Hope Center member publications

Human cells and networks of pain: Transforming pain target identification and therapeutic development
(2021) Neuron, 109 (9), pp. 1426-1429. 

Renthal, W.^a , Chamessian, A.^b , Curatolo, M.^c , Davidson, S.^d , Burton, M.^e , Dib-Hajj, S.^f g , Dougherty, P.M.^h , Ebert, A.D.ⁱ , Gereau, R.W., IV^b , Ghetti, A.^j , Gold, M.S.^k , Hoben, G.^l , Menichella, D.M.^m , Mercier, P.ⁿ , Ray, W.Z.^o , Salvemini, D.^p , Seal, R.P.^k , Waxman, S.^f g , Woolf, C.J.^q , Stucky, C.L.ⁱ , Price, T.J.^e

^a Department of Neurology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, United States
^b Department of Anesthesiology, Washington University Pain Center, Washington University School of Medicine, St LouisMO 63110, United States
^c Department of Anesthesiology and Pain Medicine, CLEAR Center for Musculoskeletal Disorder, Harborview Injury Prevention and Research Center, University of Washington, Seattle, WA 98195, United States
^d Department of Anesthesiology, University of Cincinnati, College of Medicine, Cincinnati, OH 45267, United States
^e Department of Neuroscience and Center for Advanced Pain Studies, University of Texas at Dallas, Richardson, TX 75080, United States
^f Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, United States
^g Center for Rehabilitation Research, VA Connecticut Healthcare System, West HavenCT 06516, United States
^h Department of Pain Medicine, Division of Anesthesiology and Critical Care, The University of Texas MD Anderson Cancer Center, Houston, TX 78712, United States
ⁱ Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, United States
^j AnaBios Corporation, San Diego, CA 92109, United States
^k Department of Neurobiology, Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, PA 15260, United States
^l Department of Plastic Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, United States
^m Department of Neurology and Pharmacology, Northwestern University Feinberg Medical School, Chicago, IL 60611, United States
ⁿ Department of Neurosurgery and Henry and Amelia Nasrallah Center for Neuroscience, Saint Louis University, St. Louis, MO 63117, United States
^o Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO 63110, United States
^p Department of Pharmacology and Physiology and Henry and Amelia Nasrallah Center for Neuroscience, Saint Louis University, St. Louis, MO 63103, United States
^q F.M. Kirby Neurobiology Center, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, United States

Abstract
Chronic pain is a disabling disease with limited treatment options. While animal models have revealed important aspects of pain neurobiology, therapeutic translation of this knowledge requires our understanding of these cells and networks of pain in humans. We propose a multi-institutional collaboration to rigorously and ethically address this challenge. © 2021 Elsevier Inc.

Funding details
National Center for Advancing Translational SciencesNCATSUG3TR003090
National Institute of Mental HealthNIMHR01AT011447
National Institute of Arthritis and Musculoskeletal and Skin DiseasesNIAMSR01AR077691
National Institute of General Medical SciencesNIGMSR01AR063772
National Institute of Neurological Disorders and StrokeNINDSR01NS107364, R35NS105076, RF1NS113881, R01NS070711, R01NS065926, K08NS101064, R21NS109792, K22NS096030, R37NS108278, R01NS104295
Burroughs Wellcome FundBWF
Migraine Research FoundationMRF
National Institute of Diabetes and Digestive and Kidney DiseasesNIDDKR01DK107966
Merck

Document Type: Article
Publication Stage: Final
Source: Scopus

Cell-type-specific binocular vision guides predation in mice
(2021) Neuron, 109 (9), pp. 1527-1539.e4. Cited 1 time.

