“The relationship between diffusion heterogeneity and microstructural changes in high-grade gliomas using Monte Carlo simulations” (2022) Magnetic Resonance Imaging
The relationship between diffusion heterogeneity and microstructural changes in high-grade gliomas using Monte Carlo simulations(2022) Magnetic Resonance Imaging, 85, pp. 108-120.
Lee, C.-Y.a , Bennett, K.M.b , Debbins, J.P.c , Choi, I.-Y.a d e f , Lee, P.a e f
a Hoglund Biomedical Imaging Center, University of Kansas Medical Center, Kansas City, KS, United Statesb Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO, United Statesc Neuroimaging research, Barrow Neurological Institute, Phoenix, AZ, United Statesd Department of Neurology, University of Kansas Medical Center, Kansas City, KS, United Statese Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, United Statesf Department of Radiology, University of Kansas Medical Center, Kansas City, KS, United States
AbstractPurpose: Diffusion-weighted imaging (DWI) may aid accurate tumor grading. Decreased diffusivity and increased diffusion heterogeneity measures have been observed in high-grade gliomas using the non-monoexponential models for DWI. However, DWI measures concerning tissue characteristics in terms of pathophysiological and structural changes are yet to be established. Thus, this study aims to investigate the relationship between the diffusion measurements and microstructural changes in the presence of high-grade gliomas using a three-dimensional Monte Carlo simulation with systematic changes of microstructural parameters. Methods: Water diffusion was simulated in a microenvironment along with changes associated with the presence of high-grade gliomas, including increases in cell density, nuclear volume, extracellular volume (VFex), and extracellular tortuosity (λex), and changes in membrane permeability (Pmem). DWI signals were simulated using a pulsed gradient spin-echo sequence. The sequence parameters, including the maximum gradient strength and diffusion time, were set to be comparable to those of clinical scanners and advanced human MRI systems. The DWI signals were fitted using the gamma distribution and diffusional kurtosis models with b-values up to 6000 and 2500 s/mm2, respectively. Results: The diffusivity measures (apparent diffusion coefficients (ADC), Dgamma of the gamma distribution model and Dapp of the diffusional kurtosis model) decreased with increases in cell density and λex, and a decrease in Pmem. These diffusivity measures increased with increases in nuclear volume and VFex. The diffusion heterogeneity measures (σgamma of the gamma distribution model and Kapp of the diffusional kurtosis model) increased with increases in cell density or nuclear volume at the low Pmem, and a decrease in Pmem. Increased σgamma was also associated with an increase in VFex. Conclusion: Among simulated microstructural changes, only increases in cell density at low Pmem or decreases in Pmem corresponded to both the decreased diffusivity and increased diffusion heterogeneity measures. The results suggest that increases in cell density at low Pmem or decreases in Pmem may be associated with the diffusion changes observed in high-grade gliomas. © 2021 Elsevier Inc.
Author KeywordsDiffusion; Diffusivity; Gamma; Gliomas; Heterogeneity; Kurtosis; MRI; Simulation
Funding detailsUniversity of KansasKU
Document Type: ArticlePublication Stage: FinalSource: Scopus
“The role of neural load effects in predicting individual differences in working memory function” (2021) NeuroImage
The role of neural load effects in predicting individual differences in working memory function(2021) NeuroImage, 245, art. no. 118656, .
Li, Y.P.a , Cooper, S.R.b , Braver, T.S.b
a Department of Psychology, University of Oregon, 1227 University St, Eugene, OR 97403, United Statesb Department of Psychological and Brain Sciences, Washington University in Saint Louis, 1 Brookings Drive, Saint Louis, MO 63130, United States
AbstractStudies of working memory (WM) function have tended to adopt either a within-subject approach, focusing on effects of load manipulations, or a between-subjects approach, focusing on individual differences. This dichotomy extends to WM neuroimaging studies, with different neural correlates being identified for within- and between-subjects variation in WM. Here, we examined this issue in a systematic fashion, leveraging the large-sample Human Connectome Project dataset, to conduct a well-powered, whole-brain analysis of the N-back WM task. We first demonstrate the advantages of parcellation schemes for dimension reduction, in terms of load-related effect sizes. This parcel-based approach is then utilized to directly compare the relationship between load-related (within-subject) and behavioral individual differences (between-subject) effects through both correlational and predictive analyses. The results suggest a strong linkage of within-subject and between-subject variation, with larger load-effects linked to stronger brain-behavior correlations. In frontoparietal cortex no hemispheric biases were found towards one type of variation, but the Dorsal Attention Network did exhibit greater sensitivity to between over within-subjects variation, whereas in the Somatomotor network, the reverse pattern was observed. Cross-validated predictive modeling capitalizing on this tight relationship between the two effects indicated greater predictive power for load-activated than load-deactivated parcels, while also demonstrating that load-related effect size can serve as an effective guide to feature (i.e., parcel) selection, in maximizing predictive power while maintaining interpretability. Together, the findings demonstrate an important consistency across within- and between-subjects approaches to identifying the neural substrates of WM, which can be effectively harnessed to develop more powerful predictive models. © 2021
Author KeywordsIndividual difference; Load-related effect; N-back; Parcellation; Working memory
Funding detailsNational Institutes of HealthNIHNIH Blueprint for Neuroscience ResearchMcDonnell Center for Systems NeuroscienceR37 MH066078
Document Type: ArticlePublication Stage: FinalSource: Scopus
“TREM2 modulates differential deposition of modified and non-modified Aβ species in extracellular plaques and intraneuronal deposits” (2021) Acta Neuropathologica Communications
TREM2 modulates differential deposition of modified and non-modified Aβ species in extracellular plaques and intraneuronal deposits(2021) Acta Neuropathologica Communications, 9 (1), art. no. 168, .
Joshi, P.a , Riffel, F.a , Kumar, S.a , Villacampa, N.b c , Theil, S.a , Parhizkar, S.d , Haass, C.d e f , Colonna, M.g , Heneka, M.T.b c , Arzberger, T.f h i , Herms, J.e f h , Walter, J.a
a Department of Neurology, University of Bonn, Venusberg-Campus 1, (Formerly Sigmund-Freud-Str. 25), Bonn, 53127, Germanyb Department of Neurodegenerative Diseases and Gerontopsychiatry, University Hospital Bonn, Bonn, Germanyc Neuroinflammation Unit, German Center for Neurodegenerative Diseases e. V. (DZNE), Bonn, Germanyd Biomedical Center (BMC), Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germanye Munich Cluster for Systems Neurology (SyNergy), Munich, Germanyf Molecular Neurodegeneration Unit, German Center for Neurodegenerative Diseases e.V. (DZNE) Munich, Munich, Germanyg Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United Statesh Center for Neuropathology and Prion Research, Ludwig-Maximilians-Universität München, Munich, Germanyi Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität München, Munich, Germany
AbstractProgressive accumulation of Amyloid-β (Aβ) deposits in the brain is a characteristic neuropathological hallmark of Alzheimer’s disease (AD). During disease progression, extracellular Aβ plaques undergo specific changes in their composition by the sequential deposition of different modified Aβ species. Microglia are implicated in the restriction of amyloid deposits and play a major role in internalization and degradation of Aβ. Recent studies showed that rare variants of the Triggering Receptor Expressed on Myeloid cells 2 (TREM2) are associated with an increased risk for AD. Post-translational modifications of Aβ could modulate the interaction with TREM2, and the uptake by microglia. Here, we demonstrate that genetic deletion of TREM2 or expression of a disease associated TREM2 variant in mice lead to differential accumulation of modified and non-modified Aβ species in extracellular plaques and intraneuronal deposits. Human brains with rare TREM2 AD risk variants also showed altered deposition of modified Aβ species in the different brain lesions as compared to cases with the common variant of TREM2. These findings indicate that TREM2 plays a critical role in the development and the composition of Aβ deposits, not only in extracellular plaques, but also intraneuronally, that both could contribute to the pathogenesis of AD. © 2021, The Author(s).
