Neuroimaging-based brain-age prediction in diverse forms of epilepsy: a signature of psychosis and beyond.

Epilepsy is a diverse brain disorder, and the pathophysiology of its various forms and comorbidities is largely unknown. A recent machine learning method enables us to estimate an individual's "brain-age" from MRI; this brain-age prediction is expected as a novel individual biomarker of neuropsychiatric disorders. The aims of this study were to estimate the brain-age for various categories of epilepsy and to evaluate clinical discrimination by brain-age for (1) the effect of psychosis on temporal lobe epilepsy (TLE), (2) psychogenic nonepileptic seizures (PNESs) from MRI-negative epilepsies, and (3) progressive myoclonic epilepsy (PME) from juvenile myoclonic epilepsy (JME). In total, 1196 T1-weighted MRI scans from healthy controls (HCs) were used to build a brain-age prediction model with support vector regression. Using the model, we calculated the brain-predicted age difference (brain-PAD: predicted age-chronological age) of the HCs and 318 patients with epilepsy. We compared the brain-PAD values based on the research questions. As a result, all categories of patients except for extra-temporal lobe focal epilepsy showed a significant increase in brain-PAD. TLE with hippocampal sclerosis presented a significantly higher brain-PAD than several other categories. The mean brain-PAD in TLE with inter-ictal psychosis was 10.9 years, which was significantly higher than TLE without psychosis (5.3 years). PNES showed a comparable mean brain-PAD (10.6 years) to that of epilepsy patients. PME had a higher brain-PAD than JME (22.0 vs. 9.3 years). In conclusion, neuroimaging-based brain-age prediction can provide novel insight into or clinical usefulness for the diverse symptoms of epilepsy.

Modulating brain networks associated with cognitive deficits in Parkinson's disease.

Parkinson's disease (PD) is a relatively well characterised neurological disorder that primarily affects motor and cognitive functions. This paper reviews on how transcranial direct current stimulation (tDCS) can be used to modulate brain networks associated with cognitive deficits in PD. We first provide an overview of brain network abnormalities in PD, by introducing the brain network modulation approaches such as pharmacological interventions and brain stimulation techniques. We then present the potential underlying mechanisms of tDCS technique, and specifically highlight how tDCS can be applied to modulate brain network abnormality associated with cognitive dysfunction among PD patients. More importantly, we address the limitations of existing studies and suggest possible future directions, with the aim of helping researchers to further develop the use of tDCS technique in clinical settings.

Patch-wise brain age longitudinal reliability.

We recently introduced a patch-wise technique to estimate brain age from anatomical T1-weighted magnetic resonance imaging (T1w MRI) data. Here, we sought to assess its longitudinal reliability by leveraging a unique dataset of 99 longitudinal MRI scans from a single, cognitively healthy volunteer acquired over a period of 17 years (aged 29-46 years) at multiple sites. We built a robust patch-wise brain age estimation framework on the basis of 100 cognitively healthy individuals from the MindBoggle dataset (aged 19-61 years) using the Desikan-Killiany-Tourville atlas, then applied the model to the volunteer dataset. The results show a high prediction accuracy on the independent test set (R2 = .94, mean absolute error of 0.63 years) and no statistically significant difference between manufacturers, suggesting that the patch-wise technique has high reliability and can be used for longitudinal multi-centric studies.

A novel patch-based procedure for estimating brain age across adulthood.

Aging is associated with structural alterations in many regions of the brain. Monitoring these changes contributes to increasing our understanding of the brain's morphological alterations across its lifespan, and could allow the identification of departures from canonical trajectories. Here, we introduce a novel and unique patch-based grading procedure for estimating a synthetic estimate of cortical aging in cognitively intact individuals. The cortical age metric is computed based on image similarity between an unknown (test) cortical label and known (training) cortical labels using machine learning algorithms. The proposed method was trained on a dataset of 100 cognitively intact individuals aged 19-61 years, within the 31 bilateral cortical labels of the Desikan-Killiany-Tourville parcellation, then tested on an independent test set of 78 cognitively intact individuals spanning a similar age range. The proposed patch-based framework yielded a R2 = 0.94, as well as a mean absolute error of 1.66 years, which compared favorably to the literature. These experimental results demonstrate that the proposed patch-based grading framework is a reliable and robust method to estimate brain age from image data, even with a limited training size.

Effects of aging on brain volumes in healthy individuals across adulthood.

