Brain最新文献

{"title":"Cholinergic deficiency in Parkinson's disease patients with visual hallucinations.","authors":"Emile d'Angremont, Sygrid van der Zee, Sofie Slingerland, Anne C Slomp, Erik F J de Vries, Teus van Laar, Iris E Sommer","doi":"10.1093/brain/awae186","DOIUrl":"10.1093/brain/awae186","url":null,"abstract":"<p><p>Visual hallucinations can increase the burden of disease for both patients with Parkinson's disease and their caregivers. Multiple neurotransmitters have been implicated in the neuropathology of visual hallucinations, which provide targets for treatment and prevention. In this study, we assessed the association between cholinergic denervation and visual hallucinations in Parkinson's disease in vivo, using PET imaging of the cholinergic system. A total of 38 patients with Parkinson's disease participated in this study. A group of 10 healthy subjects, matched for age, sex and education, was included for comparison. None of the participants used cholinergic drugs. Thirteen patients who had experienced visual hallucinations in the past month (VH+) were compared with 20 patients who had never experienced visual hallucinations in their lives (VH-). Cholinergic system integrity was assessed with PET imaging using 18F-fluoroethoxybenzovesamicol as the tracer. We assessed the differences in tracer uptake between groups by cluster-based analysis and by analysis of predefined regions of interest consisting of the ventral visual stream, the dorsal attentional network, the ventral attentional network and the lateral geniculate nucleus and mediodorsal nucleus of the thalamus. The Parkinson's disease group (n = 38) showed an extensive pattern of decreased tracer uptake throughout the brain compared with the controls (n = 10). Within the Parkinson's disease group, the VH+ group (n = 13) showed a cluster of decreased tracer uptake compared with the VH- group (n = 20), which covered most of the left ventral visual stream and extended towards superior temporal areas. These results were mirrored in the regions of interest-based analysis, in which the VH+ group showed the strongest deficits in the left inferior temporal gyrus and the left superior temporal gyrus compared with the VH- group. Visual hallucinations in Parkinson's disease are associated with a marked cholinergic deficiency in the left ventral visual stream and the left superior temporal lobe, in addition to an extensive global cholinergic denervation in the general Parkinson's disease population.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dopamine and deep brain stimulation accelerate the neural dynamics of volitional action in Parkinson's disease.","authors":"Richard M Köhler, Thomas S Binns, Timon Merk, Guanyu Zhu, Zixiao Yin, Baotian Zhao, Meera Chikermane, Jojo Vanhoecke, Johannes L Busch, Jeroen G V Habets, Katharina Faust, Gerd-Helge Schneider, Alessia Cavallo, Stefan Haufe, Jianguo Zhang, Andrea A Kühn, John-Dylan Haynes, Wolf-Julian Neumann","doi":"10.1093/brain/awae219","DOIUrl":"10.1093/brain/awae219","url":null,"abstract":"<p><p>The ability to initiate volitional action is fundamental to human behaviour. Loss of dopaminergic neurons in Parkinson's disease is associated with impaired action initiation, also termed akinesia. Both dopamine and subthalamic deep brain stimulation (DBS) can alleviate akinesia, but the underlying mechanisms are unknown. An important question is whether dopamine and DBS facilitate de novo build-up of neural dynamics for motor execution or accelerate existing cortical movement initiation signals through shared modulatory circuit effects. Answering these questions can provide the foundation for new closed-loop neurotherapies with adaptive DBS, but the objectification of neural processing delays prior to performance of volitional action remains a significant challenge. To overcome this challenge, we studied readiness potentials and trained brain signal decoders on invasive neurophysiology signals in 25 DBS patients (12 female) with Parkinson's disease during performance of self-initiated movements. Combined sensorimotor cortex electrocorticography and subthalamic local field potential recordings were performed OFF therapy (n = 22), ON dopaminergic medication (n = 18) and on subthalamic deep brain stimulation (n = 8). This allowed us to compare their therapeutic effects on neural latencies between the earliest cortical representation of movement intention as decoded by linear discriminant analysis classifiers and onset of muscle activation recorded with electromyography. In