Johnson, K.P.^a b , Fitzpatrick, M.J.^a b c , Zhao, L.^a , Wang, B.^a , McCracken, S.^a , Williams, P.R.^a d e , Kerschensteiner, D.^a d e f

^a John F. Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, United States
^b Graduate Program in Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, United States
^c Medical Scientist Training Program, Washington University School of Medicine, St. Louis, MO 63110, United States
^d Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, United States
^e Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, United States
^f Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, MO 63110, United States

Abstract
Predators use vision to hunt, and hunting success is one of evolution’s main selection pressures. However, how viewing strategies and visual systems are adapted to predation is unclear. Tracking predator-prey interactions of mice and crickets in 3D, we find that mice trace crickets with their binocular visual fields and that monocular mice are poor hunters. Mammalian binocular vision requires ipsi- and contralateral projections of retinal ganglion cells (RGCs) to the brain. Large-scale single-cell recordings and morphological reconstructions reveal that only a small subset (9 of 40+) of RGC types in the ventrotemporal mouse retina innervate ipsilateral brain areas (ipsi-RGCs). Selective ablation of ipsi-RGCs (<2% of RGCs) in the adult retina drastically reduces the hunting success of mice. Stimuli based on ethological observations indicate that five ipsi-RGC types reliably signal prey. Thus, viewing strategies align with a spatially restricted and cell-type-specific set of ipsi-RGCs that supports binocular vision to guide predation. © 2021 Elsevier Inc.

Author Keywords
depth perception;  ganglion cell;  hunting;  ipsilateral projection;  prey capture;  retina;  stereopsis

Funding details
Research to Prevent BlindnessRPB
National Institutes of HealthNIHEY030623, EY023341, EY027411, EY026978, EY0268, EY029975

Document Type: Article
Publication Stage: Final
Source: Scopus

Increase in trigeminal ganglion neurons that respond to both calcitonin gene-related peptide and pituitary adenylate cyclase-activating polypeptide in mouse models of chronic migraine and posttraumatic headache
(2021) Pain, 162 (5), pp. 1483-1499. 

Guo, Z., Czerpaniak, K., Zhang, J., Cao, Y.-Q.

Department of Anesthesiology and Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, United States. Dr. Zhang is now with the Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, China

Abstract
A large body of animal and human studies indicates that blocking peripheral calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP) signaling pathways may prevent migraine episodes and reduce headache frequency. To investigate whether recurring migraine episodes alter the strength of CGRP and PACAP signaling in trigeminal ganglion (TG) neurons, we compared the number of TG neurons that respond to CGRP and to PACAP (CGRP-R and PACAP-R, respectively) under normal and chronic migraine-like conditions. In a mouse model of chronic migraine, repeated nitroglycerin (NTG) administration significantly increased the number of CGRP-R and PACAP-R neurons in TG but not dorsal root ganglia. In TG neurons that express endogenous αCGRP, repeated NTG led to a 7-fold increase in the number of neurons that respond to both CGRP and PACAP (CGRP-R&PACAP-R). Most of these neurons were unmyelinated C-fiber nociceptors. This suggests that a larger fraction of CGRP signaling in TG nociceptors may be mediated through the autocrine mechanism, and the release of endogenous αCGRP can be enhanced by both CGRP and PACAP signaling pathways under chronic migraine condition. The number of CGRP-R&PACAP-R TG neurons was also increased in a mouse model of posttraumatic headache (PTH). Interestingly, low-dose interleukin-2 treatment, which completely reverses chronic migraine-related and PTH-related behaviors in mouse models, also blocked the increase in both CGRP-R and PACAP-R TG neurons. Together, these results suggest that inhibition of both CGRP and PACAP signaling in TG neurons may be more effective in treating chronic migraine and PTH than targeting individual signaling pathways. Copyright © 2020 International Association for the Study of Pain.

Document Type: Article
Publication Stage: Final
Source: Scopus

Maschi, D.^a , Gramlich, M.W.^b , Klyachko, V.A.^a

Myosin V Regulates Spatial Localization of Different Forms of Neurotransmitter Release in Central Synapses
(2021) Frontiers in Synaptic Neuroscience, 13, art. no. 650334, . 

