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Screening for Alzheimer’s disease: plasma biomarkers and what else?
Masud Husain
doi : 10.1093/brain/awac490
Brain, Volume 146, Issue 2, February 2023, Pages 407–408
When the sun rises
Karen Grazionale
doi : 10.1093/brain/awac447
Brain, Volume 146, Issue 2, February 2023, Pages 409–410
Third-generation computational approaches for genetic variant interpretation
Gregory Costain, Danielle M Andrade
doi : 10.1093/brain/awad011
Brain, Volume 146, Issue 2, February 2023, Pages 411–412
Untangling white matter fibre changes in Alzheimer's disease and small vessel disease
Elouise A Koops, Heidi I L Jacobs
doi : 10.1093/brain/awac493
Brain, Volume 146, Issue 2, February 2023, Pages 413–415,
Mechanisms underlying apathy in frontotemporal dementia
Masud Husain
doi : 10.1093/brain/awac494
Brain, Volume 146, Issue 2, February 2023, Pages 416–417
SARS-CoV-2 targets pericytes to restrict blood flow within the brain
J Scott Miners, Robert A Fisher, Seth Love
doi : 10.1093/brain/awac481
Brain, Volume 146, Issue 2, February 2023, Pages 418–420
The multifaceted role of neurofilament light chain protein in non-primary neurological diseases
Samir Abu-Rumeileh, Ahmed Abdelhak, Matteo Foschi, Lucio D'Anna, Michele Russo, Petra Steinacker, Jens Kuhle, Hayrettin Tumani, Kaj Blennow, Markus Otto
doi : 10.1093/brain/awac328
Brain, Volume 146, Issue 2, February 2023, Pages 421–437
The advancing validation and exploitation of CSF and blood neurofilament light chain protein as a biomarker of neuroaxonal damage has deeply changed the current diagnostic and prognostic approach to neurological diseases.
Common neural substrates of diverse neurodevelopmental disorders
H Moriah Sokolowski, Brian Levine
doi : 10.1093/brain/awac387
Brain, Volume 146, Issue 2, February 2023, Pages 438–447
Neurodevelopmental disorders are categorized and studied according to their manifestations as distinct syndromes. For instance, congenital prosopagnosia and dyslexia have largely non-overlapping research literatures and clinical pathways for diagnosis and intervention.
MNK1/2 contributes to periorbital hypersensitivity and hyperalgesic priming in preclinical migraine models
Jacob Lackovic, Theodore J Price, Gregory Dussor
doi : 10.1093/brain/awac386
Brain, Volume 146, Issue 2, February 2023, Pages 448–454
Migraine is thought to involve sensitization of the trigeminal nociceptive system. In preclinical pain models, activation of MNK-eIF4E signalling contributes to nociceptor sensitization and the development of persistent pain.
The top 10 most frequently involved genes in hereditary optic neuropathies in 2186 probands
Aude Rocatcher, Valérie Desquiret-Dumas, Majida Charif, Marc Ferré, Philippe Gohier, Delphine Mirebeau-Prunier, Christophe Verny, Dan Milea, Guy Lenaers, HON Collaborators Group , Dominique Bonneau, Pascal Reynier, Patrizia Amati-Bonneau
doi : 10.1093/brain/awac395
Brain, Volume 146, Issue 2, February 2023, Pages 455–460
Hereditary optic neuropathies are caused by the degeneration of retinal ganglion cells whose axons form the optic nerves, with a consistent genetic heterogeneity
Venglustat combined with imiglucerase for neurological disease in adults with Gaucher disease type 3: the LEAP trial
Raphael Schiffmann, Timothy M Cox, Jean-François Dedieu, Sebastiaan J M Gaemers, Julia B Hennermann, Hiroyuki Ida, Eugen Mengel, Pascal Minini, Pramod Mistry, Petra B Musholt, David Scott, Jyoti Sharma, M Judith Peterschmitt
doi : 10.1093/brain/awac379
Brain, Volume 146, Issue 2, February 2023, Pages 461–474
Gaucher disease type 3 is a chronic neuronopathic disorder with wide-ranging effects, including hepatosplenomegaly, anaemia, thrombocytopenia, skeletal disease and diverse neurological manifestations.