In this retrospective study, we analyzed the effects of age on brain volumes in healthy brains across adulthood. We investigated the correlations between brain volumes and age in the brains of 563 healthy individuals (age range: 20-86, 55% female) whose MRI scans and related information were drawn from the IXI database ( brain-development.org/ixi-dataset /). We conducted a regression analysis to assess the effect of age on whole-brain volumes as well as selected regional volumetric measures. The whole-brain analysis revealed a negative linear relationship between gray matter (GM) and age as well as nonlinear patterns of the relationship between age and the white matter (WM), cerebrospinal fluid (CSF), and the GM/WM ratio across adulthood. The regional volumetric analysis showed linear and non-linear age-related regional volumetric changes with aging. Our present findings contribute to the understanding of how structures in the human brain change over the adult years and will help address the pathological age-related neural changes in age-related neural disorders such as Parkinson disease and Alzheimer disease.

Predicting the occurrence of mild cognitive impairment in Parkinson's disease using structural MRI data.

Introduction: Mild cognitive impairment (MCI) is a common symptom observed in individuals with Parkinson's disease (PD) and a main risk factor for progressing to dementia. Our objective was to identify early anatomical brain changes that precede the transition from healthy cognition to MCI in PD. Methods: Structural T1-weighted magnetic resonance imaging data of PD patients with healthy cognition at baseline were downloaded from the Parkinson's Progression Markers Initiative database. Patients were divided into two groups based on the annual cognitive assessments over a 5-year time span: (i) PD patients with unstable healthy cognition who developed MCI over a 5-year follow-up (PD-UHC, n = 52), and (ii) PD patients who maintained stable healthy cognitive function over the same period (PD-SHC, n = 52). These 52 PD-SHC were selected among 192 PD-SHC patients using propensity score matching method to have similar demographic and clinical characteristics with PD-UHC at baseline. Seventy-five percent of these were used to train a support vector machine (SVM) algorithm to distinguish between the PD-UHC and PD-SHC groups, and tested on the remaining 25% of individuals. Shapley Additive Explanations (SHAP) feature analysis was utilized to identify the most informative brain regions in SVM classifier. Results: The average accuracy of classifying PD-UHC vs. PD-SHC was 80.76%, with 82.05% sensitivity and 79.48% specificity using 10-fold cross-validation. The performance was similar in the hold-out test sets with all accuracy, sensitivity, and specificity at 76.92%. SHAP analysis showed that the most influential brain regions in the prediction model were located in the frontal, occipital, and cerebellar regions as well as midbrain. Discussion: Our machine learning-based analysis yielded promising results in identifying PD individuals who are at risk of cognitive decline from the earliest disease stage and revealed the brain regions which may be linked to the prospective cognitive decline in PD before clinical symptoms emerge.

Neuroanatomical Signature of the Transition from Normal Cognition to MCI in Parkinson's Disease.

The progression of Parkinson's disease (PD) is often accompanied by cognitive decline. We had previously developed a brain age estimation program utilizing structural MRI data of 949 healthy individuals from publicly available sources. Structural MRI data of 244 PD patients who were cognitively normal at baseline was acquired from the Parkinson Progression Markers Initiative (PPMI). 192 of these showed stable normal cognitive function from baseline out to 5 years (PD-SNC), and the remaining 52 had unstable normal cognition and developed mild cognitive impairment within 5 years (PD-UNC). 105 healthy controls were also included in the analysis as a reference. First, we examined if there were any baseline differences in regional brain structure between PD-UNC and PD-SNC cohorts utilizing the three most widely used atrophy estimation pipelines, i.e., voxel-based morphometry (VBM), deformation-based morphometry and cortical thickness analyses. We then investigated if accelerated brain age estimation with our multivariate regressive machine learning algorithm was different across these groups (HC, PD-SNC, and PD-UNC). As per the VBM analysis, PD-UNC patients demonstrated a noticeable increase in GM volume in the posterior and anterior lobes of the cerebellum, sub-lobar, extra-nuclear, thalamus, and pulvinar regions when compared to PD-SNC at baseline. PD-UNC patients were observed to have significantly older brain age compared to both PD-SNC patients (p=0.009) and healthy controls (p<0.009). The increase in GM volume in the PD-UNC group could potentially indicate an inflammatory or neuronal hypertrophy response, which could serve as a biomarker for future cognitive decline among this population.

Differences in brain aging between sexes in Parkinson's disease.

