A distributed multitask multimodal approach for the prediction of Alzheimer's disease in a longitudinal study.

Predicting the progression of Alzheimer's Disease (AD) has been held back for decades due to the lack of sufficient longitudinal data required for the development of novel machine learning algorithms. This study proposes a novel machine learning algorithm for predicting the progression of Alzheimer's disease using a distributed multimodal, multitask learning method. More specifically, each individual task is defined as a regression model, which predicts cognitive scores at a single time point. Since the prediction tasks for multiple intervals are related to each other in chronological order, multitask regression models have been developed to track the relationship between subsequent tasks. Furthermore, since subjects have various combinations of recording modalities together with other genetic, neuropsychological and demographic risk factors, special attention is given to the fact that each modality may experience a specific sparsity pattern. The model is hence generalized by exploiting multiple individual multitask regression coefficient matrices for each modality. The outcome for each independent modality-specific learner is then integrated with complementary information, known as risk factor parameters, revealing the most prevalent trends of the multimodal data. This new feature space is then used as input to the gradient boosting kernel in search for a more accurate prediction. This proposed model not only captures the complex relationships between the different feature representations, but it also ignores any unrelated information which might skew the regression coefficients. Comparative assessments are made between the performance of the proposed method with several other well-established methods using different multimodal platforms. The results indicate that by capturing the interrelatedness between the different modalities and extracting only relevant information in the data, even in an incomplete longitudinal dataset, will yield minimized prediction errors.

A practical guideline for intracranial volume estimation in patients with Alzheimer's disease.

BACKGROUND: Intracranial volume (ICV) is an important normalization measure used in morphometric analyses to correct for head size in studies of Alzheimer Disease (AD). Inaccurate ICV estimation could introduce bias in the outcome. The current study provides a decision aid in defining protocols for ICV estimation in patients with Alzheimer disease in terms of sampling frequencies that can be optimally used on the volumetric MRI data, and the type of software most suitable for use in estimating the ICV measure. METHODS: Two groups of 22 subjects are considered, including adult controls (AC) and patients with Alzheimer Disease (AD). Reference measurements were calculated for each subject by manually tracing intracranial cavity by the means of visual inspection. The reliability of reference measurements were assured through intra- and inter- variation analyses. Three publicly well-known software packages (Freesurfer, FSL, and SPM) were examined in their ability to automatically estimate ICV across the groups. RESULTS: Analysis of the results supported the significant effect of estimation method, gender, cognitive condition of the subject and the interaction among method and cognitive condition factors in the measured ICV. Results on sub-sampling studies with a 95% confidence showed that in order to keep the accuracy of the interleaved slice sampling protocol above 99%, the sampling period cannot exceed 20 millimeters for AC and 15 millimeters for AD. Freesurfer showed promising estimates for both adult groups. However SPM showed more consistency in its ICV estimation over the different phases of the study. CONCLUSIONS: This study emphasized the importance in selecting the appropriate protocol, the choice of the sampling period in the manual estimation of ICV and selection of suitable software for the automated estimation of ICV. The current study serves as an initial framework for establishing an appropriate protocol in both manual and automatic ICV estimations with different subject populations.

A probabilistic approach for pediatric epilepsy diagnosis using brain functional connectivity networks.

BACKGROUND: The lives of half a million children in the United States are severely affected due to the alterations in their functional and mental abilities which epilepsy causes. This study aims to introduce a novel decision support system for the diagnosis of pediatric epilepsy based on scalp EEG data in a clinical environment. METHODS: A new time varying approach for constructing functional connectivity networks (FCNs) of 18 subjects (7 subjects from pediatric control (PC) group and 11 subjects from pediatric epilepsy (PE) group) is implemented by moving a window with overlap to split the EEG signals into a total of 445 multi-channel EEG segments (91 for PC and 354 for PE) and finding the hypothetical functional connectivity strengths among EEG channels. FCNs are then mapped into the form of undirected graphs and subjected to extraction of graph theory based features. An unsupervised labeling technique based on Gaussian mixtures model (GMM) is then used to delineate the pediatric epilepsy group from the control group. RESULTS: The study results show the existence of a statistically significant difference (p < 0.0001) between the mean FCNs of PC and PE groups. The system was able to diagnose pediatric epilepsy subjects with the accuracy of 88.8% with 81.8% sensitivity and 100% specificity purely based on exploration of associations among brain cortical regions and without a priori knowledge of diagnosis. CONCLUSIONS: The current study created the potential of diagnosing epilepsy without need for long EEG recording session and time-consuming visual inspection as conventionally employed.

