-
Genetics of immune response to Epstein-Barr virus: prospects for multiple sclerosis pathogenesis Brain (IF 14.5) Pub Date : 2024-04-17 Jesse Huang, Katarina Tengvall, Izaura Bomfim Lima, Anna Karin Hedström, Julia Butt, Nicole Brenner, Alexandra Gyllenberg, Pernilla Stridh, Mohsen Khademi, Ingemar Ernberg, Faiez Al Nimer, Ali Manouchehrinia, Jan Hillert, Lars Alfredsson, Oluf Andersen, Peter Sundström, Tim Waterboer, Tomas Olsson, Ingrid Kockum
Epstein-Barr virus (EBV) infection has been advocated as a prerequisite for developing multiple sclerosis (MS) and possibly the propagation of the disease. However, the precise mechanisms for such influences are still unclear. A large-scale study investigating the host genetics of EBV serology and related clinical manifestations, such as infectious mononucleosis (IM), may help us better understand
-
Subtitled speech: the neural mechanisms of ticker-tape synaesthesia Brain (IF 14.5) Pub Date : 2024-04-15 Fabien Hauw, Benoît Béranger, Laurent Cohen
Reading acquisition modifies areas of the brain associated with vision, with language, and their connections. Those changes enable reciprocal translation between orthography, and word sounds and meaning. Individual variability in the pre-existing cerebral substrate contributes to the range of eventual reading abilities, extending to atypical developmental patterns, including dyslexia and reading-related
-
Adaptive coding of reward in schizophrenia, its change over time and relation to apathy Brain (IF 14.5) Pub Date : 2024-04-12 Mariia Kaliuzhna, Fabien Carruzzo, Noémie Kuenzi, Philippe N Tobler, Matthias Kirschner, Tal Geffen, Teresa Katthagen, Kerem Böge, Marco M Zierhut, Florian Schlagenhauf, Stefan Kaiser
Adaptive coding of reward is the process by which neurons adapt their response to the context of available compensations. Higher rewards lead to a stronger brain response, but the increase of the response depends on the range of available rewards. A steeper increase is observed in a narrow range, and a more gradual slope in a wider range. In schizophrenia, adaptive coding appears affected in different
-
Apilimod dimesylate in C9orf72 amyotrophic lateral sclerosis: a randomized phase 2a clinical trial Brain (IF 14.5) Pub Date : 2024-04-09 Suma Babu, Katharine A Nicholson, Jeffrey D Rothstein, Andrea Swenson, Paul J Sampognaro, Pravin Pant, Eric A Macklin, Susan Spruill, Sabrina Paganoni, Tania F Gendron, Mercedes Prudencio, Leonard Petrucelli, Darrell Nix, Sean Landrette, Esther Nkrumah, Keith Fandrick, Joan Edwards, Peter R Young
Apilimod dimesylate is a first-in-class phosphoinositide kinase, FYVE-type zinc finger containing (PIKfyve) inhibitor with favourable clinical safety profile and has demonstrated activity in preclinical C9orf72 and TDP-43 amyotrophic lateral sclerosis models. In this amyotrophic lateral sclerosis clinical trial, the safety, tolerability, CNS penetrance, and modulation of pharmacodynamic target engagement
-
GDF5 as a rejuvenating treatment for age-related neuromuscular failure Brain (IF 14.5) Pub Date : 2024-04-08 Traoré Massiré, Noviello Chiara, Vergnol Amélie, Gentil Christel, Halliez Marius, Saillard Lucile, Gelin Maxime, Forand Anne, Lemaitre Mégane, Guesmia Zoheir, Cadot Bruno, Caldas Eriky, Marty Benjamin, Mougenot Nathalie, Messéant Julien, Strochlic Laure, Sadoine Jeremy, Slimani Lofti, Jolly Ariane, De la Grange Pierre, Hogrel Jean-Yves, Pietri-Rouxel France, Falcone Sestina
Sarcopenia involves a progressive loss of skeletal muscle force, quality and mass during ageing, which results in increased inability and death; however, no cure has been established thus far. Growth differentiation factor 5 (GDF5) has been described to modulate muscle mass maintenance in various contexts. For our proof of concept, we overexpressed GDF5 by AAV vector injection in Tibialis Anterior
-
More than 185 CAG repeats: a point of no return in Huntington’s disease biology Brain (IF 14.5) Pub Date : 2024-04-08 Jillian Belgrad, Anastasia Khvorova
This scientific commentary refers to ‘A CAG repeat threshold for therapeutics targeting somatic instability in Huntington’s disease’ by Aldous et al. (https://doi.org/10.1093/brain/awae063).
-
Neurocomputational model of compulsivity: Deviating from an uncertain goal-directed system Brain (IF 14.5) Pub Date : 2024-04-08 Taekwan Kim, Sang Wan Lee, Silvia Kyungjin Lho, Sun-Young Moon, Minah Kim, Jun Soo Kwon
Despite a theory that an imbalance in goal-directed versus habitual systems serve as building blocks of compulsions, research has yet to delineate how it occurs during an arbitration process between the two systems in obsessive-compulsive disorder. Inspired by a brain model that the inferior frontal cortex selectively gates the putamen to guide goal-directed or habitual actions, this study aimed to
-
Tiam1-mediated maladaptive plasticity underlying morphine tolerance and hyperalgesia Brain (IF 14.5) Pub Date : 2024-04-04 Changqun Yao, Xing Fang, Qin Ru, Wei Li, Jun Li, Zeinab Mehsein, Kimberley F Tolias, Lingyong Li
Opioid pain medications, such as morphine, remain the mainstay for treating severe and chronic pain. Prolonged morphine use, however, triggers analgesic tolerance and hyperalgesia (OIH), which can last for a long period after morphine withdrawal. How morphine induces these detrimental side effects remains unclear. Here, we show that morphine tolerance and OIH are mediated by Tiam1-coordinated synaptic
-
Functional implication for myelin regeneration in recovery from ischaemic stroke Brain (IF 14.5) Pub Date : 2024-04-04 Stavros Vagionitis, Ragnhildur Thóra Káradóttir
This scientific commentary refers to ‘Prolonged myelin deficits contribute to neuron loss and functional impairments after ischaemic stroke’ by Cheng et al. (https://doi.org/10.1093/brain/awae029).
