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Abreaction: a humble suggestion Brain (IF 10.6) Pub Date : 2025-04-17 Norman A Poole
Abreaction was once a common treatment for functional neurological disorder (FND) but has since fallen out of use. Norman Poole argues that abreaction is compatible with many findings from modern neuroscience, and should be studied and tested as a treatment for FND.
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Medial temporal lobe atrophy in Down syndrome along the Alzheimer's disease continuum Brain (IF 10.6) Pub Date : 2025-04-17 Benjamin J Buehner, Alejandra O Morcillo-Nieto, Sara E Zsadanyi, Mateus Rozalem Aranha, José Enrique Arriola-Infante, Lídia Vaqué-Alcázar, Javier Arranz, Íñigo Rodríguez-Baz, Lucia Maure Blesa, Laura Videla, Isabel Barroeta, Laura Del Hoyo Soriano, Bessy Benejam, Susana Fernández, Aida Sanjuan Hernandez, Nuria Bargalló, Sofía González-Ortiz, Sandra Giménez, Robin de Flores, Paul A Yushkevich, Daniel
Medial temporal lobe structures are among the first areas impacted by neurofibrillary tangle pathology, making volumetric changes of these areas promising biomarkers for Alzheimer's disease. To date, little is known about the integrity of these regions in individuals with Down syndrome, a population which almost invariably develops Alzheimer's disease and thus offers a unique opportunity to determine
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Cognitive and neuropsychiatric profiles distinguish atypical parkinsonian syndromes Brain (IF 10.6) Pub Date : 2025-04-16 Michele T Hu, Agustin Querejeta Coma, James B Rowe, Tanja Zerenner, Alistair Church, Riona Fumi, Alyssa Constantini, Edwin Jabbari, Marte T Jensen, Alexander Gerhard, Nicola Pavese, Christopher Kobylecki, P Nigel Leigh, Ivan Koychev, Huw Morris, Sanjay G Manohar
Atypical parkinsonian syndromes are distinguished from Parkinson’s disease by additional neurological signs and characteristic underlying neuropathology. However, they can be diagnostically challenging, rapidly progressive, and are often diagnosed late in disease course. Their different demographic features and prognoses are well studied, but the accompanying cognitive and psychiatric features may
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Intronic FGF14 GAA repeat expansions impact progression and survival in multiple system atrophy Brain (IF 10.6) Pub Date : 2025-04-16 Viorica Chelban, David Pellerin, Nirosen Vijiaratnam, Hamin Lee, Yen Yee Goh, Lauren Brown, Sara Sambin, Danielle Seilhean, Stephane Lehericy, Pablo Iruzubieta, Rahema Mohammad, Eleanor Self, Annarita Scardamaglia, Cameron Lee, Miriama Ostrozovicova, Marie-Josée Dicaire, Christine Girges, Emil K Gustavsson, David Murphy, Toby Curless, Joshua Laβ, Joanne Trinh, Timothy Rittman, James B Rowe, Marios
Partial phenotypic overlap has been suggested between multiple system atrophy (MSA) and spinocerebellar ataxia 27B, the autosomal dominant ataxia caused by an intronic GAA•TTC repeat expansion in FGF14. This study investigated the frequency of FGF14 GAA•TTC repeat expansion in clinically diagnosed and pathologically confirmed multiple system atrophy cases. We screened 657 multiple system atrophy cases
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Alterations in dopaminergic innervation and receptors in focal cortical dysplasia Brain (IF 10.6) Pub Date : 2025-04-16 Norisa Meli, Katherine Sheran, Julika Pitsch, Sabine Krabbe, Valeri Borger, Tobias Baumgartner, Albert Becker, Sandra Blaess
Focal cortical dysplasia (FCD) type 2 is the most common malformation of cortical development associated with pharmaco-resistant focal epilepsy and frequently located in the frontal cortex. Neuropathological hallmarks comprise abnormal cortical layering and enlarged, dysmorphic neuronal elements. Fundamentally altered local neuronal activity has been reported in human FCD type 2 epilepsy surgical biopsies
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What's left to explain and what's right to conclude about the neurocognition of deductive reasoning? Brain (IF 10.6) Pub Date : 2025-04-16 Carlo Reverberi,Giosuè Baggio,Paolo Cherubini
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A right frontal network for analogical and deductive reasoning Brain (IF 10.6) Pub Date : 2025-04-16 Joseph Mole, James K Ruffle, Amy Nelson, Edgar Chan, Tim Shallice, Parashkev Nachev, Lisa Cipolotti
Two of the most well-studied types of reasoning are analogical reasoning (AR) and deductive reasoning (DR). Yet, our understanding of the relationship between reasoning abilities and their neuroanatomical basis remains surprisingly limited. We aimed to conduct fine-grained anatomical mapping of performance on tests of AR, DR and fluid intelligence (Gf), in a large sample of patients with unilateral
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Reply: Understanding and misunderstanding cell counts of the human brain: the crux of biological variation. Brain (IF 10.6) Pub Date : 2025-04-15 Alain Goriely