Classification of fMRI patterns--a study of the language network segregation in pediatric localization related epilepsy.

This article describes a pattern classification algorithm for pediatric epilepsy using fMRI language-related activation maps. 122 fMRI datasets from a control group (64) and localization related epilepsy patients (58) provided by five children's hospitals were used. Each subject performed an auditory description decision task. Using the artificial data as training data, incremental Principal Component Analysis was used in order to generate the feature space while overcoming memory requirements of large datasets. The nearest-neighbor classifier (NNC) and the distance-based fuzzy classifier (DFC) were used to perform group separation into left dominant, right dominant, bilateral, and others. The results show no effect of age, age at seizure onset, seizure duration, or seizure etiology on group separation. Two sets of parameters were significant for group separation, the patient vs. control populations and handedness. Of the 122 real datasets, 90 subjects gave the same classification results across all the methods (three raters, LI, bootstrap LI, NNC, and DFC). For the remaining datasets, 18 cases for the IPCA-NNC and 21 cases for the IPCA-DFC agreed with the majority of the five classification results (three visual ratings and two LI results). Kappa values vary from 0.59 to 0.73 for NNC and 0.61 to 0.75 for DFC, which indicate good agreement between NNC or DFC with traditional methods. The proposed method as designed can serve as an alternative method to corroborate existing LI and visual rating classification methods and to resolve some of the cases near the boundaries in between categories.

Significance of normalization on anatomical MRI measures in predicting Alzheimer's disease.

This study establishes a new approach for combining neuroimaging and neuropsychological measures for an optimal decisional space to classify subjects with Alzheimer's disease (AD). This approach relies on a multivariate feature selection method with different MRI normalization techniques. Subcortical volume, cortical thickness, and surface area measures are obtained using MRIs from 189 participants (129 normal controls and 60 AD patients). Statistically significant variables were selected for each combination model to construct a multidimensional space for classification. Different normalization approaches were explored to gauge the effect on classification performance using a support vector machine classifier. Results indicate that the Mini-mental state examination (MMSE) measure is most discriminative among single-measure models, while subcortical volume combined with MMSE is the most effective multivariate model for AD classification. The study demonstrates that subcortical volumes need not be normalized, whereas cortical thickness should be normalized either by intracranial volume or mean thickness, and surface area is a weak indicator of AD with and without normalization. On the significant brain regions, a nearly perfect symmetry is observed for subcortical volumes and cortical thickness, and a significant reduction in thickness is particularly seen in the temporal lobe, which is associated with brain deficits characterizing AD.

Quasi-stationarity of EEG for intraoperative monitoring during spinal surgeries.

We present a study and application of quasi-stationarity of electroencephalogram for intraoperative neurophysiological monitoring (IONM) and an application of Chebyshev time windowing for preconditioning SSEP trials to retain the morphological characteristics of somatosensory evoked potentials (SSEP). This preconditioning was followed by the application of a principal component analysis (PCA)-based algorithm utilizing quasi-stationarity of EEG on 12 preconditioned trials. This method is shown empirically to be more clinically viable than present day approaches. In all twelve cases, the algorithm takes 4 sec to extract an SSEP signal, as compared to conventional methods, which take several minutes. The monitoring process using the algorithm was successful and proved conclusive under the clinical constraints throughout the different surgical procedures with an accuracy of 91.5%. Higher accuracy and faster execution time, observed in the present study, in determining the SSEP signals provide a much improved and effective neurophysiological monitoring process.

Induced effects of transcranial magnetic stimulation on the autonomic nervous system and the cardiac rhythm.

Several standard protocols based on repetitive transcranial magnetic stimulation (rTMS) have been employed for treatment of a variety of neurological disorders. Despite their advantages in patients that are retractable to medication, there is a lack of knowledge about the effects of rTMS on the autonomic nervous system that controls the cardiovascular system. Current understanding suggests that the shape of the so-called QRS complex together with the size of the different segments and intervals between the PQRST deflections of the heart could predict the nature of the different arrhythmias and ailments affecting the heart. This preliminary study involving 10 normal subjects from 20 to 30 years of age demonstrated that rTMS can induce changes in the heart rhythm. The autonomic activity that controls the cardiac rhythm was indeed altered by an rTMS session targeting the motor cortex using intensity below the subject's motor threshold and lasting no more than 5 minutes. The rTMS activation resulted in a reduction of the RR intervals (cardioacceleration) in most cases. Most of these cases also showed significant changes in the Poincare plot descriptor SD2 (long-term variability), the area under the low frequency (LF) power spectrum density curve, and the low frequency to high frequency (LF/HF) ratio. The RR intervals changed significantly in specific instants of time during rTMS activation showing either heart rate acceleration or heart rate deceleration.