-
Neuroinflammation is a player in coma, but in which role? Brain (IF 14.5) Pub Date : 2024-04-04 Olli Tenovuo, David J Loane
This scientific commentary refers to ‘Neuroimmune activation is associated with neurological outcome in anoxic and traumatic coma’ by Sarton et al. (https://doi.org/10.1093/brain/awae045).
-
Preserved striatal innervation maintains motor function despite severe loss of nigral dopaminergic neurons Brain (IF 14.5) Pub Date : 2024-04-04 Thomas Paß, Konrad M Ricke, Pierre Hofmann, Roy S Chowdhury, Yu Nie, Patrick Chinnery, Heike Endepols, Bernd Neumaier, André Carvalho, Lionel Rigoux, Sophie M Steculorum, Julien Prudent, Trine Riemer, Markus Aswendt, Birgit Liss, Bent Brachvogel, Rudolf J Wiesner
Degeneration of dopaminergic neurons in the substantia nigra and their striatal axon terminals causes cardinal motor symptoms of Parkinson’s disease. In idiopathic cases, high levels of mitochondrial DNA alterations leading to mitochondrial dysfunction are a central feature of these vulnerable neurons. Here we present a mouse model expressing the K320E-variant of the mitochondrial helicase Twinkle
-
Predictors of cognition after glioma surgery: connectotomy, structure-function phenotype, plasticity Brain (IF 14.5) Pub Date : 2024-04-04 Guillaume Herbet, Hugues Duffau, Emmanuel Mandonnet
Determining preoperatively the maximal extent of resection that would preserve cognitive functions is the core challenge of brain tumor surgery. Over the last decade, the methodological framework to achieve this goal has been thoroughly renewed: the population-level topographically-focused voxel-based lesion-symptom mapping has been progressively overshadowed by machine learning (ML) algorithmics,
-
Brain and cognitive changes in patients with long COVID compared with infection-recovered control subjects Brain (IF 14.5) Pub Date : 2024-04-01 Víctor M Serrano del Pueblo, Gemma Serrano-Heras, Carlos M Romero Sánchez, Pepa Piqueras Landete, Laura Rojas-Bartolome, Inmaculada Feria, Richard G M Morris, Bryan Strange, Francisco Mansilla, Linda Zhang, Beatriz Castro-Robles, Lourdes Arias-Salazar, Susana López-López, María Payá, Tomás Segura, Mónica Muñoz-López
Between 2.5 and 28% of people infected with SARS-CoV-2 suffer Long COVID or persistence of symptoms for months after acute illness. Many symptoms are neurological, but the brain changes underlying the neuropsychological impairments remain unclear. This study aimed to provide a detailed description of the cognitive profile, the pattern of brain alterations in Long COVID and the potential association
-
Skin keratinocyte-derived SIRT1 and BDNF modulate mechanical allodynia in mouse models of diabetic neuropathy Brain (IF 14.5) Pub Date : 2024-03-30 Jennifer O’Brien, Peter Niehaus, Koping Chang, Juliana Remark, Joy Barrett, Abhishikta Dasgupta, Morayo Adenegan, Mohammad Salimian, Yanni Kevas, Krish Chandrasekaran, Tibor Kristian, Rajeshwari Chellappan, Samuel Rubin, Ashley Kiemen, Catherine Pei-Ju Lu, James W Russell, Cheng-Ying Ho
Diabetic neuropathy is a debilitating disorder characterized by spontaneous and mechanical allodynia. The role of skin mechanoreceptors in the development of mechanical allodynia is unclear. We discovered that mice with diabetic neuropathy had decreased sirtuin 1 (SIRT1) deacetylase activity in foot skin, leading to reduced expression of brain-derived neurotrophic factor (BDNF) and subsequent loss
-
Cul-4 inhibition rescues spastin levels and reduces defects in hereditary spastic paraplegia models Brain (IF 14.5) Pub Date : 2024-03-29 Francesca Sardina, Claudia Carsetti, Ludovica Giorgini, Gaia Fattorini, Gianluca Cestra, Cinzia Rinaldo
Hereditary spastic paraplegias (HSPs) are degenerative motor neuron diseases characterized by progressive spasticity and weakness in the lower limbs. The most common form of HSP is due to SPG4 gene haploinsufficiency. SPG4 encodes the microtubule severing enzyme spastin. Although, there is no cure for SPG4-HSP, strategies to induce a spastin recovery are emerging as promising therapeutic approaches
-
Central visual pathways affected by degenerative retinal disease before and after gene therapy Brain (IF 14.5) Pub Date : 2024-03-28 Manzar Ashtari, Jean Bennett, David A Leopold
Genetic diseases affecting the retina can result in partial or complete loss of visual function. Leber’s Congenital Amaurosis (LCA) is a rare blinding disease, usually inherited in an autosomally recessive manner, with no cure. Retinal gene therapy has been shown to improve vision in LCA patients caused by mutations in the RPE65 gene (LCA2). However, little is known about how activity in central visual
-
Ophthalmate is a new regulator of motor functions via CaSR: Implications for movement disorders Brain (IF 14.5) Pub Date : 2024-03-27 Sammy Alhassen, Derk Hogenkamp, Hung Anh Nguyen, Saeed Al Masri, Geoffrey W Abbott, Olivier Civelli, Amal Alachkar
Dopamine's role as the principal neurotransmitter in motor functions has long been accepted. We broaden this conventional perspective by demonstrating the involvement of non-dopaminergic mechanisms. In mouse models of Parkinson's Disease (PD), we observed that L-DOPA elicited a substantial motor response even when its conversion to dopamine was blocked by inhibiting the enzyme aromatic amino acid decarboxylase