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Understanding and misunderstanding cell counts of the human brain: the crux of biological variation. Brain (IF 10.6) Pub Date : 2025-04-15 Christopher S von Bartheld
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Midbrain cytotoxic T cells as a distinct neuropathological feature of progressive supranuclear palsy Brain (IF 10.6) Pub Date : 2025-04-15 Blas Couto, Shelley L Forrest, Conor Fearon, Seojin Lee, Samantha Knott, Jun Li, Susan H Fox, Maria Carmela Tartaglia, Anthony E Lang, Gabor G Kovacs
Progressive supranuclear palsy (PSP) is a neurodegenerative disorder with 4-repeat (R) tau protein deposition. The substantia nigra (SN) and midbrain tegmentum nuclei (MBT) are consistently affected. Lymphocyte infiltrates are scarce in the brain of neurodegenerative diseases, although a few reports have described this feature in brains with the α-synucleinopathy, Parkinson’s disease (PD). To evaluate
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A digital motor score for sensitive detection of progression in Huntington’s disease Brain (IF 10.6) Pub Date : 2025-04-11 Louis-Solal Giboin, Cedric Simillion, Johannes Rennig, Atieh Bamdadian, Fiona C Kinsella, Anne V Smith, Peter McColgan, Michael Lindemann, Florian Lipsmeier, Edward J Wild, Jonas Dorn
Remote digital monitoring of Huntington’s disease (HD) has potential to enhance the development of therapeutics, but no data-driven digital motor score exists to quantify the diversity of disease manifestations and track their progression. The Huntington’s Disease Digital Motor progression Score (HDDMS), co-designed by people with HD and neurologists, is a composite score for measuring motor progression
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Single-cell dissection of the genotype-immunophenotype relationship in glioblastoma Brain (IF 10.6) Pub Date : 2025-04-11 Nishant Soni, Kavita Rawat, Zhihong Chen, Angela DiMauro, Bruno Giotti, Dolores Hambardzumyan, Alexander M Tsankov
Glioblastoma (GBM) is the most aggressive and lethal adult brain tumor. The cellular heterogeneity within the tumor microenvironment (TME) plays a critical role in the complexity of treatment and poor survival. GBM is typically classified into 3 molecular subtypes—Classical, Mesenchymal, and Proneural—associated with EGFR, NF1, and PDGFRA genetic drivers, respectively. Yet, the role of these driver
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Dysregulated cortical excitability and tau phosphorylation in a β3 integrin mouse model of autism Brain (IF 10.6) Pub Date : 2025-04-10 Carmela Vitale, Fanny Jaudon, Rafael Lujan, Martina Bartolucci, Lucia Celora, Elisa Reisoli, Riccardo Ruggeri, Andrea Petretto, Agnes Thalhammer, Lorenzo A Cingolani
Autism spectrum disorder is a complex neurodevelopmental disease characterized by altered cortical network excitability. Recent genetic studies have identified deep layer V cortical pyramidal neurons in the frontal cortex as central to autism pathophysiology, yet the cortical circuits, plasticity mechanisms and molecular signalling pathways involved remain poorly understood. Layer V pyramidal neurons
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Synaptic dysregulation in a mouse model of GRIN2D developmental and epileptic encephalopathy Brain (IF 10.6) Pub Date : 2025-04-08 JiaJie Teoh, Jane Simko, Chad R Camp, Christine J Liu, Wanqi Wang, Damian Williams, Liang Ma, Divyalakshmi Soundararajan, Caryn Martin, Noah K Taylor, Ekniel François, Sabrina Petri, Ayla Kanber, Aishwarya Ravichandra, Maria Elena Pero, Francesca Bartolini, Theresa C Swayne, Cathleen M Lutz, Aamir Zuberi, Moran Rubinstein, Moran Hausman Kedem, Hongjie Yuan, Jennifer N Gelinas, Tristan T Sands, Scott
Gain-of-function (GoF) variants in the GRIN2D gene, encoding the GluN2D subunit of the N-methyl-D-aspartate receptor (NMDAR), cause a severe developmental and epileptic encephalopathy (DEE), characterized by intractable seizures, hypotonia, and neurodevelopmental delay. We generated mice carrying the GoF V664I variant, orthologous to V667I, which is present in ∼25% of GRIN2D-DEE patients. Heterozygous
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In utero therapy for spinal muscular atrophy: closer to clinical translation Brain (IF 10.6) Pub Date : 2025-04-08 Eduardo F Tizzano, Georg Lindner, Ellie Chilcott, Richard S Finkel, Rafael J Yáñez-Muñoz
5q-Spinal muscular atrophy (SMA) has been a trailblazer in the development of advanced therapies for inherited diseases. SMA is an autosomal recessive disorder affecting mainly motor neurons in the anterior horn of the spinal cord and brainstem motor nuclei, but currently considered a systemic disease. Advances in understanding of the genetics of SMA led to the development of disease modifying therapies
