Brain communicationsPub Date : 2025-01-23eCollection Date: 2025-01-01DOI: 10.1093/braincomms/fcaf031
Lena Haag, Elisa Lancini, Renat Yakupov, Gabriel Ziegler, Yeo-Jin Yi, Falk Lüsebrink, Wenzel Glanz, Oliver Peters, Eike Jakob Spruth, Slawek Altenstein, Josef Priller, Luisa Sophie Schneider, Xiao Wang, Lukas Preis, Frederic Brosseron, Nina Roy-Kluth, Klaus Fliessbach, Michael Wagner, Steffen Wolfsgruber, Luca Kleineidam, Alfredo Ramirez, Annika Spottke, Frank Jessen, Jens Wiltfang, Anja Schneider, Niels Hansen, Ayda Rostamzadeh, Katharina Buerger, Michael Ewers, Robert Perneczky, Daniel Janowitz, Boris-Stephan Rauchmann, Stefan Teipel, Ingo Kilimann, Doreen Goerss, Christoph Laske, Matthias H Munk, Michael Heneka, Peter Dechent, Stefan Hetzer, Klaus Scheffler, Emrah Düzel, Matthew J Betts, Dorothea Hämmerer
{"title":"CSF biomarkers are differentially linked to brain areas high and low in noradrenaline, dopamine and serotonin across the Alzheimer's disease spectrum.","authors":"Lena Haag, Elisa Lancini, Renat Yakupov, Gabriel Ziegler, Yeo-Jin Yi, Falk Lüsebrink, Wenzel Glanz, Oliver Peters, Eike Jakob Spruth, Slawek Altenstein, Josef Priller, Luisa Sophie Schneider, Xiao Wang, Lukas Preis, Frederic Brosseron, Nina Roy-Kluth, Klaus Fliessbach, Michael Wagner, Steffen Wolfsgruber, Luca Kleineidam, Alfredo Ramirez, Annika Spottke, Frank Jessen, Jens Wiltfang, Anja Schneider, Niels Hansen, Ayda Rostamzadeh, Katharina Buerger, Michael Ewers, Robert Perneczky, Daniel Janowitz, Boris-Stephan Rauchmann, Stefan Teipel, Ingo Kilimann, Doreen Goerss, Christoph Laske, Matthias H Munk, Michael Heneka, Peter Dechent, Stefan Hetzer, Klaus Scheffler, Emrah Düzel, Matthew J Betts, Dorothea Hämmerer","doi":"10.1093/braincomms/fcaf031","DOIUrl":"10.1093/braincomms/fcaf031","url":null,"abstract":"<p><p>Neurotransmitter systems of noradrenaline, dopamine, serotonin and acetylcholine are implicated in cognitive functions such as memory, learning and attention and are known to be altered in neurodegenerative diseases like Alzheimer's disease. Specific brain structures involved in these systems, e.g. the locus coeruleus, the main source of noradrenaline in the cortex, are in fact affected earliest by Alzheimer's disease tau pathology. Preserved volumetric neurotransmitter specific brain areas could therefore be an important neural resource for cognitive reserve in aging. The aim of this study was to determine whether volumes of brain areas known to be high in neurotransmitter receptors are relatively preserved in individuals with lower levels of Alzheimer's disease pathology. Based on the Human Protein Atlas for neurotransmitter receptor distribution, we distinguished between 'areas high and low' in noradrenaline, dopamine, serotonin and acetylcholine and assessed associations of atrophy in those areas with CSF amyloid-ß 42/40, CSF phosphorylated tau protein and cognitive function across healthy controls (<i>n</i> = 122), individuals with subjective cognitive decline (<i>n</i> = 156), mild cognitive impairment or mild Alzheimer's disease dementia (<i>n</i> = 126) using structural equation modelling. CSF pathology markers were inversely correlated and showed a stronger association with disease severity, suggesting distinguishable interrelatedness of these biomarkers depending on the stage of Alzheimer's disease dementia. Across groups, amyloid pathology was linked to atrophy in areas high as well as low in neurotransmitter receptor densities, while tau pathology did not show any significant link to brain area volumes for any of the neurotransmitters. Within disease severity groups, individuals with more amyloid pathology showed more atrophy only in 'areas high in noradrenaline', whereas for dopamine tau pathology was linked to higher volumes in areas low in receptor density possibly indicating compensatory mechanisms. Furthermore, individuals with more tau pathology showed a selective decrease in memory function while amyloid pathology was related to a decline in executive function and language capacity as well as memory function. In summary, our analyses highlight the benefits of investigating disease-relevant factors in Alzheimer's disease using a multivariate multigroup approach. Assessing multivariate dependencies in different disease stages and across individuals revealed selective links of pathologies, cognitive decline and atrophy in particular for areas modulated by noradrenaline, dopamine and serotonin.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf031"},"PeriodicalIF":4.1,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143384523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain communicationsPub Date : 2025-01-23eCollection Date: 2025-01-01DOI: 10.1093/braincomms/fcaf003