-
Brain morphometry in former American football players: Findings from the DIAGNOSE CTE research project Brain (IF 14.5) Pub Date : 2024-03-27 Hector Arciniega, Zachary H Baucom, Fatima Tuz-Zahra, Yorghos Tripodis, Omar John, Holly Carrington, Nicholas Kim, Evdokiya E Knyazhanskaya, Leonard B Jung, Katherine Breedlove, Tim L T Wiegand, Daniel H Daneshvar, R Jarrett Rushmore, Tashrif Billah, Ofer Pasternak, Michael J Coleman, Charles H Adler, Charles Bernick, Laura J Balcer, Michael L Alosco, Inga K Koerte, Alexander P Lin, Jeffrey L Cummings
Exposure to repetitive head impacts (RHIs) in contact sports is associated with neurodegenerative disorders including chronic traumatic encephalopathy (CTE) which currently can be diagnosed only at postmortem. American football players are at higher risk of developing CTE given their exposure to RHIs. One promising approach for diagnosing CTE in vivo is to explore known neuropathological abnormalities
-
Reticulon 2 deficiency results in an autosomal recessive distal motor neuropathy with lower limb spasticity Brain (IF 14.5) Pub Date : 2024-03-26 Reza Maroofian, Payam Sarraf, Thomas J O’Brien, Mona Kamel, Arman Cakar, Nour Elkhateeb, Tracy Lau, Siddaramappa Jagdish Patil, Christopher J Record, Alejandro Horga, Miriam Essid, Laila Selim, Hanene Benrhouma, Thouraya Ben Younes, Giovanni Zifarelli, Alistair T Pagnamenta, Peter Bauer, Mukhran Khundadze, Andrea Mirecki, Sara Mahmoud Kamel, Mohamed A Elmonem, Ehsan Ghayoor Karimiani, Yalda Jamshidi
Heterozygous RTN2 variants have been previously identified in a limited cohort of families affected by autosomal dominant spastic paraplegia (SPG12-OMIM:604805) with a variable age of onset. Nevertheless, the definitive validity of SPG12 remains to be confidently confirmed due to scarcity of supporting evidence. In our study, we identified and validated seven novel or ultra-rare homozygous loss-of-function
-
Lesion network of oculogyric crises maps to brain dopaminergic transcriptomic signature Brain (IF 14.5) Pub Date : 2024-03-25 Bassam Al-Fatly, Clemens Neudorfer, Diego Kaski, Anthony E Lang, Andrea A Kühn, Michael D Fox, Andreas Horn, Christos Ganos
Oculogyric crises are acute episodes of sustained, typically upward, conjugate deviation of the eyes. Oculogyric crises usually occur as the result of acute D2-dopamine receptor blockade, but the brain areas causally involved in generating this symptom remain elusive. Here, we used data from 14 previously reported cases of lesion-induced oculogyric crises and employed lesion network mapping to identify
-
Lucretius and the neural consequences of traumatic amputation: the role of descending inhibition? Brain (IF 14.5) Pub Date : 2024-03-19 Geoffrey D Schott
Geoffrey Schott explores the writings of the Roman poet Lucretius on some of the remarkable phenomena associated with sudden amputation of a limb, and considers what those observations can tell us about the brain mechanisms that might underpin those phenomena.
-
A direct spinal cord–computer interface enables the control of the paralysed hand in spinal cord injury Brain (IF 14.5) Pub Date : 2024-03-19 Daniela Souza Oliveira, Matthias Ponfick, Dominik I Braun, Marius Osswald, Marek Sierotowicz, Satyaki Chatterjee, Douglas Weber, Bjoern Eskofier, Claudio Castellini, Dario Farina, Thomas Mehari Kinfe, Alessandro Del Vecchio
The paralysis of the muscles controlling the hand dramatically limits the quality of life of individuals living with spinal cord injury (SCI). Here, with a non-invasive neural interface, we demonstrate that eight motor complete SCI individuals (C5-C6) are still able to task-modulate in real-time the activity of populations of spinal motor neurons with residual neural pathways. In all SCI participants
-
Whole genome sequencing increases the diagnostic rate in Charcot-Marie-Tooth disease Brain (IF 14.5) Pub Date : 2024-03-14 Christopher J Record, Menelaos Pipis, Mariola Skorupinska, Julian Blake, Roy Poh, James M Polke, Kelly Eggleton, Tina Nanji, Stephan Zuchner, Andrea Cortese, Henry Houlden, Alexander M Rossor, Matilde Laura, Mary M Reilly
Charcot-Marie-Tooth disease (CMT) is one of the most common and genetically heterogeneous inherited neurological diseases, with more than 130 disease-causing genes. Whole genome sequencing (WGS) has improved diagnosis across genetic diseases, but the diagnostic impact in CMT is yet to be fully reported. We present the diagnostic results from a single specialist inherited neuropathy centre, including
-
Dominant CST3 variants cause adult onset leukodystrophy without amyloid angiopathy Brain (IF 14.5) Pub Date : 2024-03-13 Caroline G Bergner, Marjolein Breur, M Clara Soto-Bernardini, Lisa Schäfer, Julia Lier, Diana Le Duc, Linnaeus Bundalian, Susanna Schubert, David Brenner, Friedmar R Kreuz, Björn Schulte, Quinten Waisfisz, Marianna Bugiani, Wolfgang Köhler, Heinrich Sticht, Rami Abou Jamra, Marjo S van der Knaap
Leukodystrophies are rare genetic white matter disorders that have been regarded as mainly occurring in childhood. Recent years altered this perception, as a growing number of leukodystrophies was described to have an onset at adult ages. Still, many adult patients presenting with white matter changes remain without a specific molecular diagnosis. We describe a novel adult onset leukodystrophy in 16