the hypodopaminergic OFF state, we observed long latencies between motor intention and motor execution for readiness potentials and machine learning classifications. Both, dopamine and DBS significantly shortened these latencies, hinting towards a shared therapeutic mechanism for alleviation of akinesia. To investigate this further, we analysed directional cortico-subthalamic oscillatory communication with multivariate granger causality. Strikingly, we found that both therapies independently shifted cortico-subthalamic oscillatory information flow from antikinetic beta (13-35 Hz) to prokinetic theta (4-10 Hz) rhythms, which was correlated with latencies in motor execution. Our study reveals a shared brain network modulation pattern of dopamine and DBS that may underlie the acceleration of neural dynamics for augmentation of movement initiation in Parkinson's disease. Instead of producing or increasing preparatory brain signals, both therapies modulate oscillatory communication. These insights provide a link between the pathophysiology of akinesia and its' therapeutic alleviation with oscillatory network changes in other non-motor and motor domains, e.g. related to hyperkinesia or effort and reward perception. In the future, our study may inspire the development of clinical brain computer interfaces based on brain signal decoders to provide temporally precise support for action initiation in patients with brain disorders.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply: Putative benefits of vitamin D supplements in multiple sclerosis out of reach due to sample size.","authors":"Bruce V Taylor, Anne-Louise Ponsonby, Mark Stein, Robyn Lucas, Julia Morahan, Keith Dear, Helmut Butzkueven","doi":"10.1093/brain/awae246","DOIUrl":"10.1093/brain/awae246","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skin keratinocyte-derived SIRT1 and BDNF modulate mechanical allodynia in mouse models of diabetic neuropathy.","authors":"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","doi":"10.1093/brain/awae100","DOIUrl":"10.1093/brain/awae100","url":null,"abstract":"<p><p>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 of innervation in Meissner corpuscles, a mechanoreceptor expressing the BDNF receptor TrkB. When SIRT1 was depleted from skin, the mechanical allodynia worsened in diabetic neuropathy mice, likely due to retrograde degeneration of the Meissner-corpuscle innervating Aβ axons and aberrant formation of Meissner corpuscles which may have increased the mechanosensitivity. The same phenomenon was also noted in skin-keratinocyte specific BDNF knockout mice. Furthermore, overexpression of SIRT1 in skin induced Meissner corpuscle reinnervation and regeneration, resulting in significant improvement of diabetic mechanical allodynia. Overall, the findings suggested that skin-derived SIRT1 and BDNF function in the same pathway in skin sensory apparatus regeneration and highlighted the potential of developing topical SIRT1-activating compounds as a novel treatment for diabetic mechanical allodynia.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140329562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An alternative therapeutic approach to haematopoetic stem cell transplantation in early cerebral adrenoleukodystrophy.","authors":"Jeremy Chataway, Charles Wade, Elaine Murphy, David S Lynch","doi":"10.1093/brain/awae261","DOIUrl":"10.1093/brain/awae261","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in the pleiotropy of hearing difficulty with imaging-derived phenotypes: a brain-wide investigation.","authors":"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","doi":"10.1093/brain/awae077","DOIUrl":"10.1093/brain/awae077","url":null,"abstract":"<p><p>Hearing difficulty (HD) is a major health burden in older adults. While ageing-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 analysed a large-scale HD genome-wide association study (GWAS; ntotal = 501 825, 56% females) and GWAS data related to 3935 brain imaging-derived phenotypes (IDPs) assessed in up to 33 224 individuals (52% females) using multiple MRI modalities. To investigate HD pleiotropy with brain structure and function, we conducted genetic correlation, latent causal variable, Mendelian randomization and multivariable generalized linear regression analyses. Additionally, we performed local genetic correlation and multi-trait co-localization analyses to identify genomic regions and loci implicated in the pleiotropic mechanisms shared between HD and brain IDPs. We observed a widespread genetic