Adolescent alcohol use disrupts functional neurodevelopment in sensation seeking girls.

Exogenous causes, such as alcohol use, and endogenous factors, such as temperament and sex, can modulate developmental trajectories of adolescent neurofunctional maturation. We examined how these factors affect sexual dimorphism in brain functional networks in youth drinking below diagnostic threshold for alcohol use disorder (AUD). Based on the 3-year, annually acquired, longitudinal resting-state functional magnetic resonance imaging (MRI) data of 526 adolescents (12-21 years at baseline) from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) cohort, developmental trajectories of 23 intrinsic functional networks (IFNs) were analyzed for (1) sexual dimorphism in 259 participants who were no-to-low drinkers throughout this period; (2) sex-alcohol interactions in two age- and sex-matched NCANDA subgroups (N = 76 each), half no-to-low, and half moderate-to-heavy drinkers; and (3) moderating effects of gender-specific alcohol dose effects and a multifactorial impulsivity measure on IFN connectivity in all NCANDA participants. Results showed that sex differences in no-to-low drinkers diminished with age in the inferior-occipital network, yet girls had weaker within-network connectivity than boys in six other networks. Effects of adolescent alcohol use were more pronounced in girls than boys in three IFNs. In particular, girls showed greater within-network connectivity in two motor networks with more alcohol consumption, and these effects were mediated by sensation-seeking only in girls. Our results implied that drinking might attenuate the naturally diminishing sexual differences by disrupting the maturation of network efficiency more severely in girls. The sex-alcohol-dose effect might explain why women are at higher risk of alcohol-related health and psychosocial consequences than men.

Deep learning identifies morphological determinants of sex differences in the pre-adolescent brain.

The application of data-driven deep learning to identify sex differences in developing brain structures of pre-adolescents has heretofore not been accomplished. Here, the approach identifies sex differences by analyzing the minimally processed MRIs of the first 8144 participants (age 9 and 10 years) recruited by the Adolescent Brain Cognitive Development (ABCD) study. The identified pattern accounted for confounding factors (i.e., head size, age, puberty development, socioeconomic status) and comprised cerebellar (corpus medullare, lobules III, IV/V, and VI) and subcortical (pallidum, amygdala, hippocampus, parahippocampus, insula, putamen) structures. While these have been individually linked to expressing sex differences, a novel discovery was that their grouping accurately predicted the sex in individual pre-adolescents. Another novelty was relating differences specific to the cerebellum to pubertal development. Finally, we found that reducing the pattern to a single score not only accurately predicted sex but also correlated with cognitive behavior linked to working memory. The predictive power of this score and the constellation of identified brain structures provide evidence for sex differences in pre-adolescent neurodevelopment and may augment understanding of sex-specific vulnerability or resilience to psychiatric disorders and presage sex-linked learning disabilities.

Multi-task prediction of infant cognitive scores from longitudinal incomplete neuroimaging data.

Early postnatal brain undergoes a stunning period of development. Over the past few years, research on dynamic infant brain development has received increased attention, exhibiting how important the early stages of a child's life are in terms of brain development. To precisely chart the early brain developmental trajectories, longitudinal studies with data acquired over a long-enough period of infants' early life is essential. However, in practice, missing data from different time point(s) during the data gathering procedure is often inevitable. This leads to incomplete set of longitudinal data, which poses a major challenge for such studies. In this paper, prediction of multiple future cognitive scores with incomplete longitudinal imaging data is modeled into a multi-task machine learning framework. To efficiently learn this model, we account for selection of informative features (i.e., neuroimaging morphometric measurements for different time points), while preserving the structural information and the interrelation between these multiple cognitive scores. Several experiments are conducted on a carefully acquired in-house dataset, and the results affirm that we can predict the cognitive scores measured at the age of four years old, using the imaging data of earlier time points, as early as 24 months of age, with a reasonable performance (i.e., root mean square error of 0.18).

Chained regularization for identifying brain patterns specific to HIV infection.