^a Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, United States
^b Physics Department, Auburn University, Auburn, AL, United States

Abstract
Synaptic active zone (AZ) contains multiple specialized release sites for vesicle fusion. The utilization of release sites is regulated to determine spatiotemporal organization of the two main forms of synchronous release, uni-vesicular (UVR) and multi-vesicular (MVR). We previously found that the vesicle-associated molecular motor myosin V regulates temporal utilization of release sites by controlling vesicle anchoring at release sites in an activity-dependent manner. Here we show that acute inhibition of myosin V shifts preferential location of vesicle docking away from AZ center toward periphery, and results in a corresponding spatial shift in utilization of release sites during UVR. Similarly, inhibition of myosin V also reduces preferential utilization of central release sites during MVR, leading to more spatially distributed and temporally uniform MVR that occurs farther away from the AZ center. Using a modeling approach, we provide a conceptual framework that unites spatial and temporal functions of myosin V in vesicle release by controlling the gradient of release site release probability across the AZ, which in turn determines the spatiotemporal organization of both UVR and MVR. Thus myosin V regulates both temporal and spatial utilization of release sites during two main forms of synchronous release. © Copyright © 2021 Maschi, Gramlich and Klyachko.

Author Keywords
active zone;  myosin V;  neurotransmitter release;  release probability;  release site;  synaptic transmission;  vesicle docking

Funding details
National Institute of Neurological Disorders and StrokeNINDSR35 NS111596
Center for Cellular Imaging, Washington UniversityWUCCI

Document Type: Article
Publication Stage: Final
Source: Scopus

Anderson, N.C.^a , Chen, P.-F.^a , Meganathan, K.^b , Afshar Saber, W.^a , Petersen, A.J.^c , Bhattacharyya, A.^c d , Kroll, K.L.^b , Sahin, M.^a

Balancing serendipity and reproducibility: Pluripotent stem cells as experimental systems for intellectual and developmental disorders
(2021) Stem Cell Reports, . 

^a Department of Neurology, Rosamund Stone Zander Translational Neuroscience Center, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, United States
^b Department of Developmental Biology, Washington University School of Medicine, Saint Louis, MO 63110, United States
^c Waisman Center, University of Wisconsin, Madison, WI 53705, United States
^d Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, United States

Abstract
Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) and their differentiation into neural lineages is a revolutionary experimental system for studying neurological disorders, including intellectual and developmental disabilities (IDDs). However, issues related to variability and reproducibility have hindered translating preclinical findings into drug discovery. Here, we identify areas for improvement by conducting a comprehensive review of 58 research articles that utilized iPSC-derived neural cells to investigate genetically defined IDDs. Based upon these findings, we propose recommendations for best practices that can be adopted by research scientists as well as journal editors. © 2021 The Authors

Funding details
Novartis
Ipsen Biopharmaceuticals
Pfizer
LAM Therapeutics
Roche
John Merck FundJMF
Tommy Fuss Fund
National Institutes of HealthNIHR01MH124808, P50HD129966, R01NS114551
University of WashingtonUWU54HD090256
R01NS113591, T32MH112510, U54NS092090
National Institute of Neurological Disorders and StrokeNINDS
CDI-LI-2019-819
Intellectual and Developmental Disabilities Research CenterIDDRCU54HD087011, U54HD090255
Institute of Clinical and Translational SciencesICTSR03HD092640, R21NS105339
Fondation Jérôme Lejeune
U01HG007530

Document Type: Review
Publication Stage: Article in Press
Source: Scopus

Wang, C.^a , Xiong, M.^a , Gratuze, M.^a , Bao, X.^a , Shi, Y.^a , Andhey, P.S.^b , Manis, M.^a , Schroeder, C.^c , Yin, Z.^c , Madore, C.^c , Butovsky, O.^c d , Artyomov, M.^b , Ulrich, J.D.^a , Holtzman, D.M.^a

Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia
(2021) Neuron, . 

