Brain最新文献

{"title":"Quantitative susceptibility mapping at 7 T in COVID-19: brainstem effects and outcome associations.","authors":"Catarina Rua,Betty Raman,Christopher T Rodgers,Virginia F J Newcombe,Anne Manktelow,Doris A Chatfield,Stephen J Sawcer,Joanne G Outtrim,Victoria C Lupson,Emmanuel A Stamatakis,Guy B Williams,William T Clarke,Lin Qiu,Martyn Ezra,Rory McDonald,Stuart Clare,Mark Cassar,Stefan Neubauer,Karen D Ersche,Edward T Bullmore,David K Menon,Kyle Pattinson,James B Rowe","doi":"10.1093/brain/awae215","DOIUrl":"https://doi.org/10.1093/brain/awae215","url":null,"abstract":"Post-mortem studies have shown that patients dying from severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection frequently have pathological changes in their CNS, particularly in the brainstem. Many of these changes are proposed to result from para-infectious and/or post-infection immune responses. Clinical symptoms such as fatigue, breathlessness, and chest pain are frequently reported in post-hospitalized coronavirus disease 2019 (COVID-19) patients. We propose that these symptoms are in part due to damage to key neuromodulatory brainstem nuclei. While brainstem involvement has been demonstrated in the acute phase of the illness, the evidence of long-term brainstem change on MRI is inconclusive. We therefore used ultra-high field (7 T) quantitative susceptibility mapping (QSM) to test the hypothesis that brainstem abnormalities persist in post-COVID patients and that these are associated with persistence of key symptoms. We used 7 T QSM data from 30 patients, scanned 93-548 days after hospital admission for COVID-19 and compared them to 51 age-matched controls without prior history of COVID-19 infection. We correlated the patients' QSM signals with disease severity (duration of hospital admission and COVID-19 severity scale), inflammatory response during the acute illness (C-reactive protein, D-dimer and platelet levels), functional recovery (modified Rankin scale), depression (Patient Health Questionnaire-9) and anxiety (Generalized Anxiety Disorder-7). In COVID-19 survivors, the MR susceptibility increased in the medulla, pons and midbrain regions of the brainstem. Specifically, there was increased susceptibility in the inferior medullary reticular formation and the raphe pallidus and obscurus. In these regions, patients with higher tissue susceptibility had worse acute disease severity, higher acute inflammatory markers, and significantly worse functional recovery. This study contributes to understanding the long-term effects of COVID-19 and recovery. Using non-invasive ultra-high field 7 T MRI, we show evidence of brainstem pathophysiological changes associated with inflammatory processes in post-hospitalized COVID-19 survivors.","PeriodicalId":9063,"journal":{"name":"Brain","volume":null,"pages":null},"PeriodicalIF":14.5,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385358","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":"Data-driven neuroanatomical subtypes of primary progressive aphasia","authors":"Beatrice Taylor, Martina Bocchetta, Cameron Shand, Emily G Todd, Anthipa Chokesuwattanaskul, Sebastian J Crutch, Jason D Warren, Jonathan D Rohrer, Chris J D Hardy, Neil P Oxtoby","doi":"10.1093/brain/awae314","DOIUrl":"https://doi.org/10.1093/brain/awae314","url":null,"abstract":"The primary progressive aphasias are rare, language-led dementias, with three main variants: semantic, non-fluent/agrammatic, and logopenic. Whilst semantic variant has a clear neuroanatomical profile, the non-fluent/agrammatic and logopenic variants are difficult to discriminate from neuroimaging. Previous phenotype-driven studies have characterised neuroanatomical profiles of each variant on MRI. In this work we used a machine learning algorithm known as SuStaIn to discover data-driven neuroanatomical “subtype” progression profiles and performed an in-depth subtype–phenotype analysis to characterise the heterogeneity of primary progressive aphasia. Our study included 270 participants with primary progressive aphasia seen for research in the UCL Queen Square Institute of Neurology Dementia Research Centre, with follow-up scans available for 137 participants. This dataset included individuals diagnosed with all three main variants (semantic: n=94, non-fluent/agrammatic: n=109, logopenic: n=51) as well as individuals with un-specified primary progressive aphasia (n=16). A data set of 66 patients (semantic n=37, non-fluent/agrammatic: n=29) from the ALLFTD North American cohort study, was used to validate our results. MRI scans were segmented and SuStaIn was employed on 19 regions of interest to identify neuroanatomical profiles independent of the diagnosis. We assessed the assignment of subtypes and stages, as well as their longitudinal consistency. We discovered four neuroanatomical subtypes of primary progressive aphasia, labelled S1 (left temporal), S2 (insula), S3 (temporoparietal), S4 (frontoparietal), exhibiting robustness to statistical scrutiny. S1 correlated strongly with semantic variant, while S2, S3, and S4 showed mixed associations with the logopenic and non-fluent/agrammatic variants. Notably, S3 displayed a neuroanatomical signature akin to a logopenic only signature, yet a significant proportion of logopenic cases were allocated to S2. The non-fluent/agrammatic variant demonstrated diverse associations with S2, S3, and S4. No clear relationship emerged between any of the neuroanatomical subtypes and the unspecified cases. At first follow up 84% of patients’ subtype assignment was stable, and 91.9% of patients’ stage assignment was stable. We partially validated our findings in the ALLFTD dataset, finding comparable qualitative patterns. Our study, leveraging machine learning on a large primary progressive aphasia dataset, delineated four distinct neuroanatomical patterns. Our findings suggest that separable spatio-temporal neuroanatomical phenotypes do exist within the PPA spectrum, but that these are noisy, particularly for nfvPPA and lvPPA. Furthermore, these phenotypes do not always conform to standard formulations of clinico-anatomical correlation. Understanding the multifaceted profiles of the disease, encompassing neuroanatomical, molecular, clinical, and cognitive dimensions, holds potential implications for clinical decisio","PeriodicalId":9063,"journal":{"name":"Brain","volume":null,"pages":null},"PeriodicalIF":14.5,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142384346","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":"Brain repair mechanisms after cell therapy for stroke.","authors":"Ruslan Rust, Lina R Nih, Luca Liberale, Hao Yin, Mohamad El Amki, Lin Kooi Ong, Berislav V Zlokovic","doi":"10.1093/brain/awae204","DOIUrl":"10.1093/brain/awae204","url":null,"abstract":"<p><p>Cell-based therapies hold great promise for brain repair after stroke. While accumulating evidence confirms the preclinical and clinical benefits of cell therapies, the underlying mechanisms by which they promote brain repair remain unclear. Here, we briefly review endogenous mechanisms of brain repair after ischaemic stroke and then focus on how different stem and progenitor cell sources can promote brain repair. Specifically, we examine how transplanted cell grafts contribute to improved functional recovery either through direct cell replacement or by stimulating endogenous repair pathways. Additionally, we discuss recently implemented preclinical refinement methods, such as preconditioning, microcarriers, genetic safety switches and universal (immune evasive) cell transplants, as well as the therapeutic potential of these pharmacologic and genetic manipulations to further enhance the efficacy and safety of cell therapies. By gaining a deeper understanding of post-ischaemic repair mechanisms, prospective clinical trials may be further refined to advance post-stroke cell therapy to the clinic.</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/PMC11449145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141449683","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":"Piezo2 voltage-block regulates mechanical pain sensitivity.","authors":"Oscar Sánchez-Carranza, Sampurna Chakrabarti, Johannes Kühnemund, Fred Schwaller, Valérie Bégay, Jonathan Alexis García-Contreras, Lin Wang, Gary R Lewin","doi":"10.1093/brain/awae227","DOIUrl":"10.1093/brain/awae227","url":null,"abstract":"&lt;p&gt;&lt;p&gt;PIEZO2 is a trimeric mechanically-gated ion channel expressed by most sensory neurons in the dorsal root ganglia. Mechanosensitive PIEZO2 channels are also genetically required for normal touch sensation in both mice and humans. We previously showed that PIEZO2 channels are also strongly modulated by membrane voltage. Specifically, it is only at very positive voltages that all channels are available for opening by mechanical force. Conversely, most PIEZO2 channels are blocked at normal negative resting membrane potentials. The physiological function of this unusual biophysical property of PIEZO2 channels, however, remained unknown. We characterized the biophysical properties of three PIEZO2 ion channel mutations at an evolutionarily conserved arginine (R2756). Using genome engineering in mice we generated Piezo2R2756H/R2756H and Piezo2R2756K/R2756K knock-in mice to characterize the physiological consequences of altering PIEZO2 voltage sensitivity in vivo. We measured endogenous mechanosensitive currents in sensory neurons isolated from the dorsal root ganglia and characterized mechanoreceptor and nociceptor function using electrophysiology. Mice were also assessed behaviourally and morphologically. Mutations at the conserved Arginine (R2756) dramatically changed the biophysical properties of the channel relieving voltage block and lowering mechanical thresholds for channel activation. Piezo2R2756H/R2756H and Piezo2R2756K/R2756K