Pub Date : 2022-11-02eCollection Date: 2022-01-01DOI: 10.3389/fnimg.2022.1031253
Sandrine Bédard, Julien Cohen-Adad
Spinal cord cross-sectional area (CSA) is a relevant biomarker to assess spinal cord atrophy in neurodegenerative diseases. However, the considerable inter-subject variability among healthy participants currently limits its usage. Previous studies explored factors contributing to the variability, yet the normalization models required manual intervention and used vertebral levels as a reference, which is an imprecise prediction of the spinal levels. In this study we implemented a method to measure CSA automatically from a spatial reference based on the central nervous system (the pontomedullary junction, PMJ), we investigated factors to explain variability, and developed normalization strategies on a large cohort (N = 804). Following automatic spinal cord segmentation, vertebral labeling and PMJ labeling, the spinal cord CSA was computed on T1w MRI scans from the UK Biobank database. The CSA was computed using two methods. For the first method, the CSA was computed at the level of the C2-C3 intervertebral disc. For the second method, the CSA was computed at 64 mm caudally from the PMJ, this distance corresponding to the average distance between the PMJ and the C2-C3 disc across all participants. The effect of various demographic and anatomical factors was explored, and a stepwise regression found significant predictors; the coefficients of the best fit model were used to normalize CSA. CSA measured at C2-C3 disc and using the PMJ differed significantly (paired t-test, p-value = 0.0002). The best normalization model included thalamus, brain volume, sex and the interaction between brain volume and sex. The coefficient of variation went down for PMJ CSA from 10.09 (without normalization) to 8.59%, a reduction of 14.85%. For CSA at C2-C3, it went down from 9.96 to 8.42%, a reduction of 15.13 %. This study introduces an end-to-end automatic pipeline to measure and normalize cord CSA from a neurological reference. This approach requires further validation to assess atrophy in longitudinal studies. The inter-subject variability of CSA can be partly accounted for by demographics and anatomical factors.
{"title":"Automatic measure and normalization of spinal cord cross-sectional area using the pontomedullary junction.","authors":"Sandrine Bédard, Julien Cohen-Adad","doi":"10.3389/fnimg.2022.1031253","DOIUrl":"10.3389/fnimg.2022.1031253","url":null,"abstract":"<p><p>Spinal cord cross-sectional area (CSA) is a relevant biomarker to assess spinal cord atrophy in neurodegenerative diseases. However, the considerable inter-subject variability among healthy participants currently limits its usage. Previous studies explored factors contributing to the variability, yet the normalization models required manual intervention and used vertebral levels as a reference, which is an imprecise prediction of the spinal levels. In this study we implemented a method to measure CSA automatically from a spatial reference based on the central nervous system (the pontomedullary junction, PMJ), we investigated factors to explain variability, and developed normalization strategies on a large cohort (<i>N</i> = 804). Following automatic spinal cord segmentation, vertebral labeling and PMJ labeling, the spinal cord CSA was computed on T1w MRI scans from the UK Biobank database. The CSA was computed using two methods. For the first method, the CSA was computed at the level of the C2-C3 intervertebral disc. For the second method, the CSA was computed at 64 mm caudally from the PMJ, this distance corresponding to the average distance between the PMJ and the C2-C3 disc across all participants. The effect of various demographic and anatomical factors was explored, and a stepwise regression found significant predictors; the coefficients of the best fit model were used to normalize CSA. CSA measured at C2-C3 disc and using the PMJ differed significantly (paired <i>t</i>-test, <i>p</i>-value = 0.0002). The best normalization model included thalamus, brain volume, sex and the interaction between brain volume and sex. The coefficient of variation went down for PMJ CSA from 10.09 (without normalization) to 8.59%, a reduction of 14.85%. For CSA at C2-C3, it went down from 9.96 to 8.42%, a reduction of 15.13 %. This study introduces an end-to-end automatic pipeline to measure and normalize cord CSA from a neurological reference. This approach requires further validation to assess atrophy in longitudinal studies. The inter-subject variability of CSA can be partly accounted for by demographics and anatomical factors.</p>","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"1 ","pages":"1031253"},"PeriodicalIF":0.0,"publicationDate":"2022-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10319949","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}
Pub Date : 2022-10-28eCollection Date: 2022-01-01DOI: 10.3389/fnimg.2022.1012639
Suhang You, Mauricio Reyes
Contrast and texture modifications applied during training or test-time have recently shown promising results to enhance the generalization performance of deep learning segmentation methods in medical image analysis. However, a deeper understanding of this phenomenon has not been investigated. In this study, we investigated this phenomenon using a controlled experimental setting, using datasets from the Human Connectome Project and a large set of simulated MR protocols, in order to mitigate data confounders and investigate possible explanations as to why model performance changes when applying different levels of contrast and texture-based modifications. Our experiments confirm previous findings regarding the improved performance of models subjected to contrast and texture modifications employed during training and/or testing time, but further show the interplay when these operations are combined, as well as the regimes of model improvement/worsening across scanning parameters. Furthermore, our findings demonstrate a spatial attention shift phenomenon of trained models, occurring for different levels of model performance, and varying in relation to the type of applied image modification.