TRPA1 modulation by Sigma-1 receptor prevents oxaliplatin-induced painful peripheral neuropathy
Aida Marcotti, Jorge Fernández-Trillo, Alejandro González, Marta VizcaÃno-Escoto, Pablo Ros-Arlanzón, Luz Romero, José Miguel Vela, Ana Gomis, Félix Viana, Elvira de la Peña
doi : 10.1093/brain/awac273
Brain, Volume 146, Issue 2, February 2023, Pages 475–491
Chemotherapy-induced peripheral neuropathy is a frequent, disabling side effect of anticancer drugs. Oxaliplatin, a platinum compound used in the treatment of advanced colorectal cancer, often leads to a form of chemotherapy-induced peripheral neuropathy characterized by mechanical and cold hypersensitivity.
Epigenetic and integrative cross-omics analyses of cerebral white matter hyperintensities on MRI
Yunju Yang, Maria J Knol, Ruiqi Wang, Aniket Mishra, Dan Liu, Michelle Luciano, Alexander Teumer, Nicola Armstrong, Joshua C Bis, Min A Jhun, Shuo Li, Hieab H H Adams, Nasir Ahmad Aziz, Mark E Bastin, Mathieu Bourgey, Jennifer A Brody, Stefan Frenzel, Rebecca F Gottesman, Norbert Hosten, Lifang Hou, Sharon L R Kardia, Valerie Lohner, Pascale Marquis, Susana Muñoz Maniega, Claudia L Satizabal, Farzaneh A Sorond, Maria C Valdés Hernández, Cornelia M van Duijn, Meike W Vernooij, Katharina Wittfeld, Qiong Yang, Wei Zhao, Eric Boerwinkle, Daniel Levy, Ian J Deary, Jiyang Jiang, Karen A Mather, Thomas H Mosley, Bruce M Psaty, Perminder S Sachdev, Jennifer A Smith, Nona Sotoodehnia, Charles S DeCarli, Monique M B Breteler, M Arfan Ikram, Hans J Grabe, Joanna Wardlaw, W T Longstreth, Lenore J Launer, Sudha Seshadri, Stephanie Debette, Myriam Fornage
doi : 10.1093/brain/awac290
Brain, Volume 146, Issue 2, February 2023, Pages 492–506
Cerebral white matter hyperintensities on MRI are markers of cerebral small vessel disease, a major risk factor for dementia and stroke. Despite the successful identification of multiple genetic variants associated with this highly heritable condition, its genetic architecture remains incompletely understood.
Aberrant splicing of PSEN2, but not PSEN1, in individuals with sporadic Alzheimer’s disease
Meredith M Course, Kathryn Gudsnuk, C Dirk Keene, Thomas D Bird, Suman Jayadev, Paul N Valdmanis
doi : 10.1093/brain/awac294
Brain, Volume 146, Issue 2, February 2023, Pages 507–518
Alzheimer’s disease is the most common neurodegenerative disease, characterized by dementia and premature death. Early-onset familial Alzheimer’s disease is caused in part by pathogenic variants in presenilin 1 (PSEN1) and presenilin 2 (PSEN2), and alternative splicing of these two genes has been implicated in both familial and sporadic Alzheimer’s disease
Delineation of functionally essential protein regions for 242 neurodevelopmental genes
Sumaiya Iqbal, Tobias Brünger, Eduardo Pérez-Palma, Marie Macnee, Andreas Brunklaus, Mark J Daly, Arthur J Campbell, David Hoksza, Patrick May, Dennis Lal
doi : 10.1093/brain/awac381
Brain, Volume 146, Issue 2, February 2023, Pages 519–533
Neurodevelopmental disorders (NDDs), including severe paediatric epilepsy, autism and intellectual disabilities are heterogeneous conditions in which clinical genetic testing can often identify a pathogenic variant.