^a Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer Disease, Research Center, Washington University, St. Louis, MO 63110, United States
^b Department of Pathology and Immunology, Washington University, St. Louis, MO 63110, United States
^c Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, United States
^d Evergrande Center for Immunologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, United States

Abstract
The apolipoprotein E (APOE) gene is the strongest genetic risk factor for Alzheimer’s disease and directly influences tauopathy and tau-mediated neurodegeneration. ApoE4 has strong deleterious effects on both parameters. In the brain, apoE is produced and secreted primarily by astrocytes and by activated microglia. The cell-specific role of each form of apoE in the setting of neurodegeneration has not been determined. We generated P301S Tau/Aldh1l1-CreERT2/apoE3flox/flox or Tau/Aldh1l1-CreERT2/apoE4flox/flox mice. At 5.5 months of age, after the onset of tau pathology, we administered tamoxifen or vehicle and compared mice at 9.5 months of age. Removing astrocytic APOE4 markedly reduced tau-mediated neurodegeneration and decreased phosphorylated tau (pTau) pathology. Single-nucleus RNA sequencing analysis revealed striking gene expression changes in all cell types, with astrocytic APOE4 removal decreasing disease-associated gene signatures in neurons, oligodendrocytes, astrocytes, and microglia. Removal of astrocytic APOE4 decreased tau-induced synaptic loss and microglial phagocytosis of synaptic elements, suggesting a key role for astrocytic apoE in synaptic degeneration. © 2021 Elsevier Inc.

Author Keywords
APOE;  astrocyte;  microglia;  neurodegeneration;  tau

Funding details
Foundation for Barnes-Jewish Hospital3770, 4642
Office of Research Infrastructure Programs, National Institutes of HealthORIP, NIH
Office of Research Infrastructure Programs, National Institutes of HealthORIP, NIHOD021629
Cure Alzheimer’s FundCAF
Alvin J. Siteman Cancer Center
JPB Foundation
CDI-CORE-2019-813, CDI-CORE-2015-505
National Institutes of HealthNIHNS090934, AG054672, NS088137, AG051812, AG047644
National Center for Research ResourcesNCRR
Institute of Clinical and Translational SciencesICTS
Center for Cellular Imaging, Washington UniversityWUCCI
National Cancer InstituteNCIP30 CA91842
Georgia Clinical and Translational Science AllianceGaCTSAUL1TR002345

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

Kafashan, M.^a , Hyche, O.^a , Nguyen, T.^a , Smith, S.K.^a , Guay, C.S.^a , Wilson, E.^a , Labonte, A.K.^a , Guan, M.J.^a f , Lucey, B.P.^b , Ju, Y.-E.S.^b , Palanca, B.J.A.^a c d e

Perioperative sleep in geriatric cardiac surgical patients: a feasibility study using a wireless wearable device
(2021) British Journal of Anaesthesia, . 

^a Department of Anesthesiology, Washington University School of Medicine in St Louis, St Louis, MO, United States
^b Department of Neurology, Washington University School of Medicine in St Louis, St Louis, MO, United States
^c Department of Psychiatry, Washington University School of Medicine in St Louis, St Louis, MO, United States
^d Division of Biology and Biomedical Sciences, Washington University School of Medicine in St Louis, St Louis, MO, United States
^e Department of Biomedical Engineering, Washington University in St Louis, St Louis, MO, United States
^f Kansas City University of Medicine and Biosciences, Kansas City, MO, United States

Author Keywords
cardiac surgery;  electroencephalography;  geriatric;  mobile technology;  non-REM sleep;  perioperative sleep;  REM sleep

Funding details
National Institute on AgingNIA
National Institutes of HealthNIHR01AG057901

Document Type: Letter
Publication Stage: Article in Press
Source: Scopus

Acellular Nerve Allografts in Major Peripheral Nerve Repairs: An Analysis of Cases Presenting With Limited Recovery
(2021) Hand, . 