-
Digenic Leigh syndrome on the background of the m.11778G>A Leber hereditary optic neuropathy variant Brain (IF 14.5) Pub Date : 2024-03-13 Beryll Blickhäuser, Sarah L Stenton, Christiane M Neuhofer, Elisa Floride, Victoria Nesbitt, Carl Fratter, Johannes Koch, Birgit Kauffmann, Claudia Catarino, Lea Dewi Schlieben, Robert Kopajtich, Valerio Carelli, Alfredo A Sadun, Robert McFarland, Fang Fang, Chiara La Morgia, Stéphanie Paquay, Marie Cécile Nassogne, Daniele Ghezzi, Costanza Lamperti, Saskia Wortmann, Jo Poulton, Thomas Klopstock, Holger
Leigh syndrome spectrum (LSS) is a primary mitochondrial disorder defined neuropathologically by a subacute necrotizing encephalomyelopathy and characterised by bilateral basal ganglia and/or brainstem lesions. LSS is associated with variants in several mitochondrial DNA (mtDNA) genes and more than 100 nuclear genes, most often related to mitochondrial complex I (CI) dysfunction. Rarely, LSS has been
-
Paroxysmal dystonia results from the loss of RIM4 in Purkinje cells Brain (IF 14.5) Pub Date : 2024-03-13 Hyuntae Kim, Nesrine Melliti, Eva Breithausen, Katrin Michel, Sara Ferrando Colomer, Ekaterina Poguzhelskaya, Paulina Nemcova, Laura Ewell, Sandra Blaess, Albert Becker, Julika Pitsch, Dirk Dietrich, Susanne Schoch
Full-length RIM1 and 2 are key components of the presynaptic active zone that ubiquitously control excitatory and inhibitory neurotransmitter release. Here, we report that the function of the small RIM isoform RIM4, consisting of a single C2 domain, is strikingly different from that of the long isoforms. RIM4 is dispensable for neurotransmitter release but plays a postsynaptic, cell-type specific role
-
Dysregulation of extracellular potassium distinguishes healthy ageing from neurodegeneration Brain (IF 14.5) Pub Date : 2024-03-08 Fengfei Ding, Qian Sun, Carter Long, Rune Nguyen Rasmussen, Sisi Peng, Qiwu Xu, Ning Kang, Wei Song, Pia Weikop, Steven A Goldman, Maiken Nedergaard
Progressive neuronal loss is a hallmark feature distinguishing neurodegenerative diseases from normal aging. However, the underlying mechanisms remain unknown. Extracellular K+ homeostasis is a potential mediator of neuronal injury since K+ elevations increase excitatory activity. The dysregulation of extracellular K+ and potassium channel expressions during neurodegeneration could contribute to this
-
The clinical and genetic spectrum of inherited glycosylphosphatidylinositol deficiency disorders Brain (IF 14.5) Pub Date : 2024-03-08 Jai Sidpra, Sniya Sudhakar, Asthik Biswas, Flavia Massey, Valentina Turchetti, Tracy Lau, Edward Cook, Javeria Raza Alvi, Hasnaa M Elbendary, Jerry L Jewell, Antonella Riva, Alessandro Orsini, Aglaia Vignoli, Zara Federico, Jessica Rosenblum, An-Sofie Schoonjans, Matthias de Wachter, Ignacio Delgado Alvarez, Ana Felipe-Rucián, Nourelhoda A Haridy, Shahzad Haider, Mashaya Zaman, Selina Banu, Najwa Anwaar
Inherited glycosylphosphatidylinositol deficiency disorders (IGDs) are a group of rare multisystem disorders arising from pathogenic variants in glycosylphosphatidylinositol anchor pathway (GPI-AP) genes. Despite associating 24 of at least 31 GPI-AP genes with human neurogenetic disease, prior reports are limited to single genes without consideration of the GPI-AP as a whole and with limited natural
-
A cell autonomous regulator of neuronal excitability modulates tau in Alzheimer’s disease vulnerable neurons Brain (IF 14.5) Pub Date : 2024-03-07 Patricia Rodriguez-Rodriguez, Luis Enrique Arroyo-Garcia, Christina Tsagkogianni, Lechuan Li, Wei Wang, Ákos Végvári, Isabella Salas-Allende, Zakary Plautz, Angel Cedazo-Minguez, Subhash C Sinha, Olga Troyanskaya, Marc Flajolet, Vicky Yao, Jean-Pierre Roussarie
Neurons from layer II of the entorhinal cortex (ECII) are the first to accumulate tau protein aggregates and degenerate during prodromal Alzheimer’s disease (AD). Gaining insight into the molecular mechanisms underlying this vulnerability will help reveal genes and pathways at play during incipient stages of the disease. Here, we use a data-driven functional genomics approach to model ECII neurons
-
Sex differences in the pleiotropy of hearing difficulty with imaging-derived phenotypes: a brain-wide investigation Brain (IF 14.5) Pub Date : 2024-03-06 Jun He, Brenda Cabrera-Mendoza, Flavio De Angelis, Gita A Pathak, Dora Koller, Sharon G Curhan, Gary C Curhan, Adam P Mecca, Christopher H van Dyck, Renato Polimanti
Hearing difficulty (HD) is one of the major health burdens in older adults. While aging-related changes in the peripheral auditory system play an important role, genetic variation associated with brain structure and function could also be involved in HD predisposition. We analyzed a large-scale HD genome-wide association study (GWAS; Ntotal = 501,825, 56% females) and GWAS data related to 3,935 brain
-
Synaptopathy: presynaptic convergence in frontotemporal dementia and amyotrophic lateral sclerosis Brain (IF 14.5) Pub Date : 2024-03-06 Emma L Clayton, Laura Huggon, Michael A Cousin, Sarah Mizielinska