Christoph Sperber, Laura Gallucci, Marcel Arnold, Roza M Umarova
{"title":"The challenge of long-term stroke outcome prediction and how statistical correlates do not imply predictive value.","authors":"Christoph Sperber, Laura Gallucci, Marcel Arnold, Roza M Umarova","doi":"10.1093/braincomms/fcaf003","DOIUrl":"10.1093/braincomms/fcaf003","url":null,"abstract":"<p><p>Personalized prediction of stroke outcome using lesion imaging markers is still too imprecise to make a breakthrough in clinical practice. We performed a combined prediction and brain mapping study on topographic and connectomic lesion imaging data to evaluate (i) the relationship between lesion-deficit associations and their predictive value and (ii) the influence of time since stroke. In patients with first-ever ischaemic stroke, we first applied high-dimensional machine learning models on lesion topographies or structural disconnection data to model stroke severity (National Institutes of Health Stroke Scale 24 h/3 months) and functional outcome (modified Rankin Scale 3 months) in cross-validation. Second, we mapped the topographic and connectomic lesion impact on both clinical measures. We retrospectively included 685 patients [age 67.4 ± 15.1, National Institutes of Health Stroke Scale 24 h median(IQR) = 3(1; 6), modified Rankin Scale 3 months = 1(0; 2), National Institutes of Health Stroke Scale 3 months = 0(0; 2)]. <i>Predictions</i> for acute stroke severity (National Institutes of Health Stroke Scale 24 h) were better with topographic lesion imaging (<i>R</i>² = 0.41) than with disconnection data (<i>R</i>² = 0.29, <i>P</i> = 0.0015), whereas predictions at 3 months (National Institutes of Health Stroke Scale/modified Rankin Scale) were generally close to chance level. In the analysis of lesion-deficit <i>associations</i>, the correlates of more severe acute stroke (National Institutes of Health Stroke Scale 24 h > 4) and poor functional outcome (modified Rankin Scale 3 months ≥ 2) were left-lateralized. The lesion location impact of both variables corresponded in right-hemisphere stroke with peaks in primary motor regions, but it markedly differed in left-hemisphere stroke. Topographic and disconnection lesion features predict <i>acute</i> stroke severity better than the <i>3-months</i> outcome. This suggests a likely higher impact of lesion-independent factors in the longer term and highlights challenges in the prediction of global functional outcome. Prediction and brain mapping diverge, and the existence of statistically significant associations-as here for 3-months outcomes-does not imply predictive value. Routine neurological scores better capture left- than right-hemispheric lesions, further complicating the challenge of outcome prediction.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf003"},"PeriodicalIF":4.1,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Causal relationships between hippocampal volumetric traits and the risk of Alzheimer's disease: a Mendelian randomization study.","authors":"Lining Guo, Yayuan Chen, Zuhao Sun, Jiaxuan Zhao, Jia Yao, Zhihui Zhang, Minghuan Lei, Ying Zhai, Jinglei Xu, Yurong Jiang, Ying Wang, Hui Xue, Mengge Liu, Feng Liu","doi":"10.1093/braincomms/fcaf030","DOIUrl":"10.1093/braincomms/fcaf030","url":null,"abstract":"<p><p>Alzheimer's disease, a common and progressive neurodegenerative disorder, is associated with alterations in hippocampal volume, as revealed by neuroimaging research. However, the causal links between the volumes of the hippocampus and its subfield structures with Alzheimer's disease remain unknown. A genetic correlation analysis using linkage disequilibrium score regression was conducted to identify hippocampal volumetric traits linked to Alzheimer's disease. Following this, to examine the causal links between Alzheimer's disease and hippocampal volumetric traits, we applied a two-sample Mendelian randomization approach, utilizing a bidirectional framework. Seven hippocampal volumetric traits were found as genetically correlated with Alzheimer's disease in the genetic correlation analysis and were then included in the Mendelian randomization analyses. Inverse variance weighted Mendelian randomization analyses revealed that increased volumes in the left whole hippocampus, left hippocampal body, right presubiculum head and right cornu ammonis 1 head were causally related to higher risks of Alzheimer's disease. Conversely, a higher risk of Alzheimer's disease was causally associated with decreased volumes of the left hippocampal body and left whole hippocampus. These results were validated through other Mendelian randomization approaches and sensitivity analysis. Our findings uncover bidirectional causal relationships between Alzheimer's disease and hippocampal volumetric traits, suggesting not only the potential significance of these traits in predicting Alzheimer's disease but also the reciprocal influence of Alzheimer's disease on hippocampal volumes.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf030"},"PeriodicalIF":4.1,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain communicationsPub Date : 2025-01-21eCollection Date: 2025-01-01DOI: 10.1093/braincomms/fcaf023