Graph neural networks in EEG spike detection.

OBJECTIVE: This study develops new machine learning architectures that are more adept at detecting interictal epileptiform discharges (IEDs) in scalp EEG. A comparison of results using the average precision (AP) metric is made with the proposed models on two datasets obtained from Baptist Hospital of Miami and Temple University Hospital. METHODS: Applying graph neural networks (GNNs) on functional connectivity (FC) maps of different frequency sub-bands to yield a novel architecture we call FC-GNN. Attention mechanism is applied on a complete graph to let the neural network select its important edges, hence bypassing the extraction of features, a model we refer to as CA-GNN. RESULTS: On the Baptist Hospital dataset, the results were as follows: Vanilla Self-Attention →0.9029±0.0431, Hierarchical Attention →0.8546±0.0587, Vanilla Visual Geometry Group (VGG) →0.92±0.0618, Satelight →0.9219±0.046, FC-GNN →0.9731±0.0187, and CA-GNN →0.9788±0.0125. In the same order, the results on the Temple University Hospital dataset are 0.9692, 0.9113, 0.97, 0.9575, 0.963, and 0.9879. CONCLUSION: Based on the good results they yield, GNNs prove to have a strong potential in detecting epileptogenic activity. SIGNIFICANCE: This study opens the door for the discovery of the powerful role played by GNNs in capturing IEDs, which is an essential step for identifying the epileptogenic networks of the affected brain and hence improving the prospects for more accurate 3D source localization.

A transfer learning approach based on gradient boosting machine for diagnosis of Alzheimer's disease.

Early detection of Alzheimer's disease (AD) during the Mild Cognitive Impairment (MCI) stage could enable effective intervention to slow down disease progression. Computer-aided diagnosis of AD relies on a sufficient amount of biomarker data. When this requirement is not fulfilled, transfer learning can be used to transfer knowledge from a source domain with more amount of labeled data than available in the desired target domain. In this study, an instance-based transfer learning framework is presented based on the gradient boosting machine (GBM). In GBM, a sequence of base learners is built, and each learner focuses on the errors (residuals) of the previous learner. In our transfer learning version of GBM (TrGB), a weighting mechanism based on the residuals of the base learners is defined for the source instances. Consequently, instances with different distribution than the target data will have a lower impact on the target learner. The proposed weighting scheme aims to transfer as much information as possible from the source domain while avoiding negative transfer. The target data in this study was obtained from the Mount Sinai dataset which is collected and processed in a collaborative 5-year project at the Mount Sinai Medical Center. The Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset was used as the source domain. The experimental results showed that the proposed TrGB algorithm could improve the classification accuracy by 1.5 and 4.5% for CN vs. MCI and multiclass classification, respectively, as compared to the conventional methods. Also, using the TrGB model and transferred knowledge from the CN vs. AD classification of the source domain, the average score of early MCI vs. late MCI classification improved by 5%.

A Tensorized Multitask Deep Learning Network for Progression Prediction of Alzheimer's Disease.

With the advances in machine learning for the diagnosis of Alzheimer's disease (AD), most studies have focused on either identifying the subject's status through classification algorithms or on predicting their cognitive scores through regression methods, neglecting the potential association between these two tasks. Motivated by the need to enhance the prospects for early diagnosis along with the ability to predict future disease states, this study proposes a deep neural network based on modality fusion, kernelization, and tensorization that perform multiclass classification and longitudinal regression simultaneously within a unified multitask framework. This relationship between multiclass classification and longitudinal regression is found to boost the efficacy of the final model in dealing with both tasks. Different multimodality scenarios are investigated, and complementary aspects of the multimodal features are exploited to simultaneously delineate the subject's label and predict related cognitive scores at future timepoints using baseline data. The main intent in this multitask framework is to consolidate the highest accuracy possible in terms of precision, sensitivity, F1 score, and area under the curve (AUC) in the multiclass classification task while maintaining the highest similarity in the MMSE score as measured through the correlation coefficient and the RMSE for all time points under the prediction task, with both tasks, run simultaneously under the same set of hyperparameters. The overall accuracy for multiclass classification of the proposed KTMnet method is 66.85 ± 3.77. The prediction results show an average RMSE of 2.32 ± 0.52 and a correlation of 0.71 ± 5.98 for predicting MMSE throughout the time points. These results are compared to state-of-the-art techniques reported in the literature. A discovery from the multitasking of this consolidated machine learning framework is that a set of hyperparameters that optimize the prediction results may not necessarily be the same as those that would optimize the multiclass classification. In other words, there is a breakpoint beyond which enhancing further the results of one process could lead to the downgrading in accuracy for the other.