CAPRIN1 haploinsufficiency causes a neurodevelopmental disorder with language impairment, ADHD and ASD
Lisa Pavinato, Andrea Delle Vedove, Diana Carli, Marta Ferrero, Silvia Carestiato, Jennifer L Howe, Emanuele Agolini, Domenico A Coviello, Ingrid van de Laar, Ping Yee Billie Au, Eleonora Di Gregorio, Alessandra Fabbiani, Susanna Croci, Maria Antonietta Mencarelli, Lucia P Bruno, Alessandra Renieri, Danai Veltra, Christalena Sofocleous, Laurence Faivre, Benoit Mazel, Hana Safraou, Anne-Sophie Denommé-Pichon, Marjon A van Slegtenhorst, Noor Giesbertz, Richard H van Jaarsveld, Anna Childers, R Curtis Rogers, Antonio Novelli, Silvia De Rubeis, Joseph D Buxbaum, Stephen W Scherer, Giovanni Battista Ferrero, Brunhilde Wirth, Alfredo Brusco
doi : 10.1093/brain/awac278
Brain, Volume 146, Issue 2, February 2023, Pages 534–548
We describe an autosomal dominant disorder associated with loss-of-function variants in the Cell cycle associated protein 1 (CAPRIN1; MIM*601178). CAPRIN1 encodes a ubiquitous protein that regulates the transport and translation of neuronal mRNAs critical for synaptic plasticity, as well as mRNAs encoding proteins important for cell proliferation and migration in multiple cell types.
‘Hippocampal innate inflammatory gliosis only’ in pharmacoresistant temporal lobe epilepsy
Alexander Grote, Dieter-Henrik Heiland, Julia Taube, Christoph Helmstaedter, Vidhya M Ravi, Paulina Will, Elke Hattingen, Jan-Rüdiger Schüre, Juri-Alexander Witt, Annika Reimers, Christian Elger, Johannes Schramm, Albert J Becker, Daniel Delev
doi : 10.1093/brain/awac293
Brain, Volume 146, Issue 2, February 2023, Pages 549–560
Drug-resistant mesial-temporal lobe epilepsy is a devastating disease with seizure onset in the hippocampal formation. A fraction of hippocampi samples from epilepsy-surgical procedures reveals a peculiar histological pattern referred to as ‘gliosis only’ with unresolved pathogenesis and enigmatic sequelae.
Local neuronal excitation and global inhibition during epileptic fast ripples in humans
Jonathan Curot, Emmanuel Barbeau, Elodie Despouy, Marie Denuelle, Jean Christophe Sol, Jean-Albert Lotterie, Luc Valton, Adrien Peyrache
doi : 10.1093/brain/awac319
Brain, Volume 146, Issue 2, February 2023, Pages 561–575
Understanding the neuronal basis of epileptic activity is a major challenge in neurology. Cellular integration into larger scale networks is all the more challenging. In the local field potential, interictal epileptic discharges can be associated with fast ripples (200–600 Hz), which are a promising marker of the epileptogenic zone.
Local brain environment changes associated with epileptogenesis
Yoko Ikoma, Daichi Sasaki, Ko Matsui
doi : 10.1093/brain/awac355
Brain, Volume 146, Issue 2, February 2023, Pages 576–586
Plastic change of the neuronal system has traditionally been assumed to be governed primarily by the long-term potentiation/depression mechanisms of synaptic transmission. However, a rather simple shift in the ambient ion, transmitter and metabolite concentrations could have a pivotal role in generating plasticity upon the physiological process of learning and memory.
Epilepsy syndromes in cerebral palsy: varied, evolving and mostly self-limited
Monica S Cooper, Mark T Mackay, Charuta Dagia, Michael C Fahey, Katherine B Howell, Dinah Reddihough, Susan Reid, A Simon Harvey
doi : 10.1093/brain/awac274
Brain, Volume 146, Issue 2, February 2023, Pages 587–599
Seizures occur in approximately one-third of children with cerebral palsy. This study aimed to determine epilepsy syndromes in children with seizures and cerebral palsy due to vascular injury, anticipating that this would inform treatment and prognosis.