Author KeywordsAβ; Intraneuronal; Microglia; Post-translational modification; TREM2; Vascular deposits
Funding details115976Deutsche ForschungsgemeinschaftDFGWA1477/6-6Rheinische Friedrich-Wilhelms-Universität BonnUni Bonn388169927Innovative Medicines InitiativeIMI
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Rats use memory confidence to guide decisions” (2021) Current Biology
Rats use memory confidence to guide decisions(2021) Current Biology, 31 (20), pp. 4571-4583.e4.
Joo, H.R.a b c d , Liang, H.e , Chung, J.E.b c d f , Geaghan-Breiner, C.b c d , Fan, J.L.g , Nachman, B.P.h i , Kepecs, A.j , Frank, L.M.b c d k
a Medical Scientist Training Program, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, United Statesb Kavli Institute for Fundamental Neuroscience, Center for Integrative Neuroscience, University of California, San Francisco, 675 Nelson Rising Lane, San Francisco, CA 94158, United Statesc Department of Physiology, University of California, San Francisco, 401 Parnassus Avenue, San Francisco, CA 94158, United Statesd Department of Psychiatry, University of California, San Francisco, 401 Parnassus Avenue, San Francisco, CA 94158, United Statese Neuroscience Graduate Program, The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, United Statesf Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143, United Statesg Bioengineering Graduate Program, University of California, Berkeley/University of California, San Francisco, 1675 Owens Street, San Francisco, CA 94158, United Statesh Physics Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, United Statesi Berkeley Institute of Data Science, University of California, Berkeley, 190 Doe Library, Berkeley, CA 94720, United Statesj Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, United Statesk Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815, United States
AbstractMemory enables access to past experiences to guide future behavior. Humans can determine which memories to trust (high confidence) and which to doubt (low confidence). How memory retrieval, memory confidence, and memory-guided decisions are related, however, is not understood. In particular, how confidence in memories is used in decision making is unknown. We developed a spatial memory task in which rats were incentivized to gamble their time: betting more following a correct choice yielded greater reward. Rat behavior reflected memory confidence, with higher temporal bets following correct choices. We applied machine learning to identify a memory decision variable and built a generative model of memories evolving over time that accurately predicted both choices and confidence reports. Our results reveal in rats an ability thought to exist exclusively in primates and introduce a unified model of memory dynamics, retrieval, choice, and confidence. © 2021 The Author(s)
Author Keywordsbehavior; confidence; decision making; deep neural network; machine learning; memory; metamemory; rat; spatial memory
Funding detailsT32GM007618Howard Hughes Medical InstituteHHMIU.S. Department of EnergyUSDOEDE-AC02-05CH11231National Institute of Mental HealthNIMHF30MH109292, F30MH115582, R01MH097061National Institute of Neurological Disorders and StrokeNINDSU01 NS094288, U01 NS107667Nvidia
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Multicenter Validation of a Deep Learning Detection Algorithm for Focal Cortical Dysplasia” (2021) Neurology
Multicenter Validation of a Deep Learning Detection Algorithm for Focal Cortical Dysplasia(2021) Neurology, 97 (16), pp. E1571-E1582. Cited 2 times.
Gill, R.S.a , Lee, H.-M.a , Caldairou, B.a , Hong, S.-J.a , Barba, C.b , Deleo, F.c , D’Incerti, L.d , Mendes Coelho, V.C.e , Lenge, M.b , Semmelroch, M.f , Schrader, D.V.g , Bartolomei, F.h , Guye, M.i , Schulze-Bonhage, A.j , Urbach, H.j , Cho, K.H.k , Cendes, F.e , Guerrini, R.b , Jackson, G.f , Hogan, R.E.l , Bernasconi, N.a , Bernasconi, A.a
a Neuroimaging of Epilepsy Laboratory, Montreal Neurological Institute, McGill University, Montreal, QC, Canadab Pediatric Neurology Unit, Laboratories Children’s Hospital A. Meyer, University of Florence, Italyc Epilepsy Unit, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italyd Neuroradiology, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italye Department of Neurology, University of Campinas, Brazilf Florey Institute of Neuroscience and Mental Health, University of MelbourneVIC, Australiag Department of Pediatrics, British Columbia Children’s Hospital, Vancouver, Canadah Aix Marseille University, INSERM UMR 1106, Institut de Neurosciences des Systèmes, Francei Aix Marseille University, CNRS, CRMBM UMR 7339, Marseille, Francej Freiburg Epilepsy Center, Universitätsklinikum Freiburg, Germanyk Department of Neurology, Yonsei University, College of Medicine, Seoul, South Koreal Department of Neurology, Washington University, School of Medicine, St. Louis, MO, United States
AbstractBackground and Objective To test the hypothesis that a multicenter-validated computer deep learning algorithm detects MRI-negative focal cortical dysplasia (FCD). Methods We used clinically acquired 3-dimensional (3D) T1-weighted and 3D fluid-attenuated inversion recovery MRI of 148 patients (median age 23 years [range 2-55 years]; 47% female) with histologically verified FCD at 9 centers to train a deep convolutional neural network (CNN) classifier. Images were initially deemed MRI-negative in 51% of patients, in whom intracranial EEG determined the focus. For risk stratification, the CNN incorporated bayesian uncertainty estimation as a measure of confidence. To evaluate performance, detection maps were compared to expert FCD manual labels. Sensitivity was tested in an independent cohort of 23 cases with FCD (13 ± 10 years). Applying the algorithm to 42 healthy controls and 89 controls with temporal lobe epilepsy disease tested specificity. Results Overall sensitivity was 93% (137 of 148 FCD detected) using a leave-one-site-out cross-validation, with an average of 6 false positives per patient. Sensitivity in MRI-negative FCD was 85%. In 73% of patients, the FCD was among the clusters with the highest confidence; in half, it ranked the highest. Sensitivity in the independent cohort was 83% (19 of 23; average of 5 false positives per patient). Specificity was 89% in healthy and disease controls. Discussion This first multicenter-validated deep learning detection algorithm yields the highest sensitivity to date in MRI-negative FCD. By pairing predictions with risk stratification, this classifier may assist clinicians in adjusting hypotheses relative to other tests, increasing diagnostic confidence. Moreover, generalizability across age and MRI hardware makes this approach ideal for presurgical evaluation of MRI-negative epilepsy. Classification of Evidence This study provides Class III evidence that deep learning on multimodal MRI accurately identifies FCD in patients with epilepsy initially diagnosed as MRI negative. © 2021 American Academy of Neurology.
Funding detailsFondation Brain CanadaCanadian Institutes of Health ResearchIRSC123,520, MOP-57840Natural Sciences and Engineering Research Council of CanadaNSERC24779, Discovery-243141
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Persistent Opioid Use After Spine Surgery: A Prospective Cohort Study” (2021) Spine
Persistent Opioid Use After Spine Surgery: A Prospective Cohort Study(2021) Spine, 46 (20), pp. 1428-1435.
