 40) or open resection procedures (n = 40) using both reliable change index (RCI) scores and a 1-SD change metric. Results: Using RCI scores, patients undergoing open resection (12/40, 30.0%) were more likely to decline on verbal memory than those undergoing SLAH (2/40 [5.0%], p = 0.0064, Fisher’s exact test). Patients with language dominant procedures were much more likely to experience a significant verbal memory decline following open resection (9/19 [47.4%]) compared to laser ablation (2/19 [10.5%], p = 0.0293, Fisher’s exact test). 1 SD verbal memory decline frequently occurred in the open resection sample of language dominant temporal lobe patients with mesial temporal sclerosis (8/10 [80.0%]), although it rarely occurred in such patients after SLAH (2/14, 14.3%) (p = 0.0027, Fisher’s exact test). Memory improvement occurred significantly more frequently following SLAH than after open resection. Interpretation: These findings suggest that while verbal memory function can decline after laser ablation of the amygdalohippocampal complex, it is better preserved when compared to open temporal lobe resection. Our findings also highlight that the dominant hippocampus is not uniquely responsible for verbal memory. While this is at odds with our simple and common heuristic of the hippocampus in memory, it supports the findings of non-human primate studies showing that memory depends on broader medial and lateral TL regions. Copyright © 2021 Drane, Willie, Pedersen, Qiu, Voets, Millis, Soares, Saindane, Hu, Kim, Hewitt, Hakimian, Grabowski, Ojemann, Loring, Meador, Faught, Miller and Gross.
Author Keywordshippocampal function; laser interstitial thermal therapy (LITT); neural substrates of memory; open resection epilepsy surgery; verbal memory outcome
Funding detailsNational Institutes of HealthNIHK02NS070960, K23 NSO49100, L30 NS080215, R01NS088748National Institute of Neurological Disorders and StrokeNINDSK08NS105929, R21NS122011Medtronic1@110ODO16143
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Programmed Cell Death Recruits Macrophages Into the Developing Mouse Cochlea” (2021) Frontiers in Cell and Developmental Biology
Programmed Cell Death Recruits Macrophages Into the Developing Mouse Cochlea(2021) Frontiers in Cell and Developmental Biology, 9, art. no. 777836, .
Borse, V.a , Kaur, T.b , Hinton, A.a , Ohlemiller, K.a , Warchol, M.E.a
a Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO, United Statesb Department of Biomedical Sciences, School of Medicine, Creighton University, Omaha, NE, United States
AbstractProgrammed cell death (PCD) plays a critical role in the development and maturation of the cochlea. Significant remodeling occurs among cells of the greater epithelial ridge (GER) of Kölliker’s organ, leading to tissue regression and formation of the inner sulcus. In mice, this event normally occurs between postnatal days 5–15 (P5-15) and is regulated by thyroid hormone (T3). During this developmental time period, the cochlea also contains a large population of macrophages. Macrophages are frequently involved in the phagocytic clearance of dead cells, both during development and after injury, but the role of macrophages in the developing cochlea is unknown. This study examined the link between developmental cell death in the GER and the recruitment of macrophages into this region. Cell death in the basal GER begins at P5 and enhanced numbers of macrophages were observed at P7. This pattern of macrophage recruitment was unchanged in mice that were genetically deficient for CX3CR1, the receptor for fractalkine (a known macrophage chemoattractant). We found that injection of T3 at P0 and P1 caused GER cell death to begin at P3, and this premature PCD was accompanied by earlier recruitment of macrophages. We further found that depletion of macrophages from the developing cochlea (using CX3CR1DTR/+ mice and treatment with the CSF1R antagonist BLZ945) had no effect on the pattern of GER regression. Together, these findings suggest that macrophages are recruited into the GER region after initiation of developmental PCD, but that they are not essential for GER regression during cochlear remodeling. Copyright © 2021 Borse, Kaur, Hinton, Ohlemiller and Warchol.
Author Keywordscell death; cochlea; development; GER; macrophage; thyroid hormone
Funding detailsNational Institutes of HealthNIH
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Biodistribution of Biomimetic Drug Carriers, Mononuclear Cells, and Extracellular Vesicles, in Nonhuman Primates” (2021) Advanced Biology
Biodistribution of Biomimetic Drug Carriers, Mononuclear Cells, and Extracellular Vesicles, in Nonhuman Primates(2021) Advanced Biology, .
Haney, M.J.a b , Yuan, H.c , Shipley, S.T.d , Wu, Z.c , Zhao, Y.a b , Pate, K.e , Frank, J.E.c , Massoud, N.d , Stewart, P.W.f , Perlmutter, J.S.g , Batrakova, E.V.a b
a Center for NanotechFnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United Statesb Eshelman School of Pharmacy, University of North Carolina at Chapel, Hill, Chapel Hill, NC 27599, United Statesc Department of Radiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, United Statesd Division of Comparative Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United Statese Division of Comparative Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, United Statesf Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United Statesg School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
AbstractDiscovery of novel drug delivery systems to the brain remains a key task for successful treatment of neurodegenerative disorders. Herein, the biodistribution of immunocyte-based carriers, peripheral blood mononuclear cells (PBMCs), and monocyte-derived EVs are investigated in adult rhesus macaques using longitudinal PET/MRI imaging. 64Cu-labeled drug carriers are introduced via different routes of administration: intraperitoneal (IP), intravenous (IV), or intrathecal (IT) injection. Whole body PET/MRI (or PET/CT) images are acquired at 1, 24, and 48 h post injection of 64Cu-labeled drug carriers, and standardized uptake values (SUVmean and SUVmax) in the main organs are estimated. The brain retention for both types of carriers increases based on route of administration: IP < IV < IT. Importantly, a single IT injection of PBMCs produces higher brain retention compared to IT injection of EVs. In contrast, EVs show superior brain accumulation compared to the cells when administered via IP and IV routes, respectively. Finally, a comprehensive chemistry panel of blood samples demonstrates no cytotoxic effects of either carrier. Overall, living cells and EVs have a great potential to be used for drug delivery to the brain. When identifying the ideal drug carrier, the route of administration could make big differences in CNS drug delivery. © 2021 The Authors. Advanced Biology published by Wiley-VCH GmbH
Author Keywordsbrain bioavailability; drug delivery system; extracellular vesicles; monocytes; nonhuman primates
Funding details17846, MJFF‐009726National Institutes of HealthNIH1R01NS112019, 1RO1 NS102412Eshelman Institute for Innovation, University of North Carolina at Chapel HillEII UNC 38‐124
Document Type: ArticlePublication Stage: Article in PressSource: Scopus