{"title":"Influence of contrast and texture based image modifications on the performance and attention shift of U-Net models for brain tissue segmentation.","authors":"Suhang You, Mauricio Reyes","doi":"10.3389/fnimg.2022.1012639","DOIUrl":"10.3389/fnimg.2022.1012639","url":null,"abstract":"<p><p>Contrast and texture modifications applied during training or test-time have recently shown promising results to enhance the generalization performance of deep learning segmentation methods in medical image analysis. However, a deeper understanding of this phenomenon has not been investigated. In this study, we investigated this phenomenon using a controlled experimental setting, using datasets from the Human Connectome Project and a large set of simulated MR protocols, in order to mitigate data confounders and investigate possible explanations as to why model performance changes when applying different levels of contrast and texture-based modifications. Our experiments confirm previous findings regarding the improved performance of models subjected to contrast and texture modifications employed during training and/or testing time, but further show the interplay when these operations are combined, as well as the regimes of model improvement/worsening across scanning parameters. Furthermore, our findings demonstrate a spatial attention shift phenomenon of trained models, occurring for different levels of model performance, and varying in relation to the type of applied image modification.</p>","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"1 ","pages":"1012639"},"PeriodicalIF":0.0,"publicationDate":"2022-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10319939","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}
Pub Date : 2022-10-04eCollection Date: 2022-01-01DOI: 10.3389/fnimg.2022.971201
Corey H Allen, J Michael Maurer, Bethany G Edwards, Aparna R Gullapalli, Carla L Harenski, Keith A Harenski, Vince D Calhoun, Kent A Kiehl
Previous work in incarcerated men suggests that individuals scoring high on psychopathy exhibit aberrant resting-state paralimbic functional network connectivity (FNC). However, it is unclear whether similar results extend to women scoring high on psychopathy. This study examined whether psychopathic traits [assessed via the Hare Psychopathy Checklist - Revised (PCL-R)] were associated with aberrant inter-network connectivity, intra-network connectivity (i.e., functional coherence within a network), and amplitude of fluctuations across limbic and surrounding paralimbic regions among incarcerated women (n = 297). Resting-state networks were identified by applying group Independent Component Analysis to resting-state fMRI scans. We tested the association of psychopathic traits (PCL-R Factor 1 measuring interpersonal/affective psychopathic traits and PCL-R Factor 2 assessing lifestyle/antisocial psychopathic traits) to the three FNC measures. PCL-R Factor 1 scores were associated with increased low-frequency fluctuations in executive control and attentional networks, decreased high-frequency fluctuations in executive control and visual networks, and decreased intra-network FNC in default mode network. PCL-R Factor 2 scores were associated with decreased high-frequency fluctuations and default mode networks, and both increased and decreased intra-network functional connectivity in visual networks. Similar to previous analyses in incarcerated men, our results suggest that psychopathic traits among incarcerated women are associated with aberrant intra-network amplitude fluctuations and connectivity across multiple networks including limbic and surrounding paralimbic regions.
{"title":"Aberrant resting-state functional connectivity in incarcerated women with elevated psychopathic traits.","authors":"Corey H Allen, J Michael Maurer, Bethany G Edwards, Aparna R Gullapalli, Carla L Harenski, Keith A Harenski, Vince D Calhoun, Kent A Kiehl","doi":"10.3389/fnimg.2022.971201","DOIUrl":"10.3389/fnimg.2022.971201","url":null,"abstract":"<p><p>Previous work in incarcerated men suggests that individuals scoring high on psychopathy exhibit aberrant resting-state paralimbic functional network connectivity (FNC). However, it is unclear whether similar results extend to women scoring high on psychopathy. This study examined whether psychopathic traits [assessed <i>via</i> the Hare Psychopathy Checklist - Revised (PCL-R)] were associated with aberrant inter-network connectivity, intra-network connectivity (i.e., functional coherence within a network), and amplitude of fluctuations across limbic and surrounding paralimbic regions among incarcerated women (<i>n</i> = 297). Resting-state networks were identified by applying group Independent Component Analysis to resting-state fMRI scans. We tested the association of psychopathic traits (PCL-R Factor 1 measuring interpersonal/affective psychopathic traits and PCL-R Factor 2 assessing lifestyle/antisocial psychopathic traits) to the three FNC measures. PCL-R Factor 1 scores were associated with increased low-frequency fluctuations in executive control and attentional networks, decreased high-frequency fluctuations in executive control and visual networks, and decreased intra-network FNC in default mode network. PCL-R Factor 2 scores were associated with decreased high-frequency fluctuations and default mode networks, and both increased and decreased intra-network functional connectivity in visual networks. Similar to previous analyses in incarcerated men, our results suggest that psychopathic traits among incarcerated women are associated with aberrant intra-network amplitude fluctuations and connectivity across multiple networks including limbic and surrounding paralimbic regions.</p>","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"1 ","pages":"971201"},"PeriodicalIF":0.0,"publicationDate":"2022-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10338074","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}
Pub Date : 2022-09-22eCollection Date: 2022-01-01DOI: 10.3389/fnimg.2022.917806
Guillaume Theaud, Manon Edde, Matthieu Dumont, Clément Zotti, Mauro Zucchelli, Samuel Deslauriers-Gauthier, Rachid Deriche, Pierre-Marc Jodoin, Maxime Descoteaux