Uhrbrand, P.a b , Helmig, P.b c , Haroutounian, S.d , Vistisen, S.T.a b , Nikolajsen, L.a b
a Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmarkb Department of Clinical Medicine, Aarhus University, Aarhus, Denmarkc Department of Orthopedic Surgery, Aarhus University Hospital, Aarhus, Denmarkd Department of Anesthesiology, Washington University, St. Louis, MO
AbstractSTUDY DESIGN: Single-center, investigator-initiated, prospective cohort study. OBJECTIVE: This study aimed to determine patient-reported reasons for persistent opioid use following elective spine surgery, assess the frequency of withdrawal symptoms, and characterize pain-related care sought after discharge. SUMMARY OF BACKGROUND DATA: Patients are often prescribed opioids at discharge from hospital following surgery. Several studies have shown that a large number of patients fail to discontinue opioid treatment and use opioids even months to years after surgery. Spine surgery has proven to be a high-risk procedure in regard to persistent opioid use. There is, however, limited evidence on why patients continue to take opioids. METHODS: Three hundred patients, scheduled to undergo spine surgery at Aarhus University Hospital, Denmark, were included. Baseline characteristics and discharge data on opioid consumption were collected. Data on opioid consumption, patient-reported reasons for opioid use, withdrawal symptoms, and pain-related care sought were collected at 3- and 6-month follow-up via a REDCap survey. RESULTS: Before surgery, opioid use was reported in 53% of patients. Three months after surgery, opioid use was reported in 60% of preoperative opioid-users and in 9% of preoperative opioid non-users. Patients reported the following reasons for postoperative opioid use: treatment of surgery-related pain (53%), treatment of surgery-related pain combined with other reasons (37%), and reasons not related to spine surgery (10%). Withdrawal symptoms were experienced by 33% of patients during the first 3 months after surgery and were associated with failure to discontinue opioid treatment (P < 0.001). Half of patients (52%) contacted health care after discharge with pain-related topics the first 3 months. CONCLUSION: Patients use opioids after spine surgery for reasons other than surgery-related pain. Withdrawal symptoms are frequent even though patients are given tapering plans at discharge. Further studies should address how to facilitate successful and safe opioid tapering in patients undergoing spine surgery.Level of Evidence: 3. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Document Type: ArticlePublication Stage: FinalSource: Scopus
“A Phase I Study of the Combination of Pexidartinib and Sirolimus to Target Tumor-Associated Macrophages in Unresectable Sarcoma and Malignant Peripheral Nerve Sheath Tumors” (2021) Clinical Cancer Research
A Phase I Study of the Combination of Pexidartinib and Sirolimus to Target Tumor-Associated Macrophages in Unresectable Sarcoma and Malignant Peripheral Nerve Sheath Tumors(2021) Clinical Cancer Research, 27 (20), pp. 5519-5527.
Manji, G.A.a b c , van Tine, B.A.d e f , Lee, S.M.g , Raufi, A.G.c h , Pellicciotta, I.c , Hirbe, A.C.d e f , Pradhan, J.c , Chen, A.i , Rabadan, R.i , Schwartz, G.K.a b c
a Division of Hematology and Oncology, Columbia University Irving Medical Center, New York, NY, United Statesb New York Presbyterian Hospital, Herbert Irving Pavilion, New York, NY, United Statesc Herbert Irving Comprehensive Cancer Center, New York, NY, United Statesd Division of Medical Oncology, Department of Medicine, Washington University, St. Louis, MO, United Statese Division of Pediatric Hematology/ Oncology, St. Louis Children’s Hospital, St Louis, MO, United Statesf Siteman Cancer Center, St. Louis, MO, United Statesg Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, United Statesh Division of Hematology-Oncology, Lifespan Cancer Institute, Warren-Alpert Medical School of Brown University, Providence, RI, United Statesi Program for Mathematical Genomics, Departments of Systems Biology and Biomedical Informatics, Columbia University, New York, NY, United States
AbstractPurpose: To evaluate the safety and tolerability in phase I first-inhuman combination therapy with pexidartinib, an inhibitor of colony-stimulating factor-1 receptor, and sirolimus, an mTOR inhibitor, to target tumor-associated macrophage (TAM) polarization in soft tissue sarcomas (STS). Patients and Methods: This multicenter phase I study used the time-to-event continual reassessment method (TITE-CRM) to study the combination of sirolimus, doses ranging from 2 to 6 mg, with pexidartinib, doses ranging from 600 to 1,000 mg, both provided continuously on a 28-day cycle, in patients with advanced sarcoma. A total of 24 patients [8 malignant peripheral nerve sheath tumor, 3 tenosynovial giant cell tumor (TGCT), 5 leiomyosarcoma, and 8 with other sarcoma subtypes] were enrolled. The median age was 46 years, 56% were male, and 61% had >2 prior lines of therapy. Results: The recommended phase II dose was 2 mg of sirolimus combined with 1,000 mg of pexidartinib daily. Of the 18 evaluable subjects, 5 experienced dose-limiting toxicities (2 elevated aspartate aminotransferase/alanine aminotransferase, 2 elevated sirolimus trough levels, and 1 grade 5 dehydration). Most common grade 2 or higher treatment-related adverse events included anemia, fatigue, neutropenia, and lymphopenia. Clinical benefit was observed in 12 of 18 (67%) evaluable subjects with 3 partial responses (all in TGCT) and 9 stable disease. Tissue staining indicated a decreased proportion of activated M2 macrophages within tumor samples with treatment. Conclusions: Pexidartinib can be safely administered with sirolimus. These findings support further investigation of this combination to determine clinical efficacy. Clinicaltrials.gov identifier NCT02584647. ©2021 The Authors; Published by the American Association for Cancer Research
Funding detailsFDA-R01U.S. Food and Drug AdministrationFDAPfizerAstraZenecaGlaxoSmithKlineGSKCytokineticsCYTKDaiichi-Sankyo
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Optimal Method for Fetal Brain Age Prediction Using Multiplanar Slices From Structural Magnetic Resonance Imaging” (2021) Frontiers in Neuroscience
Optimal Method for Fetal Brain Age Prediction Using Multiplanar Slices From Structural Magnetic Resonance Imaging(2021) Frontiers in Neuroscience, 15, art. no. 714252, .
