A WORLDWIDE ENIGMA STUDY ON EPILEPSY-RELATED GRAY AND WHITE MATTER COMPROMISE ACROSS THE ADULT LIFESPAN.

Objectives: Temporal lobe epilepsy (TLE) is commonly associated with mesiotemporal pathology and widespread alterations of grey and white matter structures. Evidence supports a progressive condition although the temporal evolution of TLE is poorly defined. This ENIGMA-Epilepsy study utilized multimodal magnetic resonance imaging (MRI) data to investigate structural alterations in TLE patients across the adult lifespan. We charted both grey and white matter changes and explored the covariance of age-related alterations in both compartments. Methods: We studied 769 TLE patients and 885 healthy controls across an age range of 17-73 years, from multiple international sites. To assess potentially non-linear lifespan changes in TLE, we harmonized data and combined median split assessments with cross-sectional sliding window analyses of grey and white matter age-related changes. Covariance analyses examined the coupling of grey and white matter lifespan curves. Results: In TLE, age was associated with a robust grey matter thickness/volume decline across a broad cortico-subcortical territory, extending beyond the mesiotemporal disease epicentre. White matter changes were also widespread across multiple tracts with peak effects in temporo-limbic fibers. While changes spanned the adult time window, changes accelerated in cortical thickness, subcortical volume, and fractional anisotropy (all decreased), and mean diffusivity (increased) after age 55 years. Covariance analyses revealed strong limbic associations between white matter tracts and subcortical structures with cortical regions. Conclusions: This study highlights the profound impact of TLE on lifespan changes in grey and white matter structures, with an acceleration of aging-related processes in later decades of life. Our findings motivate future longitudinal studies across the lifespan and emphasize the importance of prompt diagnosis as well as intervention in patients.

Non-linear processing and reinforcement learning to predict rTMS treatment response in depression.

BACKGROUND: Forecasting the efficacy of repetitive transcranial magnetic stimulation (rTMS) therapy can lead to substantial time and cost savings by preventing futile treatments. To achieve this objective, we've formulated a machine learning approach aimed at categorizing patients with major depressive disorder (MDD) into two groups: individuals who respond (R) positively to rTMS treatment and those who do not respond (NR). METHODS: Preceding the commencement of treatment, we obtained resting-state EEG data from 106 patients diagnosed with MDD, employing 32 electrodes for data collection. These patients then underwent a 7-week course of rTMS therapy, and 54 of them exhibited positive responses to the treatment. Employing Independent Component Analysis (ICA) on the EEG data, we successfully pinpointed relevant brain sources that could potentially serve as markers of neural activity within the dorsolateral prefrontal cortex (DLPFC). These identified sources were further scrutinized to estimate the sources of activity within the sensor domain. Then, we integrated supplementary physiological data and implemented specific criteria to yield more realistic estimations when compared to conventional EEG analysis. In the end, we selected components corresponding to the DLPFC region within the sensor domain. Features were derived from the time-series data of these relevant independent components. To identify the most significant features, we used Reinforcement Learning (RL). In categorizing patients into two groups - R and NR to rTMS treatment - we utilized three distinct classification algorithms including K-Nearest Neighbor (KNN), Support Vector Machine (SVM), and Multilayer Perceptron (MLP). We assessed the performance of these classifiers through a ten-fold cross-validation method. Additionally, we conducted a statistical test to evaluate the discriminative capacity of these features between responders and non-responders, opening the door for further exploration in this field. RESULTS: We identified EEG features that can anticipate the response to rTMS treatment. The most robust discriminators included EEG beta power, the sum of bispectrum diagonal elements in the delta and beta frequency bands. When these features were combined into a single vector, the classification of responders and non-responders achieved impressive performance, with an accuracy of 95.28 %, specificity at 94.23 %, sensitivity reaching 96.29 %, and precision standing at 94.54 %, all achieved using SVM. CONCLUSIONS: The results of this study suggest that the proposed approach, utilizing power, non-linear, and bispectral features extracted from relevant independent component time-series, has the capability to forecast the treatment outcome of rTMS for MDD patients based solely on a single pre-treatment EEG recording session. The achieved findings demonstrate the superior performance of our method compared to previous techniques.