Peters, B.R.^a b , Wood, M.D.^a , Hunter, D.A.^a , Mackinnon, S.E.^a

^a Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO, United States
^b Division of Plastic and Reconstructive Surgery, Department of Surgery, Oregon Health Science Univeristy, Portland, OR, United States

Abstract
Background: Acellular nerve allografts have been used successfully and with increasing frequency to reconstruct nerve injuries. As their use has been expanded to treat longer gap, larger diameter nerve injuries, some failed cases have been reported. We present the histomorphometry of 5 such cases illustrating these limitations and review the current literature of acellular nerve allografts. Methods: Between 2014 and 2019, 5 patients with iatrogenic nerve injuries to the median or ulnar nerve reconstructed with an AxoGen AVANCE nerve allograft at an outside hospital were treated in our center with allograft excision and alternative reconstruction. These patients had no clinical or electrophysiological evidence of recovery, and allograft specimens at the time of surgery were sent for histomorphological examination. Results: Three patients with a median and 2 with ulnar nerve injury were included. Histology demonstrated myelinated axons present in all proximal native nerve specimens. In 2 cases, axons failed to regenerate into the allograft and in 3 cases, axonal regeneration diminished or terminated within the allograft. Conclusions: The reported cases demonstrate the importance of evaluating the length and the function of nerves undergoing acellular nerve allograft repair. In long length, large-diameter nerves, the use of acellular nerve allografts should be carefully considered. © The Author(s) 2021.

Author Keywords
allograft;  autograft;  basic science;  diagnosis;  nerve;  nerve injury;  nerve reconstruction;  nerve regeneration

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

Central vein sign and other radiographic features distinguishing myelin oligodendrocyte glycoprotein antibody disease from multiple sclerosis and aquaporin-4 antibody-positive neuromyelitis optica
(2021) Multiple Sclerosis Journal, . 

Ciotti, J.R., Eby, N.S., Brier, M.R., Wu, G.F., Chahin, S., Cross, A.H., Naismith, R.T.

Department of Neurology, Washington University in St. Louis, St. Louis, MO, United States

Abstract
Background: Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) can radiographically mimic multiple sclerosis (MS) and aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD). Central vein sign (CVS) prevalence has not yet been well-established in MOGAD. Objective: Characterize the magnetic resonance imaging (MRI) appearance and CVS prevalence of MOGAD patients in comparison to matched cohorts of MS and AQP4+ NMOSD. Methods: Clinical MRIs from 26 MOGAD patients were compared to matched cohorts of MS and AQP4+ NMOSD. Brain MRIs were assessed for involvement within predefined regions of interest. CVS was assessed by overlaying fluid-attenuated inversion recovery (FLAIR) and susceptibility-weighted sequences. Topographic analyses were performed on spinal cord and orbital MRIs when available. Results: MOGAD patients had fewer brain lesions and average CVS+ rate of 12.1%, compared to 44.4% in MS patients (p = 0.0008). MOGAD spinal cord and optic nerve involvement was lengthier than MS (5.8 vs 1.0 vertebral segments, p = 0.020; 3.0 vs 0.5 cm, p < 0.0001). MOGAD patients tended to have bilateral/anterior optic nerve pathology with perineural contrast enhancement, contrasting with posterior optic nerve involvement in NMOSD. Conclusion: CVS+ rate and longer segments of involvement in the spinal cord and optic nerve can differentiate MOGAD from MS, but do not discriminate as well between MOGAD and AQP4+ NMOSD. © The Author(s), 2021.

Author Keywords
central vein sign;  magnetic resonance imaging;  multiple sclerosis;  Myelin oligodendrocyte glycoprotein antibody disease;  neuromyelitis optica spectrum disorder

Funding details
Biogen
National Multiple Sclerosis Society
National Institutes of HealthNIH
Roche

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

MS can be considered a primary progressive disease in all cases, but some patients have superimposed relapses – No
(2021) Multiple Sclerosis Journal, . 

Cross, A.H., Naismith, R.T.

Department of Neurology, Washington University School of Medicine, Saint LouisMO, United States

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

Measures of resting state EEG rhythms for clinical trials in Alzheimer’s disease: Recommendations of an expert panel
(2021) Alzheimer’s and Dementia, . 