Human Immunodeficiency Virus (HIV) infection continues to have major adverse public health and clinical consequences despite the effectiveness of combination Antiretroviral Therapy (cART) in reducing HIV viral load and improving immune function. As successfully treated individuals with HIV infection age, their cognition declines faster than reported for normal aging. This phenomenon underlines the importance of improving long-term care, which requires a better understanding of the impact of HIV on the brain. In this paper, automated identification of patients and brain regions affected by HIV infection are modeled as a classification problem, whose solution is determined in two steps within our proposed Chained-Regularization framework. The first step focuses on selecting the HIV pattern (i.e., the most informative constellation of brain region measurements for distinguishing HIV infected subjects from healthy controls) by constraining the search for the optimal parameter setting of the classifier via group sparsity (ℓ2,1-norm). The second step improves classification accuracy by constraining the parameterization with respect to the selected measurements and the Euclidean regularization (ℓ2-norm). When applied to the cortical and subcortical structural Magnetic Resonance Images (MRI) measurements of 65 controls and 65 HIV infected individuals, this approach is more accurate in distinguishing the two cohorts than more common models. Finally, the brain regions of the identified HIV pattern concur with the HIV literature that uses traditional group analysis models.

Anatomy-guided joint tissue segmentation and topological correction for 6-month infant brain MRI with risk of autism.

Tissue segmentation of infant brain MRIs with risk of autism is critically important for characterizing early brain development and identifying biomarkers. However, it is challenging due to low tissue contrast caused by inherent ongoing myelination and maturation. In particular, at around 6 months of age, the voxel intensities in both gray matter and white matter are within similar ranges, thus leading to the lowest image contrast in the first postnatal year. Previous studies typically employed intensity images and tentatively estimated tissue probabilities to train a sequence of classifiers for tissue segmentation. However, the important prior knowledge of brain anatomy is largely ignored during the segmentation. Consequently, the segmentation accuracy is still limited and topological errors frequently exist, which will significantly degrade the performance of subsequent analyses. Although topological errors could be partially handled by retrospective topological correction methods, their results may still be anatomically incorrect. To address these challenges, in this article, we propose an anatomy-guided joint tissue segmentation and topological correction framework for isointense infant MRI. Particularly, we adopt a signed distance map with respect to the outer cortical surface as anatomical prior knowledge, and incorporate such prior information into the proposed framework to guide segmentation in ambiguous regions. Experimental results on the subjects acquired from National Database for Autism Research demonstrate the effectiveness to topological errors and also some levels of robustness to motion. Comparisons with the state-of-the-art methods further demonstrate the advantages of the proposed method in terms of both segmentation accuracy and topological correctness.

Joint feature-sample selection and robust diagnosis of Parkinson's disease from MRI data.

Parkinson's disease (PD) is an overwhelming neurodegenerative disorder caused by deterioration of a neurotransmitter, known as dopamine. Lack of this chemical messenger impairs several brain regions and yields various motor and non-motor symptoms. Incidence of PD is predicted to double in the next two decades, which urges more research to focus on its early diagnosis and treatment. In this paper, we propose an approach to diagnose PD using magnetic resonance imaging (MRI) data. Specifically, we first introduce a joint feature-sample selection (JFSS) method for selecting an optimal subset of samples and features, to learn a reliable diagnosis model. The proposed JFSS model effectively discards poor samples and irrelevant features. As a result, the selected features play an important role in PD characterization, which will help identify the most relevant and critical imaging biomarkers for PD. Then, a robust classification framework is proposed to simultaneously de-noise the selected subset of features and samples, and learn a classification model. Our model can also de-noise testing samples based on the cleaned training data. Unlike many previous works that perform de-noising in an unsupervised manner, we perform supervised de-noising for both training and testing data, thus boosting the diagnostic accuracy. Experimental results on both synthetic and publicly available PD datasets show promising results. To evaluate the proposed method, we use the popular Parkinson's progression markers initiative (PPMI) database. Our results indicate that the proposed method can differentiate between PD and normal control (NC), and outperforms the competing methods by a relatively large margin. It is noteworthy to mention that our proposed framework can also be used for diagnosis of other brain disorders. To show this, we have also conducted experiments on the widely-used ADNI database. The obtained results indicate that our proposed method can identify the imaging biomarkers and diagnose the disease with favorable accuracies compared to the baseline methods.

Federated learning with knowledge distillation for multi-organ segmentation with partially labeled datasets.

The state-of-the-art multi-organ CT segmentation relies on deep learning models, which only generalize when trained on large samples of carefully curated data. However, it is challenging to train a single model that can segment all organs and types of tumors since most large datasets are partially labeled or are acquired across multiple institutes that may differ in their acquisitions. A possible solution is Federated learning, which is often used to train models on multi-institutional datasets where the data is not shared across sites. However, predictions of federated learning can be unreliable after the model is locally updated at sites due to 'catastrophic forgetting'. Here, we address this issue by using knowledge distillation (KD) so that the local training is regularized with the knowledge of a global model and pre-trained organ-specific segmentation models. We implement the models in a multi-head U-Net architecture that learns a shared embedding space for different organ segmentation, thereby obtaining multi-organ predictions without repeated processes. We evaluate the proposed method using 8 publicly available abdominal CT datasets of 7 different organs. Of those datasets, 889 CTs were used for training, 233 for internal testing, and 30 volumes for external testing. Experimental results verified that our proposed method substantially outperforms other state-of-the-art methods in terms of accuracy, inference time, and the number of parameters.