Hong, J.a b , Yun, H.J.b c , Park, G.d , Kim, S.a , Ou, Y.b c e f , Vasung, L.b c , Rollins, C.K.g , Ortinau, C.M.h , Takeoka, E.i , Akiyama, S.j , Tarui, T.i , Estroff, J.A.e , Grant, P.E.b c e , Lee, J.-M.k , Im, K.b c
a Department of Electronic Engineering, Hanyang University, Seoul, South Koreab Fetal Neonatal Neuroimaging and Developmental Science Center, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United Statesc Division of Newborn Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United Statesd USC Mark, Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, CA, United Statese Department of Radiology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United Statesf Computational Health Informatics Program, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United Statesg Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United Statesh Department of Pediatrics, Washington University in St. Louis, St. Louis, MO, United Statesi Mother Infant Research Institute, Tufts Medical Center, Boston, MA, United Statesj Center for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Japank Department of Biomedical Engineering, Hanyang University, Seoul, South Korea
AbstractThe accurate prediction of fetal brain age using magnetic resonance imaging (MRI) may contribute to the identification of brain abnormalities and the risk of adverse developmental outcomes. This study aimed to propose a method for predicting fetal brain age using MRIs from 220 healthy fetuses between 15.9 and 38.7 weeks of gestational age (GA). We built a 2D single-channel convolutional neural network (CNN) with multiplanar MRI slices in different orthogonal planes without correction for interslice motion. In each fetus, multiple age predictions from different slices were generated, and the brain age was obtained using the mode that determined the most frequent value among the multiple predictions from the 2D single-channel CNN. We obtained a mean absolute error (MAE) of 0.125 weeks (0.875 days) between the GA and brain age across the fetuses. The use of multiplanar slices achieved significantly lower prediction error and its variance than the use of a single slice and a single MRI stack. Our 2D single-channel CNN with multiplanar slices yielded a significantly lower stack-wise MAE (0.304 weeks) than the 2D multi-channel (MAE = 0.979, p < 0.001) and 3D (MAE = 1.114, p < 0.001) CNNs. The saliency maps from our method indicated that the anatomical information describing the cortex and ventricles was the primary contributor to brain age prediction. With the application of the proposed method to external MRIs from 21 healthy fetuses, we obtained an MAE of 0.508 weeks. Based on the external MRIs, we found that the stack-wise MAE of the 2D single-channel CNN (0.743 weeks) was significantly lower than those of the 2D multi-channel (1.466 weeks, p < 0.001) and 3D (1.241 weeks, p < 0.001) CNNs. These results demonstrate that our method with multiplanar slices accurately predicts fetal brain age without the need for increased dimensionality or complex MRI preprocessing steps. © Copyright © 2021 Hong, Yun, Park, Kim, Ou, Vasung, Rollins, Ortinau, Takeoka, Akiyama, Tarui, Estroff, Grant, Lee and Im.
Author Keywordsage prediction; brain age; deep learning; fetal brain; fetal MRI
Funding detailsNational Institutes of HealthNIHK23NS101120, R01NS114087National Institute of Neurological Disorders and StrokeNINDSNational Institute of Biomedical Imaging and BioengineeringNIBIBR01EB017337American Heart AssociationAHA19IPLOI34660336Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNICHDR01HD100009, U01HD087211Ministry of Health and WelfareMOHWHI19C0755Korea Health Industry Development InstituteKHIDIInstitute for Information and Communications Technology PromotionIITPMinistry of Science and ICT, South KoreaMSIT2020-0-01373
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Sensory Percepts Elicited by Chronic Macro-Sieve Electrode Stimulation of the Rat Sciatic Nerve” (2021) Frontiers in Neuroscience
Sensory Percepts Elicited by Chronic Macro-Sieve Electrode Stimulation of the Rat Sciatic Nerve(2021) Frontiers in Neuroscience, 15, art. no. 758427, .
Chandra, N.S.a , McCarron, W.M.b , Yan, Y.b , Ruiz, L.C.a , Sallinger, E.G.c , Birenbaum, N.K.a , Burton, H.d , Green, L.e , Moran, D.W.a , Ray, W.Z.b , MacEwan, M.R.b
a Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United Statesb Department of Neurosurgery, Washington University School of Medicine in St. Louis, St. Louis, MO, United Statesc Department of Biology, Washington University in St. Louis, St. Louis, MO, United Statesd Department of Neuroscience, Washington University School of Medicine in St. Louis, St. Louis, MO, United Statese Department of Psychological Brain Sciences, Washington University in St. Louis, St. Louis, MO, United States
AbstractObjective: Intuitive control of conventional prostheses is hampered by their inability to provide the real-time tactile and proprioceptive feedback of natural sensory pathways. The macro-sieve electrode (MSE) is a candidate interface to amputees’ truncated peripheral nerves for introducing sensory feedback from external sensors to facilitate prosthetic control. Its unique geometry enables selective control of the complete nerve cross-section by current steering. Unlike previously studied interfaces that target intact nerve, the MSE’s implantation requires transection and subsequent regeneration of the target nerve. Therefore, a key determinant of the MSE’s suitability for this task is whether it can elicit sensory percepts at low current levels in the face of altered morphology and caliber distribution inherent to axon regeneration. The present in vivo study describes a combined rat sciatic nerve and behavioral model developed to answer this question. Approach: Rats learned a go/no-go detection task using auditory stimuli and then underwent surgery to implant the MSE in the sciatic nerve. After healing, they were trained with monopolar electrical stimuli with one multi-channel and eight single-channel stimulus configurations. Psychometric curves derived by the method of constant stimuli (MCS) were used to calculate 50% detection thresholds and associated psychometric slopes. Thresholds and slopes were calculated at two time points 3 weeks apart. Main Results: For the multi-channel stimulus configuration, the average current required for stimulus detection was 19.37 μA (3.87 nC) per channel. Single-channel thresholds for leads located near the nerve’s center were, on average, half those of leads located near the periphery (54.92 μA vs. 110.71 μA, or 10.98 nC vs. 22.14 nC). Longitudinally, 3 of 5 leads’ thresholds decreased or remained stable over the 3-week span. The remaining two leads’ thresholds increased by 70–74%, possibly due to scarring or device failure. Significance: This work represents an important first step in establishing the MSE’s viability as a sensory feedback interface. It further lays the groundwork for future experiments that will extend this model to the study of other devices, stimulus parameters, and task paradigms. © Copyright © 2021 Chandra, McCarron, Yan, Ruiz, Sallinger, Birenbaum, Burton, Green, Moran, Ray and MacEwan.
Author Keywordsmacro-sieve electrode; nerve regeneration; peripheral nerve stimulation; rat behavior; regenerative electrode; sciatic nerve; sensorimotor restoration; sensory feedback
Funding detailsWashington University in St. LouisWUSTL2017-WRHope Center for Neurological Disorders
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Measurements From Ears With Endolymphatic Hydrops and 2-Hydroxypropyl-Beta-Cyclodextrin Provide Evidence That Loudness Recruitment Can Have a Cochlear Origin” (2021) Frontiers in Surgery
Measurements From Ears With Endolymphatic Hydrops and 2-Hydroxypropyl-Beta-Cyclodextrin Provide Evidence That Loudness Recruitment Can Have a Cochlear Origin(2021) Frontiers in Surgery, 8, art. no. 687490, .
Lefler, S.M.a , Duncan, R.K.b , Goodman, S.S.c , Guinan, J.J., Jr.d e , Lichtenhan, J.T.a
a Department of Otolaryngology, Washington University School of Medicine in St. Louis, Saint Louis, MO, United Statesb Department of Otolaryngology-Head and Neck Surgery, Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI, United Statesc Department of Communication Sciences and Disorders, University of Iowa, Iowa City, IA, United Statesd Eaton-Peabody Laboratories, Massachusetts Eye and Ear, Boston, MA, United Statese Department of Otolaryngology, Harvard Medical School, Boston, MA, United States
AbstractBackground: Loudness recruitment is commonly experienced by patients with putative endolymphatic hydrops. Loudness recruitment is abnormal loudness growth with high-level sounds being perceived as having normal loudness even though hearing thresholds are elevated. The traditional interpretation of recruitment is that cochlear amplification has been reduced. Since the cochlear amplifier acts primarily at low sound levels, an ear with elevated thresholds from reduced cochlear amplification can have normal processing at high sound levels. In humans, recruitment can be studied using perceptual loudness but in animals physiological measurements are used. Recruitment in animal auditory-nerve responses has never been unequivocally demonstrated because the animals used had damage to sensory and neural cells, not solely a reduction of cochlear amplification. Investigators have thus looked for, and found, evidence of recruitment in the auditory central nervous system (CNS). While studies on CNS recruitment are informative, they cannot rule out the traditional interpretation of recruitment originating in the cochlea. Design: We used techniques that could assess hearing function throughout entire frequency- and dynamic-range of hearing. Measurements were made from two animal models: guinea-pig ears with endolymphatic-sac-ablation surgery to produce endolymphatic hydrops, and naïve guinea-pig ears with cochlear perfusions of 13 mM 2-Hydroxypropyl-Beta-Cyclodextrin (HPBCD) in artificial perilymph. Endolymphatic sac ablation caused low-frequency loss. Animals treated with HPBCD had hearing loss at all frequencies. None of these animals had loss of hair cells or synapses on auditory nerve fibers. Results: In ears with endolymphatic hydrops and those perfused with HPBCD, auditory-nerve based measurements at low frequencies showed recruitment compared to controls. Recruitment was not found at high frequencies (> 4 kHz) where hearing thresholds were normal in ears with endolymphatic hydrops and elevated in ears treated with HPBCD. Conclusions: We found compelling evidence of recruitment in auditory-nerve data. Such clear evidence has never been shown before. Our findings suggest that, in patients suspected of having endolymphatic hydrops, loudness recruitment may be a good indication that the associated low-frequency hearing loss originates from a reduction of cochlear amplification, and that measurements of recruitment could be used in differential diagnosis and treatment monitoring of Ménière’s disease. © Copyright © 2021 Lefler, Duncan, Goodman, Guinan and Lichtenhan.