Repetitive transcranial magnetic stimulation (rTMS) as a tool for cognitive enhancement in healthy adults: a review study.

As human beings, we have always sought to expand on our abilities, including our cognitive and motor skills. One of the still-underrated tools employed to this end is repetitive transcranial magnetic stimulation (rTMS). Until recently, rTMS was almost exclusively used in studies with rehabilitation purposes. Only a small strand of literature has focused on the application of rTMS on healthy people with the aim of enhancing cognitive abilities such as decision-making, working memory, attention, source memory, cognitive control, learning, computational speed, risk-taking, and impulsive behaviors. It, therefore, seems that the findings in this particular field are the indirect results of rehabilitation research. In this review paper, we have set to investigate such studies and evaluate the rTMS effectuality in terms of how it improves the cognitive skills in healthy subjects. Furthermore, since the most common brain site used for rTMS protocols is the dorsolateral prefrontal cortex (DLPFC), we have added theta burst stimulation (TBS) wave patterns that are similar to brain patterns to increase the effectiveness of this method. The results of this study can help people who have high-risk jobs including firefighters, surgeons, and military officers with their job performance.

Accuracy of artificial intelligence CT quantification in predicting COVID-19 subjects' prognosis.

BACKGROUND: Artificial intelligence (AI)-aided analysis of chest CT expedites the quantification of abnormalities and may facilitate the diagnosis and assessment of the prognosis of subjects with COVID-19. OBJECTIVES: This study investigates the performance of an AI-aided quantification model in predicting the clinical outcomes of hospitalized subjects with COVID-19 and compares it with radiologists' performance. SUBJECTS AND METHODS: A total of 90 subjects with COVID-19 (men, n = 59 [65.6%]; age, 52.9±16.7 years) were recruited in this cross-sectional study. Quantification of the total and compromised lung parenchyma was performed by two expert radiologists using a volumetric image analysis software and compared against an AI-assisted package consisting of a modified U-Net model for segmenting COVID-19 lesions and an off-the-shelf U-Net model augmented with COVID-19 data for segmenting lung volume. The fraction of compromised lung parenchyma (%CL) was calculated. Based on clinical results, the subjects were divided into two categories: critical (n = 45) and noncritical (n = 45). All admission data were compared between the two groups. RESULTS: There was an excellent agreement between the radiologist-obtained and AI-assisted measurements (intraclass correlation coefficient = 0.88, P < 0.001). Both the AI-assisted and radiologist-obtained %CLs were significantly higher in the critical subjects (P = 0.009 and 0.02, respectively) than in the noncritical subjects. In the multivariate logistic regression analysis to distinguish the critical subjects, an AI-assisted %CL ≥35% (odds ratio [OR] = 17.0), oxygen saturation level of <88% (OR = 33.6), immunocompromised condition (OR = 8.1), and other comorbidities (OR = 15.2) independently remained as significant variables in the models. Our proposed model obtained an accuracy of 83.9%, a sensitivity of 79.1%, and a specificity of 88.6% in predicting critical outcomes. CONCLUSIONS: AI-assisted measurements are similar to quantitative radiologist-obtained measurements in determining lung involvement in COVID-19 subjects.

Effective Connectivity Estimation by a Hybrid Neural Network, Empirical Wavelet Transform, and Bayesian Optimization.