Modern tractography algorithms such as anatomically-constrained tractography (ACT) are based on segmentation maps of white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF). These maps are generally estimated from a T1-weighted (T1w) image and then registered in diffusion weighted images (DWI) space. Registration of T1w to diffusion space and partial volume estimation are challenging and rarely voxel-perfect. Diffusion-based segmentation would, thus, potentially allow not to have higher quality anatomical priors injected in the tractography process. On the other hand, even if FA-based tractography is possible without T1 registration, the literature shows that this technique suffers from multiple issues such as holes in the tracking mask and a high proportion of generated broken and anatomically implausible streamlines. Therefore, there is an important need for a tissue segmentation algorithm that works directly in the native diffusion space. We propose DORIS, a DWI-based deep learning segmentation algorithm. DORIS outputs 10 different tissue classes including WM, GM, CSF, ventricles, and 6 other subcortical structures (putamen, pallidum, hippocampus, caudate, amygdala, and thalamus). DORIS was trained and validated on a wide range of subjects, including 1,000 individuals from 22 to 90 years old from clinical and research DWI acquisitions, from 5 public databases. In the absence of a "true" ground truth in diffusion space, DORIS used a silver standard strategy from Freesurfer output registered onto the DWI. This strategy is extensively evaluated and discussed in the current study. Segmentation maps provided by DORIS are quantitatively compared to Freesurfer and FSL-fast and the impacts on tractography are evaluated. Overall, we show that DORIS is fast, accurate, and reproducible and that DORIS-based tractograms produce bundles with a longer mean length and fewer anatomically implausible streamlines.
{"title":"DORIS: A diffusion MRI-based 10 tissue class deep learning segmentation algorithm tailored to improve anatomically-constrained tractography.","authors":"Guillaume Theaud, Manon Edde, Matthieu Dumont, Clément Zotti, Mauro Zucchelli, Samuel Deslauriers-Gauthier, Rachid Deriche, Pierre-Marc Jodoin, Maxime Descoteaux","doi":"10.3389/fnimg.2022.917806","DOIUrl":"10.3389/fnimg.2022.917806","url":null,"abstract":"<p><p>Modern tractography algorithms such as anatomically-constrained tractography (ACT) are based on segmentation maps of white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF). These maps are generally estimated from a T1-weighted (T1w) image and then registered in diffusion weighted images (DWI) space. Registration of T1w to diffusion space and partial volume estimation are challenging and rarely voxel-perfect. Diffusion-based segmentation would, thus, potentially allow not to have higher quality anatomical priors injected in the tractography process. On the other hand, even if FA-based tractography is possible without T1 registration, the literature shows that this technique suffers from multiple issues such as holes in the tracking mask and a high proportion of generated broken and anatomically implausible streamlines. Therefore, there is an important need for a tissue segmentation algorithm that works directly in the native diffusion space. We propose <b>DORIS</b>, a DWI-based deep learning segmentation algorithm. DORIS outputs 10 different tissue classes including WM, GM, CSF, ventricles, and 6 other subcortical structures (putamen, pallidum, hippocampus, caudate, amygdala, and thalamus). DORIS was trained and validated on a wide range of subjects, including 1,000 individuals from 22 to 90 years old from clinical and research DWI acquisitions, from 5 public databases. In the absence of a \"true\" ground truth in diffusion space, DORIS used a silver standard strategy from Freesurfer output registered onto the DWI. This strategy is extensively evaluated and discussed in the current study. Segmentation maps provided by DORIS are quantitatively compared to Freesurfer and FSL-fast and the impacts on tractography are evaluated. Overall, we show that DORIS is fast, accurate, and reproducible and that DORIS-based tractograms produce bundles with a longer mean length and fewer anatomically implausible streamlines.</p>","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"1 ","pages":"917806"},"PeriodicalIF":0.0,"publicationDate":"2022-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9957254","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}
Pub Date : 2022-09-13eCollection Date: 2022-01-01DOI: 10.3389/fnimg.2022.947526
Madhura Baxi, Suheyla Cetin-Karayumak, George Papadimitriou, Nikos Makris, Andre van der Kouwe, Bruce Jenkins, Tara L Moore, Douglas L Rosene, Marek Kubicki, Yogesh Rathi
Postmortem studies are currently considered a gold standard for investigating brain structure at the cellular level. To investigate cellular changes in the context of human development, aging, or disease treatment, non-invasive in-vivo imaging methods such as diffusion MRI (dMRI) are needed. However, dMRI measures are only indirect measures and require validation in gray matter (GM) in the context of their sensitivity to the underlying cytoarchitecture, which has been lacking. Therefore, in this study we conducted direct comparisons between in-vivo dMRI measures and histology acquired from the same four rhesus monkeys. Average and heterogeneity of fractional anisotropy and trace from diffusion tensor imaging and mean squared displacement (MSD) and return-to-origin-probability from biexponential model were calculated in nine cytoarchitectonically different GM regions using dMRI data. DMRI measures were compared with corresponding histology measures of regional average and heterogeneity in cell area density. Results show that both average and heterogeneity in trace and MSD measures are sensitive to the underlying cytoarchitecture (cell area density) and capture different aspects of cell composition and organization. Trace and MSD thus would prove valuable as non-invasive imaging biomarkers in future studies investigating GM cytoarchitectural changes related to development and aging as well as abnormal cellular pathologies in clinical studies.