Parkinson's disease (PD) is linked to faster brain aging. Male sex is associated with higher prevalence, severe symptoms, and a faster progression rate in PD. There remains a significant gap in understanding the function of sex in the process of brain aging in PD. The structural T1-weighted MRI-driven brain-predicted age difference (i.e., Brain-PAD: the actual age subtracted from the brain-predicted age) was computed in a group of 373 people with PD (mean age ± SD: 61.37 ± 9.81, age range: 33-85, 34% female) from the Parkinson's Progression Marker Initiative database using a robust brain-age estimation framework that was trained on 949 healthy subjects. Linear regression models were used to investigate the association between Brain-PAD and clinical variables in PD, stratified by sex. Males with Parkinson's disease (PD-M) exhibited a significantly higher mean Brain-PAD than their female counterparts (PD-F) (t(256) = 2.50, p = 0.012). In the propensity score-matched PD-M group (PD-M*), Brain-PAD was found to be associated with a decline in general cognition, a worse degree of sleep behavior disorder, reduced visuospatial acuity, and caudate atrophy. Conversely, no significant links were observed between these factors and Brain-PAD in the PD-F group. Having 'older' looking brains in PD-M than PD-F supports the idea that sex plays a vital function in PD, such that the PD mechanism may be different in males and females. This study has the potential to broaden our understanding of dissimilarities in brain aging between sexes in the context of PD.

Improving brain age prediction with anatomical feature attention-enhanced 3D-CNN.

Currently, significant progress has been made in predicting brain age from structural Magnetic Resonance Imaging (sMRI) data using deep learning techniques. However, despite the valuable structural information they contain, the traditional engineering features known as anatomical features have been largely overlooked in this context. To address this issue, we propose an attention-based network design that integrates anatomical and deep convolutional features, leveraging an anatomical feature attention (AFA) module to effectively capture salient anatomical features. In addition, we introduce a fully convolutional network, which simplifies the extraction of deep convolutional features and overcomes the high computational memory requirements associated with deep learning. Our approach outperforms several widely-used models on eight publicly available datasets (n = 2501), with a mean absolute error (MAE) of 2.20 years in predicting brain age. Comparisons with deep learning models lacking the AFA module demonstrate that our fusion model effectively improves overall performance. These findings provide a promising approach for combining anatomical and deep convolutional features from sMRI data to predict brain age, with potential applications in clinical diagnosis and treatment, particularly for populations with age-related cognitive decline or neurological disorders.

Cocaine Destroys Gray Matter Brain Cells and Accelerates Brain Aging.

Introduction: Cocaine use disorder (CUD) is a substance use disorder characterized by a strong desire to obtain, consume, and misuse cocaine. Little is known about how cocaine affects the structure of the brain. In this study, we first investigated the anatomical brain changes in individuals with CUD compared to their matched healthy controls, and then explored whether these anatomical brain abnormalities contribute to considerably accelerated brain aging among this population. Methods: At the first stage, we used anatomical magnetic resonance imaging (MRI) data, voxel-based morphometry (VBM), and deformation-based morphometry techniques to uncover the morphological and macroscopic anatomical brain changes in 74 CUD patients compared to 62 age- and sex-matched healthy controls (HCs) obtained from the SUDMEX CONN dataset, the Mexican MRI dataset of patients with CUD. Then, we computed brain-predicted age difference (i.e., brain-PAD: the brain-predicted age minus the actual age) in CUD and HC groups using a robust brain age estimation framework. Using a multiple regression analysis, we also investigated the regional gray matter (GM) and white matter (WM) changes associated with the brain-PAD. Results: Using a whole-brain VBM analysis, we observed widespread gray matter atrophy in CUD patients located in the temporal lobe, frontal lobe, insula, middle frontal gyrus, superior frontal gyrus, rectal gyrus, and limbic lobe regions compared to the HCs. In contrast, we did not observe any swelling in the GM, changes in the WM, or local brain tissue atrophy or expansion between the CUD and HC groups. Furthermore, we found a significantly higher brain-PAD in CUD patients compared to matched HCs (mean difference = 2.62 years, Cohen's d = 0.54; t-test = 3.16, p = 0.002). The regression analysis showed significant negative changes in GM volume associated with brain-PAD in the CUD group, particularly in the limbic lobe, subcallosal gyrus, cingulate gyrus, and anterior cingulate regions. Discussion: The results of our investigation reveal that chronic cocaine use is linked to significant changes in gray matter, which hasten the process of structural brain aging in individuals who use the drug. These findings offer valuable insights into the impact of cocaine on the composition of the brain.