A study of the longitudinal changes in multiple cerebrospinal fluid and volumetric magnetic resonance imaging biomarkers on converter and non-converter Alzheimer's disease subjects with consideration for their amyloid beta status.

INTRODUCTION: This study aims to determine whether newly introduced biomarkers Visinin-like protein-1 (VILIP-1), chitinase-3-like protein 1 (YKL-40), synaptosomal-associated protein 25 (SNAP-25), and neurogranin (NG) in cerebrospinal fluid are useful in evaluating the asymptomatic and early symptomatic stages of Alzheimer's disease (AD). It further aims to shed new insight into the differences between stable subjects and those who progress to AD by associating cerebrospinal fluid (CSF) biomarkers and specific magnetic resonance imaging (MRI) regions with disease progression, more deeply exploring how such biomarkers relate to AD pathology. METHODS: We examined baseline and longitudinal changes over a 7-year span and the longitudinal interactions between CSF and MRI biomarkers for subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We stratified all CSF (140) and MRI (525) cohort participants into five diagnostic groups (including converters) further dichotomized by CSF amyloid beta (Aß) status. Linear mixed models were used to compare within-person rates of change across diagnostic groups and to evaluate the association of CSF biomarkers as predictors of magnetic resonance imaging (MRI) biomarkers. CSF biomarkers and disease-prone MRI regions are assessed for CSF proteins levels and brain structural changes. RESULTS: VILIP-1 and SNAP-25 displayed within-person increments in early symptomatic, amyloid-positive groups. CSF amyloid-positive (Aß+) subjects showed elevated baseline levels of total tau (tTau), phospho-tau181 (pTau), VILIP-1, and NG. YKL-40, SNAP-25, and NG are positively intercorrelated. Aß+ subjects showed negative MRI biomarker changes. YKL-40, tTau, pTau, and VILIP-1 are longitudinally associated with MRI biomarkers atrophy. DISCUSSION: Converters (CNc, MCIc) highlight the evolution of biomarkers during the disease progression. Results show that underlying amyloid pathology is associated with accelerated cognitive impairment. CSF levels of Aß42, pTau, tTau, VILIP-1, and SNAP-25 show utility to discriminate between mild cognitive impairment (MCI) converter and control subjects (CN). Higher levels of YKL-40 in the Aß+ group were longitudinally associated with declines in temporal pole and entorhinal thickness. Increased levels of tTau, pTau, and VILIP-1 in the Aß+ groups were longitudinally associated with declines in hippocampal volume. These CSF biomarkers should be used in assessing the characterization of the AD progression.

Real-time frequency-independent single-Lead and single-beat myocardial infarction detection.

This study proposes a novel real-time frequency-independent myocardial infarction detector for Lead II electrocardiograms. The underlying Deep-LSTM network is trained using the PTB-XL database, the largest to date publicly available electrocardiography dataset, and is tested over the same and the older PTB database. By testing the model over distinct datasets, collected under different conditions and from different patients, a more realistic measure of the performance can be gauged from the deployed system. The detector is trained over 3589 myocardial infarction (MI) patients and 7115 healthy controls (HC) while it is evaluated on 1076 MIs and 1840 HCs. The proposed algorithm, achieved an accuracy of 77.12%, recall/sensitivity of 75.85%, and a specificity of 83.02% over the entire PTB database; 85.07%, 81.54%, 87.31% over the PTB-XL validation set (fold 9), and 84.17%, 78.37%, 87.55% over the PTB-XL test set (fold 10). The model also achieves stable performance metrics over the frequency range of 202 Hz to 2.8 kHz. The processing time is dependent on the sampling frequency, ranging from 130 ms at 202 Hz to 1.8 s at 2.8 kHz. Such outcome is within the time required for real-time processing (less than 300 ms for fast heartbeats), between 202 Hz and 500 Hz making the algorithm practically real-time. Therefore, the proposed MI detector could be readily deployed onto existing wearable and/or portable devices and test instruments; potentially having significant societal and clinical impact in the lives of patients at risk for myocardial infarction.