{"title":"Investigating the contribution of cytoarchitecture to diffusion MRI measures in gray matter using histology.","authors":"Madhura Baxi, Suheyla Cetin-Karayumak, George Papadimitriou, Nikos Makris, Andre van der Kouwe, Bruce Jenkins, Tara L Moore, Douglas L Rosene, Marek Kubicki, Yogesh Rathi","doi":"10.3389/fnimg.2022.947526","DOIUrl":"10.3389/fnimg.2022.947526","url":null,"abstract":"<p><p>Postmortem studies are currently considered a gold standard for investigating brain structure at the cellular level. To investigate cellular changes in the context of human development, aging, or disease treatment, non-invasive <i>in-vivo</i> imaging methods such as diffusion MRI (dMRI) are needed. However, dMRI measures are only indirect measures and require validation in gray matter (GM) in the context of their sensitivity to the underlying cytoarchitecture, which has been lacking. Therefore, in this study we conducted direct comparisons between <i>in-vivo</i> dMRI measures and histology acquired from the same four rhesus monkeys. Average and heterogeneity of fractional anisotropy and trace from diffusion tensor imaging and mean squared displacement (MSD) and return-to-origin-probability from biexponential model were calculated in nine cytoarchitectonically different GM regions using dMRI data. DMRI measures were compared with corresponding histology measures of regional average and heterogeneity in cell area density. Results show that both average and heterogeneity in trace and MSD measures are sensitive to the underlying cytoarchitecture (cell area density) and capture different aspects of cell composition and organization. Trace and MSD thus would prove valuable as non-invasive imaging biomarkers in future studies investigating GM cytoarchitectural changes related to development and aging as well as abnormal cellular pathologies in clinical studies.</p>","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"1 ","pages":"947526"},"PeriodicalIF":0.0,"publicationDate":"2022-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9968649","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}
Pub Date : 2022-09-07eCollection Date: 2022-01-01DOI: 10.3389/fnimg.2022.963125
Donglin Wang, Qiang Wu, Don Hong
Functional magnetic resonance imaging (fMRI)-based study of functional connections in the brain has been highlighted by numerous human and animal studies recently, which have provided significant information to explain a wide range of pathological conditions and behavioral characteristics. In this paper, we propose the use of a graph neural network, a deep learning technique called graphSAGE, to investigate resting state fMRI (rs-fMRI) and extract the default mode network (DMN). Comparing typical methods such as seed-based correlation, independent component analysis, and dictionary learning, real data experiment results showed that the graphSAGE is more robust, reliable, and defines a clearer region of interests. In addition, graphSAGE requires fewer and more relaxed assumptions, and considers the single subject analysis and group subjects analysis simultaneously.