A Review of Neuroimaging-Driven Brain Age Estimation for Identification of Brain Disorders and Health Conditions.

BACKGROUND: Neuroimage analysis has made it possible to perform various anatomical analyses of the brain regions and helps detect different brain conditions/ disorders. Recently, neuroimaging-driven estimation of brain age is introduced as a robust biomarker for detecting different diseases and health conditions. OBJECTIVE: To present a comprehensive review of brain age frameworks concerning: i) designing view: an overview of brain age frameworks based on image modality and methods used, and ii) clinical aspect: an overview of the application of brain age frameworks for detection of neurological disorders or health conditions. METHODS: PubMed is explored to collect 136 articles from January 2010 to June 2021 using "Brain Age Estimation" and "Brain Imaging," along with combinations of other radiological terms. RESULTS & CONCLUSION: The studies presented in this review are evidence of using brain age estimation methods in detecting various brain diseases/conditions. The survey also highlights tools and methods for brain age estimation and addresses some future research directions.

Brain Age Prediction With Improved Least Squares Twin SVR.

Alzheimer's disease (AD) is the prevalent form of dementia and shares many aspects with the aging pattern of the abnormal brain. Machine learning models like support vector regression (SVR) based models have been successfully employed in the estimation of brain age. However, SVR is computationally inefficient than twin support vector machine based models. Hence, different twin support vector machine based models like twin SVR (TSVR), ε-TSVR, and Lagrangian TSVR (LTSVR) models have been used for the regression problems. ε-TSVR and LTSVR models seek a pair of ε-insensitive proximal planes for generation of end regressor. However, SVR and TSVR based models have several drawbacks- i) SVR model is computationally inefficient compared to the TSVR based models. ii) Twin SVM based models involve the computation of matrix inverse which is intractable in real world scenario's. iii) Both TSVR and LTSVR models are based on empirical risk minimization principle and hence may be prone to overfitting. iv) TSVR and LTSVR assume that the matrices appearing in their formulation are positive definite which may not be satisfied in real world scenario's. To overcome these issues, we formulate improved least squares twin support vector regression (ILSTSVR). The proposed ILSTSVR modifies the TSVR by replacing the inequality constraints with the equality constraints and minimizes the slack variables using squares of L2 norm instead of L1. Also, we introduce a different Lagrangian function to avoid the computation of matrix inverses. We evaluated the proposed ILSTSVR model on the subjects including cognitively healthy, mild cognitive impairment and Alzheimer's disease for brain-age estimation. Experimental evaluation and statistical tests demonstrate the efficiency of the proposed ILSTSVR model for brain-age prediction.

Diagnosis of Schizophrenia: A Comprehensive Evaluation.

Machine learning models have been successfully employed in the diagnosis of Schizophrenia disease. The impact of classification models and the feature selection techniques on the diagnosis of Schizophrenia have not been evaluated. Here, we sought to access the performance of classification models along with different feature selection approaches on the structural magnetic resonance imaging data. The data consist of 72 subjects with Schizophrenia and 74 healthy control subjects. We evaluated different classification algorithms based on support vector machine (SVM), random forest, kernel ridge regression and randomized neural networks. Moreover, we evaluated T-Test, Receiver Operator Characteristics (ROC), Wilcoxon, entropy, Bhattacharyya, Minimum Redundancy Maximum Relevance (MRMR) and Neighbourhood Component Analysis (NCA) as the feature selection techniques. Based on the evaluation, SVM based models with Gaussian kernel proved better compared to other classification models and Wilcoxon feature selection emerged as the best feature selection approach. Moreover, in terms of data modality the performance on integration of the grey matter and white matter proved better compared to the performance on the grey and white matter individually. Our evaluation showed that classification algorithms along with the feature selection approaches impact the diagnosis of Schizophrenia disease. This indicates that proper selection of the features and the classification models can improve the diagnosis of Schizophrenia.

Neuroimaging-Based Brain Age Estimation: A Promising Personalized Biomarker in Neuropsychiatry.