Frontotemporal dementia and amyotrophic lateral sclerosis are common forms of neurodegenerative disease which share overlapping genetics and pathologies. Crucially, no significantly disease-modifying treatments are available for either disease. Identifying the earliest changes which initiate neuronal dysfunction is important for designing effective intervention therapeutics. The genes mutated in genetic
-
Distinctive antibody responses to Mycobacterium tuberculosis in pulmonary and brain infection Brain (IF 14.5) Pub Date : 2024-03-05 Marianna Spatola, Nadège Nziza, Edward B Irvine, Deniz Cizmeci, Wonyeong Jung, Le Hong Van, Le Thanh Hoang Nhat, Vu Thi Ngoc Ha, Nguyen Hoan Phu, Ho Dang Trung Nghia, Guy Thwaites, Douglas A Lauffenburger, Sarah Fortune, Nguyen Thuy Thuong Thuong, Galit Alter
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), remains a global health burden. While Mtb is primarily a respiratory pathogen, it can spread to other organs, including the brain and meninges, causing TB meningitis (TBM). However, little is known about the immunological mechanisms that leads to differential disease across organs. Attention has focused on differences in T
-
Nav1.8 in small dorsal root ganglion neurons contributes to vincristine-induced mechanical allodynia Brain (IF 14.5) Pub Date : 2024-03-04 Ana Paula Nascimento de Lima, Huiran Zhang, Lubin Chen, Philip R Effraim, Carolina Gomis-Perez, Xiaoyang Cheng, Jianying Huang, Stephen G Waxman, Sulayman D Dib-Hajj
Vincristine-induced peripheral neuropathy (VIPN) is a common side effect of vincristine treatment, which is accompanied by pain and can be dose-limiting. The molecular mechanisms that underlie vincristine-induced pain are not well understood. We have established an animal model to investigate pathophysiological mechanisms of vincristine induced pain. Our previous studies have shown that the tetrodotoxin-sensitive
-
The human subthalamic nucleus transiently inhibits active attentional processes Brain (IF 14.5) Pub Date : 2024-03-04 Cheol Soh, Mario Hervault, Nathan H Chalkley, Cathleen M Moore, Andrea Rohl, Qiang Zhang, Ergun Y Uc, Jeremy D W Greenlee, Jan R Wessel
The subthalamic nucleus (STN) of the basal ganglia is key to the inhibitory control of movement. Consequently, it is a primary target for the neurosurgical treatment of movement disorders like Parkinson’s Disease, where modulating the STN via deep-brain stimulation (DBS) can release excess inhibition of thalamo-cortical motor circuits. However, the STN is also anatomically connected to other thalamo-cortical
-
Vaccination with structurally adapted fungal protein fibrils induces immunity to Parkinson’s disease Brain (IF 14.5) Pub Date : 2024-03-01 Verena Pesch, José Miguel Flores-Fernandez, Sara Reithofer, Liang Ma, Pelin Özdüzenciler, Yannick Busch, Aishwarya Sriraman, YongLiang Wang, Sara Amidian, Chiara V M Kroepel, Laura Müller, Yi Lien, Olivia Rudtke, Benedikt Frieg, Gunnar F Schröder, Holger Wille, Gültekin Tamgüney
The pathological misfolding and aggregation of soluble α-synuclein into toxic oligomers and insoluble amyloid fibrils causes Parkinson’s disease, a progressive age-related neurodegenerative disease for which there is no cure. HET-s is a soluble fungal protein that can form assembled amyloid fibrils in its prion state. We engineered HET-s(218-298) to form four different fibrillar vaccine candidates
-
HLA-DQB1*05 subtypes and not DRB1*10:01 mediates risk in anti-IgLON5 disease Brain (IF 14.5) Pub Date : 2024-03-01 Selina M Yogeshwar, Sergio Muñiz-Castrillo, Lidia Sabater, Vicente Peris-Sempere, Vamsee Mallajosyula, Guo Luo, Han Yan, Eric Yu, Jing Zhang, Ling Lin, Flavia Fagundes Bueno, Xuhuai Ji, Géraldine Picard, Véronique Rogemond, Anne Laurie Pinto, Anna Heidbreder, Romana Höftberger, Francesc Graus, Josep Dalmau, Joan Santamaria, Alex Iranzo, Bettina Schreiner, Maria Pia Giannoccaro, Rocco Liguori, Takayoshi
Anti-IgLON5 disease is a rare and likely underdiagnosed subtype of autoimmune encephalitis. The disease displays a heterogeneous phenotype that includes sleep, movement, and bulbar-associated dysfunction. Presence of IgLON5-antibodies in CSF/serum, together with a strong association with HLA-DRB1*10:01∼DQB1*05:01, support an autoimmune basis. In this study, a multicentric HLA study of 87 anti-IgLON5
-
Atrophy network mapping of clinical subtypes and main symptoms in frontotemporal dementia Brain (IF 14.5) Pub Date : 2024-02-29 Min Chu, Deming Jiang, Dan Li, Shaozhen Yan, Li Liu, Haitian Nan, Yingtao Wang, Yihao Wang, Ailing Yue, Liankun Ren, Kewei Chen, Pedro Rosa-Neto, Jie Lu, Liyong Wu
Frontotemporal Dementia (FTD) is a disease of high heterogeneity, apathy and disinhibition present in all subtypes of FTD and imposes a significant burden on families/society. Traditional neuroimaging analysis has limitations in elucidating the network localization due to individual clinical and neuroanatomical variability. The study aims to identify the atrophy network map associated with different
-
A machine learning approach for gene prioritization in Parkinson’s disease Brain (IF 14.5) Pub Date : 2024-02-28 Aymeric Lanore, Aymeric Basset, Suzanne Lesage
This scientific commentary refers to ‘Machine learning nominates the inositol pathway and novel genes in Parkinson’s disease’ by Yu et al. (https://doi.org/10.1093/brain/awad345).