{"title":"Extracting default mode network based on graph neural network for resting state fMRI study.","authors":"Donglin Wang, Qiang Wu, Don Hong","doi":"10.3389/fnimg.2022.963125","DOIUrl":"10.3389/fnimg.2022.963125","url":null,"abstract":"<p><p>Functional magnetic resonance imaging (fMRI)-based study of functional connections in the brain has been highlighted by numerous human and animal studies recently, which have provided significant information to explain a wide range of pathological conditions and behavioral characteristics. In this paper, we propose the use of a graph neural network, a deep learning technique called graphSAGE, to investigate resting state fMRI (rs-fMRI) and extract the default mode network (DMN). Comparing typical methods such as seed-based correlation, independent component analysis, and dictionary learning, real data experiment results showed that the graphSAGE is more robust, reliable, and defines a clearer region of interests. In addition, graphSAGE requires fewer and more relaxed assumptions, and considers the single subject analysis and group subjects analysis simultaneously.</p>","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"1 ","pages":"963125"},"PeriodicalIF":0.0,"publicationDate":"2022-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9966266","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}
Pub Date : 2022-07-13eCollection Date: 2022-01-01DOI: 10.3389/fnimg.2022.952084
Xueqi Guo, Sule Tinaz, Nicha C Dvornek
Parkinson's disease (PD) is a common and complex neurodegenerative disorder with five stages on the Hoehn and Yahr scaling. Characterizing brain function alterations with progression of early stage disease would support accurate disease staging, development of new therapies, and objective monitoring of disease progression or treatment response. Functional magnetic resonance imaging (fMRI) is a promising tool in revealing functional connectivity (FC) differences and developing biomarkers in PD. While fMRI and FC data have been utilized for diagnosis of PD through application of machine learning approaches such as support vector machine and logistic regression, the characterization of FC changes in early-stage PD has not been investigated. Given the complexity and non-linearity of fMRI data, we propose the use of a long short-term memory (LSTM) network to distinguish the early stages of PD and understand related functional brain changes. The study included 84 subjects (56 in stage 2 and 28 in stage 1) from the Parkinson's Progression Markers Initiative (PPMI), the largest-available public PD dataset. Under a repeated 10-fold stratified cross-validation, the LSTM model reached an accuracy of 71.63%, 13.52% higher than the best traditional machine learning method and 11.56% higher than a CNN model, indicating significantly better robustness and accuracy compared with other machine learning classifiers. Finally, we used the learned LSTM model weights to select the top brain regions that contributed to model prediction and performed FC analyses to characterize functional changes with disease stage and motor impairment to gain better insight into the brain mechanisms of PD.
帕金森病(Parkinson's disease,PD)是一种常见而复杂的神经退行性疾病,按霍恩和雅尔评分法可分为五个阶段。描述早期疾病进展过程中大脑功能的变化有助于准确地进行疾病分期、开发新的疗法以及客观地监测疾病进展或治疗反应。功能磁共振成像(fMRI)是揭示功能连接(FC)差异和开发帕金森病生物标记物的一种有前途的工具。虽然通过应用支持向量机和逻辑回归等机器学习方法,fMRI 和 FC 数据已被用于诊断帕金森病,但早期帕金森病的 FC 变化特征尚未得到研究。鉴于 fMRI 数据的复杂性和非线性,我们建议使用长短期记忆(LSTM)网络来区分早期帕金森病并了解相关的脑功能变化。该研究纳入了帕金森病进展标志物倡议(PPMI)中的 84 名受试者(56 名处于第二阶段,28 名处于第一阶段),这是目前最大的帕金森病公开数据集。在重复 10 倍分层交叉验证的情况下,LSTM 模型的准确率达到了 71.63%,比最佳传统机器学习方法高出 13.52%,比 CNN 模型高出 11.56%,这表明与其他机器学习分类器相比,LSTM 的鲁棒性和准确率明显更高。最后,我们利用学习到的 LSTM 模型权重选择了对模型预测有贡献的顶级脑区,并进行了 FC 分析,以表征随疾病分期和运动障碍而发生的功能变化,从而更好地了解 PD 的脑机制。
{"title":"Characterization of Early Stage Parkinson's Disease From Resting-State fMRI Data Using a Long Short-Term Memory Network.","authors":"Xueqi Guo, Sule Tinaz, Nicha C Dvornek","doi":"10.3389/fnimg.2022.952084","DOIUrl":"10.3389/fnimg.2022.952084","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a common and complex neurodegenerative disorder with five stages on the Hoehn and Yahr scaling. Characterizing brain function alterations with progression of early stage disease would support accurate disease staging, development of new therapies, and objective monitoring of disease progression or treatment response. Functional magnetic resonance imaging (fMRI) is a promising tool in revealing functional connectivity (FC) differences and developing biomarkers in PD. While fMRI and FC data have been utilized for diagnosis of PD through application of machine learning approaches such as support vector machine and logistic regression, the characterization of FC changes in early-stage PD has not been investigated. Given the complexity and non-linearity of fMRI data, we propose the use of a long short-term memory (LSTM) network to distinguish the early stages of PD and understand related functional brain changes. The study included 84 subjects (56 in stage 2 and 28 in stage 1) from the Parkinson's Progression Markers Initiative (PPMI), the largest-available public PD dataset. Under a repeated 10-fold stratified cross-validation, the LSTM model reached an accuracy of 71.63%, 13.52% higher than the best traditional machine learning method and 11.56% higher than a CNN model, indicating significantly better robustness and accuracy compared with other machine learning classifiers. Finally, we used the learned LSTM model weights to select the top brain regions that contributed to model prediction and performed FC analyses to characterize functional changes with disease stage and motor impairment to gain better insight into the brain mechanisms of PD.