It is now possible to estimate an individual's brain age via brain scans and machine-learning models. This validated technique has opened up new avenues for addressing clinical questions in neurology, and, in this review, we summarize the many clinical applications of brain-age estimation in neuropsychiatry and general populations. We first provide an introduction to typical neuroimaging modalities, feature extraction methods, and machine-learning models that have been used to develop a brain-age estimation framework. We then focus on the significant findings of the brain-age estimation technique in the field of neuropsychiatry as well as the usefulness of the technique for addressing clinical questions in neuropsychiatry. These applications may contribute to more timely and targeted neuropsychiatric therapies. Last, we discuss the practical problems and challenges described in the literature and suggest some future research directions.

The accuracy of T1-weighted voxel-wise and region-wise metrics for brain age estimation.

INTRODUCTION: The brain age score has recently been introduced for robust monitoring of brain morphological alterations throughout the lifespan, prediction of mortality risk, and early detection of neurological disorders. METHODS: We assessed the brain age prediction accuracy of the widely used T1-weighted voxel-wise and region-wise metrics (i.e., T1-weighted magnetic resonance imaging [MRI]-wise metrics)) separately and their integration. We assessed 788 healthy individuals (age, 18-94 years) in a training set to build a brain age estimation framework based on different T1-weighted MRI-wise metrics (15 different metrics in total) and then validated each T1-weighted MRI-wise metric in an independent test set comprising 88 healthy individuals. We also assessed the accuracy of each T1-weighted MRI-wise metric in a clinical set of 70 patients with mild cognitive impairment and another of 30 patients with Alzheimer's disease. RESULTS: Integration of gray matter voxel-wise maps and all region-wise metrics achieved the highest brain age prediction accuracy (mean absolute error, 4.63 years). These metrics on their own achieved lower accuracy (mean absolute error, 4.97 years and 5.75 years, respectively). DISCUSSION: For tracing brain atrophy levels in neurological disorders at the clinical level, integration of voxel-wise and region-wise metrics may contribute to a more sensitive brain age framework than when these metrics are used on their own.

Brain age estimation using multi-feature-based networks.

Studying brain aging improves our understanding in differentiating typical and atypical aging. Directly utilizing traditional morphological features for brain age estimation did not show significant performance in healthy controls (HCs), which may be due to the negligence of the information of structural similarities among cortical regions. For this issue, the multi-feature-based network (MFN) built upon morphological features can be employed to describe these similarities. Based on this, we hypothesized that the MFN is more efficient and robust than traditional morphological features in brain age estimating. In this work, we used six different types of morphological features (i.e., cortical volume, cortical thickness, curvature index, folding index, local gyrification index, and surface area) to build individual MFN for brain age estimation. The efficacy of MFN was estimated on 2501 HCs with T1-weighted structural magnetic resonance imaging (sMRI) data and compared with traditional morphological features. We attained a mean absolute error (MAE) of 3.73 years using the proposed method on an independent test set, whereas a mean absolute error of 5.30 years was derived from morphological features. Our experimental results demonstrated that the MFN is an efficient and robust metric for estimating brain age.

Predicting Brain Age Using Machine Learning Algorithms: A Comprehensive Evaluation.

Machine learning (ML) algorithms play a vital role in the brain age estimation frameworks. The impact of regression algorithms on prediction accuracy in the brain age estimation frameworks have not been comprehensively evaluated. Here, we sought to assess the efficiency of different regression algorithms on brain age estimation. To this end, we built a brain age estimation framework based on a large set of cognitively healthy (CH) individuals ( N = 788) as a training set followed by different regression algorithms (22 different algorithms in total). We then quantified each regression-algorithm on independent test sets composed of 88 CH individuals, 70 mild cognitive impairment patients as well as 30 Alzheimer's disease patients. The prediction accuracy in the independent test set (i.e., CH set) varied in regression algorithms mean absolute error (MAE) from 4.63 to 7.14 yrs, R2 from 0.76 to 0.88. The highest and lowest prediction accuracies were achieved by Quadratic Support Vector Regression algorithm (MAE = 4.63 yrs, R2 = 0.88, 95% CI = [-1.26, 1.42]) and Binary Decision Tree algorithm (MAE = 7.14 yrs, R2 = 0.76, 95% CI = [-1.50, 2.62]), respectively. Our experimental results demonstrate that the prediction accuracy in brain age frameworks is affected by regression algorithms, indicating that advanced machine learning algorithms can lead to more accurate brain age predictions in clinical settings.

Monitoring Alzheimer's Disease Progression in Mild Cognitive Impairment Stage Using Machine Learning-Based FDG-PET Classification Methods.