knock-in mice that were homozygous for gain-of-function mutations were viable and were tested for sensory changes. Surprisingly, mechanosensitive currents in nociceptors, neurons that detect noxious mechanical stimuli, were substantially sensitized in Piezo2 knock-in mice, but mechanosensitive currents in most mechanoreceptors that underlie touch sensation were only mildly affected by the same mutations. Single-unit electrophysiological recordings from sensory neurons innervating the glabrous skin revealed that rapidly-adapting mechanoreceptors that innervate Meissner's corpuscles exhibited slightly decreased mechanical thresholds in Piezo2 knock-in mice. Consistent with measurements of mechanically activated currents in isolated sensory neurons essentially all cutaneous nociceptors, both fast conducting Aδ-mechanonociceptors and unmyelinated C-fibre nociceptors were substantially more sensitive to mechanical stimuli and indeed acquired receptor properties similar to ultrasensitive touch receptors in Piezo2 knock-in mice. Mechanical stimuli also induced enhanced ongoing activity in cutaneous nociceptors in Piezo2 knock-in mice and hyper-sensitive PIEZO2 channels were sufficient alone to drive ongoing activity, even in isolated nociceptive neurons. Consistently, Piezo2 knock-in mice showed substantial behavioural hypersensitivity to noxious mechanical stimuli. Our data indicate that ongoing activity and sensitization of nociceptors, phenomena commonly found in human chronic pain syndromes, can be driven by relieving t","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/PMC11449130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562648","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":"The immune system in Parkinson's disease: what we know so far.","authors":"Cintia Roodveldt, Liliana Bernardino, Ozgur Oztop-Cakmak, Milorad Dragic, Kari E Fladmark, Sibel Ertan, Busra Aktas, Carlos Pita, Lucia Ciglar, Gaetan Garraux, Caroline Williams-Gray, Rodrigo Pacheco, Marina Romero-Ramos","doi":"10.1093/brain/awae177","DOIUrl":"10.1093/brain/awae177","url":null,"abstract":"<p><p>Parkinson's disease is characterized neuropathologically by the degeneration of dopaminergic neurons in the ventral midbrain, the accumulation of α-synuclein (α-syn) aggregates in neurons and chronic neuroinflammation. In the past two decades, in vitro, ex vivo and in vivo studies have consistently shown the involvement of inflammatory responses mediated by microglia and astrocytes, which may be elicited by pathological α-syn or signals from affected neurons and other cell types, and are directly linked to neurodegeneration and disease development. Apart from the prominent immune alterations seen in the CNS, including the infiltration of T cells into the brain, more recent studies have demonstrated important changes in the peripheral immune profile within both the innate and adaptive compartments, particularly involving monocytes, CD4+ and CD8+ T cells. This review aims to integrate the consolidated understanding of immune-related processes underlying the pathogenesis of Parkinson's disease, focusing on both central and peripheral immune cells, neuron-glia crosstalk as well as the central-peripheral immune interaction during the development of Parkinson's disease. Our analysis seeks to provide a comprehensive view of the emerging knowledge of the mechanisms of immunity in Parkinson's disease and the implications of this for better understanding the overall pathogenesis of this disease.</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/PMC11449148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141236655","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":"The visual cortex in the blind but not the auditory cortex in the deaf becomes multiple-demand regions.","authors":"Hasan Duymuş, Mohini Verma, Yasemin Güçlütürk, Mesut Öztürk, Ayşe B Varol, Şehmus Kurt, Tamer Gezici, Berhan F Akgür, İrem Giray, Elif E Öksüz, Ausaf A Farooqui","doi":"10.1093/brain/awae187","DOIUrl":"10.1093/brain/awae187","url":null,"abstract":"<p><p>The fate of deprived sensory cortices (visual regions in the blind and auditory regions in the deaf) exemplifies the extent to which experience can change brain regions. These regions are frequently seen to activate during tasks involving other sensory modalities, leading many authors to infer that these regions have started to process sensory information of other modalities. However, such observations can also imply that these regions are now activating in response to any task event, regardless of the sensory modality. Activating in response to task events, irrespective of the sensory modality involved, is a feature of the multiple-demands (MD) network. This is a set of regions within the frontal and parietal cortices that activate in response to any kind of control demand. Thus, demands as diverse as attention, perceptual difficulty, rule-switching, updating