Accurately measuring nonlinear effective connectivity is a crucial step in investigating brain functions. Brain signals like EEG is nonstationary. Many effective connectivity methods have been proposed but they have drawbacks in their models such as a weakness in proposing a way for hyperparameter and time lag selection as well as dealing with non-stationarity of the time series. This paper proposes an effective connectivity model based on a hybrid neural network model which uses Empirical Wavelet Transform (EWT) and a long short-term memory network (LSTM). The best hyperparameters and time lag are selected using Bayesian Optimization (BO). Due to the importance of generalizability in neural networks and calculating GC, an algorithm was proposed to choose the best generalizable weights. The model was evaluated using simulated and real EEG data consisting of attention deficit hyperactivity disorder (ADHD) and healthy subjects. The proposed model's performance on simulated data was evaluated by comparing it with other neural networks, including LSTM, CNN-LSTM, GRU, RNN, and MLP, using a Blocked cross-validation approach. GC of the simulated data was compared with GRU, linear Granger causality (LGC), Kernel Granger Causality (KGC), Partial Directed Coherence (PDC), and Directed Transfer Function (DTF). Our results demonstrated that the proposed model was superior to the mentioned models. Another advantage of our model is robustness against noise. The results showed that the proposed model can identify the connections in noisy conditions. The comparison of the effective connectivity of ADHD and the healthy group showed that the results are in accordance with previous studies.

Hyposmia and apathy in early, de novo Parkinson's disease: Lessons from structural brain connectivity.

INTRODUCTION: The neuroanatomical structures implicated in olfactory and emotional processing overlap significantly. Our understanding of the relationship between hyposmia and apathy, common manifestations of early Parkinson's disease (PD), is inadequate. MATERIALS AND METHODS: We analyzed data on 40 patients with early de-novo idiopathic PD enrolled within 2 years of motor symptom onset in the Parkinson's Progression Markers Initiative (PPMI) study. To be included in the analysis, patients must have smell dysfunction but no apathy at the baseline visit and had completed a diffusion MRI (dMRI) at the baseline visit and at the 48-month follow-up visit. We used the FMRIB Software Library's diffusion tool kit to measure fractional anisotropy (FA) in six regions of interest on dMRI: bilateral anterior corona radiata, left cingulum, left superior corona radiata, genu and body of the corpus callosum. We compared the FA in each region from the dMRI done at the beginning of the study with the follow up studies at 4 years. RESULTS: We found a significant decrease of FA at the bilateral anterior corona radiata, and the genu and body of the corpus callosum comparing baseline scans with follow up images at 4-years after starting the study. CONCLUSION: Structural connectivity changes associated with apathy can be seen early in PD patients with smell dysfunction.

Neural modulation enhancement using connectivity-based EEG neurofeedback with simultaneous fMRI for emotion regulation.

Emotion regulation plays a key role in human behavior and overall well-being. Neurofeedback is a non-invasive self-brain training technique used for emotion regulation to enhance brain function and treatment of mental disorders through behavioral changes. Previous neurofeedback research often focused on using activity from a single brain region as measured by fMRI or power from one or two EEG electrodes. In a new study, we employed connectivity-based EEG neurofeedback through recalling positive autobiographical memories and simultaneous fMRI to upregulate positive emotion. In our novel approach, the feedback was determined by the coherence of EEG electrodes rather than the power of one or two electrodes. We compared the efficiency of this connectivity-based neurofeedback to traditional activity-based neurofeedback through multiple experiments. The results showed that connectivity-based neurofeedback effectively improved BOLD signal change and connectivity in key emotion regulation regions such as the amygdala, thalamus, and insula, and increased EEG frontal asymmetry, which is a biomarker for emotion regulation and treatment of mental disorders such as PTSD, anxiety, and depression and coherence among EEG channels. The psychometric evaluations conducted both before and after the neurofeedback experiments revealed that participants demonstrated improvements in enhancing positive emotions and reducing negative emotions when utilizing connectivity-based neurofeedback, as compared to traditional activity-based and sham neurofeedback approaches. These findings suggest that connectivity-based neurofeedback may be a superior method for regulating emotions and could be a useful alternative therapy for mental disorders, providing individuals with greater control over their brain and mental functions.