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Mitochondrial damage is associated with an early immune response in inclusion body myositis Brain (IF 10.6) Pub Date : 2025-04-08 Felix Kleefeld, Emily Cross, Daniel Lagos, Sara Walli, Benedikt Schoser, Andreas Hentschel, Tobias Ruck, Christopher Nelke, Katrin Hahn, Denisa Hathazi, Andrew L Mammen, Maria Casal-Dominguez, Marta Gut, Ivo Glynne Gut, Simon Heath, Anne Schänzer, Hans-Hilmar Goebel, Iago Pinal-Fernandez, Andreas Roos, Corinna Preuße, Werner Stenzel, Rita Horvath
Polymyositis with mitochondrial pathology (PM-Mito) was first identified in 1997 as a subtype of idiopathic inflammatory myopathy. Recent findings demonstrated significant molecular similarities between PM-Mito and Inclusion Body Myositis (IBM), suggesting a trajectory from early to late IBM and prompting the inclusion of PM-Mito as an IBM precursor (early IBM) within the IBM spectrum. Both PM-Mito
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Astrocytic Kir4.1 ion channel deficit drives persistent inflammatory facial pain in males Brain (IF 10.6) Pub Date : 2025-04-04 Sarah Mountadem, Karine Herault, Cedric Peirs, Gisela da Silva Borges, Daniel L Voisin, Myriam Antri, Radhouane Dallel
Chronic facial pain, a frequent and disabling condition, is maintained by central sensitization, which results in pain hypersensitivity. Although it is well established that reactive astrocytes play a key role in persistent pain mechanisms, the role of disruption of the normal capacity of astrocytes to maintain neuronal homeostasis is much less known. Here we show that persistent facial inflammation
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Non-invasive spinal neuromodulation enables stepping in children with complete spinal cord injury Brain (IF 10.6) Pub Date : 2025-04-04 Kathryn Lucas, Goutam Singh, Luis R Alvarado, Molly King, Nicole Stepp, Parth Parikh, Beatrice Ugiliweneza, Yury Gerasimenko, Andrea L Behrman
Paralysis is assumed permanent in persons with motor-complete spinal cord injury (SCI). However, spinal epidural stimulation combined with activity-based locomotor training (ABLT) and cognitive intent enabled two adults with motor-complete SCI to walk with a walker. Transcutaneous spinal stimulation (scTS), also capable of promoting a cyclic step-like pattern, might be a viable alternative in children
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The interneuron hypothesis of amyotrophic lateral sclerosis. Brain (IF 10.6) Pub Date : 2025-04-03 Bryan J Traynor
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Persistent Na+ current couples spreading depolarization to seizures in Scn8a gain of function mice Brain (IF 10.6) Pub Date : 2025-04-03 Isamu Aiba, Yao Ning, Jeffrey L Noebels
Spreading depolarization (SD) is a slowly propagating wave of massive cellular depolarization that transiently impairs the function of affected brain regions. While SD typically arises as an isolated hemispheric event, we previously reported that reducing M-type potassium current (IKM) by ablation of Kcnq2 in forebrain excitatory neurons results in tightly coupled spontaneous bilateral seizure-SD complexes
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Asymmetry in amyotrophic lateral sclerosis: clinical, neuroimaging and histological observations Brain (IF 10.6) Pub Date : 2025-04-03 Katie Yoganathan, Thanuja Dharmadasa, Alicia Northall, Kevin Talbot, Alexander G Thompson, Martin R Turner
Amyotrophic lateral sclerosis is a progressive neurodegenerative disease of the motor system marked by significant phenotypic heterogeneity. Motor symptoms in the limbs consistently emerge focally and asymmetrically and, whilst variable, the pattern of regional progression related to the balance of clinical upper and lower motor neuron signs, upper versus lower limb onset and hand dominance to some
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SNAP25 variant I67N: synaptic phenotypes, drug response and proteome changes in human neurons Brain (IF 10.6) Pub Date : 2025-04-02 Maiken Østergaard, Paola Barbagallo, Henriette Reventlow S Frederiksen, Wendy K Chung, Rikke S Møller, Martin Røssel Larsen, Kristine Freude, Matthijs Verhage, Jakob Balslev Sørensen
SNAREopathies constitute a group of severe genetic neurodevelopmental disorders caused by de novo variants that disturb the synaptic release machinery. These neurodevelopmental disorders comprise highly diverse clinical phenotypes, usually including developmental delay, epilepsy, intellectual disability, and sometimes autism spectrum disorder. Despite major progress in genetic testing, current treatments
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Characterization of severe COL6-related dystrophy due to the recurrent variant COL6A1 c.930+189C>T Brain (IF 10.6) Pub Date : 2025-04-02 A Reghan Foley, Véronique Bolduc, Fady Guirguis, Sandra Donkervoort, Ying Hu, Rotem Orbach, Riley M McCarty, Apurva Sarathy, Gina Norato, Beryl B Cummings, Monkol Lek, Anna Sarkozy, Russell J Butterfield, Janbernd Kirschner, Andrés Nascimento, Daniel Natera-de Benito, Susana Quijano-Roy, Tanya Stojkovic, Luciano Merlini, Giacomo Comi, Monique Ryan, Denise McDonald, Pinki Munot, Grace Yoon, Edward Leung