Vision-based estimation of fatigue and engagement in cognitive training sessions.

Computerized cognitive training (CCT) is a scalable, well-tolerated intervention that has promise for slowing cognitive decline. The effectiveness of CCT is often affected by a lack of effective engagement. Mental fatigue is a the primary factor for compromising effective engagement in CCT, particularly in older adults at risk for dementia. There is a need for scalable, automated measures that can constantly monitor and reliably detect mental fatigue during CCT. Here, we develop and validate a novel Recurrent Video Transformer (RVT) method for monitoring real-time mental fatigue in older adults with mild cognitive impairment using their video-recorded facial gestures during CCT. The RVT model achieved the highest balanced accuracy (79.58%) and precision (0.82) compared to the prior models for binary and multi-class classification of mental fatigue. We also validated our model by significantly relating to reaction time across CCT tasks (Waldχ2=5.16,p=0.023). By leveraging dynamic temporal information, the RVT model demonstrates the potential to accurately measure real-time mental fatigue, laying the foundation for future CCT research aiming to enhance effective engagement by timely prevention of mental fatigue.

Metadata-conditioned generative models to synthesize anatomically-plausible 3D brain MRIs.

Recent advances in generative models have paved the way for enhanced generation of natural and medical images, including synthetic brain MRIs. However, the mainstay of current AI research focuses on optimizing synthetic MRIs with respect to visual quality (such as signal-to-noise ratio) while lacking insights into their relevance to neuroscience. To generate high-quality T1-weighted MRIs relevant for neuroscience discovery, we present a two-stage Diffusion Probabilistic Model (called BrainSynth) to synthesize high-resolution MRIs conditionally-dependent on metadata (such as age and sex). We then propose a novel procedure to assess the quality of BrainSynth according to how well its synthetic MRIs capture macrostructural properties of brain regions and how accurately they encode the effects of age and sex. Results indicate that more than half of the brain regions in our synthetic MRIs are anatomically plausible, i.e., the effect size between real and synthetic MRIs is small relative to biological factors such as age and sex. Moreover, the anatomical plausibility varies across cortical regions according to their geometric complexity. As is, the MRIs generated by BrainSynth significantly improve the training of a predictive model to identify accelerated aging effects in an independent study. These results indicate that our model accurately capture the brain's anatomical information and thus could enrich the data of underrepresented samples in a study. The code of BrainSynth will be released as part of the MONAI project at https://github.com/Project-MONAI/GenerativeModels.

Medical Image Segmentation Review: The Success of U-Net.

Automatic medical image segmentation is a crucial topic in the medical domain and successively a critical counterpart in the computer-aided diagnosis paradigm. U-Net is the most widespread image segmentation architecture due to its flexibility, optimized modular design, and success in all medical image modalities. Over the years, the U-Net model has received tremendous attention from academic and industrial researchers who have extended it to address the scale and complexity created by medical tasks. These extensions are commonly related to enhancing the U-Net's backbone, bottleneck, or skip connections, or including representation learning, or combining it with a Transformer architecture, or even addressing probabilistic prediction of the segmentation map. Having a compendium of different previously proposed U-Net variants makes it easier for machine learning researchers to identify relevant research questions and understand the challenges of the biological tasks that challenge the model. In this work, we discuss the practical aspects of the U-Net model and organize each variant model into a taxonomy. Moreover, to measure the performance of these strategies in a clinical application, we propose fair evaluations of some unique and famous designs on well-known datasets. Furthermore, we provide a comprehensive implementation library with trained models. In addition, for ease of future studies, we created an online list of U-Net papers with their possible official implementation. All information is gathered in a GitHub repository https://github.com/NITR098/Awesome-U-Net.

TransUNet: Rethinking the U-Net architecture design for medical image segmentation through the lens of transformers.