Deep Learning Methods for Identification of White Matter Fiber Tracts: Review of State-of-the-Art and Future Prospective.

Quantitative analysis of white matter fiber tracts from diffusion Magnetic Resonance Imaging (dMRI) data is of great significance in health and disease. For example, analysis of fiber tracts related to anatomically meaningful fiber bundles is highly demanded in pre-surgical and treatment planning, and the surgery outcome depends on accurate segmentation of the desired tracts. Currently, this process is mainly done through time-consuming manual identification performed by neuro-anatomical experts. However, there is a broad interest in automating the pipeline such that it is fast, accurate, and easy to apply in clinical settings and also eliminates the intra-reader variabilities. Following the advancements in medical image analysis using deep learning techniques, there has been a growing interest in using these techniques for the task of tract identification as well. Recent reports on this application show that deep learning-based tract identification approaches outperform existing state-of-the-art methods. This paper presents a review of current tract identification approaches based on deep neural networks. First, we review the recent deep learning methods for tract identification. Next, we compare them with respect to their performance, training process, and network properties. Finally, we end with a critical discussion of open challenges and possible directions for future works.

Curvature analysis of perisylvian epilepsy.

PURPOSE: We assess whether alterations in the convolutional anatomy of the deep perisylvian area (DPSA) might indicate focal epileptogenicity. MATERIALS AND METHODS: The DPSA of each hemisphere was segmented on MRI and a 3D gray-white matter interface (GWMI) geometrical model was constructed. Comparative visual and quantitative assessment of the convolutional anatomy of both the left and right DPSA models was performed. Both the density of thorn-like contours (peak percentage) and coarse interface curvatures was computed using Gaussian curvature and shape index, respectively. The proposed method was applied to a total of 14 subjects; 7 patients with an epileptogenic DPSA and 7 non-epileptic subjects. RESULTS: A high peak percentage correlated well with the epileptogenic DPSA. It distinguished between patients and non-epileptic subjects (P = 0.029) and identified laterality of the epileptic focus in all but one case. A diminished regional curvature also identified epileptogenicity (P = 0.016) and, moreover, its laterality (P = 0.001). CONCLUSION: An increased peak percentage from a global view of the GWMI of the DPSA provides some indication of a propensity toward a focal or regional DPSA epileptogenicity. A diminished convolutional anatomy (i.e., smoothing effect) appears also to coincide with the epileptogenic site in the DPSA and to distinguish laterality.

Machine learning approaches and non-linear processing of extracted components in frontal region to predict rTMS treatment response in major depressive disorder.

Predicting the therapeutic result of repetitive transcranial magnetic stimulation (rTMS) treatment could save time and costs as ineffective treatment can be avoided. To this end, we presented a machine-learning-based strategy for classifying patients with major depression disorder (MDD) into responders (R) and nonresponders (NR) to rTMS treatment. Resting state EEG data were recorded using 32 electrodes from 88 MDD patients before treatment. Then, patients underwent 7 weeks of rTMS, and 46 of them responded to treatment. By applying Independent Component Analysis (ICA) on EEG, we identified the relevant brain sources as possible indicators of neural activity in the dorsolateral prefrontal cortex (DLPFC). This was served through estimating the generators of activity in the sensor domain. Subsequently, we added physiological information and placed certain terms and conditions to offer a far more realistic estimation than the classic EEG. Ultimately, those components mapped in accordance with the region of the DLPFC in the sensor domain were chosen. Features extracted from the relevant ICs time series included permutation entropy (PE), fractal dimension (FD), Lempel-Ziv Complexity (LZC), power spectral density, correlation dimension (CD), features based on bispectrum, frontal and prefrontal cordance, and a combination of them. The most relevant features were selected by a Genetic Algorithm (GA). For classifying two groups of R and NR, K-Nearest Neighbor (KNN), Support Vector Machine (SVM), and Multilayer Perceptron (MLP) were applied to predict rTMS treatment response. To evaluate the performance of classifiers, a 10-fold cross-validation method was employed. A statistical test was used to assess the capability of features in differentiating R and NR for further research. EEG characteristics that can predict rTMS treatment response were discovered. The strongest discriminative indicators were EEG beta power, the sum of bispectrum diagonal elements in delta and beta bands, and CD. The Combined feature vector classified R and NR with a high performance of 94.31% accuracy, 92.85% specificity, 95.65% sensitivity, and 92.85% precision using SVM. This result indicates that our proposed method with power and nonlinear and bispectral features from relevant ICs time-series can predict the treatment outcome of rTMS for MDD patients only by one session pretreatment EEG recording. The obtained results show that the proposed method outperforms previous methods.