Babiloni, C.^a b , Arakaki, X.^c , Azami, H.^d , Bennys, K.^e , Blinowska, K.^f g , Bonanni, L.^h , Bujan, A.ⁱ , Carrillo, M.C.^j , Cichocki, A.^k l m , de Frutos-Lucas, J.ⁿ , Del Percio, C.^a , Dubois, B.^o p , Edelmayer, R.^j , Egan, G.^q , Epelbaum, S.^o p , Escudero, J.^r , Evans, A.^s , Farina, F.^t , Fargo, K.^j , Fernández, A.ⁿ , Ferri, R.^u , Frisoni, G.^v w , Hampel, H.^x , Harrington, M.G.^c , Jelic, V.^y , Jeong, J.^z , Jiang, Y.^aa , Kaminski, M.^g , Kavcic, V.^ab , Kilborn, K.^ac , Kumar, S.^ad , Lam, A.^ae , Lim, L.^af , Lizio, R.^ag , Lopez, D.ⁿ , Lopez, S.^a , Lucey, B.^ah , Maestú, F.ⁿ , McGeown, W.J.^ai , McKeith, I.^aj , Moretti, D.V.^v , Nobili, F.^ak al , Noce, G.^ag , Olichney, J.^am , Onofrj, M.^h , Osorio, R.^an , Parra-Rodriguez, M.^ai , Rajji, T.^ad , Ritter, P.^ao ap , Soricelli, A.^ag aq , Stocchi, F.^ar , Tarnanas, I.^as at , Taylor, J.P.^aj , Teipel, S.^au av , Tucci, F.^a , Valdes-Sosa, M.^aw , Valdes-Sosa, P.^aw ax , Weiergräber, M.^ay , Yener, G.^az , Guntekin, B.^ba bb