-
Would you believe your own consciousness? Brain (IF 14.5) Pub Date : 2024-02-27 Riccardo Fesce, Joanne Ursell, Patricia Taylor
Can we ever fully believe what someone tells us about themselves? Riccardo Fesce et al, awarded joint runners up of the Brain Essay Competition 2023, consider whether asking consciousness about itself will ever yield credible and reliable answers.
-
Neuroimmune activation is associated with neurological outcome in anoxic and traumatic coma Brain (IF 14.5) Pub Date : 2024-02-27 Benjamine Sarton, Clovis Tauber, Estéban Fridman, Patrice Péran, Beatrice Riu, Hélène Vinour, Adrian David, Thomas Geeraerts, Fanny Bounes, Vincent Minville, Clément Delmas, Anne-Sophie Salabert, Jean François Albucher, Benoit Bataille, Jean Marc Olivot, Alain Cariou, Lionel Naccache, Pierre Payoux, Nicholas Schiff, Stein Silva
The pathophysiological underpinnings of critically disrupted brain connectomes resulting in coma are poorly understood, but inflammation is potentially an important but still undervalued factor. Here we present a first-in-human prospective study using translocator protein 18 kDa (TSPO) radioligand (F18-DPA714) for PET imaging, to allow in vivo neuroimmune activation quantification on patients with
-
Novel insight into atogepant mechanisms of action in migraine prevention Brain (IF 14.5) Pub Date : 2024-02-27 Agustin Melo-Carrillo, Andrew M Strassman, Ron Broide, Aubrey Adams, Brett Dabruzzo, Mitchell Brin, Rami Burstein
Recently, we showed that while atogepant - a small-molecule calcitonin gene-related peptide (CGRP) receptor antagonist - does not fully prevent activation of nociceptors, it significantly reduces a cortical spreading depression (CSD)-induced early response probability in C-fibers and late response probability in A™-fibers. The current study investigates atogepant effect on CSD-induced activation and
-
How do we get from hyperexcitability to excitotoxicity in amyotrophic lateral sclerosis? Brain (IF 14.5) Pub Date : 2024-02-26 G Lorenzo Odierna, Steve Vucic, Marcus Dyer, Tracey Dickson, Adele Woodhouse, Catherine Blizzard
Amyotrophic lateral sclerosis is a devastating neurodegenerative disease that, at present, has no effective cure. Evidence of increased circulating glutamate and hyperexcitability of the motor cortex in patients with amyotrophic lateral sclerosis have provided an empirical support base for the ‘dying forward’ excitotoxicity hypothesis. The hypothesis postulates that increased activation of upper motor
-
Limitation of life sustaining therapy in disorders of consciousness: ethics and practice Brain (IF 14.5) Pub Date : 2024-02-22 India A Lissak, Michael J Young
Clinical conversations surrounding the continuation or limitation of life-sustaining treatments (LLST) are both challenging and tragically necessary for patients with Disorders of Consciousness (DoC) following severe brain injury. Divergent cultural, philosophical, and religious perspectives contribute to vast heterogeneity in clinical approaches to LLST – as reflected in regional differences and inter-clinician
-
ZSCAN10 deficiency causes a neurodevelopmental disorder with characteristic oto-facial malformations Brain (IF 14.5) Pub Date : 2024-02-22 Lucia Laugwitz, Fubo Cheng, Stephan C Collins, Alexander Hustinx, Nicolas Navarro, Simon Welsch, Helen Cox, Tzung-Chien Hsieh, Aswinkumar Vijayananth, Rebecca Buchert, Benjamin Bender, Stephanie Efthymiou, David Murphy, Faisal Zafar, Nuzhat Rana, Ute Grasshoff, Ruth J Falb, Mona Grimmel, Annette Seibt, Wenxu Zheng, Hamid Ghaedi, Marie Thirion, Sébastien Couette, Reza Azizimalamiri, Saeid Sadeghian
Neurodevelopmental disorders are major indications for genetic referral and have been linked to more than 1,500 loci including genes encoding transcriptional regulators. The dysfunction of transcription factors often results in characteristic syndromic presentations, however, at least half of these patients lack a genetic diagnosis. The implementation of machine learning approaches has the potential
-
A CAG repeat threshold for therapeutics targeting somatic instability in Huntington’s disease Brain (IF 14.5) Pub Date : 2024-02-22 Sarah G Aldous, Edward J Smith, Christian Landles, Georgina F Osborne, Maria Cañibano-Pico, Iulia M Nita, Jemima Phillips, Yongwei Zhang, Bo Jin, Marissa B Hirst, Caroline L Benn, Brian C Bond, Winfried Edelmann, Jonathan R Greene, Gillian P Bates
The Huntington’s disease mutation is a CAG repeat expansion in the huntingtin gene that results in an expanded polyglutamine tract in the huntingtin protein. The CAG repeat is unstable, and expansions of hundreds of CAGs have been detected in Huntington’s disease post-mortem brains. The age of disease onset can be predicted partially from the length of the CAG repeat as measured in blood. Onset age
-