Simultaneous electroencephalography-functional magnetic resonance imaging for assessment of human brain function.

Electroencephalography (EEG) and functional Magnetic Resonance Imaging (MRI) have long been used as tools to examine brain activity. Since both methods are very sensitive to changes of synaptic activity, simultaneous recording of EEG and fMRI can provide both high temporal and spatial resolution. Therefore, the two modalities are now integrated into a hybrid tool, EEG-fMRI, which encapsulates the useful properties of the two. Among other benefits, EEG-fMRI can contribute to a better understanding of brain connectivity and networks. This review lays its focus on the methodologies applied in performing EEG-fMRI studies, namely techniques used for the recording of EEG inside the scanner, artifact removal, and statistical analysis of the fMRI signal. We will investigate simultaneous resting-state and task-based EEG-fMRI studies and discuss their clinical and technological perspectives. Moreover, it is established that the brain regions affected by a task-based neural activity might not be limited to the regions in which they have been initiated. Advanced methods can help reveal the regions responsible for or affected by a developed neural network. Therefore, we have also looked into studies related to characterization of structure and dynamics of brain networks. The reviewed literature suggests that EEG-fMRI can provide valuable complementary information about brain neural networks and functions.

Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression.

Epilepsy is associated with genetic risk factors and cortico-subcortical network alterations, but associations between neurobiological mechanisms and macroscale connectomics remain unclear. This multisite ENIGMA-Epilepsy study examined whole-brain structural covariance networks in patients with epilepsy and related findings to postmortem epilepsy risk gene expression patterns. Brain network analysis included 578 adults with temporal lobe epilepsy (TLE), 288 adults with idiopathic generalized epilepsy (IGE), and 1328 healthy controls from 18 centres worldwide. Graph theoretical analysis of structural covariance networks revealed increased clustering and path length in orbitofrontal and temporal regions in TLE, suggesting a shift towards network regularization. Conversely, people with IGE showed decreased clustering and path length in fronto-temporo-parietal cortices, indicating a random network configuration. Syndrome-specific topological alterations reflected expression patterns of risk genes for hippocampal sclerosis in TLE and for generalized epilepsy in IGE. These imaging-transcriptomic signatures could potentially guide diagnosis or tailor therapeutic approaches to specific epilepsy syndromes.

Global and local shape features of the hippocampus based on Laplace-Beltrami eigenvalues and eigenfunctions: a potential application in the lateralization of temporal lobe epilepsy.