Jacopo Pasquini, Michael J Firbank, Laura Best, Victoria Foster, Charlotte Stewart, Vincenzo Silani, Rory Durcan, Gemma Roberts, George Petrides, Roberto Ceravolo, David J Brooks, Kirstie N Anderson, Nicola Pavese
{"title":"Substantia nigra and locus coeruleus microstructural abnormalities in isolated rapid eye movement sleep behaviour disorder and Parkinson's disease.","authors":"Jacopo Pasquini, Michael J Firbank, Laura Best, Victoria Foster, Charlotte Stewart, Vincenzo Silani, Rory Durcan, Gemma Roberts, George Petrides, Roberto Ceravolo, David J Brooks, Kirstie N Anderson, Nicola Pavese","doi":"10.1093/braincomms/fcaf023","DOIUrl":"10.1093/braincomms/fcaf023","url":null,"abstract":"<p><p>Substantia nigra (SN) and locus coeruleus (LC) are two catecholaminergic, neuromelanin-rich nuclei that are affected in Parkinson's disease (PD) and may show neuroimaging abnormalities before the onset of motor manifestations. The simultaneous, multimodal investigation of their microstructural abnormalities may provide useful insights on the spatial diffusion and tissue characteristics of neurodegeneration, and this may in turn help develop markers for disease-modifying clinical trials. Therefore, through neuromelanin-sensitive and diffusion MRI, we aimed to investigate microstructural abnormalities in those nuclei in isolated REM sleep behaviour disorder (iRBD) and PD. Fourteen participants with polysomnography-confirmed iRBD, 18 with PD and 18 healthy controls were scanned with structural, neuromelanin-sensitive and neurite orientation dispersion and density imaging (NODDI) MRI. iRBD participants also underwent dopamine transporter imaging. SN neuromelanin and NODDI diffusion parameters and LC neuromelanin signals were extracted. Motor and global cognitive assessments were also collected. iRBD and PD participants showed significantly reduced neuromelanin contrast in the LC middle section compared with healthy controls. PD also showed significantly reduced caudal LC and posterior SN neuromelanin signal. No differences in SN NODDI parameters were detected between iRBD and healthy controls. Five iRBD participants showed reduced striatal dopamine transporter. In the combined disease groups (iRBD and PD), significant associations were shown between SN neuromelanin signal and neurite density index (<i>r</i> = -0.610, corr-<i>p</i> = 0.001) and between SN neurite density index and free water fraction (<i>r</i> = 0.417, corr-<i>p</i> = 0.042). In the same group, motor scores were negatively associated with nigral neuromelanin signal (<i>r</i> = -0.404, corr-<i>p</i> = 0.044) and free water fraction (<i>r</i> = 0.486, corr-<i>p</i> = 0.018). In conclusion, iRBD participants showed significant neuromelanin loss in the LC, with a minority showing initial nigrostriatal dopaminergic abnormalities. Across the entire iRBD-PD spectrum, the association between SN neuromelanin signal loss, diffusion parameters and motor scores has the potential to capture different yet related aspects of SN degeneration.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf023"},"PeriodicalIF":4.1,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain communicationsPub Date : 2025-01-21eCollection Date: 2025-01-01DOI: 10.1093/braincomms/fcaf006
Seyyed Bahram Borgheai, Enrico Opri, Faical Isbaine, Eric R Cole, Roohollah Jafari Deligani, Nealen G Laxpati, Benjamin B Risk, Jon T Willie, Robert E Gross, Nicholas AuYong, Cameron C McIntyre, Svjetlana Miocinovic