L-serine treatment in patients with GRIN-related encephalopathy: A phase 2A, non-randomized study Brain (IF 14.5) Pub Date : 2024-02-21 Natalia Juliá-Palacios, Mireia Olivella, Mariya Sigatullina Bondarenko, Salvador Ibáñez-Micó, Beatriz Muñoz-Cabello, Olga Alonso-Luengo, Víctor Soto-Insuga, Deyanira García-Navas, Laura Cuesta-Herraiz, Patricia Andreo-Lillo, Sergio Aguilera-Albesa, Antonio Hedrera-Fernández, Elena González Alguacil, Rocío Sánchez-Carpintero, Fernando Martín del Valle, Erika Jiménez González, Lourdes Cean Cabrera, Ines
GRIN-related disorders are rare developmental encephalopathies with variable manifestations and limited therapeutic options. Here, we present the first non-randomized, open-label, single-arm trial (NCT04646447) designed to evaluate tolerability and efficacy of L-serine in children with GRIN genetic variants leading to loss-of-function. In this phase 2A trial, patients aged 2–18 years with GRIN loss-of-function
-
Distinct neuronal circuits mediate cortical hyperexcitability in amyotrophic lateral sclerosis Brain (IF 14.5) Pub Date : 2024-02-20 Nathan Pavey, Andrew Hannaford, Mehdi van den Bos, Matthew C Kiernan, Parvathi Menon, Steve Vucic
Cortical hyperexcitability is an important pathophysiological mechanism in amyotrophic lateral sclerosis (ALS), reflecting a complex interaction of inhibitory and facilitatory interneuronal processes that evolves in the degenerating brain. The advances in physiological techniques have made it possible to interrogate progressive changes in the motor cortex. Specifically, the direction of transcranial
-
Biallelic variants in SNUPN cause a limb girdle muscular dystrophy with myofibrillar-like features Brain (IF 14.5) Pub Date : 2024-02-17 Pablo Iruzubieta, Alberto Damborenea, Mihaela Ioghen, Simon Bajew, Roberto Fernandez-Torrón, Ana Töpf, Álvaro Herrero-Reiriz, Diana Epure, Katharina Vill, Aurelio Hernández-Laín, María Manterola, Mikel Azkargorta, Oihane Pikatza-Menoio, Laura Pérez-Fernandez, Mikel García-Puga, Gisela Gaina, Alexandra Bastian, Ioana Streata, Maggie C Walter, Wolfgang Müller-Felber, Simone Thiele, Saioa Moragón, Nerea
Alterations in RNA-splicing are a molecular hallmark of several neurological diseases, including muscular dystrophies where mutations in genes involved in RNA metabolism or characterised by alterations in RNA splicing have been described. Here, we present five patients from two unrelated families with a limb-girdle muscular dystrophy (LGMD) phenotype carrying a biallelic variant in SNUPN gene. Snurportin-1
-
HSV-1 reactivation results in post-herpetic neuralgia by upregulating Prmt6 and inhibiting cGAS-STING Brain (IF 14.5) Pub Date : 2024-02-17 Erliang Kong, Tong Hua, Jian Li, Yongchang Li, Mei Yang, Ruifeng Ding, Haowei Wang, Huawei Wei, Xudong Feng, Chaofeng Han, Hongbin Yuan
Chronic varicella zoster virus (VZV) infection induced neuroinflammatory condition is the critical pathology of postherpetic neuralgia (PHN). The immune escape mechanism of VZV remains to be elusive. Due to mice have no VZV infection receptor, herpes simplex virus type 1 (HSV-1) infection is a well-established PHN mice model. Transcriptional expression analysis identified that the protein arginine
-
Phenoconversion in pure autonomic failure: a multicentre prospective longitudinal cohort study Brain (IF 14.5) Pub Date : 2024-02-17 Patricio Millar Vernetti, Lucy Norcliffe-Kaufmann, Jose-Alberto Palma, Italo Biaggioni, Cyndya A Shibao, Amanda Peltier, Roy Freeman, Christopher Gibbons, David S Goldstein, Phillip A Low, Wolfgang Singer, Elizabeth A Coon, Mitchell G Miglis, Gregor K Wenning, Alessandra Fanciulli, Steven Vernino, Rebecca A Betensky, Horacio Kaufmann
We aimed to describe the clinical features of patients with pure autonomic failure (PAF) preceding phenoconversion that could be useful as predictive markers for advancing α-synuclein-associated neurodegeneration of the brain. Patients diagnosed with PAF were evaluated at 8 Centers (7-US based and 1 European) and enrolled in a longitudinal observational cohort study (NCT01799915). Subjects underwent
-
Anatomo-functional basis of emotional and motor resonance elicited by facial expressions Brain (IF 14.5) Pub Date : 2024-02-16 Maria Del Vecchio, Pietro Avanzini, Marzio Gerbella, Sara Costa, Flavia Maria Zauli, Piergiorgio d’Orio, Elena Focacci, Ivana Sartori, Fausto Caruana
Simulation theories predict that the observation of other’s expressions modulates neural activity in the same centers controlling their production. This hypothesis has been developed by two models, postulating that the visual input is directly projected either to the motor system for action recognition (motor resonance) or to emotional/interoceptive regions for emotional contagion and social synchronization
-
Deep brain stimulation: a tale of two targets … and closing the loop Brain (IF 14.5) Pub Date : 2024-02-12 Ludvic Zrinzo
This scientific commentary refers to ‘At home adaptive dual target deep brain stimulation in Parkinson disease with proportional control’ by Schmidt et al. (https://doi.org/10.1093/brain/awad429).