Using magnetic resonance (MR) images to evaluate changes in the shape of the hippocampus has been an active research topic. This paper presents a new shape analysis approach to quantify and visualize deformations of the hippocampus in epilepsy. The proposed method is based on Laplace-Beltrami (LB) eigenvalues and eigenfunctions as isometric invariant shape features, and thus, the procedure does not require any image registration. In addition to the LB-based shape features, total hippocampal volume and surface area are calculated using manually segmented images. Theses shape and volumetric descriptors are used to distinguish the patients with temporal lobe epilepsy (TLE) (N = 55) from healthy control subjects (N = 12, age = 32.2 ± 9.1, sex (M/F) = 6/6) and patients with right TLE (N = 26, age = 45.1 ± 11.0, sex (M/F) = 9/17) from left TLE (N = 29, age = 45.4 ± 11.9, sex (M/F) = 10/19). Experimental results illustrate the usefulness of the proposed approach for the diagnosis and lateralization of TLE with 93.0% and 86.4% of the cases, respectively. Moreover, the proposed method outperforms the volumetric analysis in terms of both sensitivity (94.9% vs. 88.1%) and specificity (83.3% vs. 50.0%) of the lateralization. The analysis of local hippocampal thickness variations suggests significant deformation in both ipsilateral and contralateral hippocampi of epileptic patients, while there were no differences between right and left hippocampi in controls. It is anticipated that the proposed method could be advantageous in the presurgical evaluation of patients with drug-resistant epilepsy; however, further validation of the method using a larger dataset is required.

Multivariate Gaussian Copula Mutual Information to Estimate Functional Connectivity with Less Random Architecture.

Recognition of a brain region's interaction is an important field in neuroscience. Most studies use the Pearson correlation to find the interaction between the regions. According to the experimental evidence, there is a nonlinear dependence between the activities of different brain regions that is ignored by Pearson correlation as a linear measure. Typically, the average activity of each region is used as input because it is a univariate measure. This dimensional reduction, i.e., averaging, leads to a loss of spatial information across voxels within the region. In this study, we propose using an information-theoretic measure, multivariate mutual information (mvMI), as a nonlinear dependence to find the interaction between regions. This measure, which has been recently proposed, simplifies the mutual information calculation complexity using the Gaussian copula. Using simulated data, we show that the using this measure overcomes the mentioned limitations. Additionally using the real resting-state fMRI data, we compare the level of significance and randomness of graphs constructed using different methods. Our results indicate that the proposed method estimates the functional connectivity more significantly and leads to a smaller number of random connections than the common measure, Pearson correlation. Moreover, we find that the similarity of the estimated functional networks of the individuals is higher when the proposed method is used.

Multi-scale convolutional neural network for automated AMD classification using retinal OCT images.

BACKGROUND AND OBJECTIVE: Age-related macular degeneration (AMD) is the most common cause of blindness in developed countries, especially in people over 60 years of age. The workload of specialists and the healthcare system in this field has increased in recent years mainly due to three reasons: 1) increased use of retinal optical coherence tomography (OCT) imaging technique, 2) prevalence of population aging worldwide, and 3) chronic nature of AMD. Recent advancements in the field of deep learning have provided a unique opportunity for the development of fully automated diagnosis frameworks. Considering the presence of AMD-related retinal pathologies in varying sizes in OCT images, our objective was to propose a multi-scale convolutional neural network (CNN) that can capture inter-scale variations and improve performance using a feature fusion strategy across convolutional blocks. METHODS: Our proposed method introduces a multi-scale CNN based on the feature pyramid network (FPN) structure. This method is used for the reliable diagnosis of normal and two common clinical characteristics of dry and wet AMD, namely drusen and choroidal neovascularization (CNV). The proposed method is evaluated on the national dataset gathered at Hospital (NEH) for this study, consisting of 12649 retinal OCT images from 441 patients, and the UCSD public dataset, consisting of 108312 OCT images from 4686 patients. RESULTS: Experimental results show the superior performance of our proposed multi-scale structure over several well-known OCT classification frameworks. This feature combination strategy has proved to be effective on all tested backbone models, with improvements ranging from 0.4% to 3.3%. In addition, gradual learning has proved to be effective in improving performance in two consecutive stages. In the first stage, the performance was boosted from 87.2%±2.5% to 92.0%±1.6% using pre-trained ImageNet weights. In the second stage, another performance boost from 92.0%±1.6% to 93.4%±1.4% was observed as a result of fine-tuning the previous model on the UCSD dataset. Lastly, generating heatmaps provided additional proof for the effectiveness of our multi-scale structure, enabling the detection of retinal pathologies appearing in different sizes. CONCLUSION: The promising quantitative results of the proposed architecture, along with qualitative evaluations through generating heatmaps, prove the suitability of the proposed method to be used as a screening tool in healthcare centers assisting ophthalmologists in making better diagnostic decisions.