{"title":"Neural pathway activation in the subthalamic region depends on stimulation polarity.","authors":"Seyyed Bahram Borgheai, Enrico Opri, Faical Isbaine, Eric R Cole, Roohollah Jafari Deligani, Nealen G Laxpati, Benjamin B Risk, Jon T Willie, Robert E Gross, Nicholas AuYong, Cameron C McIntyre, Svjetlana Miocinovic","doi":"10.1093/braincomms/fcaf006","DOIUrl":"10.1093/braincomms/fcaf006","url":null,"abstract":"<p><p>Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease; however, there is limited understanding of which subthalamic pathways are recruited in response to stimulation. Here, by focusing on the polarity of the stimulus waveform (cathodic versus anodic), our goal was to elucidate biophysical mechanisms that underlie electrical stimulation in the human brain. In clinical studies, cathodic stimulation more easily triggers behavioural responses, but anodic DBS broadens the therapeutic window. This suggests that neural pathways involved respond preferentially depending on stimulus polarity. To experimentally compare the activation of therapeutically relevant pathways during cathodic and anodic subthalamic nucleus (STN) DBS, pathway activation was quantified by measuring evoked potentials resulting from antidromic or orthodromic activation in 15 Parkinson's disease patients undergoing DBS implantation. Cortical evoked potentials (cEPs) were recorded using subdural electrocorticography, DBS local evoked potentials (DLEPs) were recorded from non-stimulating contacts, and electromyography activity was recorded from arm and face muscles. We measured (i) the amplitude of short-latency cEP, previously demonstrated to reflect activation of the cortico-STN hyperdirect pathway, (ii) DLEP amplitude thought to reflect activation of STN-globus pallidus (GP) pathway and (iii) amplitudes of very short-latency cEPs and motor evoked potentials for activation of corticospinal/bulbar tract (CSBT). We constructed recruitment and strength-duration curves for each EP/pathway to compare the excitability for different stimulation polarities. We compared experimental data with the most advanced DBS computational models. Our results provide experimental evidence that subcortical cathodic and anodic stimulation activate the same pathways in the STN region and that cathodic stimulation is in general more efficient. However, relative efficiency varies for different pathways so that anodic stimulation is the least efficient in activating CSBT, more efficient in activating the hyperdirect pathway and as efficient as cathodic in activating STN-GP pathway. Our experiments confirm biophysical model predictions regarding neural activations in the central nervous system and provide evidence that stimulus polarity has differential effects on passing axons, terminal synapses, and local neurons. Comparison of experimental results with clinical DBS studies provides further evidence that the hyperdirect pathway may be involved in the therapeutic mechanisms of DBS.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf006"},"PeriodicalIF":4.1,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluating conversion from mild cognitive impairment to Alzheimer's disease with structural MRI: a machine learning study.","authors":"Daniela Vecchio, Federica Piras, Federica Natalizi, Nerisa Banaj, Clelia Pellicano, Fabrizio Piras","doi":"10.1093/braincomms/fcaf027","DOIUrl":"10.1093/braincomms/fcaf027","url":null,"abstract":"<p><p>Alzheimer's disease is a disabling neurodegenerative disorder for which no effective treatment currently exists. To predict the diagnosis of Alzheimer's disease could be crucial for patients' outcome, but current Alzheimer's disease biomarkers are invasive, time consuming or expensive. Thus, developing MRI-based computational methods for Alzheimer's disease early diagnosis would be essential to narrow down the phenotypic measures predictive of cognitive decline. Amnestic mild cognitive impairment (aMCI) is associated with higher risk for Alzheimer's disease, and here, we aimed to identify MRI-based quantitative rules to predict aMCI to possible Alzheimer's disease conversion, applying different machine learning algorithms sequentially. At baseline, T1-weighted brain images were collected for 104 aMCI patients and processed to obtain 146 volumetric measures of cerebral grey matter regions [regions of interest (ROIs)]. One year later, patients were classified as converters (aMCI-c = 32) or non-converters, i.e. clinically and neuropsychologically stable (aMCI-s = 72) based on cognitive performance. Feature selection was performed by random forest (RF), and the identified seven ROIs volumetric data were used to implement support vector machine (SVM) and decision tree (DT) classification algorithms. Both SVM and DT reached an average accuracy of 86% in identifying aMCI-c and aMCI-s. DT found a critical threshold volume of the right entorhinal cortex (EC-r) as the first feature for differentiating aMCI-c/aMCI-s. Almost all aMCI-c had an EC-r volume <1286 mm<sup>3</sup>, while more than half of the aMCI-s patients had a volume above the identified threshold for this structure. Other key regions for the classification between aMCI-c/aMCI-s were the left lateral occipital (LOC-l), the middle temporal gyrus and the temporal pole cortices. Our study reinforces previous evidence suggesting that the morphometry of the EC-r and LOC-l best predicts aMCI to Alzheimer's disease conversion. Further investigations are needed prior to deeming our findings as a broadly applicable predictive framework. However, here, a first indication was derived for volumetric thresholds that, being easy to obtain, may assist in early identification of Alzheimer's disease in clinical practice, thus contributing to establishing MRI as a useful non-invasive prognostic instrument for dementia onset.