-
Graphs and the idiographic brain Brain (IF 14.5) Pub Date : 2024-02-12 Michael S Elmalem, Parashkev Nachev, Ashwani Jha
This scientific commentary refers to ‘Integrating direct electrical brain stimulation with the human connectome’ by Coletta et al. (https://doi.org/10.1093/brain/awad402).
-
A neuroanatomical and cognitive model of impaired social behaviour in frontotemporal dementia Brain (IF 14.5) Pub Date : 2024-02-09 Matthew A Rouse, Richard J Binney, Karalyn Patterson, James B Rowe, Matthew A Lambon Ralph
Impaired social cognition is a core deficit in frontotemporal dementia (FTD). It is most commonly associated with the behavioural-variant of FTD, with atrophy of the orbitofrontal and ventromedial prefrontal cortex. Social cognitive changes are also common in semantic dementia, with atrophy centred on the anterior temporal lobes. The impairment of social behaviour in FTD has typically been attributed
-
Cerebrospinal fluid biomarker panel for synaptic dysfunction in a broad spectrum of neurodegenerative diseases Brain (IF 14.5) Pub Date : 2024-02-06 Johanna Nilsson, Alexa Pichet Binette, Sebastian Palmqvist, Wagner S Brum, Shorena Janelidze, Nicholas J Ashton, Nicola Spotorno, Erik Stomrud, Johan Gobom, Henrik Zetterberg, Ann Brinkmalm, Kaj Blennow, Oskar Hansson
Synaptic dysfunction and degeneration is likely the key pathophysiology for the progression of cognitive decline in various dementia disorders. Synaptic status can be monitored by measurement of synaptic proteins in cerebrospinal fluid (CSF). In the current study, the aim was to investigate and compare both known and new synaptic proteins as potential biomarkers of synaptic dysfunction, especially
-
Spike ripples localize the epileptogenic zone best: an international intracranial study Brain (IF 14.5) Pub Date : 2024-02-06 Wen Shi, Dana Shaw, Katherine G Walsh, Xue Han, Uri T Eden, Robert M Richardson, Stephen V Gliske, Julia Jacobs, Benjamin H Brinkmann, Gregory A Worrell, William C Stacey, Birgit Frauscher, John Thomas, Mark A Kramer, Catherine J Chu
We evaluated whether spike ripples, the combination of epileptiform spikes and ripples, provide a reliable and improved biomarker for the epileptogenic zone (EZ) compared to other leading interictal biomarkers in a multicenter, international study. We first validated an automated spike ripple detector on intracranial EEG recordings. We then applied this detector to subjects from four centers who subsequently
-
Plasma VEGFA and PGF impact longitudinal tau and cognition in preclinical Alzheimer’s disease Brain (IF 14.5) Pub Date : 2024-02-04 Hyun-Sik Yang, Wai-Ying W Yau, Becky C Carlyle, Bianca A Trombetta, Can Zhang, Zahra Shirzadi, Aaron P Schultz, Jeremy J Pruzin, Colleen D Fitzpatrick, Dylan R Kirn, Jennifer S Rabin, Rachel F Buckley, Timothy J Hohman, Dorene M Rentz, Rudolph E Tanzi, Keith A Johnson, Reisa A Sperling, Steven E Arnold, Jasmeer P Chhatwal
Vascular dysfunction is increasingly recognized as an important contributor to the pathogenesis of Alzheimer’s disease. Alterations in vascular endothelial growth factor (VEGF) pathways have been implicated as potential mechanisms. However, the specific impact of VEGF proteins in preclinical Alzheimer’s disease and their relationships with other Alzheimer’s disease and vascular pathologies during this
-
Engineered Wnt7a ligands rescue blood–brain barrier and cognitive deficits in a COVID-19 mouse model Brain (IF 14.5) Pub Date : 2024-02-02 Troy N Trevino, Avital B Fogel, Guliz Otkiran, Seshadri B Niladhuri, Mark A Sanborn, Jacob Class, Ali A Almousawi, Benoit Vanhollebeke, Leon M Tai, Jalees Rehman, Justin M Richner, Sarah E Lutz
Respiratory infection with SARS-CoV-2 causes systemic vascular inflammation and cognitive impairment. We sought to identify the underlying mechanisms mediating cerebrovascular dysfunction and inflammation following mild respiratory SARS-CoV-2 infection. To this end, we conduced unbiased transcriptional analysis to identify brain endothelial cell signaling pathways dysregulated by mouse adapted SARS-CoV-2
-
Impaired value-based decision-making in Parkinson’s disease apathy Brain (IF 14.5) Pub Date : 2024-02-02 William Gilmour, Graeme Mackenzie, Mathias Feile, Louise Tayler-Grint, Szabolcs Suveges, Jennifer A Macfarlane, Angus D Macleod, Vicky Marshall, Iris Q Grunwald, J Douglas Steele, Tom Gilbertson
Apathy is a common and disabling complication of Parkinson’s disease characterised by reduced goal-directed behaviour. Several studies have reported dysfunction within prefrontal cortical regions and projections from brainstem nuclei whose neuromodulators include dopamine, serotonin and noradrenaline. Work in animal and human neuroscience have confirmed contributions of these neuromodulators on aspects
-
The historical context of migraine stigma Brain (IF 14.5) Pub Date : 2024-02-01 William Young
The social and psychological stigma of disease can be profound. William Young, awarded joint runner-up of the Brain Essay Competition 2023, discusses how for people with migraine, this stigma can be a huge burden which excludes and disenfranchises them from many areas of normal life.