Collagen VI-related dystrophies (COL6-RDs) manifest with a spectrum of clinical phenotypes, ranging from Ullrich congenital muscular dystrophy (UCMD), presenting with prominent congenital symptoms and characterised by progressive muscle weakness, joint contractures and respiratory insufficiency, to Bethlem muscular dystrophy, with milder symptoms typically recognised later and at times resembling a
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Traumatic brain injury or head impacts from contact sports are associated with tau astrogliopathy Brain (IF 10.6) Pub Date : 2025-04-01 John D Arena, William Stewart, Gabor G Kovacs, Edward B Lee, John L Robinson, Virginia M-Y Lee, John Q Trojanowski, Andrea L C Schneider, Douglas H Smith, Victoria E Johnson
Exposure to traumatic brain injury (TBI) and/or repetitive head impacts (RHI) increases the risk of a range of neurodegenerative pathologies, including chronic traumatic encephalopathy neuropathologic change (CTE-NC). Astrocytic tau pathology reminiscent of aging-related tau astrogliopathy (ARTAG) is a component feature of CTE-NC in many cases. Yet the relationship between TBI/RHI exposure and wider
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Neuropsychiatric symptoms in sporadic Creutzfeldt-Jakob disease Brain (IF 10.6) Pub Date : 2025-03-31 Jennifer Zitser, Sven Forner, Katherine Wong, Jin Chengshi, John Neuhaus, Jennifer Martindale, Ben J Raudabaugh, Kendra Benisano, Kelly Goodman-O’Leary, Stacy Metcalf, Mee-Ohk Kim, Marwa Hakimi, Isabelle E Allen, Bruce L Miller, Howard J Rosen, Katherine P Rankin, Michael D Geschwind
Although neuropsychiatric symptoms are not part of diagnostic criteria for sporadic Creutzfeldt-Jakob disease a few retrospective studies and our clinical experience have suggested they are prominent and often occur early. The objective of our study was to assess prospectively the neuropsychiatric features in sCJD (and their impact on caregivers) and compare them with five other neurodegenerative diseases:
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Cortical stimulation predicts language decline following SEEG radiofrequency thermocoagulation Brain (IF 10.6) Pub Date : 2025-03-30 Emily Cockle, Charles B Malpas, Honor Coleman, Alissandra McIlroy, Joshua Laing, Patrick Kwan, Martin Hunn, Matthew Gutman, Cecilia Harb, Catherine Meade, Wendyl D’Souza, Amy Halliday, Kristian Bulluss, Simon Vogrin, Rubina Alpitsis, Terence J O’Brien, Genevieve Rayner, Andrew Neal
SEEG cortical stimulation enables individualised mapping of language networks. Regions associated with induced language deficits are marked as ‘language-positive’ and considered important in supporting function. It remains unclear, however, whether small lesions in ‘language-positive’ sites created by radiofrequency thermocoagulation are sufficient to cause language deficits. Thirty-six consecutive
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Heterozygous RAB3A variants cause cerebellar ataxia by a partial loss-of-function mechanism Brain (IF 10.6) Pub Date : 2025-03-30 Holger Hengel, Shabab B Hannan, Selina Reich, Danique Beijer, Johanna Roller, Bernd K Gilsbach, Christian Johannes Gloeckner, Daniel Greene, Dagmar Timmann, Christel Depienne, Andrew Mumford, Mary O’Driscoll, Andrea H Nemeth, Julie Lundberg, Lance H Rodan, Ange-Line Bruel, Julian Delanne, Tine Deconinck, Jonathan Baets, Ziv Gan-Or, Guy Rouleau, Oksana Suchowersky, Mehrdad A Estiar, Stephen Reich, Camilo
RAB3A encodes a small GTP-binding protein that is abundant in brain synaptic vesicles and crucial for the release of neurotransmitters and synaptic plasticity. Here we identified RAB3A as a candidate gene for autosomal dominant cerebellar ataxia by two independent approaches: linkage in a large dominant ataxia family and, in parallel, an untargeted computational genetic association approach, analyzing
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Combinatorial approaches increasing neuronal activity accelerate recovery after spinal cord injury Brain (IF 10.6) Pub Date : 2025-03-29 Bing Chen, Siddharth Gaikwad, Robert H Powell, Hang Jin Jo, Allison Kessler, David Chen, C J Heckman, Linda Jones, James Guest, Jonathan Wolpaw, Martin Oudega, Andrew R Blight, Monica A Perez
Combinatorial approaches targeting multiple aspects of spinal cord injury (SCI) pathophysiology are needed to maximize functional recovery. We hypothesized that strengthening corticospinal synapses via Hebbian stimulation and increasing neuronal transmission with 4-aminopyridine (4-AP, a potassium blocker) could accelerate locomotor recovery in individuals with chronic SCI. Participants were randomly
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Inferring the ‘functions’ of tracts: a cautionary note Brain (IF 10.6) Pub Date : 2025-03-28 Emiel van den Hoven, Cornelius Weiller, Marco Reisert, Michel Rijntjes
This scientific commentary refers to ‘The inferior fronto-occipital fasciculus: bridging phylogeny, ontogeny and functional anatomy’ by Giampiccolo et al. (https://doi.org/10.1093/brain/awaf055).