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf027"},"PeriodicalIF":4.1,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain communicationsPub Date : 2025-01-21eCollection Date: 2025-01-01DOI: 10.1093/braincomms/fcae370
Veronika Vadinova, Sonia L E Brownsett, Kimberley L Garden, Tracy Roxbury, Katherine O'Brien, David A Copland, Katie L McMahon, Aleksi J Sihvonen
{"title":"Early subacute frontal callosal microstructure and language outcomes after stroke.","authors":"Veronika Vadinova, Sonia L E Brownsett, Kimberley L Garden, Tracy Roxbury, Katherine O'Brien, David A Copland, Katie L McMahon, Aleksi J Sihvonen","doi":"10.1093/braincomms/fcae370","DOIUrl":"10.1093/braincomms/fcae370","url":null,"abstract":"<p><p>The integrity of the frontal segment of the corpus callosum, forceps minor, is particularly susceptible to age-related degradation and has been associated with cognitive outcomes in both healthy and pathological ageing. The predictive relevance of forceps minor integrity in relation to cognitive outcomes following a stroke remains unexplored. Our goal was to evaluate whether the heterogeneity of forceps minor integrity, assessed early after stroke onset (2-6 weeks), contributes to explaining variance in longitudinal outcomes in post-stroke aphasia. Both word- and sentence-level tasks were employed to assess language comprehension and language production skills in individuals with first-ever left-hemisphere stroke during the early subacute and chronic phases of recovery (<i>n</i> = 25). Structural and diffusion neuroimaging data from the early subacute phase were used to quantify stroke lesion load and bilateral forceps minor radial diffusivity. Multiple linear regression models examined whether early subacute radial diffusivity within the forceps minor, along with other factors (stroke lesion load, age, sex and education), explained variance in early subacute performance and longitudinal recovery (i.e. change in behavioural performance). Increased early subacute radial diffusivity in the forceps minor was associated with poor early subacute comprehension (<i>t</i> = -2.36, <i>P</i> = 0.02) but not production (<i>P</i> = 0.35) when controlling for stroke lesion load, age, sex and education. When considering longitudinal recovery, early subacute radial diffusivity in the forceps minor was not linked to changes in performance in either comprehension (<i>P</i> = 0.11) or production (<i>P</i> = 0.36) under the same control variables. The examination of various language components and processes led to novel insights: (i) language comprehension may be more susceptible to white matter brain health than language production and (ii) the influence of white matter brain health is reflected in early comprehension performance rather than longitudinal changes in comprehension. These results suggest that evaluating baseline callosal integrity is a valuable approach for assessing the risk of impaired language comprehension post-stroke, while also underscoring the importance of nuanced analyses of behavioural outcomes to enhance our understanding of the clinical applicability of baseline brain health measures.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcae370"},"PeriodicalIF":4.1,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Multidimensional structural analyses revealed a correlation between thalamic atrophy and white matter degeneration in idiopathic dystonia.","authors":"Jinping Xu, Qinxiu Cheng, Yue Zhang, Yuhan Luo, Linchang Zhong, Huiming Liu, Haoran Zhang, Zhengkun Yang, Jiana Zhang, Zilin Ou, Zhicong Yan, Kangqiang Peng, Gang Liu","doi":"10.1093/braincomms/fcaf026","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf026","url":null,"abstract":"<p><p>Although aberrant changes in grey and white matter are core features of idiopathic dystonia, few studies have explored the correlation between grey and white matter changes in this disease. This study aimed to investigate the coupling correlation between morphological and microstructural alterations in patients with idiopathic dystonia. Structural T1 