Author Keywords2-hydroxypropyl-beta-cyclodextrin; auditory nerve overlapped waveform; endolymphatic hydrops; loudness recruitment; low-frequency hearing
Funding detailsNational Institutes of HealthNIHR01 DC014997National Institute on Deafness and Other Communication DisordersNIDCD
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Reimagining pilocytic astrocytomas in the context of pediatric low-grade gliomas” (2021) Neuro-Oncology
Reimagining pilocytic astrocytomas in the context of pediatric low-grade gliomas(2021) Neuro-Oncology, 23 (10), pp. 1634-1646.
Milde, T.a b c , Rodriguez, F.J.d , Barnholtz-Sloan, J.S.e f g , Patil, N.f g , Eberhart, C.G.d , Gutmann, D.H.h
a Hopp Children’s Cancer Center (KiTZ), Heidelberg, Germanyb Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germanyc Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germanyd Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United Statese Department of Population and Quantitative Health Sciences, Case Western Reserve School of Medicine, Cleveland, OH, United Statesf University Hospitals, Cleveland, OH, United Statesg Central Brain Tumor Registry of the United States (CBTRUS), Hinsdale, IL, United Statesh Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
AbstractPediatric low-grade gliomas (pLGGs) are the most common brain tumor in children and are associated with lifelong clinical morbidity. Relative to their high-grade adult counterparts or other malignant childhood brain tumors, there is a paucity of authenticated preclinical models for these pLGGs and an incomplete understanding of their molecular and cellular pathogenesis. While large-scale genomic profiling efforts have identified the majority of pathogenic driver mutations, which converge on the MAPK/ERK signaling pathway, it is now appreciated that these events may not be sufficient by themselves for gliomagenesis and clinical progression. In light of the recent World Health Organization reclassification of pLGGs, and pilocytic astrocytoma (PA), in particular, we review our current understanding of these pediatric brain tumors, provide a conceptual framework for future mechanistic studies, and outline the challenges and pressing needs for the pLGG clinical and research communities. © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Author KeywordsBRAF; cellular senescence; low-grade glioma; MEK; neurofibromatosis type 1; pediatric brain tumor; pilocytic astrocytoma; tumor microenvironment
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Clinical considerations for routine auditory and vestibular monitoring in patients with cystic fibrosis” (2021) American Journal of Audiology
Clinical considerations for routine auditory and vestibular monitoring in patients with cystic fibrosis(2021) American Journal of Audiology, 30 (3S), pp. 800-809. Cited 1 time.
Garinis, A.C.a b c , Poling, G.L.d , Rubenstein, R.C.e , Konrad-Martin, D.a b , Hullar, T.E.a b , Baguley, D.M.f g , Burrows, H.L.h , Chisholm, J.A.i , Custer, A.j , Hawe, L.D.k , Hunter, L.L.l , Marras, T.K.m , Ortiz, C.E.h , Petersen, L.n , Steyger, P.S.a o , Winthrop, K.p , Zettner, E.M.q , Clark, K.a r s , Hungerford, M.a , Vachhani, J.J.a , Brewer, C.C.i
a National Center for Rehabilitative Auditory Research, VA Portland Health Care SystemOR, United Statesb Department of Otolaryngology-Head & Neck Surgery, Oregon Health & Science University, Portland, United Statesc Oregon Hearing Research Center, Oregon Health & Science University, Portland, United Statesd Department of Otolaryngology — Head and Neck Surgery, Division of Audiology, Mayo Clinic, Rochester, MN, United Statese Division of Allergy and Pulmonary Medicine, Department of Pediatrics, Washington University in St. Louis School of MedicineMO, United Statesf Hearing Sciences, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, United Kingdomg National Institute for Health Research Biomedical Research Centre, University of Nottingham, United Kingdomh Audiology and Speech Center, Walter Reed National Military Medical Center, BethesdaMD, United Statesi Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, BethesdaMD, United Statesj Department of Audiology, The Ohio State University Comprehensive Cancer Hospital–Arthur G. James Cancer Hospital and Richard J. Solve Research Institute, Columbus, United Statesk School of Speech, Language, and Hearing Sciences, San Diego State UniversityCA, United Statesl Communication Sciences Research Center, Cincinnati Children’s Hospital Medical CenterOH, United Statesm Division of Respiratory Medicine, Toronto Western Hospital, University Health Network and University of Toronto, Canadan Department of Health and Rehabilitation Sciences, University of Cape Town, South Africao Translational Hearing Center, Biomedical Sciences, Creighton University, Omaha, NE, United Statesp School of Public Health, Oregon Health & Science University, Portland, United Statesq Department of Otolaryngology-Head & Neck Surgery, Division of Audiology, University of California, San Diego, United Statesr Hearing Center of Excellence, Department of Defense, San Antonio, TX, United Statess Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, United States
AbstractPurpose: Specific classes of antibiotics, such as aminoglycosides, have well-established adverse events producing permanent hearing loss, tinnitus, and balance and/or vestibular problems (i.e., ototoxicity). Although these antibiotics are frequently used to treat pseudomonas and other bacterial infections in patients with cystic fibrosis (CF), there are no formalized recommendations describing approaches to implementation of guideline adherent ototoxicity monitoring as part of CF clinical care. Method: This consensus statement was developed by the International Ototoxicity Management Working Group (IOMG) Ad Hoc Committee on Aminoglycoside Antibiotics to address the clinical need for ototoxicity management in CF patients treated with known ototoxic medications. These clinical protocol considerations were created using consensus opinion from a community of international experts and available evidence specific to patients with CF, as well as published national and international guidelines on ototoxicity monitoring. Results: The IOMG advocates four clinical recommendations for implementing routine and guideline adherent ototoxicity management in patients with CF. These are (a) including questions about hearing, tinnitus, and balance/vestibular problems as part of the routine CF case history for all patients; (b) utilizing timely point-of-care measures; (c) establishing a baseline and conducting posttreatment evaluations for each course of intravenous ototoxic drug treatment; and (d) repeating annual hearing and vestibular evaluations for all patients with a history of ototoxic antibiotic exposure. Conclusion: Increased efforts for implementation of an ototoxicity management program in the CF care team model will improve identification of ototoxicity signs and symptoms, allow for timely therapeutic follow-up, and provide the clinician and patient an opportunity to make an informed decision about potential treatment modifications to minimize adverse events. © 2021 American Speech-Language-Hearing Association.