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CXCR3-mediated natural killer cell infiltration exacerbates white matter injury after intracerebral haemorrhage Brain (IF 10.6) Pub Date : 2025-03-23 Anson C K Ng, Cuiting Zhang, Tsz Lung Lam, Karrie M Kiang, Vaness N C Ng, Zhiyuan Zhu, Jiaxin Liu, Wenwei Tu, Wanjun Tang, Katrina C W Chau, Kwan Man, Gilberto K K Leung
Intracerebral haemorrhage (ICH), a subtype of stroke, carries a grim prognosis. Inflammatory response during the early phase of ICH is a major perpetuator of neurological damage. Recent clinical studies suggest the possible participation of the CXC chemokine receptor 3 (CXCR3)-chemokine system in mediating neuroimmune crosstalk, which exacerbates neurological dysfunction and may serve as a potential
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ADAT3 variants disrupt the activity of the ADAT tRNA deaminase complex and impair neuronal migration Brain (IF 10.6) Pub Date : 2025-03-23 Jordi Del-Pozo-Rodriguez, Peggy Tilly, Romain Lecat, Hugo Rolando Vaca, Laureline Mosser, Elena Brivio, Till Balla, Marina Vitoria Gomes, Elizabeth Ramos-Morales, Noémie Schwaller, Thalia Salinas-Giegé, Grace VanNoy, Eleina M England, Alysia Kern Lovgren, Melanie O’Leary, Maya Chopra, Naomi Meave Ojeda, Mehran Beiraghi Toosi, Atieh Eslahi, Masoome Alerasool, Majid Mojarrad, Lynn S Pais, Rebecca C Yeh
The ADAT2/ADAT3 (ADAT) complex catalyzes the adenosine to inosine modification at the wobble position of eukaryotic tRNAs. Mutations in ADAT3, the catalytically inactive subunit of the ADAT2/ADAT3 complex, have been identified in patients presenting with severe neurodevelopmental disorders. Yet, the physiological function of ADAT2/ADAT3 complex during brain development remains totally unknown. Here
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The relationship between kidney health and neurodegenerative diseases Brain (IF 10.6) Pub Date : 2025-03-23 Melody Zuo, Le Chang, Nikita Neale, Lyza Maameri, Sadaf Gawhary, Frida Lona-Durazo, Sarah A Gagliano Taliun
Neurodegenerative diseases are multi-faceted disorders influenced by and affecting more than just the brain and nervous system. Here, we provide a review of the potential links, including mechanistic and genetic, between kidney health and neurodegeneration, mainly dementia and the two most prevalent late-onset neurodegenerative disorders, Alzheimer’s disease and Parkinson’s disease. We also discuss
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Effects of focal brain damage on political behaviour across different political ideologies Brain (IF 10.6) Pub Date : 2025-03-23 Shan H Siddiqi, Stephanie Balters, Giovanna Zamboni, Shira Cohen-Zimerman, Jordan H Grafman
Intense political behavior is associated with brain regions involved in emotional and cognitive processing. However, it remains unclear if this neuroanatomy is causal, compensatory, or otherwise correlated. We employed lesion network mapping in a cross-sectional study of 124 male military Veterans with penetrating head trauma. 40-45 years after the injury, participants reported current political behavior
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Structural network-specific effect of extreme capsule stimulation for drug-resistant focal epilepsy Brain (IF 10.6) Pub Date : 2025-03-23 Yueyang Cheng, Di Wang, Xiaohua Zhang, Guangyuan Jin, Di Wu, Qiao Wang, Jialin Du, Lei Qi, Cuiping Xu, Zichen Qiao, Xiaopeng Wang, Junliang Ge, Siyi Wang, Hao Yan, Xueyuan Wang, Huaqiang Zhang, Tao Yu, Yuping Wang, Fang-Cheng Yeh, Guoguang Zhao, Liankun Ren
Treatment for drug-resistant epilepsy in poor candidates for resection surgeries remains challenging. The prevailing deep brain stimulation of subcortical nuclei is effective but exhibits heterogeneous efficacy and unpredictable side effects. Therefore, the investigation of novel DBS targets holds paramount importance. Here, we focused on the unique structure known as the extreme capsule (EC), being
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Novel modelling approaches to elucidate the genetic architecture of resilience to Alzheimer's disease Brain (IF 10.6) Pub Date : 2025-03-21 Jared M Phillips, Logan C Dumitrescu, Derek B Archer, Alexandra N Regelson, Shubhabrata Mukherjee, Michael L Lee, Seo-Eun Choi, Phoebe Scollard, Emily H Trittschuh, Walter A Kukull, Sarah Biber, Jesse Mez, Emily R Mahoney, Michelle Clifton, Julia B Libby, Skylar Walters, William S Bush, Corinne D Engelman, Qiongshi Lu, David W Fardo, Keith F Widaman, Rachel F Buckley, Elizabeth C Mormino, R Elizabeth
Up to 30% of older adults meet pathological criteria for a diagnosis of Alzheimer’s disease at autopsy yet never show signs of cognitive impairment. Recent work has highlighted genetic drivers of this resilience, or better-than-expected cognitive performance given a level of neuropathology, that allow the aged brain to protect itself from the downstream consequences of amyloid and tau deposition. However