PET Imaging of Tau Pathology and Amyloid-ß, and MRI for Alzheimer's Disease Feature Fusion and Multimodal Classification.

BACKGROUND: Machine learning is a promising tool for biomarker-based diagnosis of Alzheimer's disease (AD). Performing multimodal feature selection and studying the interaction between biological and clinical AD can help to improve the performance of the diagnosis models. OBJECTIVE: This study aims to formulate a feature ranking metric based on the mutual information index to assess the relevance and redundancy of regional biomarkers and improve the AD classification accuracy. METHODS: From the Alzheimer's Disease Neuroimaging Initiative (ADNI), 722 participants with three modalities, including florbetapir-PET, flortaucipir-PET, and MRI, were studied. The multivariate mutual information metric was utilized to capture the redundancy and complementarity of the predictors and develop a feature ranking approach. This was followed by evaluating the capability of single-modal and multimodal biomarkers in predicting the cognitive stage. RESULTS: Although amyloid-ß deposition is an earlier event in the disease trajectory, tau PET with feature selection yielded a higher early-stage classification F1-score (65.4%) compared to amyloid-ß PET (63.3%) and MRI (63.2%). The SVC multimodal scenario with feature selection improved the F1-score to 70.0% and 71.8% for the early and late-stage, respectively. When age and risk factors were included, the scores improved by 2 to 4%. The Amyloid-Tau-Neurodegeneration [AT(N)] framework helped to interpret the classification results for different biomarker categories. CONCLUSION: The results underscore the utility of a novel feature selection approach to reduce the dimensionality of multimodal datasets and enhance model performance. The AT(N) biomarker framework can help to explore the misclassified cases by revealing the relationship between neuropathological biomarkers and cognition.

Dynamics and Distant Effects of Frontal/Temporal Epileptogenic Focus Using Functional Connectivity Maps.

OBJECTIVE: Connectivity patterns of interictal epileptiform discharges are all subtle indicators of where the three-dimensional (3D) source of a seizure could be located. These specific patterns are explored in the recorded electroencephalogram (EEG) signals of 20 individuals diagnosed with focal epilepsy to assess how their functional brain maps could be affected by the 3D onset of a seizure. METHODS: Functional connectivity maps, estimated by phase synchrony among EEG electrodes, were obtained by applying a data-driven recurrence-based method. This is augmented through a novel approach for selecting optimal parameters that produce connectivity matrices that are deemed significant for assessing epileptiform activity in context to the 3D source localization of seizure onset. These functional connectivity matrices were evaluated in different brain areas to gauge the regional effects of the 3D epileptic source. RESULTS: Empirical evaluations indicate high synchronization in the temporal and frontal areas of the effected epileptic hemisphere, whereas strong links connect the irritated area to frontal and temporal lobes of the opposite hemisphere. CONCLUSION: Epileptic activity originating in the temporal or frontal areas is seen to affect these areas in both hemispheres. SIGNIFICANCE: The results obtained express the dynamics of focal epilepsy in context to both the epileptogenic zone and the affected distant areas of the brain.

Gaussian discriminative component analysis for early detection of Alzheimer's disease: A supervised dimensionality reduction algorithm.