Clinical, serological and genetic predictors of response to immunotherapy in anti-IgLON5 disease
Thomas Grüter, Franziska E Möllers, Anja Tietz, Justina Dargvainiene, Nico Melzer, Anna Heidbreder, Christine Strippel, Andrea Kraft, Romana Höftberger, Florian Schöberl, Franziska S Thaler, Jonathan Wickel, Ha-Yeun Chung, Frank Seifert, Marlene Tschernatsch, Michael Nagel, Jan Lewerenz, Sven Jarius, Brigitte C Wildemann, Lucie de Azevedo, Fedor Heidenreich, Raphaela Heusgen, Ulrich Hofstadt-van Oy, Andreas Linsa, Jannis Justus Maaß, Til Menge, Marius Ringelstein, David J Pedrosa, Josef Schill, Thomas Seifert-Held, Caspar Seitz, Silke Tonner, Christian Urbanek, Simone Zittel, Robert Markewitz, Mirjam Korporal-Kuhnke, Thomas Schmitter, Carsten Finke, Norbert Brüggemann, Corinna I Bien, Ingo Kleiter, Ralf Gold, Klaus-Peter Wandinger, Gregor Kuhlenbäumer, Frank Leypoldt, Ilya Ayzenberg, for the German Network for Research on Autoimmune Encephalitis (GENERATE)
doi : 10.1093/brain/awac090
Brain, Volume 146, Issue 2, February 2023, Pages 600–611
Anti-IgLON5 disease is a newly defined clinical entity characterized by a progressive course with high disability and mortality rate. While precise pathogenetic mechanisms remain unclear, features characteristic of both autoimmune and neurodegenerative diseases were reported.
Functional reconstruction of the basal ganglia neural circuit by human striatal neurons in hypoxic–ischaemic injured brain
Xiaoli Ji, Yingying Zhou, Qinqin Gao, Hui He, Ziyan Wu, Ban Feng, Yuting Mei, Yan Cheng, Wenhao Zhou, Yuejun Chen, Man Xiong
doi : 10.1093/brain/awac358
Brain, Volume 146, Issue 2, February 2023, Pages 612–628
Perinatal hypoxic–ischaemic encephalopathy is the leading cause of neonatal death and permanent neurological deficits, while the basal ganglia is one of the major nuclei that is selectively and greatly affected in the brains of hypoxic–ischaemic encephalopathy patients, especially in severe cases.
Shh activation restores interneurons and cognitive function in newborns with intraventricular haemorrhage
Bokun Cheng, Deep R Sharma, Ajeet Kumar, Hardik Sheth, Alex Agyemang, Michael Aschner, Xusheng Zhang, Praveen Ballabh
doi : 10.1093/brain/awac271
Brain, Volume 146, Issue 2, February 2023, Pages 629–644
Premature infants with germinal matrix haemorrhage–intraventricular haemorrhage (GMH-IVH) suffer from neurobehavioural deficits as they enter childhood and adolescence.
Polygenic risk score association with multiple sclerosis susceptibility and phenotype in Europeans
Hengameh Shams, Xiaorong Shao, Adam Santaniello, Gina Kirkish, Adil Harroud, Qin Ma, Noriko Isobe, University of California San Francisco MS-EPIC Team , Catherine A Schaefer, Jacob L McCauley, Bruce A C Cree, Alessandro Didonna, Sergio E Baranzini, Nikolaos A Patsopoulos, Stephen L Hauser, Lisa F Barcellos, Roland G Henry, Jorge R Oksenberg
doi : 10.1093/brain/awac092
Brain, Volume 146, Issue 2, February 2023, Pages 645–656
Polygenic inheritance plays a pivotal role in driving multiple sclerosis susceptibility, an inflammatory demyelinating disease of the CNS. We developed polygenic risk scores (PRS) of multiple sclerosis and assessed associations with both disease status and severity in cohorts of European descent.
Distinct movement disorders in contactin-associated-protein-like-2 antibody-associated autoimmune encephalitis
Felix Gövert, Ligia Abrante, Jos Becktepe, Bettina Balint, Christos Ganos, Ulrich Hofstadt-van Oy, Christos Krogias, James Varley, Sarosh R Irani, Sofija Paneva, Maarten J Titulaer, Juna M de Vries, Agnita J W Boon, Marco W J Schreurs, Bastien Joubert, Jerome Honnorat, Alberto Vogrig, Helena Ariño, Lidia Sabater, Josep Dalmau, Sangeeta Scotton, Saiju Jacob, Nico Melzer, Christian G Bien, Christian Geis, Jan Lewerenz, Harald Prüss, Klaus-Peter Wandinger, Günther Deuschl, Frank Leypoldt on behalf of the GENERATE Investigators
doi : 10.1093/brain/awac276
Brain, Volume 146, Issue 2, February 2023, Pages 657–667
Autoimmune encephalitis can be classified into antibody-defined subtypes, which can manifest with immunotherapy-responsive movement disorders sometimes mimicking non-inflammatory aetiologies. In the elderly, anti-LGI1 and contactin associated protein like 2 (CASPR2) antibody-associated diseases compose a relevant fraction of autoimmune encephalitis.