Medical image segmentation is crucial for healthcare, yet convolution-based methods like U-Net face limitations in modeling long-range dependencies. To address this, Transformers designed for sequence-to-sequence predictions have been integrated into medical image segmentation. However, a comprehensive understanding of Transformers' self-attention in U-Net components is lacking. TransUNet, first introduced in 2021, is widely recognized as one of the first models to integrate Transformer into medical image analysis. In this study, we present the versatile framework of TransUNet that encapsulates Transformers' self-attention into two key modules: (1) a Transformer encoder tokenizing image patches from a convolution neural network (CNN) feature map, facilitating global context extraction, and (2) a Transformer decoder refining candidate regions through cross-attention between proposals and U-Net features. These modules can be flexibly inserted into the U-Net backbone, resulting in three configurations: Encoder-only, Decoder-only, and Encoder+Decoder. TransUNet provides a library encompassing both 2D and 3D implementations, enabling users to easily tailor the chosen architecture. Our findings highlight the encoder's efficacy in modeling interactions among multiple abdominal organs and the decoder's strength in handling small targets like tumors. It excels in diverse medical applications, such as multi-organ segmentation, pancreatic tumor segmentation, and hepatic vessel segmentation. Notably, our TransUNet achieves a significant average Dice improvement of 1.06% and 4.30% for multi-organ segmentation and pancreatic tumor segmentation, respectively, when compared to the highly competitive nn-UNet, and surpasses the top-1 solution in the BrasTS2021 challenge. 2D/3D Code and models are available at https://github.com/Beckschen/TransUNet and https://github.com/Beckschen/TransUNet-3D, respectively.

An Explainable Geometric-Weighted Graph Attention Network for Identifying Functional Networks Associated with Gait Impairment.

One of the hallmark symptoms of Parkinson's Disease (PD) is the progressive loss of postural reflexes, which eventually leads to gait difficulties and balance problems. Identifying disruptions in brain function associated with gait impairment could be crucial in better understanding PD motor progression, thus advancing the development of more effective and personalized therapeutics. In this work, we present an explainable, geometric, weighted-graph attention neural network (xGW-GAT) to identify functional networks predictive of the progression of gait difficulties in individuals with PD. xGW-GAT predicts the multi-class gait impairment on the MDS-Unified PD Rating Scale (MDS-UPDRS). Our computational- and data-efficient model represents functional connectomes as symmetric positive definite (SPD) matrices on a Riemannian manifold to explicitly encode pairwise interactions of entire connectomes, based on which we learn an attention mask yielding individual- and group-level explain-ability. Applied to our resting-state functional MRI (rs-fMRI) dataset of individuals with PD, xGW-GAT identifies functional connectivity patterns associated with gait impairment in PD and offers interpretable explanations of functional subnetworks associated with motor impairment. Our model successfully outperforms several existing methods while simultaneously revealing clinically-relevant connectivity patterns. The source code is available at https://github.com/favour-nerrise/xGW-GAT.

An Explainable Geometric-Weighted Graph Attention Network for Identifying Functional Networks Associated with Gait Impairment.

One of the hallmark symptoms of Parkinson's Disease (PD) is the progressive loss of postural reflexes, which eventually leads to gait difficulties and balance problems. Identifying disruptions in brain function associated with gait impairment could be crucial in better understanding PD motor progression, thus advancing the development of more effective and personalized therapeutics. In this work, we present an explainable, geometric, weighted-graph attention neural network (xGW-GAT) to identify functional networks predictive of the progression of gait difficulties in individuals with PD. xGW-GAT predicts the multi-class gait impairment on the MDS-Unified PD Rating Scale (MDS-UPDRS). Our computational- and data-efficient model represents functional connectomes as symmetric positive definite (SPD) matrices on a Riemannian manifold to explicitly encode pairwise interactions of entire connectomes, based on which we learn an attention mask yielding individual- and group-level explainability. Applied to our resting-state functional MRI (rs-fMRI) dataset of individuals with PD, xGW-GAT identifies functional connectivity patterns associated with gait impairment in PD and offers interpretable explanations of functional subnetworks associated with motor impairment. Our model successfully outperforms several existing methods while simultaneously revealing clinically-relevant connectivity patterns. The source code is available at https://github.com/favour-nerrise/xGW-GAT.

CCA identifies a neurophysiological marker of adaptation capacity that is reliably linked to internal locus of control of cognition in amnestic MCI.