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Impaired reward sensitivity in Parkinson's depression is unresponsive to dopamine treatment. Brain (IF 10.6) Pub Date : 2025-03-19 Harry Costello,Yumeya Yamamori,Karel Kieslich,Mackenzie Murphy,Kamilla Bobyreva,Anette-Eleonore Schrag,Robert Howard,Jonathan P Roiser
Willingness to exert effort for a given goal is dependent on the magnitude of the potential rewards and effort costs of an action. Such effort-based decision making is an essential component of motivation, in which the dopaminergic system plays a key role. Depression in Parkinson's disease (PD) is common, disabling and has poor outcomes. Motivational symptoms such as apathy and anhedonia, are prominent
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Reward circuit local field potential modulations precede risk taking Brain (IF 10.6) Pub Date : 2025-03-18 Natasha C Hughes, Helen Qian, Derek J Doss, Ghassan S Makhoul, Michael Zargari, Zixiang Zhao, Balbir Singh, Zhengyang Wang, Jenna N Fulton, Graham W Johnson, Rui Li, Benoit M Dawant, Dario J Englot, Christos Constantinidis, Shawniqua Williams Roberson, Sarah K Bick
Risk-taking behaviour is a symptom of multiple neuropsychiatric disorders and often lacks effective treatments. Reward circuitry regions including the amygdala, orbitofrontal cortex, insula, and anterior cingulate have been implicated in risk-taking, but electrophysiological activity predictive of risk taking in these regions is not well understood in humans. Identifying local field potential frequency
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Large-scale profiling of antibody reactivity to glycolipids in patients with Guillain-Barré syndrome. Brain (IF 10.6) Pub Date : 2025-03-17 Robin C M Thomma,Susan K Halstead,Laura C de Koning,Evelin E J A Wiegers,Dawn S Gourlay,Anne P Tio-Gillen,Wouter van Rijs,Henning Andersen,Giovanni Antonini,Samuel Arends,Shahram Attarian,Fabio A Barroso,Kathleen J Bateman,Luana Benedetti,Peter Van den Bergh,Jan Bürmann,Mark Busby,Carlos Casasnovas,Efthimios Dardiotis,Amy Davidson,Thomas E Feasby,Janev Fehmi,Giuliana Galassi,Tania Garcia-Sobrino,Volkan
Guillain-Barré syndrome is an acute polyradiculoneuropathy in which preceding infections often elicit the production of antibodies that target peripheral nerve antigens, principally gangliosides. Anti-ganglioside antibodies are thought to play a key role in the clinical diversity of the disease and can be helpful in clinical practice. Extensive research into clinical associations of individual anti-ganglioside
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Activated αβ T- and reduced mucosa-associated invariant T cells in LGI1- and CASPR2-encephalitis. Brain (IF 10.6) Pub Date : 2025-03-17 Daniela Esser,Louisa Müller-Miny,Michael Heming,Manuela Paunovic,Martijn van Duijn,Ligia Abrante Cabrera,Katharina M Mair,Christine Strippel,Saskia Räuber,Justina Dargvainiene,Stjepana Kovac,Catharina C Gross,Nina Fransen,Robin van Steenhoven,Péter Körtvélyessy,Werner Stenzel,Romana Höftberger,Eric Bindels,Christian G Bien,Heinz Wiendl,Sven G Meuth,Jan Bauer,Nico Melzer,Maarten J Titulaer,Frank Leypoldt
Anti-Leucine-rich glioma inactivated-1 (LGI1) and anti-contactin-associated-protein-2 (CASPR2) autoimmune encephalitis (AIE) are common and characterized by pathogenic antibodies targeting neuronal autoantigens. However, the drivers of the antibody-secreting cells (ASC) and involvement of T cells remain unresolved. We performed single cell RNA-sequencing of fresh cerebrospinal fluid (CSF) and parallel
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Genome-wide association study of neuropathological features in Lewy body disease Brain (IF 10.6) Pub Date : 2025-03-17 Rebecca R Valentino, Shunsuke Koga, Alexandra I Soto-Beasley, Daisuke Ono, Mikolaj A Wieczorek, Patrick W Johnson, Launia J White, Molly M Watkins, Melissa E Murray, Koji Kasanuki, Pamela J McLean, Wolfdieter Springer, Ryan J Uitti, Julie A Fields, Hugo Botha, Vijay K Ramanan, Kejal Kantarci, Val J Lowe, Clifford R Jack, Jose Bras, Rita Guerreiro, Nilufer Ertekin-Taner, Rodolfo Savica, Jonathan Graff-Radford
Studies assessing genetic associations with neuropathological features in Lewy body disease (LBD) have been limited to candidate gene investigations, and therefore information is lacking regarding the genetic architecture of the neuropathology of LBD. In the current study, we examined a large series of neuropathologically-confirmed LBD cases (N=980 in the discovery series, N=503 in the replication
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How modular are modules in visual cortex? Brain (IF 10.6) Pub Date : 2025-03-13 Martin N Hebart
This scientific commentary refers to ‘Visual feature processing in a large stroke cohort: evidence against modular organization’ by Lugtmeijer, Sobolewska et al. (https://doi.org/10.1093/brain/awaf009).