Effect of nusinersen on motor, respiratory and bulbar function in early-onset spinal muscular atrophy
Astrid Pechmann, Max Behrens, Katharina Dörnbrack, Adrian Tassoni, Sabine Stein, Sibylle Vogt, Daniela Zöller, Günther Bernert, Tim Hagenacker, Ulrike Schara-Schmidt, Inge Schwersenz, Maggie C Walter, Matthias Baumann, Manuela Baumgartner, Marcus Deschauer, Astrid Eisenkölbl, Marina Flotats-Bastardas, Andreas Hahn, Veronka Horber, Ralf A Husain, Sabine Illsinger, Jessika Johannsen, Cornelia Köhler, Heike Kölbel, Monika Müller, Arpad von Moers, Kurt Schlachter, Gudrun Schreiber, Oliver Schwartz, Martin Smitka, Elisabeth Steiner, Eva Stögmann, Regina Trollmann, Katharina Vill, Claudia Weiß, Gert Wiegand, Andreas Ziegler, Hanns Lochmüller, Janbernd Kirschner, the SMArtCARE study group
doi : 10.1093/brain/awac252
Brain, Volume 146, Issue 2, February 2023, Pages 668–677
5q-associated spinal muscular atrophy is a rare neuromuscular disorder with the leading symptom of a proximal muscle weakness. Three different drugs have been approved by the European Medicines Agency and Food and Drug Administration for the treatment of spinal muscular atrophy patients, however, long-term experience is still scarce.
Disentangling the effects of Alzheimer’s and small vessel disease on white matter fibre tracts
Anna Dewenter, Mina A Jacob, Mengfei Cai, Benno Gesierich, Paul Hager, Anna Kopczak, Davina Biel, Michael Ewers, Anil M Tuladhar, Frank-Erik de Leeuw, Martin Dichgans, Nicolai Franzmeier, Marco Duering, for the SVDs@target Consortium and Alzheimer’s Disease Neuroimaging Initiative (ADNI)
doi : 10.1093/brain/awac265
Brain, Volume 146, Issue 2, February 2023, Pages 678–689
Alzheimer’s disease and cerebral small vessel disease are the two leading causes of cognitive decline and dementia and coexist in most memory clinic patients. White matter damage as assessed by diffusion MRI is a key feature in both Alzheimer’s and cerebral small vessel disease.
Plasma biomarkers and genetics in the diagnosis and prediction of Alzheimer’s disease
Joshua Stevenson-Hoare, Amanda Heslegrave, Ganna Leonenko, Dina Fathalla, Eftychia Bellou, Lauren Luckcuck, Rachel Marshall, Rebecca Sims, Bryan Paul Morgan, John Hardy, Bart de Strooper, Julie Williams, Henrik Zetterberg, Valentina Escott-Price
doi : 10.1093/brain/awac128
Brain, Volume 146, Issue 2, February 2023, Pages 690–699
Plasma biomarkers for Alzheimer’s disease-related pathologies have undergone rapid developments during the past few years, and there are now well-validated blood tests for amyloid and tau pathology, as well as neurodegeneration and astrocytic activation.
Tau positron emission tomography in preclinical Alzheimer’s disease
doi : 10.1093/brain/awac299
Brain, Volume 146, Issue 2, February 2023, Pages 700–711
Rates of tau accumulation in cognitively unimpaired older adults are subtle, with magnitude and spatial patterns varying in recent reports. Regional accumulation also likely varies in the degree to which accumulation is amyloid-β-dependent. Thus, there is a need to evaluate the pattern and consistency of tau accumulation across multiple cognitively unimpaired cohorts and how these patterns relate to amyloid burden, in order to design optimal tau end points for clinical trials.
Effort avoidance as a core mechanism of apathy in frontotemporal dementia
Raphaël Le Bouc, Nicolas Borderies, Guilhem Carle, Chloé Robriquet, Fabien Vinckier, Jean Daunizeau, Carole Azuar, Richard Levy, Mathias Pessiglione
doi : 10.1093/brain/awac427
Brain, Volume 146, Issue 2, February 2023, Pages 712–726
Apathy is a core symptom in patients with behavioural variant frontotemporal dementia (bvFTD). It is defined by the observable reduction in goal-directed behaviour, but the underlying mechanisms are poorly understood.