Locus of control (LOC) describes whether an individual thinks that they themselves (internal LOC) or external factors (external LOC) have more influence on their lives. LOC varies by domain, and a person's LOC for their intellectual capacities (LOC-Cognition) may be a marker of resilience in older adults at risk for dementia, with internal LOC-Cognition relating to better outcomes and improved treatment adherence. Vagal control, a key component of parasympathetic autonomic nervous system (ANS) regulation, may reflect a neurophysiological biomarker of internal LOC-Cognition. We used canonical correlation analysis (CCA) to identify a shared neurophysiological marker of ANS regulation from electrocardiogram (during auditory working memory) and functional connectivity (FC) data. A canonical variable from root mean square of successive differences (RMSSD) time series and between-network FC was significantly related to internal LOC-Cognition (ß = 0.266, SE = 0.971, CI = [0.190, 4.073], p = 0.031) in 65 participants (mean age = 74.7, 32 female) with amnestic mild cognitive impairment (aMCI). Follow-up data from 55 of these individuals (mean age = 73.6, 22 females) was used to show reliability of this relationship (ß = 0.271, SE = 0.971, CI = [0.033, 2.630], p = 0.047), and a second sample (40 participants with aMCI/healthy cognition, mean age = 72.7, 24 females) showed that the canonical vector biomarker generalized to visual working memory (ß = 0.36, SE = 0.136, CI = [0.023, 0.574], p = 0.037), but not inhibition task RMSSD data (ß = 0.08, SE = 1.486, CI = [- 0.354, 0.657], p = 0.685). This canonical vector may represent a biomarker of autonomic regulation that explains how some older adults maintain internal LOC-Cognition as dementia progresses. Future work should further test the causality of this relationship and the modifiability of this biomarker.

LSOR: Longitudinally-Consistent Self-Organized Representation Learning.

Interpretability is a key issue when applying deep learning models to longitudinal brain MRIs. One way to address this issue is by visualizing the high-dimensional latent spaces generated by deep learning via self-organizing maps (SOM). SOM separates the latent space into clusters and then maps the cluster centers to a discrete (typically 2D) grid preserving the high-dimensional relationship between clusters. However, learning SOM in a high-dimensional latent space tends to be unstable, especially in a self-supervision setting. Furthermore, the learned SOM grid does not necessarily capture clinically interesting information, such as brain age. To resolve these issues, we propose the first self-supervised SOM approach that derives a high-dimensional, interpretable representation stratified by brain age solely based on longitudinal brain MRIs (i.e., without demographic or cognitive information). Called Longitudinally-consistent Self-Organized Representation learning (LSOR), the method is stable during training as it relies on soft clustering (vs. the hard cluster assignments used by existing SOM). Furthermore, our approach generates a latent space stratified according to brain age by aligning trajectories inferred from longitudinal MRIs to the reference vector associated with the corresponding SOM cluster. When applied to longitudinal MRIs of the Alzheimer's Disease Neuroimaging Initiative (ADNI, N=632), LSOR generates an interpretable latent space and achieves comparable or higher accuracy than the state-of-the-art representations with respect to the downstream tasks of classification (static vs. progressive mild cognitive impairment) and regression (determining ADAS-Cog score of all subjects). The code is available at https://github.com/ouyangjiahong/longitudinal-som-single-modality.

Generating Realistic Brain MRIs via a Conditional Diffusion Probabilistic Model.

As acquiring MRIs is expensive, neuroscience studies struggle to attain a sufficient number of them for properly training deep learning models. This challenge could be reduced by MRI synthesis, for which Generative Adversarial Networks (GANs) are popular. GANs, however, are commonly unstable and struggle with creating diverse and high-quality data. A more stable alternative is Diffusion Probabilistic Models (DPMs) with a fine-grained training strategy. To overcome their need for extensive computational resources, we propose a conditional DPM (cDPM) with a memory-efficient process that generates realistic-looking brain MRIs. To this end, we train a 2D cDPM to generate an MRI subvolume conditioned on another subset of slices from the same MRI. By generating slices using arbitrary combinations between condition and target slices, the model only requires limited computational resources to learn interdependencies between slices even if they are spatially far apart. After having learned these dependencies via an attention network, a new anatomy-consistent 3D brain MRI is generated by repeatedly applying the cDPM. Our experiments demonstrate that our method can generate high-quality 3D MRIs that share a similar distribution to real MRIs while still diversifying the training set. The code is available at https://github.com/xiaoiker/mask3DMRI_diffusion and also will be released as part of MONAI, at https://github.com/Project-MONAI/GenerativeModels.

One-shot Federated Learning on Medical Data using Knowledge Distillation with Image Synthesis and Client Model Adaptation.