correlation of HD with 120 IDPs in females, 89 in males and 171 in the sex-combined analysis. The latent causal variable analysis showed that some of these genetic correlations could be due to cause-effect relationships. For seven of them, the causal effects were also confirmed by the Mendelian randomization approach: vessel volume→HD in the sex-combined analysis; hippocampus volume→HD, cerebellum grey matter volume→HD, primary visual cortex volume→HD and HD→fluctuation amplitudes of node 46 in resting-state functional MRI dimensionality 100 in females; global mean thickness→HD and HD→mean orientation dispersion index in superior corona radiata in males. The local genetic correlation analysis identified 13 pleiotropic regions between HD and these seven IDPs. We also observed a co-localization signal for the rs13026575 variant between HD, primary visual cortex volume and SPTBN1 transcriptomic regulation in females. Brain structure and function may have a role in the sex differences in HD predisposition via possible cause-effect relationships and shared regulatory mechanisms.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140058655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomechanical instability of the brain-CSF interface in hydrocephalus.","authors":"Phan Q Duy, Neel H Mehta, Kristopher T Kahle","doi":"10.1093/brain/awae155","DOIUrl":"10.1093/brain/awae155","url":null,"abstract":"<p><p>Hydrocephalus, characterized by progressive expansion of the CSF-filled ventricles (ventriculomegaly), is the most common reason for brain surgery. 'Communicating' (i.e. non-obstructive) hydrocephalus is classically attributed to a primary derangement in CSF homeostasis, such as choroid plexus-dependent CSF hypersecretion, impaired cilia-mediated CSF flow currents, or decreased CSF reabsorption via the arachnoid granulations or other pathways. Emerging data suggest that abnormal biomechanical properties of the brain parenchyma are an under-appreciated driver of ventriculomegaly in multiple forms of communicating hydrocephalus across the lifespan. We discuss recent evidence from human and animal studies that suggests impaired neurodevelopment in congenital hydrocephalus, neurodegeneration in elderly normal pressure hydrocephalus and, in all age groups, inflammation-related neural injury in post-infectious and post-haemorrhagic hydrocephalus, can result in loss of stiffness and viscoelasticity of the brain parenchyma. Abnormal brain biomechanics create barrier alterations at the brain-CSF interface that pathologically facilitates secondary enlargement of the ventricles, even at normal or low intracranial pressures. This 'brain-centric' paradigm has implications for the diagnosis, treatment and study of hydrocephalus from womb to tomb.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Explaining slow seizure propagation with white matter tractography.","authors":"Abdullah Azeem, Chifaou Abdallah, Nicolás von Ellenrieder, Charbel El Kosseifi, Birgit Frauscher, Jean Gotman","doi":"10.1093/brain/awae192","DOIUrl":"10.1093/brain/awae192","url":null,"abstract":"<p><p>Epileptic seizures recorded with stereo-EEG can take a fraction of a second or several seconds to propagate from one region to another. What explains such propagation patterns? We combine tractography and stereo-EEG to determine the relationship between seizure propagation and the white matter architecture and to describe seizure propagation mechanisms. Patient-specific spatiotemporal seizure propagation maps were combined with tractography from diffusion imaging of matched subjects from the Human Connectome Project. The onset of seizure activity was marked on a channel-by-channel basis by two board-certified neurologists for all channels involved in the seizure. We measured the tract connectivity (number of tracts) between regions-of-interest pairs among the seizure onset zone, regions of seizure spread and non-involved regions. We also investigated how tract-connected the seizure onset zone is to regions of early seizure spread compared with regions of late spread. Comparisons were made after correcting for differences in distance. Sixty-nine seizures were marked across 26 patients with drug-resistant epilepsy; 11 were seizure free after surgery (Engel IA) and 15 were not (Engel IB-Engel IV). The seizure onset zone was more tract-connected to regions of seizure spread than to non-involved regions (P < 0.0001); however, regions of seizure spread were not differentially tract-connected to other regions of seizure spread compared