</p>","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"1 ","pages":"952084"},"PeriodicalIF":0.0,"publicationDate":"2022-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10420717","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}
Pub Date : 2022-07-11eCollection Date: 2022-01-01DOI: 10.3389/fnimg.2022.924811
Ruaridh A Clark, Keith Smith, Javier Escudero, Agustín Ibáñez, Mario A Parra
The prevalence of dementia, including Alzheimer's disease (AD), is on the rise globally with screening and intervention of particular importance and benefit to those with limited access to healthcare. Electroencephalogram (EEG) is an inexpensive, scalable, and portable brain imaging technology that could deliver AD screening to those without local tertiary healthcare infrastructure. We study EEG recordings of subjects with sporadic mild cognitive impairment (MCI) and prodromal familial, early-onset, AD for the same working memory tasks using high- and low-density EEG, respectively. A challenge in detecting electrophysiological changes from EEG recordings is that noise and volume conduction effects are common and disruptive. It is known that the imaginary part of coherency (iCOH) can generate functional connectivity networks that mitigate against volume conduction, while also erasing true instantaneous activity (zero or π-phase). We aim to expose topological differences in these iCOH connectivity networks using a global network measure, eigenvector alignment (EA), shown to be robust to network alterations that emulate the erasure of connectivities by iCOH. Alignments assessed by EA capture the relationship between a pair of EEG channels from the similarity of their connectivity patterns. Significant alignments-from comparison with random null models-are seen to be consistent across frequency ranges (delta, theta, alpha, and beta) for the working memory tasks, where consistency of iCOH connectivities is also noted. For high-density EEG recordings, stark differences in the control and sporadic MCI results are observed with the control group demonstrating far more consistent alignments. Differences between the control and pre-dementia groupings are detected for significant correlation and iCOH connectivities, but only EA suggests a notable difference in network topology when comparing between subjects with sporadic MCI and prodromal familial AD. The consistency of alignments, across frequency ranges, provides a measure of confidence in EA's detection of topological structure, an important aspect that marks this approach as a promising direction for developing a reliable test for early onset AD.
包括阿尔茨海默病(AD)在内的痴呆症发病率在全球范围内呈上升趋势,对于那些医疗条件有限的人群来说,筛查和干预尤为重要和有益。脑电图(EEG)是一种价格低廉、可扩展的便携式脑成像技术,可为那些没有当地三级医疗保健基础设施的人提供痴呆症筛查。我们研究了散发性轻度认知障碍(MCI)和前驱家族性早发性注意力缺失症受试者的脑电图记录,分别使用高密度和低密度脑电图完成相同的工作记忆任务。从脑电图记录中检测电生理变化的一个挑战是,噪声和体积传导效应是常见的干扰因素。众所周知,一致性的虚部(iCOH)可以生成功能连接网络,减轻体积传导的影响,同时也会消除真实的瞬时活动(零相或π相)。我们的目的是利用一种全局网络测量方法--特征向量配准(EA)来揭示这些 iCOH 连接网络中的拓扑差异。通过 EA 评估的对齐情况可从一对脑电图通道连接模式的相似性中捕捉到它们之间的关系。从与随机空模型的比较中可以看出,在工作记忆任务中,不同频率范围(delta、theta、alpha 和 beta)的显著排列是一致的,iCOH 的连通性也是一致的。在高密度脑电图记录中,对照组和散发性 MCI 结果显示出明显的差异,对照组显示出更为一致的排列。对照组和痴呆前期组在显著相关性和 iCOH 连接性方面存在差异,但在比较散发性 MCI 受试者和前驱家族性 AD 受试者时,只有 EA 表明网络拓扑结构存在显著差异。在不同频率范围内,排列的一致性为 EA 检测拓扑结构提供了一个信心度量,而这一重要方面标志着这种方法有望成为开发早期 AD 可靠检测方法的一个方向。
{"title":"Robust Assessment of EEG Connectivity Patterns in Mild Cognitive Impairment and Alzheimer's Disease.","authors":"Ruaridh A Clark, Keith Smith, Javier Escudero, Agustín Ibáñez, Mario A Parra","doi":"10.3389/fnimg.2022.924811","DOIUrl":"10.3389/fnimg.2022.924811","url":null,"abstract":"<p><p>The prevalence of dementia, including Alzheimer's disease (AD), is on the rise globally with screening and intervention of particular importance and benefit to those with limited access to healthcare. Electroencephalogram (EEG) is an inexpensive, scalable, and portable brain imaging technology that could deliver AD screening to those without local tertiary healthcare infrastructure. We study EEG recordings of subjects with sporadic mild cognitive impairment (MCI) and prodromal familial, early-onset, AD for the same working memory tasks using high- and low-density EEG, respectively. A challenge in detecting electrophysiological changes from EEG recordings is that noise and volume conduction effects are common and disruptive. It is known that the imaginary part of coherency (iCOH) can generate functional connectivity networks that mitigate against volume conduction, while also erasing true instantaneous activity (zero or π-phase). We aim to expose topological differences in