working memory, inhibiting responses, decision-making and difficult arithmetic all activate the same set of regions that are thought to instantiate domain-general cognitive control and underpin fluid intelligence. We investigated whether deprived sensory cortices, or foci within them, become part of the MD network. We tested whether the same foci within the visual regions of the blind and auditory regions of the deaf activated in response to different control demands. We found that control demands related to updating auditory working memory, difficult tactile decisions, time-duration judgments and sensorimotor speed all activated the entire bilateral occipital regions in the blind but not in the sighted. These occipital regions in the blind were the only regions outside the canonical frontoparietal MD regions to show such activation in response to multiple control demands. Furthermore, compared with the sighted, these occipital regions in the blind had higher functional connectivity with frontoparietal MD regions. Early deaf, in contrast, did not activate their auditory regions in response to different control demands, showing that auditory regions do not become MD regions in the deaf. We suggest that visual regions in the blind do not take a new sensory role but become part of the MD network, and this is not a response of all deprived sensory cortices but a feature unique to the visual regions.</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/PMC11449128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305391","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":"Leriglitazone halts disease progression in adult patients with early cerebral adrenoleukodystrophy.","authors":"Marianne Golse, Isabelle Weinhofer, Bernardo Blanco, Magali Barbier, Elise Yazbeck, Camille Huiban, Boris Chaumette, Bertrand Pichon, Ali Fatemi, Silvia Pascual, Marc Martinell, Johannes Berger, Vincent Perlbarg, Damien Galanaud, Fanny Mochel","doi":"10.1093/brain/awae169","DOIUrl":"10.1093/brain/awae169","url":null,"abstract":"<p><p>Cerebral adrenoleukodystrophy (CALD) is an X-linked rapidly progressive demyelinating disease leading to death usually within a few years. The standard of care is haematopoietic stem cell transplantation (HSCT), but many men are not eligible due to age, absence of a matched donor or lesions of the corticospinal tracts (CST). Based on the ADVANCE study showing that leriglitazone decreases the occurrence of CALD, we treated 13 adult CALD patients (19-67 years of age) either not eligible for HSCT (n = 8) or awaiting HSCT (n = 5). Patients were monitored every 3 months with standardized neurological scores, plasma biomarkers and brain MRI comprising lesion volumetrics and diffusion tensor imaging. The disease stabilized clinically and radiologically in 10 patients with up to 2 years of follow-up. Five patients presented with gadolinium enhancing CST lesions that all turned gadolinium negative and, remarkably, regressed in four patients. Plasma neurofilament light chain levels stabilized in all 10 patients and correlated with lesion load. The two patients who continued to deteriorate were over 60 years of age with prominent cognitive impairment. One patient died rapidly from coronavirus disease 2019. These results suggest that leriglitazone can arrest disease progression in adults with early-stage CALD and may be an alternative treatment to HSCT.</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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141236652","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":"Putative benefits of vitamin D supplements in multiple sclerosis out of reach due to sample size.","authors":"Cato E A Corsten, Beatrijs H A Wokke, Joost Smolders","doi":"10.1093/brain/awae238","DOIUrl":"10.1093/brain/awae238","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":"141625892","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":"Brain morphometry in former American football players: findings from the DIAGNOSE CTE research project.","authors":"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, Eric M Reiman, Robert A Stern, Martha E Shenton, Sylvain Bouix","doi":"10.1093/brain/awae098","DOIUrl":"10.1093/brain/awae098","url":null,"abstract":"<p><p>Exposure to repetitive head impacts in contact sports is associated with neurodegenerative disorders including chronic traumatic encephalopathy (CTE), which currently can be diagnosed only at post-mortem. American football players are at higher risk of developing CTE given their exposure to repetitive head impacts. One promising approach for diagnosing CTE in vivo is to explore known neuropathological abnormalities at post-mortem in living individuals using structural MRI. MRI brain morphometry was evaluated in 170 male former American football players ages 45-74 years (n = 114 professional; n = 56 college) and 54 same-age unexposed asymptomatic male controls (n = 54, age