One-shot federated learning (FL) has emerged as a promising solution in scenarios where multiple communication rounds are not practical. Notably, as feature distributions in medical data are less discriminative than those of natural images, robust global model training with FL is non-trivial and can lead to overfitting. To address this issue, we propose a novel one-shot FL framework leveraging Image Synthesis and Client model Adaptation (FedISCA) with knowledge distillation (KD). To prevent overfitting, we generate diverse synthetic images ranging from random noise to realistic images. This approach (i) alleviates data privacy concerns and (ii) facilitates robust global model training using KD with decentralized client models. To mitigate domain disparity in the early stages of synthesis, we design noise-adapted client models where batch normalization statistics on random noise (synthetic images) are updated to enhance KD. Lastly, the global model is trained with both the original and noise-adapted client models via KD and synthetic images. This process is repeated till global model convergence. Extensive evaluation of this design on five small- and three large-scale medical image classification datasets reveals superior accuracy over prior methods. Code is available at https://github.com/myeongkyunkang/FedISCA.

Bridging the Gap between Deep Learning and Hypothesis-Driven Analysis via Permutation Testing.

A fundamental approach in neuroscience research is to test hypotheses based on neuropsychological and behavioral measures, i.e., whether certain factors (e.g., related to life events) are associated with an outcome (e.g., depression). In recent years, deep learning has become a potential alternative approach for conducting such analyses by predicting an outcome from a collection of factors and identifying the most "informative" ones driving the prediction. However, this approach has had limited impact as its findings are not linked to statistical significance of factors supporting hypotheses. In this article, we proposed a flexible and scalable approach based on the concept of permutation testing that integrates hypothesis testing into the data-driven deep learning analysis. We apply our approach to the yearly self-reported assessments of 621 adolescent participants of the National Consortium of Alcohol and Neurodevelopment in Adolescence (NCANDA) to predict negative valence, a symptom of major depressive disorder according to the NIMH Research Domain Criteria (RDoC). Our method successfully identifies categories of risk factors that further explain the symptom.

Disentangling Normal Aging From Severity of Disease via Weak Supervision on Longitudinal MRI.

The continuous progression of neurological diseases are often categorized into conditions according to their severity. To relate the severity to changes in brain morphometry, there is a growing interest in replacing these categories with a continuous severity scale that longitudinal MRIs are mapped onto via deep learning algorithms. However, existing methods based on supervised learning require large numbers of samples and those that do not, such as self-supervised models, fail to clearly separate the disease effect from normal aging. Here, we propose to explicitly disentangle those two factors via weak-supervision. In other words, training is based on longitudinal MRIs being labelled either normal or diseased so that the training data can be augmented with samples from disease categories that are not of primary interest to the analysis. We do so by encouraging trajectories of controls to be fully encoded by the direction associated with brain aging. Furthermore, an orthogonal direction linked to disease severity captures the residual component from normal aging in the diseased cohort. Hence, the proposed method quantifies disease severity and its progression speed in individuals without knowing their condition. We apply the proposed method on data from the Alzheimer's Disease Neuroimaging Initiative (ADNI, N =632 ). We then show that the model properly disentangled normal aging from the severity of cognitive impairment by plotting the resulting disentangled factors of each subject and generating simulated MRIs for a given chronological age and condition. Moreover, our representation obtains higher balanced accuracy when used for two downstream classification tasks compared to other pre-training approaches. The code for our weak-supervised approach is available at https://github.com/ouyangjiahong/longitudinal-direction-disentangle.

A Novel Explainability Approach for Technology-Driven Translational Research on Brain Aging.

Brain aging leads to difficulties in functional independence. Mitigating these difficulties can benefit from technology that predicts, monitors, and modifies brain aging. Translational research prioritizes solutions that can be causally linked to specific pathophysiologies at the same time as demonstrating improvements in impactful real-world outcome measures. This poses a challenge for brain aging technology that needs to address the tension between mechanism-driven precision and clinical relevance. In the current opinion, by synthesizing emerging mechanistic, translational, and clinical research-related frameworks, and our own development of technology-driven brain aging research, we suggest incorporating the appreciation of four desiderata (causality, informativeness, transferability, and fairness) of explainability into early-stage research that designs and tests brain aging technology. We apply a series of work on electrocardiography-based "peripheral" neuroplasticity markers from our work as an illustration of our proposed approach. We believe this novel approach will promote the development and adoption of brain aging technology that links and addresses brain pathophysiology and functional independence in the field of translational research.