these iCOH connectivity networks using a global network measure, eigenvector alignment (EA), shown to be robust to network alterations that emulate the erasure of connectivities by iCOH. Alignments assessed by EA capture the relationship between a pair of EEG channels from the similarity of their connectivity patterns. Significant alignments-from comparison with random null models-are seen to be consistent across frequency ranges (delta, theta, alpha, and beta) for the working memory tasks, where consistency of iCOH connectivities is also noted. For high-density EEG recordings, stark differences in the control and sporadic MCI results are observed with the control group demonstrating far more consistent alignments. Differences between the control and pre-dementia groupings are detected for significant correlation and iCOH connectivities, but only EA suggests a notable difference in network topology when comparing between subjects with sporadic MCI and prodromal familial AD. The consistency of alignments, across frequency ranges, provides a measure of confidence in EA's detection of topological structure, an important aspect that marks this approach as a promising direction for developing a reliable test for early onset AD.</p>","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"1 ","pages":"924811"},"PeriodicalIF":0.0,"publicationDate":"2022-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9963614","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}
Pub Date : 2022-06-17eCollection Date: 2022-01-01DOI: 10.3389/fnimg.2022.883968
Keith M Smith, John M Starr, Javier Escudero, Agustin Ibañez, Mario A Parra
Alzheimer's Disease (AD) shows both complex alterations of functional dependencies between brain regions and a decreased ability to perform Visual Short-Term Memory Binding (VSTMB) tasks. Recent advances in network neuroscience toward understanding the complexity of hierarchical brain function here enables us to establish a link between these two phenomena. Here, we study data on two types of dementia at Mild Cognitive Impairment (MCI) stage-familial AD patients (E280A mutation of the presenilin-1 gene) and elderly MCI patients at high risk of sporadic AD, both with age-matched controls. We analyzed Electroencephalogram (EEG) signals recorded during the performance of Visual Short-Term Memory (VSTM) tasks by these participants. Functional connectivity was computed using the phase-lag index in Alpha and Beta; and network analysis was employed using network indices of hierarchical spread (degree variance) and complexity. Hierarchical characteristics of EEG functional connectivity networks revealed abnormal patterns in familial MCI VSTMB function and sporadic MCI VSTMB function. The middle-aged familial MCI binding network displayed a larger degree variance in lower Beta compared to healthy controls (p = 0.0051, Cohen's d = 1.0124), while the elderly sporadic MCI binding network displayed greater hierarchical complexity in Alpha (p = 0.0140, Cohen's d = 1.1627). Characteristics in healthy aging were not shown to differ. These results indicate that activity in MCI exhibits cross-frequency network reorganization characterized by increased heterogeneity of node roles in the functional hierarchy. Aging itself is not found to cause VSTM functional hierarchy differences.
阿尔茨海默病(AD)既表现出大脑区域之间功能依赖性的复杂变化,也表现出执行视觉短时记忆绑定(VSTMB)任务能力的下降。网络神经科学在理解大脑分层功能的复杂性方面取得的最新进展使我们能够在这两种现象之间建立联系。在这里,我们研究了两种处于轻度认知障碍(MCI)阶段的痴呆症患者--家族性 AD 患者(presenilin-1 基因 E280A 突变)和散发性 AD 高风险老年 MCI 患者--以及年龄匹配对照组的数据。我们分析了这些参与者在完成视觉短时记忆(VSTM)任务时记录的脑电图(EEG)信号。我们使用阿尔法和贝塔的相位滞后指数计算功能连接性,并使用分层扩散(度方差)和复杂性网络指数进行网络分析。脑电图功能连接网络的层次特征显示了家族性 MCI VSTMB 功能和散发性 MCI VSTMB 功能的异常模式。与健康对照组相比,中年家族性 MCI 结合网络在低 Beta 部分显示出更大的程度方差(p = 0.0051,Cohen's d = 1.0124),而老年散发性 MCI 结合网络在 Alpha 部分显示出更大的层次复杂性(p = 0.0140,Cohen's d = 1.1627)。健康老龄人的特征没有显示出差异。这些结果表明,MCI 中的活动表现出跨频率网络重组,其特点是功能层次结构中节点作用的异质性增加。衰老本身并不会导致 VSTM 功能层次的差异。
{"title":"Abnormal Functional Hierarchies of EEG Networks in Familial and Sporadic Prodromal Alzheimer's Disease During Visual Short-Term Memory Binding.","authors":"Keith M Smith, John M Starr, Javier Escudero, Agustin Ibañez, Mario A Parra","doi":"10.3389/fnimg.2022.883968","DOIUrl":"10.3389/fnimg.2022.883968","url":null,"abstract":"<p><p>Alzheimer's Disease (AD) shows both complex alterations of functional dependencies between brain regions and a decreased ability to perform Visual Short-Term Memory Binding (VSTMB) tasks. Recent advances in network neuroscience toward understanding the complexity of hierarchical brain function here enables us to establish a link between these two phenomena. Here, we study data on two types of dementia at Mild Cognitive Impairment (MCI) stage-familial AD patients (E280A mutation of the presenilin-1 gene) and elderly MCI patients at high risk of sporadic AD, both with age-matched controls. We analyzed Electroencephalogram (EEG) signals recorded during the performance of Visual Short-Term Memory (VSTM) tasks by these participants. Functional connectivity was computed using the phase-lag index in Alpha and Beta; and network analysis was employed using network indices of hierarchical