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Modulating inhibitory synaptic plasticity to restore basal ganglia dynamics in Parkinson’s disease Brain (IF 10.6) Pub Date : 2025-03-12 Kiah A Spencer, Alexandra Boogers, Srdjan Sumarac, David B J Crompton, Leon A Steiner, Luka Zivkovic, Yijinmide Buren, Alexandre Boutet, Andres M Lozano, Suneil K Kalia, William D Hutchison, Alfonso Fasano, Luka Milosevic
Parkinson’s disease is characterized, in part, by hypoactivity of direct pathway inhibitory projections from striatum to the globus pallidus internus (GPi) and indirect pathway inhibitory projections from globus pallidus externus (GPe) to the subthalamic nucleus (STN). In people with Parkinson’s disease (n=32), we explored the potential use of intracranial stimulation for eliciting long-term potentiation
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Parvalbumin neurons mediate neurological phenotypes of anti-NMDAR encephalitis Brain (IF 10.6) Pub Date : 2025-03-12 Yi-Fan Feng, Zi-Ke Zeng, You Ni, Yue Hu, Ke-Xin Yang, Fang Cai, Qin-Ming Zhou, Ming Chen, Xiao-Na Zhu, Sheng Chen, Ji Hu
Patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, often present with severe psychiatric symptoms, yet the neuropathological mechanisms underlying their cognitive deficits remain insufficiently understood. In this study, we constructed an animal model using anti-NMDAR IgG purified from the serum of patients with anti-NMDAR encephalitis, and we used IgG obtained from healthy
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MRI R2* captures inflammation in disconnected brain structures after stroke: a translational study Brain (IF 10.6) Pub Date : 2025-03-12 Ismail Koubiyr, Takayuki Yamamoto, Laurent Petit, Nadège Dubourdieu, Elena Avignone, Elise Cozensa, Chloé Galmiche, Hikaru Fukutomi, Igor Sibon, Vincent Dousset, Michel Thiebaut de Schotten, Aude Panatier, Marion Tible, Thomas Tourdias
Ischemic strokes disrupt brain networks, leading to remote effects in key regions like the thalamus, a critical hub for brain functions. However, non-invasive methods to quantify these remote consequences still need to be explored. This study aimed to demonstrate that MRI-derived R2* changes can capture iron accumulation linked with inflammation secondary to stroke-induced disconnection. In order to
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Transcallosal inhibition does not influence subacute motor recovery in mild-to-moderate stroke Brain (IF 10.6) Pub Date : 2025-03-11 Emily Fokas, Myriam Taga, Leticia Hayes, Charalambos C Charalambous, Sharmila Raju, Ziyue Wang, Yongzhao Shao, Pietro Mazzoni, Valentin Stepanov, Els Fieremans, Heidi Schambra
After stroke, upper extremity (UE) motor recovery may be mediated in part by transcallosal projections between hemispheres. The interhemispheric competition model posits that transcallosal inhibition (TI) from the contralesional hemisphere is abnormally strengthened following stroke and interferes with motor recovery. This model has recently been questioned. In this longitudinal study, we aimed to
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Why the threat of psychosocial reductionism to patients in psychiatry and medicine is rather ignored. Brain (IF 10.6) Pub Date : 2025-03-10 Thomas H J Molmans
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Raised intracranial pressure alters cortical vascular function and cephalic allodynia Brain (IF 10.6) Pub Date : 2025-03-08 Olivia Grech, Eloisa Rubio-Beltran, Emily C Stanyer, Alejandro Labastida-Ramirez, Gareth G Lavery, Lisa J Hill, Philip R Holland, Alexandra J Sinclair
Raised intracranial pressure (ICP) is associated with altered cerebral hemodynamics and cephalic pain. The relationship between the algetic response and cortical neurovascular changes in raised ICP is unclear. This study aimed to evaluate this relationship and determine if lowering ICP (using a glucagon like peptide-1 receptor agonist) could ameliorate the algetic response. We also sought to explore
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On the responsibilities of intellectuals and the rise of bullshit jobs in universities. Brain (IF 10.6) Pub Date : 2025-03-06 Masud Husain
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Vessel size and clinical features in vasculitic neuropathy: dichotomy or continuum? Brain (IF 10.6) Pub Date : 2025-03-06 Robert D M Hadden, Michael P Collins
This scientific commentary refers to ‘Distinctive clinical features in biopsy-proven nerve large-arteriole vasculitis and microvasculitis’ by Soontrapa et al. (https://doi.org/10.1093/brain/awae406).
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Stereo-EEG propagating source reconstruction identifies new surgical targets for epilepsy patients Brain (IF 10.6) Pub Date : 2025-03-06 Brandon J Thio, Nishant Sinha, Kathryn A Davis, Saurabh R Sinha, Warren M Grill
Epilepsy surgery can eliminate seizures in patients with drug-resistant focal epilepsy. Surgical intervention requires proper identification of the epileptic network and often involves implanting stereo-EEG electrodes in patients where non-invasive methods are insufficient. However, only ∼60% of patients achieve seizure-freedom following surgery. Quantitative methods have been developed to help improve
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Fetal malformations of cortical development: review and clinical guidance Brain (IF 10.6) Pub Date : 2025-03-06 Jeffrey B Russ, Sonika Agarwal, Charu Venkatesan, Barbara Scelsa, Brigitte Vollmer, Tomo Tarui, Andrea C Pardo, Monica E Lemmon, Sarah B Mulkey, Anthony R Hart, Usha D Nagaraj, Jeffrey A Kuller, Matthew T Whitehead, Jennifer L Cohen, Juliana S Gebb, Orit A Glenn, Mary E Norton, Dawn Gano
Malformations of cortical development (MCDs) are a heterogeneous family of congenital brain malformations that originate from disturbed development of the cerebral cortex. MCDs can arise from primary genetic disorders that lead to dysfunction of the molecular processes controlling neuronal proliferation, neuronal migration, cortical folding, or cortical organization. MCDs can also result from secondary
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Towards precision MRI biomarkers in epilepsy with normative modelling Brain (IF 10.6) Pub Date : 2025-03-05 Remika Mito, James Cole, Sila Genc, Graeme Jackson, Andrew Zalesky
Epilepsy is recognised as one of the leading targets for precision medicine, following on from the successes in cancer therapy, due to its substantial clinical heterogeneity and divergent therapeutic options. To bring personalised care to the epilepsies, there is a need for appropriate precision biomarkers that can identify disease processes or predict treatment outcomes at the individual patient level
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Harnessing psychedelics for stroke recovery: therapeutic potential and mechanisms Brain (IF 10.6) Pub Date : 2025-03-05 Yuefeng Yang, Yibo Wang, Xiaohui Wang
Yang et al. propose that psychedelics hold untapped potential for improving stroke recovery through their unique ability to modulate neuroplasticity, reduce neuroinflammation, and enhance cognitive and psychological resilience.