Funding detailsNational Institute on Deafness and Other Communication DisordersNIDCD1R01DC017425, 1R01DC017867, 1R21DC016128-01A1, DC004555, DC016680, ZIA-DC000064Cystic Fibrosis FoundationCFFGARINI1A90National Institute on Handicapped ResearchNIHRNational Institute for Health ResearchNIHRDepartment of Health and Social CareDH
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Pathology Features of Immune and Inflammatory Myopathies, Including a Polymyositis Pattern, Relate Strongly to Serum Autoantibodies” (2021) Journal of Neuropathology and Experimental Neurology
Pathology Features of Immune and Inflammatory Myopathies, Including a Polymyositis Pattern, Relate Strongly to Serum Autoantibodies(2021) Journal of Neuropathology and Experimental Neurology, 80 (9), pp. 812-820.
Pestronk, A.a b , Choksi, R.a
a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United Statesb Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
AbstractWe asked whether myopathology features of immune or inflammatory myopathies (IIM), without reference to clinical or laboratory attributes, correlate with serum autoantibodies. Retrospective study included 148 muscle biopsies with: B-cell inflammatory foci (BIM), myovasculopathy, perimysial pathology (IMPP), myofiber necrosis without perimysial or vessel damage or inflammation (MNec), inflammation and myofiber vacuoles or mitochondrial pathology (IM-VAMP), granulomas, chronic graft-versus-host disease, or none of these criteria. 18 IIM-related serum autoantibodies were tested. Strong associations between myopathology and autoantibodies included: BIM with PM/Scl-100 (63%; odds ratio [OR] = 72); myovasculopathies with TIF1-γ or NXP2 (70%; OR = 72); IMPP with Jo-1 (33%; OR = 28); MNec with SRP54 (23%; OR = 37); IM-VAMP with NT5C1a (95%; OR = 83). Hydroxymethylglutaryl-CoA reductase (HMGCR) antibodies related to presence of myofiber necrosis across all groups (82%; OR = 9), but not to one IIM pathology group. Our results validate characterizations of IIM by myopathology features, showing strong associations with some serum autoantibodies, another objective IIM-related marker. BIM with PM/Scl-100 antibodies can be described pathologically as polymyositis. Tif1-γ and NXP2 antibodies are both common in myovasculopathies. HMGCR antibodies associate with myofiber necrosis, but not one IIM pathology subtype. Relative association strengths of IIM-related autoantibodies to IIM myopathology features versus clinical characteristics require further study. © 2021 American Association of Neuropathologists, Inc. All rights reserved.
Author KeywordsAutoantibodies; B-cells; Immune; Inflammatory; Myopathy; Myositis; Necrosis
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Processing pipeline for image reconstructed fNIRS analysis using both MRI templates and individual anatomy” (2021) Neurophotonics
Processing pipeline for image reconstructed fNIRS analysis using both MRI templates and individual anatomy(2021) Neurophotonics, 8 (2), art. no. 025010, .
Forbes, S.H.a , Wijeakumar, S.b , Eggebrecht, A.T.c , Magnotta, V.A.d , Spencer, J.P.a
a University of East Anglia, School of Psychology, Lawrence Stenhouse Building, Norwich, United Kingdomb University of Nottingham, School of Psychology, University Park, Nottingham, United Kingdomc Washington University, Mallinckrodt Institute of Radiology, St Louis, MO, United Statesd University of Iowa, Department of Radiology, Iowa City, IA, United States
AbstractSignificance: Image reconstruction of fNIRS data is a useful technique for transforming channel-based fNIRS into a volumetric representation and managing spatial variance based on optode location. We present an innovative integrated pipeline for image reconstruction of fNIRS data using either MRI templates or individual anatomy. Aim: We demonstrate a pipeline with accompanying code to allow users to clean and prepare optode location information, prepare and standardize individual anatomical images, create the light model, run the 3D image reconstruction, and analyze data in group space. Approach: We synthesize a combination of new and existing software packages to create a complete pipeline, from raw data to analysis. Results: This pipeline has been tested using both templates and individual anatomy, and on data from different fNIRS data collection systems. We show high temporal correlations between channel-based and image-based fNIRS data. In addition, we demonstrate the reliability of this pipeline with a sample dataset that included 74 children as part of a longitudinal study taking place in Scotland. We demonstrate good correspondence between data in channel space and image reconstructed data. Conclusions: The pipeline presented here makes a unique contribution by integrating multiple tools to assemble a complete pipeline for image reconstruction in fNIRS. We highlight further issues that may be of interest to future software developers in the field. © The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.
Author Keywordsdiffuse optical tomography; functional near infra-red spectroscopy; image reconstruction; individual anatomy
Funding detailsNational Institutes of HealthNIHBill and Melinda Gates FoundationBMGFR01HD083287
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Investigating the Link Between Depression, Cognition, and Motivation in Late Childhood” (2021) Child Psychiatry and Human Development
Investigating the Link Between Depression, Cognition, and Motivation in Late Childhood(2021) Child Psychiatry and Human Development, .
Steinberger, D.C.a c , Barch, D.M.a b
a Department of Psychological & Brain Sciences, Washington University in St. Louis, Saint Louis, MO, United Statesb Department of Psychiatry, Washington University in St. Louis, Saint Louis, MO, United Statesc Somerville, United States
AbstractResearch has revealed broad cognitive deficits (e.g., memory, learning) in depression, and that motivation may account for this link. We tested the state (i.e., only present during depression), trait (i.e., underlying vulnerability) and scar (i.e., lasting corollary) hypotheses of cognitive dysfunction in depression. We additionally tested subjective motivation as a mediator of the concurrent depression-cognition link. In a longitudinal sample of 11,878 children ages 9–11, we found no evidence of a concurrent state or longitudinal trait or scar relationship between depression and cognition. The pattern of depression-cognition relationships—which precluded a mediator analysis—in our childhood sample is a departure from previous studies. Our findings indicate that cognitive deficits are not strongly associated with depression in childhood, in contrast with the impairment commonly seen in older individuals with depression. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Author KeywordsChildren; Cognitive function; Depression; Longitudinal analysis; Motivation
Funding detailsNational Institutes of HealthNIHU01DA041022, U01DA041028, U01DA041048, U01DA041089, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, U24DA041147
Document Type: ArticlePublication Stage: Article in PressSource: Scopus
“Franz Joseph Gall on God and religion: ‘Dieu et Cerveau, rien que Dieu et cerveau!’” (2021) Journal of the History of the Behavioral Sciences
Franz Joseph Gall on God and religion: “Dieu et Cerveau, rien que Dieu et cerveau!”(2021) Journal of the History of the Behavioral Sciences, .