Topographic divergence of atypical cortical asymmetry and atrophy patterns in temporal lobe epilepsy.

Temporal lobe epilepsy, a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter structural alterations in temporal lobe epilepsy relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry; or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated. Here, we addressed this gap using the multisite ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 temporal lobe epilepsy patients and 1418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in temporal lobe epilepsy, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity calculated using 207 healthy controls obtained from Human Connectome Project and an independent dataset containing 23 temporal lobe epilepsy patients and 53 healthy controls and examined clinical associations using machine learning. We identified a marked divergence in the spatial distribution of atypical inter-hemispheric asymmetry and regional atrophy mapping. The former revealed a temporo-limbic disease signature while the latter showed diffuse and bilateral patterns. Our findings were robust across individual sites and patients. Cortical atrophy was significantly correlated with disease duration and age at seizure onset, while degrees of asymmetry did not show a significant relationship to these clinical variables. Our findings highlight that the mapping of atypical inter-hemispheric asymmetry and regional atrophy tap into two complementary aspects of temporal lobe epilepsy-related pathology, with the former revealing primary substrates in ipsilateral limbic circuits and the latter capturing bilateral disease effects. These findings refine our notion of the neuropathology of temporal lobe epilepsy and may inform future discovery and validation of complementary MRI biomarkers in temporal lobe epilepsy.

Longitudinal clustering analysis and prediction of Parkinson's disease progression using radiomics and hybrid machine learning.

BACKGROUND: We employed machine learning approaches to (I) determine distinct progression trajectories in Parkinson's disease (PD) (unsupervised clustering task), and (II) predict progression trajectories (supervised prediction task), from early (years 0 and 1) data, making use of clinical and imaging features. METHODS: We studied PD-subjects derived from longitudinal datasets (years 0, 1, 2 & 4; Parkinson's Progressive Marker Initiative). We extracted and analyzed 981 features, including motor, non-motor, and radiomics features extracted for each region-of-interest (ROIs: left/right caudate and putamen) using our standardized standardized environment for radiomics analysis (SERA) radiomics software. Segmentation of ROIs on dopamine transposer - single photon emission computed tomography (DAT SPECT) images were performed via magnetic resonance images (MRI). After performing cross-sectional clustering on 885 subjects (original dataset) to identify disease subtypes, we identified optimal longitudinal trajectories using hybrid machine learning systems (HMLS), including principal component analysis (PCA) + K-Means algorithms (KMA) followed by Bayesian information criterion (BIC), Calinski-Harabatz criterion (CHC), and elbow criterion (EC). Subsequently, prediction of the identified trajectories from early year data was performed using multiple HMLSs including 16 Dimension Reduction Algorithms (DRA) and 10 classification algorithms. RESULTS: We identified 3 distinct progression trajectories. Hotelling's t squared test (HTST) showed that the identified trajectories were distinct. The trajectories included those with (I, II) disease escalation (2 trajectories, 27% and 38% of patients) and (III) stable disease (1 trajectory, 35% of patients). For trajectory prediction from early year data, HMLSs including the stochastic neighbor embedding algorithm (SNEA, as a DRA) as well as locally linear embedding algorithm (LLEA, as a DRA), linked with the new probabilistic neural network classifier (NPNNC, as a classifier), resulted in accuracies of 78.4% and 79.2% respectively, while other HMLSs such as SNEA + Lib_SVM (library for support vector machines) and t_SNE (t-distributed stochastic neighbor embedding) + NPNNC resulted in 76.5% and 76.1% respectively. CONCLUSIONS: This study moves beyond cross-sectional PD subtyping to clustering of longitudinal disease trajectories. We conclude that combining medical information with SPECT-based radiomics features, and optimal utilization of HMLSs, can identify distinct disease trajectories in PD patients, and enable effective prediction of disease trajectories from early year data.