SARS-CoV-2 triggers pericyte-mediated cerebral capillary constriction
Chanawee Hirunpattarasilp, Greg James, Jaturon Kwanthongdee, Felipe Freitas, Jiandong Huo, Huma Sethi, Josef T Kittler, Raymond J Owens, Laura E McCoy, David Attwell
doi : 10.1093/brain/awac272
Brain, Volume 146, Issue 2, February 2023, Pages 727–738
The SARS-CoV-2 receptor, ACE2, is found on pericytes, contractile cells enwrapping capillaries that regulate brain, heart and kidney blood flow. ACE2 converts vasoconstricting angiotensin II into vasodilating angiotensin-(1-7).
COVID-19 vaccination and Guillain-Barré syndrome: analyses using the National Immunoglobulin Database
Ryan Y S Keh, Sophie Scanlon, Preeti Datta-Nemdharry, Katherine Donegan, Sally Cavanagh, Mark Foster, David Skelland, James Palmer, Pedro M Machado, Stephen Keddie, Aisling S Carr, Michael P Lunn, BPNS/ABN COVID-19 Vaccine GBS Study Group
doi : 10.1093/brain/awac067
Brain, Volume 146, Issue 2, February 2023, Pages 739–748
Vaccination against viruses has rarely been associated with Guillain-Barré syndrome (GBS), and an association with the COVID-19 vaccine is unknown. We performed a population-based study of National Health Service data in England and a multicentre surveillance study from UK hospitals to investigate the relationship between COVID-19 vaccination and GBS.
RNA profiling of human dorsal root ganglia reveals sex differences in mechanisms promoting neuropathic pain
Pradipta R Ray, Stephanie Shiers, James P Caruso, Diana Tavares-Ferreira, Ishwarya Sankaranarayanan, Megan L Uhelski, Yan Li, Robert Y North, Claudio Tatsui, Gregory Dussor, Michael D Burton, Patrick M Dougherty, Theodore J Price
doi : 10.1093/brain/awac266
Brain, Volume 146, Issue 2, February 2023, Pages 749–766
Neuropathic pain is a leading cause of high-impact pain, is often disabling and is poorly managed by current therapeutics.
Negative symptoms, striatal dopamine and model-free reward decision-making in schizophrenia
Felix Brandl, Franziska Knolle, Mihai Avram, Claudia Leucht, Igor Yakushev, Josef Priller, Stefan Leucht, Sibylle Ziegler, Klaus Wunderlich, Christian Sorg
doi : 10.1093/brain/awac268
Brain, Volume 146, Issue 2, February 2023, Pages 767–777
Negative symptoms, such as lack of motivation or social withdrawal, are highly prevalent and debilitating in patients with schizophrenia. Underlying mechanisms of negative symptoms are incompletely understood, thereby preventing the development of targeted treatments.
Auditory stimulation and deep learning predict awakening from coma after cardiac arrest
Florence M Aellen, Sigurd L Alnes, Fabian Loosli, Andrea O Rossetti, Frédéric Zubler, Marzia De Lucia, Athina Tzovara
doi : 10.1093/brain/awac340
Brain, Volume 146, Issue 2, February 2023, Pages 778–788
Assessing the integrity of neural functions in coma after cardiac arrest remains an open challenge. Prognostication of coma outcome relies mainly on visual expert scoring of physiological signals, which is prone to subjectivity and leaves a considerable number of patients in a ‘grey zone’, with uncertain prognosis.
The importance of collaboration in neuroscience
Richard E Brown
doi : 10.1093/brain/awac423
Brain, Volume 146, Issue 2, February 2023, Pages 789–790
Correction to: Multi-method investigation of factors influencing amyloid onset and impairment in three cohorts
doi : 10.1093/brain/awac390
Brain, Volume 146, Issue 2, February 2023, Page e11
Correction to: The lower motor neuron homunculus
doi : 10.1093/brain/awac383
Brain, Volume 146, Issue 2, February 2023, Page e12
Correction to: Emotional bias modification weakens game-related compulsivity and reshapes frontostriatal pathways
doi : 10.1093/brain/awac410
Brain, Volume 146, Issue 2, February 2023, Page e13