range 45-74). Cortical thickness and volume of regions of interest were selected based on established CTE pathology findings and were assessed using FreeSurfer. Group differences and interactions with age and exposure factors were evaluated using a generalized least squares model. A separate logistic regression and independent multinomial model were performed to predict each traumatic encephalopathy syndrome (TES) diagnosis, core clinical features and provisional level of certainty for CTE pathology using brain regions of interest. Former college and professional American football players (combined) showed significant cortical thickness and/or volume reductions compared to unexposed asymptomatic controls in the hippocampus, amygdala, entorhinal cortex, parahippocampal gyrus, insula, temporal pole and superior frontal gyrus. Post hoc analyses identified group-level differences between former professional players and unexposed asymptomatic controls in the hippocampus, amygdala, entorhinal cortex, parahippocampal gyrus, insula and superior frontal gyrus. Former college players showed significant volume reductions in the hippocampus, amygdala and superior frontal gyrus compared to the unexposed asymptomatic controls. We did not observe Age × Group interactions for brain morphometric measures. Interactions between morphometry and exposure measures were limited to a single significant positive association between the age of first exposure to organized tackle football and right insular volume. We found no significant relationship between brain morphometric measures and the TES diagnosis core clinical features and provisional level of certainty for CTE pathology outcomes. These findings suggested that MRI morphometrics detect abnormalities in individuals with a history of repetitive head impact exposure that resemble the anatomic distribution of pathological findings from post-mortem CTE studies. The lack of findings associating MRI measures with exposure metrics (except for one significant relationship) or TES diagnosis and core clinical features suggested that brain morphometry must be complemented by other types of measures to characterize individuals with repetitive head impacts.</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/PMC11449133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140292700","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":"Default mode network electrophysiological dynamics and causal role in creative thinking.","authors":"Eleonora Bartoli, Ethan Devara, Huy Q Dang, Rikki Rabinovich, Raissa K Mathura, Adrish Anand, Bailey R Pascuzzi, Joshua Adkinson, Yoed N Kenett, Kelly R Bijanki, Sameer A Sheth, Ben Shofty","doi":"10.1093/brain/awae199","DOIUrl":"10.1093/brain/awae199","url":null,"abstract":"<p><p>The default mode network (DMN) is a widely distributed, intrinsic brain network thought to play a crucial role in internally directed cognition. The present study employs stereo-EEG in 13 human patients, obtaining high resolution neural recordings across multiple canonical DMN regions during two processes that have been associated with creative thinking: spontaneous and divergent thought. We probe these two DMN-associated higher cognitive functions through mind wandering and alternate uses tasks, respectively. Our results reveal DMN recruitment during both tasks, as well as a task-specific dissociation in spatiotemporal response dynamics. When compared to the fronto-parietal network, DMN activity was characterized by a stronger increase in gamma band power (30-70 Hz) coupled with lower theta band power (4-8 Hz). The difference in activity between the two networks was especially strong during the mind wandering task. Within the DMN, we found that the tasks showed different dynamics, with the alternate uses task engaging the DMN more during the initial stage of the task, and mind wandering in the later stage. Gamma power changes were mainly driven by lateral DMN sites, while theta power displayed task-specific effects. During alternate uses task, theta changes did not show spatial differences within the DMN, while mind wandering was associated to an early lateral and late dorsomedial DMN engagement. Furthermore, causal manipulations of DMN regions using direct cortical stimulation preferentially decreased the originality of responses in the alternative uses task, without affecting fluency or mind wandering. Our results suggest that DMN activity is flexibly modulated as a function of specific cognitive processes and supports its causal role in divergent thinking. These findings shed light on the neural constructs supporting different forms of cognition and provide causal evidence for the role of DMN in the generation of original connections among concepts.</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/PMC11449134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417660","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}