Probing fMRI brain connectivity and activity changes during emotion regulation by EEG neurofeedback.

Despite the existence of several emotion regulation studies using neurofeedback, interactions among a small number of regions were evaluated, and therefore, further investigation is needed to understand the interactions of the brain regions involved in emotion regulation. We implemented electroencephalography (EEG) neurofeedback with simultaneous functional magnetic resonance imaging (fMRI) using a modified happiness-inducing task through autobiographical memories to upregulate positive emotion. Then, an explorative analysis of whole brain regions was done to understand the effect of neurofeedback on brain activity and the interaction of whole brain regions involved in emotion regulation. The participants in the control and experimental groups were asked to do emotion regulation while viewing positive images of autobiographical memories and getting sham or real (based on alpha asymmetry) EEG neurofeedback, respectively. The proposed multimodal approach quantified the effects of EEG neurofeedback in changing EEG alpha power, fMRI blood oxygenation level-dependent (BOLD) activity of prefrontal, occipital, parietal, and limbic regions (up to 1.9% increase), and functional connectivity in/between prefrontal, parietal, limbic system, and insula in the experimental group. New connectivity links were identified by comparing the brain functional connectivity between experimental conditions (Upregulation and View blocks) and also by comparing the brain connectivity of the experimental and control groups. Psychometric assessments confirmed significant changes in positive and negative mood states in the experimental group by neurofeedback. Based on the exploratory analysis of activity and connectivity among all brain regions involved in emotion regions, we found significant BOLD and functional connectivity increases due to EEG neurofeedback in the experimental group, but no learning effect was observed in the control group. The results reveal several new connections among brain regions as a result of EEG neurofeedback which can be justified according to emotion regulation models and the role of those regions in emotion regulation and recalling positive autobiographical memories.

Localizing Epileptic Foci Using Simultaneous EEG-fMRI Recording: Template Component Cross-Correlation.

Conventional EEG-fMRI methods have been proven to be of limited use in the sense that they cannot reveal the information existing in between the spikes. To resolve this issue, the current study obtains the epileptic components time series detected on EEG and uses them to fit the Generalized Linear Model (GLM), as a substitution for classical regressors. This approach allows for a more precise localization, and equally importantly, the prediction of the future behavior of the epileptic generators. The proposed method approaches the localization process in the component domain, rather than the electrode domain (EEG), and localizes the generators through investigating the spatial correlation between the candidate components and the spike template, as well as the medical records of the patient. To evaluate the contribution of EEG-fMRI and concordance between fMRI and EEG, this method was applied on the data of 30 patients with refractory epilepsy. The results demonstrated the significant numbers of 29 and 24 for concordance and contribution, respectively, which mark improvement as compared to the existing literature. This study also shows that while conventional methods often fail to properly localize the epileptogenic zones in deep brain structures, the proposed method can be of particular use. For further evaluation, the concordance level between IED-related BOLD clusters and Seizure Onset Zone (SOZ) has been quantitatively investigated by measuring the distance between IED/SOZ locations and the BOLD clusters in all patients. The results showed the superiority of the proposed method in delineating the spike-generating network compared to conventional EEG-fMRI approaches. In all, the proposed method goes beyond the conventional methods by breaking the dependency on spikes and using the outside-the-scanner spike templates and the selected components, achieving an accuracy of 97%. Doing so, this method contributes to improving the yield of EEG-fMRI and creates a more realistic perception of the neural behavior of epileptic generators which is almost without precedent in the literature.