BACKGROUND: We previously introduced a machine learning-based Alzheimer's Disease Designation (MAD) framework for identifying AD-related metabolic patterns among neurodegenerative subjects. OBJECTIVE: We sought to assess the efficiency of our MAD framework for tracing the longitudinal brain metabolic changes in the prodromal stage of AD. METHODS: MAD produces subject scores using five different machine-learning algorithms, which include a general linear model (GLM), two different approaches of scaled subprofile modeling, and two different approaches of a support vector machine. We used our pre-trained MAD framework, which was trained based on metabolic brain features of 94 patients with AD and 111 age-matched cognitively healthy (CH) individuals. The MAD framework was applied on longitudinal independent test sets including 54 CHs, 51 stable mild cognitive impairment (sMCI), and 39 prodromal AD (pAD) patients at the time of the clinical diagnosis of AD, and two years prior. RESULTS: The GLM showed excellent performance with area under curve (AUC) of 0.96 in distinguishing sMCI from pAD patients at two years prior to the time of the clinical diagnosis of AD while other methods showed moderate performance (AUC: 0.7-0.8). Significant annual increment of MAD scores were identified using all five algorithms in pAD especially when it got closer to the time of diagnosis (p < 0.001), but not in sMCI. The increased MAD scores were also significantly associated with cognitive decline measured by Mini-Mental State Examination in pAD (q < 0.01). CONCLUSION: These results suggest that MAD may be a relevant tool for monitoring disease progression in the prodromal stage of AD.

Neuroimaging-derived brain age is associated with life satisfaction in cognitively unimpaired elderly: A community-based study.

With the widespread increase in elderly populations, the quality of life and mental health in old age are issues of great interest. The human brain changes with age, and the brain aging process is biologically complex and varies widely among individuals. In this cross-sectional study, to clarify the effects of mental health, as well as common metabolic factors (e.g., diabetes) on healthy brain aging in late life, we analyzed structural brain MRI findings to examine the relationship between predicted brain age and life satisfaction, depressive symptoms, resilience, and lifestyle-related factors in elderly community-living individuals with unimpaired cognitive function. We extracted data from a community-based cohort study in Arakawa Ward, Tokyo. T1-weighted images of 773 elderly participants aged ≥65 years were analyzed, and the predicted brain age of each subject was calculated by machine learning from anatomically standardized gray-matter images. Specifically, we examined the relationships between the brain-predicted age difference (Brain-PAD: real age subtracted from predicted age) and life satisfaction, depressive symptoms, resilience, alcohol consumption, smoking, diabetes, hypertension, and dyslipidemia. Brain-PAD showed significant negative correlations with life satisfaction (Spearman's rs= -0.102, p = 0.005) and resilience (rs= -0.105, p = 0.004). In a multiple regression analysis, life satisfaction (p = 0.038), alcohol use (p = 0.040), and diabetes (p = 0.002) were independently correlated with Brain-PAD. Thus, in the cognitively unimpaired elderly, higher life satisfaction was associated with a 'younger' brain, whereas diabetes and alcohol use had negative impacts on life satisfaction. Subjective life satisfaction, as well as the prevention of diabetes and alcohol use, may protect the brain from accelerated aging.

Clinical Application of Machine Learning Models for Brain Imaging in Epilepsy: A Review.

Epilepsy is a common neurological disorder characterized by recurrent and disabling seizures. An increasing number of clinical and experimental applications of machine learning (ML) methods for epilepsy and other neurological and psychiatric disorders are available. ML methods have the potential to provide a reliable and optimal performance for clinical diagnoses, prediction, and personalized medicine by using mathematical algorithms and computational approaches. There are now several applications of ML for epilepsy, including neuroimaging analyses. For precise and reliable clinical applications in epilepsy and neuroimaging, the diverse ML methodologies should be examined and validated. We review the clinical applications of ML models for brain imaging in epilepsy obtained from a PubMed database search in February 2021. We first present an overview of typical neuroimaging modalities and ML models used in the epilepsy studies and then focus on the existing applications of ML models for brain imaging in epilepsy based on the following clinical aspects: (i) distinguishing individuals with epilepsy from healthy controls, (ii) lateralization of the temporal lobe epilepsy focus, (iii) the identification of epileptogenic foci, (iv) the prediction of clinical outcomes, and (v) brain-age prediction. We address the practical problems and challenges described in the literature and suggest some future research directions.