BACKGROUND: Using multiple modalities of biomarkers, several machine leaning-based approaches have been proposed to characterize patterns of structural, functional and metabolic differences discernible from multimodal neuroimaging data for Alzheimer's disease (AD). Current investigations report several studies using binary classification often augmented with local feature selection methods, while fewer other studies address the challenging problem of multiclass classification. NEW METHOD: To assess the merits of each of these research directions, this study introduces a supervised Gaussian discriminative component analysis (GDCA) algorithm, which can effectively delineate subtle changes of early mild cognitive impairment (EMCI) group in relation to the cognitively normal control (CN) group. Using 251 CN, 297 EMCI, 196 late MCI (LMCI), and 162 AD subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and considering both structural and functional (metabolic) information from magnetic resonance imaging (MRI) and positron emission tomography (PET) modalities as input, the proposed method conducts a dimensionality reduction algorithm taking into consideration the interclass information to define an optimal eigenspace that maximizes the discriminability of selected eigenvectors. RESULTS: The proposed algorithm achieves an accuracy of 79.25 % for delineating EMCI from CN using 38.97 % of Gaussian discriminative components (i.e., dimensionality reduction). Moreover, for detecting the different stages of AD, a multiclass classification experiment attained an overall accuracy of 67.69 %, and more notably, discriminates MCI and AD groups from the CN group with an accuracy of 75.28 % using 48.90 % of the Gaussian discriminative components. COMPARISON WITH EXISTING METHOD(S): The classification results of the proposed GDCA method outperform the more recently published state-of-the-art methods in AD-related multiclass classification tasks, and seems to be the most stable and reliable in terms of relating the most relevant features to the optimal classification performance. CONCLUSION: The proposed GDCA model with its high prospects for multiclass classification has a high potential for deployment as a computer aided clinical diagnosis system for AD.

A Gaussian-based model for early detection of mild cognitive impairment using multimodal neuroimaging.

BACKGROUND: Diagnosis of early mild cognitive impairment (EMCI) as a prodromal stage of Alzheimer's disease (AD) with its delineation from the cognitively normal (CN) group remains a challenging but essential step for the planning of early treatment. Although several studies have focused on the MCI diagnosis, this study introduces the early stage of MCI to assess more thoroughly the earliest signs of disease manifestation and progression. NEW METHOD: We used random forest feature selection model with a Gaussian-based algorithm to perform method evaluation. This integrated method serves to define multivariate normal distributions in order to classify different stages of AD, with the focus placed on detecting EMCI subjects in the most challenging classification of CN vs. EMCI. RESULTS: Using 896 participants classified into the four categories of CN, EMCI, late mild cognitive impairment (LMCI) and AD, the results show that the EMCI group can be delineated from the CN group with a relatively high accuracy of 78.8% and sensitivity of 81.3%. COMPARISON WITH EXISTING METHOD(S): The feature selection model and classifier are compared with some other prominent algorithms. Although higher accuracy has been achieved using the Gaussian process (GP) model (78.8%) over the SVM classifier (75.6%) for CN vs. EMCI classification, with 0.05 being the cutoff for significance, and based on student's t-test, it was determined that the differences for accuracy, sensitivity, specificity between the GP method and support vector machine (SVM) are not statistically significant. CONCLUSION: Addressing the challenging classification of CN vs. EMCI provides useful information to help clinicians and researchers determine essential measures that can help in the early detection of AD.

A survey on applications and analysis methods of functional magnetic resonance imaging for Alzheimer's disease.

BACKGROUND: Functional magnetic resonance imaging (fMRI) is an MRI-based neuroimaging technique that measures brain activity on the basis of blood oxygenation level. This study reviews the main fMRI methods reported in the literature and their related applications in clinical and preclinical studies, focusing on relating functional brain networks in the prodromal stages of Alzheimer's disease (AD), with a focus on the transition phases from cognitively normal (CN) to mild cognitive impairment (MCI) and from MCI to AD. NEW METHOD: The purpose of this study is to present and compare different approaches of supervised and unsupervised fMRI analyses and to highlight the different applications of fMRI in the diagnosis of MCI and AD. RESULTS: Survey article asserts that brain network disruptions of a given dysfunction or in relation to disease prone areas of the brain in neurodegenerative dementias could be extremely useful in ascertaining the extent of cognitive deficits at the different stages of the disease. Identifying the earliest changes in these activity patterns is essential for the early planning of treatment and therapeutic protocols. COMPARISON WITH EXISTING METHODS: Analysis methods such as independent component analysis (ICA) and graph theory-based approaches are strong analytical techniques most suitable for functional connectivity investigations. However, graph theory-based approaches have received more attention due to the higher performance they achieve in both functional and effective connectivity studies. CONCLUSION: This article shows that the disruption of brain connectivity patterns of MCI and AD could be associated with cognitive decline, an interesting finding that could augment the prospects for early diagnosis. More importantly, results reveal that changes in functional connectivity as obtained through fMRI precede detection of cortical thinning in structural MRI and amyloid deposition in positron emission tomography (PET). However, a major challenge in using fMRI as a single imaging modality, like all other imaging modalities used in isolation, is in relating a particular disruption in functional connectivity in relation to a specific disease. This is a challenge that requires more thorough investigation, and one that could perhaps be overcome through multimodal neuroimaging by consolidating the strengths of these individual imaging modalities.