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Serotonergic dysfunction in patients with impulse control disorders in Parkinson’s disease Brain (IF 10.6) Pub Date : 2025-03-05 Stéphane Prange, Elise Metereau, Hélène Klinger, Marine Huddlestone, Melinda De Oliveira, Sandra Duperrier, Pierre Courault, Jérôme Redoute, Léon Tremblay, Véronique Sgambato, Sophie Lancelot, Stéphane Thobois
Impulse control disorders (ICDs) are frequent and particularly distressing neuropsychiatric symptoms in patients with Parkinson’s disease (PD) which are related to impaired behavioural inhibition. Multiple PET imaging studies indicate that striatal dopaminergic abnormalities contribute to hyperdopaminergic functioning in PD patients with ICD (PDICD+) and to the dysregulation of the limbic fronto-striatal
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CD21lo B cell subsets are recruited to the central nervous system in acute neuromyelitis optica Brain (IF 10.6) Pub Date : 2025-03-05 Ryusei Nishigori, Mio Hamatani, Hiroyuki Yoshitomi, Kimitoshi Kimura, Masaki Takata, Shinji Ashida, Chihiro Fujii, Hirofumi Ochi, Ryosuke Takahashi, Takayuki Kondo, Hideki Ueno
Neuromyelitis optica (NMO) is an acute inflammatory demyelinating disease of the CNS. The presence of astrocyte-targeted AQP4-immunoglobulin G (IgG) in peripheral blood is a major factor in its diagnosis. Previous studies show that AQP4-IgG directly contributes to CNS inflammation, and B cells play a central pathogenic role in NMO. However, where and how B cell response is altered remains controversial
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The presence and prognosis of nerve pathology following whiplash injury: a prospective cohort study Brain (IF 10.6) Pub Date : 2025-03-05 Joel Fundaun, Colette Ridehalgh, Soraya Koushesh, Alex Novak, Macarena Tejos-Bravo, Stephen Bremner, Georgios Baskozos, Andrew Dilley, Annina B Schmid
Whiplash Associated Disorders (WAD) affect 20-50 million individuals globally each year, with up to 50% developing persistent pain. WAD grade II (WADII) is the most common type and is characterised by neck symptoms and musculoskeletal signs without apparent nerve injury on routine diagnostic testing. However, emerging evidence suggests nerve pathology may be present in some people with WADII. This
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p75NTR modulation prevents cellular, cortical activity and cognitive dysfunctions caused by perinatal hypoxia Brain (IF 10.6) Pub Date : 2025-03-05 Bidisha Chattopadhyaya, Karen K Y Lee, Maria Isabel Carreño-Muñoz, Andrea Paris-Rubianes, Marisol Lavertu-Jolin, Martin Berryer, Frank M Longo, Graziella Di Cristo
Children who experienced moderate perinatal hypoxia are at risk of developing long-lasting subtle cognitive and behavioural deficits, including learning disabilities and emotional problems. Understanding the underlying mechanisms is an essential step for designing targeted therapy. Fast-spiking, parvalbumin-positive (PV) GABAergic interneurons modulate the generation of gamma oscillations, which in
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Myopathic aggregation-prone variants in the TDP-43 prion-like domain: genetics paving the way Brain (IF 10.6) Pub Date : 2025-03-04 Pedro Ervilha Pereira, Jan L De Bleecker, Elke Bogaert, Bart Dermaut
While neuropathological and genetic studies have established the crucial involvement of TDP-43 proteinopathy in the pathogenesis of ALS (Amyotrophic Lateral Sclerosis), FTD (Frontotemporal Dementia) and related neurodegenerative disorders, multiple studies have described the presence of TDP-43 inclusions in muscular disorders, including inclusion body myositis but also other related rimmed vacuole
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Post-mortem validation of in vivo TSPO PET as a microglial biomarker Brain (IF 10.6) Pub Date : 2025-03-04 Sasvi S Wijesinghe, James B Rowe, Hannah D Mason, Kieren S J Allinson, Reuben Thomas, Davi S Vontobel, Tim D Fryer, Young T Hong, Mehtap Bacioglu, Maria Grazia Spillantini, Jelle van den Ameele, John T O’Brien, Sanne Kaalund, Maura Malpetti, Annelies Quaegebeur
Neuroinflammation is a feature of many neurodegenerative diseases, and is quantified in vivo by PET imaging with radioligands for the translocator protein (TSPO, e.g. [11C]-PK11195). TSPO radioligand binding correlates with clinical severity and predicts clinical progression. However, the cellular substrate of altered TSPO binding is controversial and requires neuropathological validation. We used
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TSC2 loss in neural progenitor cells suppresses mRNA translation of neurodevelopmental genes Brain (IF 10.6) Pub Date : 2025-03-04 Pauline Martin, Krzysztof J Szkop, Francis Robert, Srirupa Bhattacharyya, Roberta L Beauchamp, Jacob Brenner, Nicholas E Redmond, Sidong Huang, Serkan Erdin, Ola Larsson, Vijaya Ramesh
Tuberous sclerosis complex (TSC) is an inherited multi-system neurocutaneous disorder where patients often present with neurodevelopmental manifestations such as epilepsy and TSC-associated neuropsychiatric disorder (TAND) that includes autism spectrum disorder (ASD). TSC is caused by inactivating mutations in TSC1 or TSC2 tumor suppressor genes, with encoded proteins hamartin (TSC1) and tuberin (TSC2)