^a Department of Physiology and Pharmacology “Vittorio Erspamer”, Sapienza University of Rome, Rome, Italy
^b San Raffaele of Cassino, Cassino (FR), Italy
^c Huntington Medical Research Institutes, Pasadena, CA, United States
^d Department of Neurology and Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States
^e Centre Mémoire de Ressources et de Recherche (CMRR), Centre Hospitalier, Universitaire de Montpellier, Montpellier, France
^f Institute of BiocyberneticsWarsaw, Poland
^g Faculty of Physics University of Warsaw and Nalecz, Warsaw, Poland
^h Department of Neuroscience Imaging and Clinical Sciences and CESI, University “G. D’Annunzio” of Chieti-Pescara, Chieti, Italy
ⁱ Psychological Neuroscience Lab, School of Psychology, University of Minho, Minho, Portugal
^j Division of Medical & Scientific Relations, Alzheimer’s Association, Chicago, IL, United States
^k Skolkowo Institute of Science and Technology (SKOLTECH)Moscow, Russian Federation
^l Systems Research Institute PASWarsaw, Poland
^m Nicolaus Copernicus University (UMK), Torun, Poland
ⁿ Laboratory of Cognitive and Computational Neuroscience, Center for Biomedical Technology, Universidad Complutense and Universidad Politécnica de Madrid, Madrid, Spain
^o Department of Neurology, Pitié-Salpêtrière Hospital, AP-HP, Boulevard de l’hôpital, Institute of Memory and Alzheimer’s Disease (IM2A), Paris, France
^p ICM, INSERM U1127, CNRS UMR 7225, Sorbonne Université, Institut du Cerveau et de la Moelle épinière, Paris, France
^q Foundation Director of the Monash Biomedical Imaging (MBI) Research Facilities, Monash University, Clayton, Australia
^r School of Engineering, Institute for Digital Communications, The University of Edinburgh, Edinburgh, United Kingdom
^s Department of Neurology and Neurosurgery, McGill University, Montreal, Canada
^t Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland
^u Oasi Research Institute – IRCCS, Troina, Italy
^v IRCCS San Giovanni di Dio Fatebenefratelli, Brescia, Italy
^w Memory Clinic and LANVIE – Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland
^x GRC n° 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l’hôpital, Sorbonne University, Paris, France
^y Division of Clinical Geriatrics, NVS Department, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
^z Department of Bio and Brain Engineering/Program of Brain and Cognitive Engineering Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea
^aa Department of Behavioral Science, College of Medicine, University of Kentucky, Lexington, KY, United States
^ab Institute of Gerontology, Wayne State University, Detroit, MI, United States
^ac School of Psychology, University of Glasgow, Glasgow, United Kingdom
^ad Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, ON, Canada
^ae MGH Epilepsy Service, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
^af Vielight Inc., Toronto, ON, Canada
^ag IRCCS SDN, Napoli, Italy
^ah Washington University School of Medicine in St. Louis, St. Louis, MO, United States
^ai School of Psychological Sciences and Health, University of Strathclyde, Glasgow, United Kingdom
^aj Newcastle upon Tyne, Translational and Clinical Research Institute, Newcastle University, United Kingdom
^ak Department of Neuroscience (DINOGMI), University of Genoa, Genoa, Italy
^al Clinica Neurologica, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
^am UC Davis Department of Neurology and Center for Mind and Brain, Davis, CA, United States
^an Center for Brain Health, Department of Psychiatry, NYU Langone Medical Center, New York, NY, United States
^ao Brain Simulation Section, Department of Neurology, Charité Universitätsmedizin and Berlin Institute of Health, Berlin, Germany
^ap Bernstein Center for Computational Neuroscience, Berlin, Germany
^aq Department of Motor Sciences and Healthiness, University of Naples Parthenope, Naples, Italy
^ar IRCCS San Raffaele Pisana, Rome, Italy
^as Global Brain Health Institute, University of California San Francisco, San Francisco, United States
^at Global Brain Health Institute, Trinity College Dublin, Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland
^au Department of Psychosomatic Medicine, University of Rostock, Rostock, Germany
^av German Center for Neurodegenerative Diseases (DZNE) – Rostock/Greifswald, Rostock, Germany
^aw Cuban Neuroscience Center, Havana, Cuba
^ax Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China
^ay Experimental Neuropsychopharmacology, BfArM), Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, Bonn, Germany
^az Departments of Neurosciences and Department of Neurology, Dokuz Eylül University Medical School, Izmir, Turkey
^ba Department of Biophysics, School of Medicine, Istanbul Medipol University, Istanbul, Turkey
^bb REMER, Clinical Electrophysiology, Neuroimaging and Neuromodulation Lab, Istanbul Medipol University, Istanbul, Turkey

Abstract
The Electrophysiology Professional Interest Area (EPIA) and Global Brain Consortium endorsed recommendations on candidate electroencephalography (EEG) measures for Alzheimer’s disease (AD) clinical trials. The Panel reviewed the field literature. As most consistent findings, AD patients with mild cognitive impairment and dementia showed abnormalities in peak frequency, power, and “interrelatedness” at posterior alpha (8-12 Hz) and widespread delta (< 4 Hz) and theta (4-8 Hz) rhythms in relation to disease progression and interventions. The following consensus statements were subscribed: (1) Standardization of instructions to patients, resting state EEG (rsEEG) recording methods, and selection of artifact-free rsEEG periods are needed; (2) power density and “interrelatedness” rsEEG measures (e.g., directed transfer function, phase lag index, linear lagged connectivity, etc.) at delta, theta, and alpha frequency bands may be use for stratification of AD patients and monitoring of disease progression and intervention; and (3) international multisectoral initiatives are mandatory for regulatory purposes. © 2021 the Alzheimer’s Association

Author Keywords
Alzheimer’s disease;  biomarkers;  clinical trials;  dementia;  electroencephalography (EEG);  eyes-closed resting state condition;  The Alzheimer’s Association International Society to Advance Alzheimer’s Research and Treatment (ISTAART)

Funding details
European CommissionEC
785907, 945539, 826421, ERC 683049
Deutsche ForschungsgemeinschaftDFGCRC 1315, RI 2073/6‐1, CRC 936
National Institute on AgingNIAK76 AG054863

Document Type: Review
Publication Stage: Article in Press
Source: Scopus