Eling, P.a , Finger, S.b
a Department of Psychology, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlandsb Department of Psychological and Brain Sciences, and Program in History of Medicine, Washington University, St. Louis, MO, United States
AbstractFranz Joseph Gall’s (1758–1828) doctrine of many faculties of mind with corresponding cortical organs led him to be accused of materialism, fatalism, and even atheism. Yet little has been written about the specific charges he felt forced to respond to in Vienna, while visiting the German States, or in Paris, where he published his books. This article examines these accusations and Gall’s responses. It also looks at what Gall wrote about a cortical faculty for God and religion and seeing intelligent design in the functional organization of the brain. Additionally, it presents what can be gleaned about his private thoughts on God and organized religion. We conclude that Gall was sincere in his admiration for and belief in God the Creator, but that as an enlightened scientist was recognizing the need to separate metaphysics from the laws of nature when presenting his new science of man. © 2021 The Authors. Journal of The History of the Behavioral Sciences published by Wiley Periodicals LLC
Author Keywordsfatalism; Franz Joseph Gall; materialism; phrenology; religion
Document Type: ArticlePublication Stage: Article in PressSource: Scopus
“TicTimer Web: software for measuring tic suppression remotely (version 1; peer review: awaiting peer review)” (2021) F1000Research
TicTimer Web: software for measuring tic suppression remotely [version 1; peer review: awaiting peer review](2021) F1000Research, 9, pp. 1-5.
Black, J.K.a , Koller, J.M.b c , Black, K.J.b c d e
a Department of Mechanical Engineering, Brigham Young University, Provo, Utah 84602, United Statesb Department of Psychiatry, Washington University in St. Louis, St. Louis, Missouri 63110, United Statesc Department of Radiology, Washington University in St. Louis, St. Louis, Missouri 63110, United Statesd Department of Neurology, Washington University in St. Louis, St. Louis, Missouri 63110, United Statese Department of Neuroscience, Washington University in St. Louis, St. Louis, Missouri 63110, United States
AbstractWoods and Himle developed a standardized tic suppression paradigm (TSP) for the experimental setting, to quantify the effects of intentional tic suppression in Tourette syndrome. We previously provided a computer program to facilitate recording tic occurrence and to automate reward delivery during the several experimental conditions of the TSP. The present article describes a web-based program that performs the same functions. Implementing this program on the web allows research sessions to be performed remotely, in tandem with a video calling program. Relevant data for each session, such as the timing of tics and dispensed rewards, are stored in plain text files for later analysis. Expected applications include research on Tourette syndrome and related disorders © 2020. Black JK 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 work is properly cited
Author Keywordsreinforcement (psychology); reward; software; tc disorders; Tourette syndrome
Funding detailsNational Institutes of HealthNIHR01MH104030
Document Type: ArticlePublication Stage: FinalSource: Scopus
“Personality Associations With Amyloid and Tau: Results From the Baltimore Longitudinal Study of Aging and Meta-analysis” (2021) Biological Psychiatry
Personality Associations With Amyloid and Tau: Results From the Baltimore Longitudinal Study of Aging and Meta-analysis(2021) Biological Psychiatry, .
Terracciano, A.a c , Bilgel, M.c , Aschwanden, D.a , Luchetti, M.b , Stephan, Y.f , Moghekar, A.R.d , Wong, D.F.e , Ferrucci, L.c , Sutin, A.R.b , Resnick, S.M.c
a Department of Geriatrics, Florida State University College of Medicine, Tallahassee, FL, United Statesb Department of Behavioral Sciences and Social Medicine, Florida State University College of Medicine, Tallahassee, FL, United Statesc Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, United Statesd Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United Statese Department of Radiology, Washington University School of Medicine, St. Louis, MO, United Statesf Euromov, University of Montpellier, Montpellier, France
AbstractBackground: Higher neuroticism and lower conscientiousness are risk factors for Alzheimer’s disease and related dementias, but the underlying neuropathological correlates remain unclear. Our aim was to examine whether personality traits are associated with amyloid and tau neuropathology in a new sample and meta-analyses. Methods: Participants from the BLSA (Baltimore Longitudinal Study of Aging) completed the Revised NEO Personality Inventory and underwent amyloid (11C-labeled Pittsburgh compound B) and tau (18F-flortaucipir) positron emission tomography. Results: Among cognitively normal BLSA participants, neuroticism was associated with higher cortical amyloid burden (odds ratio 1.68, 95% confidence interval 1.20–2.34), and conscientiousness was associated with lower cortical amyloid burden (odds ratio 0.61, 95% confidence interval 0.44–0.86). These associations remained significant after accounting for age, sex, education, depressive symptoms, hippocampal volume, and APOE ε4. Similar associations were found with tau in the entorhinal cortex. Random-effects meta-analyses of 12 studies found that higher neuroticism (N = 3015, r = 0.07, p =.008) and lower conscientiousness (N = 2990, r = −0.11, p <.001) were associated with more amyloid deposition. Meta-analyses of 8 studies found that higher neuroticism (N = 2231, r = 0.15, p <.001) and lower conscientiousness (N = 2206, r = −0.14, p <.001) were associated with more tau pathology. The associations were moderated by cognitive status, with stronger effects in cognitively normal compared with heterogeneous samples, suggesting that the associations between personality and proteopathies are not phenomena that emerge with neuropsychiatric clinical symptoms. Conclusions: By aggregating results across samples, this study advances knowledge on the association between personality and neuropathology. Neuroticism and conscientiousness may contribute to resistance against amyloid and tau neuropathology. © 2021 Society of Biological Psychiatry
Author KeywordsAlzheimer disease; Amyloid; Meta-analysis; Neuropsychiatric disorders; Personality; Tau
Funding detailsNational Institutes of HealthNIHR01AG053297, R01AG068093National Institute on AgingNIA
Document Type: ArticlePublication Stage: Article in PressSource: Scopus
“Apolipoprotein E ɛ4–related effects on cognition are limited to the Alzheimer’s disease spectrum” (2021) GeroScience
Apolipoprotein E ɛ4–related effects on cognition are limited to the Alzheimer’s disease spectrum(2021) GeroScience, .