Greater Regional Cortical Thickness is Associated with Selective Vulnerability to Atrophy in Alzheimer's Disease, Independent of Amyloid Load and APOE Genotype.

BACKGROUND: Regional cortical thickness (rCTh) among cognitively normal (CN) adults (rCThCN) varies greatly between brain regions, as does the vulnerability to neurodegeneration. OBJECTIVE: The goal of this study was to: 1) rank order rCThCN for various brain regions, and 2) explore their vulnerability to neurodegeneration in Alzheimer's disease (AD) within these brain regions. METHODS: The relationship between rCTh among the CN group (rCThCN) and the percent difference in CTh (% CThDiff) in each region between the CN group and AD patients was examined. Pearson correlation analysis was performed accounting for amyloid-ß (Aß) protein and APOE genotype using 210 age, gender, and APOE matched CN (n = 105, age range: 56-90) and AD (n = 105, age range: 56-90) ADNI participants. RESULTS: Strong positive correlations were observed between rCThCN and % CThDiff accounting for Aß deposition and APOE status. Regions, such as the entorhinal cortex, which had the greatest CTh in the CN state, were also the regions which had the greatest % CThDiff. CONCLUSIONS: Regions with the greatest CTh at the CN stage are found to aggregate in disease prone regions of AD, namely in the medial temporal lobe, including the temporal pole, ERC, parahippocampal gyrus, fusiform and the middle and inferior temporal gyrus. Although rCTh has been found to vary considerably across the different regions of the brain, our results indicate that regions with the greatest CTh at the CN stage are actually regions which have been found to be most vulnerable to neurodegeneration in AD.

A cognitive stress test for prodromal Alzheimer's disease: Multiethnic generalizability.

INTRODUCTION: Culturally fair cognitive assessments sensitive to detecting changes associated with prodromal Alzheimer's disease are needed. METHODS: Performance of Hispanic and non-Hispanic older adults on the Loewenstein-Acevedo Scale of Semantic Interference and Learning (LASSI-L) was examined in persons with amnestic mild cognitive impairment (aMCI) or normal cognition. The association between a novel cognitive marker, the failure to recover from proactive semantic interference (frPSI), and cortical thinning was explored. RESULTS: English-speaking aMCI participants scored lower than cognitively normal participants on all LASSI-L indices, while Spanish-speaking aMCI participants scored lower in learning, frPSI, and delayed recall. Healthy controls obtained equivalent scores on all indices except retroactive semantic interference. English-speaking and Spanish-speaking aMCI participants had equivalent scores except English speaker's greater vulnerability to frPSI. Across aMCI groups, frPSI was associated with cortical thinning of the entorhinal cortex and precuneus (r = -0.45 to r = 0.52; P < .005). DISCUSSION: In diverse populations, LASSI-L performance differentiated patients with aMCI from cognitively normal older adults and was associated with thinning in Alzheimer's disease-prone regions, suggesting its clinical utility.

A Robust Edge Detection Approach in the Presence of High Impulse Noise Intensity through Switching Adaptive Median and Fixed Weighted Mean Filtering.

This study introduces a robust edge detection method that relies on an integrated process for denoising images in the presence of high impulse noise. This process is shown to be resilient to impulse (or salt and pepper) noise even under high intensity levels. The proposed switching adaptive median and fixed weighted mean filter (SAMFWMF) is shown to yield optimal edge detection and edge detail preservation, an outcome we validate through high correlation, structural similarity index and peak signal to noise ratio measures. For comparative purposes, a comprehensive analysis of other denoising filters is provided based on these various validation metrics. The nonmaximum suppression method and new edge following maximum-sequence are two techniques used to track the edges and overcome edge discontinuities and noisy pixels, especially in the presence of high-intensity noise levels. After applying predefined thresholds to the grayscale image and thus obtaining a binary image, several morphological operations are used to remove the unwanted edges and noisy pixels, perform edge thinning to ultimately provide the desired edge connectivity which results in an optimal edge detection method. The obtained results are compared to other existing state-of-the-art denoising filters and other edge detection methods in support of our assertion that the proposed method is resilient to impulse noise even under high-intensity levels.