with non-involved regions. In seizure-free patients only, regions of seizure spread were more tract-connected to the seizure onset zone than to other regions of spread (P < 0.0001). Over the temporal evolution of a seizure, the seizure onset zone was significantly more tract-connected to regions of early spread compared with regions of late spread in seizure-free patients only (P < 0.0001). By integrating information on structure, we demonstrate that seizure propagation is likely to be mediated by white matter tracts. The pattern of connectivity between seizure onset zone, regions of spread and non-involved regions demonstrates that the onset zone might be largely responsible for seizures propagating throughout the brain, rather than seizures propagating to intermediate points, from which further propagation takes place. Our findings also suggest that seizure propagation over seconds might be the result of a continuous bombardment of action potentials from the seizure onset zone to regions of spread. In non-seizure-free patients, the paucity of tracts from the presumed seizure onset zone to regions of spread suggests that the onset zone was missed. Fully understanding the structure-propagation relationship might eventually provide insight into selecting the correct targets for epilepsy surgery.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic insights into allodynia in diabetic peripheral neuropathy.","authors":"Masud Husain","doi":"10.1093/brain/awae280","DOIUrl":"https://doi.org/10.1093/brain/awae280","url":null,"abstract":"","PeriodicalId":9063,"journal":{"name":"Brain","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Connecting dementia risk loci to the CSF proteome identifies pathophysiological leads for dementia.","authors":"Lianne M Reus, Iris E Jansen, Betty M Tijms, Pieter Jelle Visser, Niccoló Tesi, Sven J van der Lee, Lisa Vermunt, Carel F W Peeters, Lisa A De Groot, Yanaika S Hok-A-Hin, Alice Chen-Plotkin, David J Irwin, William T Hu, Lieke H Meeter, John C van Swieten, Henne Holstege, Marc Hulsman, Afina W Lemstra, Yolande A L Pijnenburg, Wiesje M van der Flier, Charlotte E Teunissen, Marta Del Campo Milan","doi":"10.1093/brain/awae090","DOIUrl":"10.1093/brain/awae090","url":null,"abstract":"<p><p>Genome-wide association studies have successfully identified many genetic risk loci for dementia, but exact biological mechanisms through which genetic risk factors contribute to dementia remains unclear. Integrating CSF proteomic data with dementia risk loci could reveal intermediate molecular pathways connecting genetic variance to the development of dementia. We tested to what extent effects of known dementia risk loci can be observed in CSF levels of 665 proteins [proximity extension-based (PEA) immunoassays] in a deeply-phenotyped mixed memory clinic cohort [n = 502, mean age (standard deviation, SD) = 64.1 (8.7) years, 181 female (35.4%)], including patients with Alzheimer's disease (AD, n = 213), dementia with Lewy bodies (DLB, n = 50) and frontotemporal dementia (FTD, n = 93), and controls (n = 146). Validation was assessed in independent cohorts (n = 99 PEA platform, n = 198, mass reaction monitoring-targeted mass spectroscopy and multiplex assay). We performed additional analyses stratified according to diagnostic status (AD, DLB, FTD and controls separately), to explore whether associations between CSF proteins and genetic variants were specific to disease or not. We identified four AD risk loci as protein quantitative trait loci (pQTL): CR1-CR2 (rs3818361, P = 1.65 × 10-8), ZCWPW1-PILRB (rs1476679, P = 2.73 × 10-32), CTSH-CTSH (rs3784539, P = 2.88 × 10-24) and HESX1-RETN (rs186108507, P = 8.39 × 10-8), of which the first three pQTLs showed direct replication in the independent cohorts. We identified one AD-specific association between a rare genetic variant of TREM2 and CSF IL6 levels (rs75932628, P = 3.90 × 10-7). DLB risk locus GBA showed positive trans effects on seven inter-related CSF levels in DLB patients only. No pQTLs were identified for FTD loci, either for the total sample as for analyses performed within FTD only. Protein QTL variants were involved in the immune system, highlighting the importance of this system in the pathophysiology of dementia. We further identified pQTLs in stratified analyses for AD and DLB, hinting at disease-specific pQTLs in dementia. Dissecting the contribution of risk loci to neurobiological processes aids in understanding disease mechanisms underlying dementia.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}