Fernández, A.a b , Vaquero, L.a b , Bajo, R.c d , Zuluaga, P.c , Weiner, M.W.e , Saykin, A.J.f , Trojanowski, J.Q.g , Shaw, L.h , Toga, A.W.i , Beckett, L.j , Jack, C.R.k , Aisen, P.l , Petersen, R.C.k , Morris, J.C.m , Jagust, W.n , ADNI-Alzheimer’s Disease Neuroimaging Initiativeo
a Legal Medicine, Psychiatry, and Pathology Department, Faculty of Medicine, Complutense University of Madrid, Pza. Ramón Y Cajal, s/n, Ciudad Universitaria, Madrid, 28040, Spainb Laboratory of Cognitive & Computational Neuroscience, Complutense and Polytechnic Universities of Madrid Joint Laboratory, Centre for Biomedical Technology, Pozuelo de Alarcón, Spainc Statistics & Operations Research Department, Faculty of Medicine, Complutense University of Madrid, Madrid, Spaind Electrical Engineering & Bioengineering Group (EE&B), Industrial Engineering Department, University of La Laguna, Tenerife, Spaine University of California San Francisco—School of Medicine, Northern California Institute for research and education, USCF—VA Medical Center, 4150 Clement St., San Fancisco, CA 94,121, United Statesf Center for Neuroimaging, School of Medicine, Indiana University, RADY, Indianapolis, IN GH4324, United Statesg Center for Neurodegenerative Disease Research, School of Medicine, University of Pennsylvania, 3600 Spruce Street, 3d floor Maloney Building, Philadelphia, PA 10,104–4283, United Statesh Hospital of the University of Pennsylvania, Pathology and Laboratory Medicine Dept, 7.103 Founders Pavilion, 3400 Spruce st., Philadelphia, PA 19104, United Statesi USC Institute for Neuroimaging and Neuroinformatics, Keck School of Medicine—University of Southern California, SHN 2025 Zonal Av., Health Sciences Campus, Los Angeles, CA 90,033, United Statesj Department of Public Health Sciences—University of California, Medical Sciences 1-C, One-Shield’s Ave., Davis, CA 95,616, United Statesk Mayo’s Alzheimer’s Disease Research Center—Mayo Clinic, 200 First St. SW, Rochester, MN 55,905, United Statesl Alzheimer’s Therapeutic Research Institute—Keck School of Medicine, University of Southern California, ATRI 9860 Mesa Rim Road, Health Sciences Campus, San Diego, CA 92,121, United Statesm Center for Advanced Medicine—Memory Diagnostic Center, Washington University, 4921 Parkview Place, St Louis, MO 63,110, United Statesn Helen Wills Neuroscience Institute, University of California, 132 Barker Hall, MC#3190, Berkeley, CA 94,720, United States
AbstractWhether the deleterious effects of APOE4 are restricted to the Alzheimer’s disease (AD) spectrum or cause cognitive impairment irrespectively of the development of AD is still a matter of debate, and the focus of this study. Our analyses included APOE4 genotype, neuropsychological variables, amyloid-βeta (Aβ) and Tau markers, FDG-PET values, and hippocampal volumetry data derived from the healthy controls sample of the ADNI database. We formed 4 groups of equal size (n = 30) based on APOE4 carriage and amyloid-PET status. Baseline and follow-up (i.e., 48 months post-baseline) results indicated that Aβ-positivity was the most important factor to explain poorer cognitive performance, while APOE4 only exerted a significant effect in Aβ-positive subjects. Additionally, multiple regression analyses evidenced that, within the Aβ-positive sample, hippocampal volumetry explained most of the variability in cognitive performance for APOE4 carriers. These findings represent a strong support for the so-called preclinical/prodromal hypothesis, which states that the reported differences in cognitive performance between healthy carriers and non-carriers are mainly due to the APOE4’s capability to increase the risk of AD. Moreover, our results reinforce the notion that a synergistic interaction of Aβ and APOE4 elicits a neurodegenerative process in the hippocampus that might be the main cause of impaired cognitive performance. © 2021, The Author(s).
Author KeywordsAmyloid markers; ApoE4; Cognitive deterioration; Cognitive phenotype; Healthy aging; Preclinical and prodromal Alzheimer’s disease
Funding detailsNational Institutes of HealthNIHU01 AG024904U.S. Department of DefenseDODW81XWH-12-2-0012National Institute on AgingNIANational Institute of Biomedical Imaging and BioengineeringNIBIBAlzheimer’s Disease Neuroimaging InitiativeADNI
Document Type: ArticlePublication Stage: Article in PressSource: Scopus
“Pain induces adaptations in ventral tegmental area dopamine neurons to drive anhedonia-like behavior” (2021) Nature Neuroscience
Pain induces adaptations in ventral tegmental area dopamine neurons to drive anhedonia-like behavior(2021) Nature Neuroscience, .
Markovic, T.a b c d , Pedersen, C.E.e f , Massaly, N.a b c , Vachez, Y.M.a b c , Ruyle, B.a b c , Murphy, C.A.a , Abiraman, K.a , Shin, J.H.g , Garcia, J.J.c , Yoon, H.J.a b c , Alvarez, V.A.g , Bruchas, M.R.e f , Creed, M.C.a b c d h i , Morón, J.A.a b c d h
a Department of Anesthesiology, Washington University in St. Louis, St. Louis, MO, United Statesb Pain Center, Washington University in St. Louis, St. Louis, MO, United Statesc School of Medicine, Washington University in St. Louis, St. Louis, MO, United Statesd Department of Neuroscience, Washington University in St. Louis, St. Louis, MO, United Statese Center for the Neurobiology of Addiction, Pain and Emotion, Departments of Anesthesiology and Pharmacology, University of Washington, Seattle, WA, United Statesf Department of Bioengineering, University of Washington, Seattle, WA, United Statesg Laboratory on Neurobiology of Compulsive Behaviors, National Institute on Alcohol Abuse and Alcoholism, Center on Compulsive Behaviors, Intramural Research Program, NIH, Bethesda, MD, United Statesh Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, United Statesi Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States
AbstractThe persistence of negative affect in pain leads to co-morbid symptoms such as anhedonia and depression—major health issues in the United States. The neuronal circuitry and contribution of specific cellular populations underlying these behavioral adaptations remains unknown. A common characteristic of negative affect is a decrease in motivation to initiate and complete goal-directed behavior, known as anhedonia. We report that in rodents, inflammatory pain decreased the activity of ventral tegmental area (VTA) dopamine (DA) neurons, which are critical mediators of motivational states. Pain increased rostromedial tegmental nucleus inhibitory tone onto VTA DA neurons, making them less excitable. Furthermore, the decreased activity of DA neurons was associated with reduced motivation for natural rewards, consistent with anhedonia-like behavior. Selective activation of VTA DA neurons was sufficient to restore baseline motivation and hedonic responses to natural rewards. These findings reveal pain-induced adaptations within VTA DA neurons that underlie anhedonia-like behavior. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
Funding detailsR01-DA049924National Institutes of HealthNIHDA041781, DA041883, DA042499, DA042581, DA045463National Institute on Drug AbuseNIDAR21-DA047127Brain and Behavior Research FoundationBBRF27197Whitehall Foundation2017-12-54Israel National Road Safety AuthorityNRSAF31DA051124National Alliance for Research on Schizophrenia and DepressionNARSAD
Document Type: ArticlePublication Stage: Article in PressSource: Scopus
“Structure of Venezuelan equine encephalitis virus in complex with the LDLRAD3 receptor” (2021) Nature
Structure of Venezuelan equine encephalitis virus in complex with the LDLRAD3 receptor(2021) Nature, 598 (7882), pp. 672-676.
Basore, K.a , Ma, H.b , Kafai, N.M.a b , Mackin, S.a b , Kim, A.S.a b , Nelson, C.A.a , Diamond, M.S.a b c d , Fremont, D.H.a c d e
a Department of Pathology & Immunology, Washington University School of Medicine, St Louis, MO, United Statesb Department of Medicine, Washington University School of Medicine, St Louis, MO, United Statesc Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO, United Statesd The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St Louis, MO, United Statese Department of Biochemistry & Molecular Biophysics, Washington University School of Medicine, St Louis, MO, United States
AbstractLDLRAD3 is a recently defined attachment and entry receptor for Venezuelan equine encephalitis virus (VEEV)1, a New World alphavirus that causes severe neurological disease in humans. Here we present near-atomic-resolution cryo-electron microscopy reconstructions of VEEV virus-like particles alone and in a complex with the ectodomains of LDLRAD3. Domain 1 of LDLRAD3 is a low-density lipoprotein receptor type-A module that binds to VEEV by wedging into a cleft created by two adjacent E2–E1 heterodimers in one trimeric spike, and engages domains A and B of E2 and the fusion loop in E1. Atomic modelling of this interface is supported by mutagenesis and anti-VEEV antibody binding competition assays. Notably, VEEV engages LDLRAD3 in a manner that is similar to the way that arthritogenic alphaviruses bind to the structurally unrelated MXRA8 receptor, but with a much smaller interface. These studies further elucidate the structural basis of alphavirus–receptor interactions, which could inform the development of therapies to mitigate infection and disease against multiple members of this family. © 2021, The Author(s).
Funding detailsNational Institutes of HealthNIHHHSN272201700060C, R01AI164653, T32AI007172
Document Type: ArticlePublication Stage: FinalSource: Scopus