spread (degree variance) and complexity. Hierarchical characteristics of EEG functional connectivity networks revealed abnormal patterns in familial MCI VSTMB function and sporadic MCI VSTMB function. The middle-aged familial MCI binding network displayed a larger degree variance in lower Beta compared to healthy controls (<i>p</i> = <i>0.0051</i>, Cohen's <i>d</i> = 1.0124), while the elderly sporadic MCI binding network displayed greater hierarchical complexity in Alpha (<i>p</i> = <i>0.0140</i>, Cohen's <i>d</i> = 1.1627). Characteristics in healthy aging were not shown to differ. These results indicate that activity in MCI exhibits cross-frequency network reorganization characterized by increased heterogeneity of node roles in the functional hierarchy. Aging itself is not found to cause VSTM functional hierarchy differences.</p>","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"1 ","pages":"883968"},"PeriodicalIF":0.0,"publicationDate":"2022-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10338072","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}
Pub Date : 2022-06-02eCollection Date: 2022-01-01DOI: 10.3389/fnimg.2022.828767
Swati Rane Levendovszky
Introduction: Alzheimer's disease (AD) is a degenerative disease characterized by pathological accumulation of amyloid and phosphorylated tau. Typically, the early stage of AD, also called mild cognitive impairment (MCI), shows amyloid pathology. A small but significant number of individuals with MCI do not exhibit amyloid pathology but have elevated phosphorylated tau levels (A-T+ MCI). We used CSF amyloid and phosphorylated tau to identify the individuals with A+T+ and A-T+ MCI as well as cognitively normal (A-T-) controls. To increase the sample size, we leveraged the Global Alzheimer's Association Interactive Network and identified 137 MCI+ and 61 A-T+ MCI participants. We compared baseline and longitudinal, hippocampal, and cortical atrophy between groups.
Methods: We applied ComBat harmonization to minimize site-related variability and used FreeSurfer for all measurements.
Results: Harmonization reduced unwanted variability in cortical thickness by 3.4% and in hippocampal volume measurement by 10.3%. Cross-sectionally, widespread cortical thinning with age was seen in the A+T+ and A-T+ MCI groups (p < 0.0005). A decrease in the hippocampal volume with age was faster in both groups (p < 0.05) than in the controls. Longitudinally also, hippocampal atrophy rates were significant (p < 0.05) when compared with the controls. No longitudinal cortical thinning was observed in A-T+ MCI group.
Discussion: A-T+ MCI participants showed similar baseline cortical thickness patterns with aging and longitudinal hippocampal atrophy rates as participants with A+T+ MCI, but did not show longitudinal cortical atrophy signature.
{"title":"Cross-Sectional and Longitudinal Hippocampal Atrophy, Not Cortical Thinning, Occurs in Amyloid-Negative, p-Tau-Positive, Older Adults With Non-Amyloid Pathology and Mild Cognitive Impairment.","authors":"Swati Rane Levendovszky","doi":"10.3389/fnimg.2022.828767","DOIUrl":"10.3389/fnimg.2022.828767","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease (AD) is a degenerative disease characterized by pathological accumulation of amyloid and phosphorylated tau. Typically, the early stage of AD, also called mild cognitive impairment (MCI), shows amyloid pathology. A small but significant number of individuals with MCI do not exhibit amyloid pathology but have elevated phosphorylated tau levels (A-T+ MCI). We used CSF amyloid and phosphorylated tau to identify the individuals with A+T+ and A-T+ MCI as well as cognitively normal (A-T-) controls. To increase the sample size, we leveraged the Global Alzheimer's Association Interactive Network and identified 137 MCI+ and 61 A-T+ MCI participants. We compared baseline and longitudinal, hippocampal, and cortical atrophy between groups.</p><p><strong>Methods: </strong>We applied ComBat harmonization to minimize site-related variability and used FreeSurfer for all measurements.</p><p><strong>Results: </strong>Harmonization reduced unwanted variability in cortical thickness by 3.4% and in hippocampal volume measurement by 10.3%. Cross-sectionally, widespread cortical thinning with age was seen in the A+T+ and A-T+ MCI groups (<i>p</i> < 0.0005). A decrease in the hippocampal volume with age was faster in both groups (<i>p</i> < 0.05) than in the controls. Longitudinally also, hippocampal atrophy rates were significant (<i>p</i> < 0.05) when compared with the controls. No longitudinal cortical thinning was observed in A-T+ MCI group.</p><p><strong>Discussion: </strong>A-T+ MCI participants showed similar baseline cortical thickness patterns with aging and longitudinal hippocampal atrophy rates as participants with A+T+ MCI, but did not show longitudinal cortical atrophy signature.</p>","PeriodicalId":73094,"journal":{"name":"Frontiers in neuroimaging","volume":"1 ","pages":"828767"},"PeriodicalIF":0.0,"publicationDate":"2022-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10319942","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}