imaging and diffusion tensor imaging were performed on a relatively large cohort of patients. Multidimensional structural analyses, including voxel-based analyses, voxel-based morphology, fixel-based analyses and surface-based morphometry, were performed to explore these structural alterations. Probabilistic tractography and correlation analyses were employed to examine these relationships. A total of 147 patients with idiopathic dystonia and 137 healthy controls were recruited in this study. There were no significant differences in the cortical morphometry between patients with idiopathic dystonia and healthy controls using voxel- and surface-based morphometry. However, the grey matter volume of the bilateral thalamus, fractional anisotropy in the right anterior corona radiata, right retrolenticular part of the internal capsule and right posterior corona radiata, and the fibre density and cross-section combined in the fibre tract connecting the left ventral posterolateral thalamic nucleus and left area 5 m, were significantly decreased in patients with idiopathic dystonia compared with those in healthy controls. Furthermore, the reduced grey matter volume in the right thalamus not only correlated with the disease duration but also with the reduced fractional anisotropy in the right posterior corona radiata and decreased the fibre density and cross-section combined in the fibre tract connecting the left ventral posterolateral thalamic nucleus and the left area 5 m in patients with idiopathic dystonia. These findings suggest that the thalamus is structurally impaired in idiopathic dystonia and that microstructural disruption in thalamocortical projections occurs secondary to thalamic atrophy.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf026"},"PeriodicalIF":4.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain communicationsPub Date : 2025-01-20eCollection Date: 2025-01-01DOI: 10.1093/braincomms/fcaf018
Elliz P Scheijbeler, Willem de Haan, Emma M Coomans, Anouk den Braber, Jori Tomassen, Mara Ten Kate, Elles Konijnenberg, Lyduine E Collij, Elsmarieke van de Giessen, Frederik Barkhof, Pieter Jelle Visser, Cornelis J Stam, Alida A Gouw
{"title":"Amyloid-β deposition predicts oscillatory slowing of magnetoencephalography signals and a reduction of functional connectivity over time in cognitively unimpaired adults.","authors":"Elliz P Scheijbeler, Willem de Haan, Emma M Coomans, Anouk den Braber, Jori Tomassen, Mara Ten Kate, Elles Konijnenberg, Lyduine E Collij, Elsmarieke van de Giessen, Frederik Barkhof, Pieter Jelle Visser, Cornelis J Stam, Alida A Gouw","doi":"10.1093/braincomms/fcaf018","DOIUrl":"10.1093/braincomms/fcaf018","url":null,"abstract":"<p><p>With the ongoing developments in the field of anti-amyloid therapy for Alzheimer's disease, it is crucial to better understand the longitudinal associations between amyloid-β deposition and altered network activity in the living human brain. We included 110 cognitively unimpaired individuals (67.9 ± 5.7 years), who underwent [<sup>18</sup>F]flutemetamol (amyloid-β)-PET imaging and resting-state magnetoencephalography (MEG) recording at baseline and 4-year follow-up. We tested associations between baseline amyloid-β deposition and MEG measures (oscillatory power and functional connectivity). Next, we examined the relationship between baseline amyloid-β deposition and longitudinal MEG measures, as well as between baseline MEG measures and longitudinal amyloid-β deposition. Finally, we assessed associations between longitudinal changes in both amyloid-β deposition and MEG measures. Analyses were performed using linear mixed models corrected for age, sex and family. At baseline, amyloid-β deposition in orbitofrontal-posterior cingulate regions (i.e. early Alzheimer's disease regions) was associated with higher theta (4-8 Hz) power (<i>β</i> = 0.17, <i>P</i> < 0.01) in- and lower functional connectivity [inverted Joint Permutation Entropy (JPE<sub>inv</sub>) theta, <i>β</i> = -0.24, <i>P</i> < 0.001] of these regions, lower whole-brain beta (13-30 Hz) power (<i>β</i> = -0.13, <i>P</i> < 0.05) and lower whole-brain functional connectivity (JPE<sub>inv</sub> theta, <i>β</i> = -0.18, <i>P</i> < 0.001). Whole-brain amyloid-β deposition was associated with higher whole-brain theta power (<i>β</i> = 0.17, <i>P</i> < 0.05), lower whole-brain beta power (<i>β</i> = -0.13, <i>P</i> < 0.05) and lower whole-brain functional connectivity (JPE<sub>inv</sub> theta, <i>β</i> = -0.21, <i>P</i> < 0.001). Baseline amyloid-β deposition in early Alzheimer's disease regions also predicted future oscillatory slowing, reflected by increased theta power over time in early Alzheimer's disease regions and across the whole brain (<i>β</i> = 0.11, <i>β</i> = 0.08, <i>P</i> < 0.001), as well as decreased whole-brain beta power over time (<i>β</i> = -0.04, <i>P</i> < 0.05). Baseline amyloid-β deposition in early Alzheimer's disease regions also predicted a reduction in functional connectivity between these regions and the rest of the brain over time (JPE<sub>inv</sub> theta, <i>β</i> = -0.07, <i>P</i> < 0.05). Baseline whole-brain amyloid-β deposition was associated with increased whole-brain theta power over time (<i>β</i> = 0.08, <i>P</i> < 0.01). Baseline MEG measures were not associated with longitudinal amyloid-β deposition. Longitudinal changes in amyloid-β deposition in early Alzheimer's disease regions were associated with longitudinal changes in functional connectivity of early Alzheimer's disease regions (JPE<sub>inv</sub> theta, <i>β</i> = -0.19, <i>P</i> < 0.05) and the whole brain [corrected amplitude envelope correlations alpha (8-13 Hz), <i>β</i> = -0.22, <i>P","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf018"},"PeriodicalIF":4.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11851009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143505993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain communicationsPub Date : 2025-01-20eCollection Date: 2025-01-01DOI: 10.1093/braincomms/fcaf028
Angeliki Vakrinou, Susanna Pagni, James D Mills, Lisa M Clayton, Simona Balestrini, Sanjay M Sisodiya
{"title":"Adult phenotypes of genetic developmental and epileptic encephalopathies.","authors":"Angeliki Vakrinou, Susanna Pagni, James D Mills, Lisa M Clayton, Simona Balestrini, Sanjay M Sisodiya","doi":"10.1093/braincomms/fcaf028","DOIUrl":"https://doi.org/10.1093/braincomms/fcaf028","url":null,"abstract":"<p><p>Developmental and epileptic encephalopathies constitute a group of severe epilepsies, with seizure onset typically occurring in infancy or childhood, and diverse clinical manifestations, including neurodevelopmental deficits and multimorbidities. Many have genetic aetiologies, identified in up to 50% of individuals. Whilst classically considered paediatric disorders, most are compatible with survival into adulthood, but their adult phenotypes remain inadequately understood. This cross-sectional study presents detailed phenotypes of 129 adults (age range 17-71 years), with genetic developmental and epileptic encephalopathies involving causal variants in 42 genes. We describe diverse disease aspects, and we sought genetic insights from the age-related trends of expression of the genes involved. Most developmental and epileptic encephalopathies (69.7%) are epileptic encephalopathies in adulthood, with the presence of epileptic encephalopathy correlating with worse cognitive phenotypes (<i>P</i> = 0.0007). However, phenotypic variability was observed, ranging from those with epileptic encephalopathy to seizure-free individuals with normal EEG or intermediate clinical and EEG phenotypes. This variability was found across individual genes and age-related gene expression trends, suggesting that other influential factors are likely at play. Mobility, feeding and communication impairments were common, with significant dependence on others for activities of daily living. Neurological and psychiatric comorbidities were most prevalent, along with additional systemic comorbidities observed, particularly musculoskeletal, cardiac and gastrointestinal conditions, highlighting the need for comprehensive and multisystemic monitoring. Despite an average diagnostic delay of 25.2 years, aetiology-based therapeutic interventions were feasible for 54.8% of the cohort, underscoring the critical need for genome-wide genetic testing for adults with these phenotypes. Optimizing seizure control remains necessary, but it may not be sufficient to ensure good outcomes, which may differ significantly from childhood metrics, like cognitive function and independence in daily living. Therapies addressing additional aspects beyond seizures are necessary for improving overall outcomes. Understanding the intricate relationship between molecular pathways and the age-related trends of gene expression is crucial for development of appropriate gene-specific therapies and timely intervention. Whilst prospective data are also needed to define these complexities, such studies of necessity take years to acquire: insights from adults can inform care strategies for both paediatric and adult populations now.</p>","PeriodicalId":93915,"journal":{"name":"Brain communications","volume":"7 1","pages":"fcaf028"},"PeriodicalIF":4.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}