Richard M. Leahy

Wenhui Cui, Woojae Jeong, Philipp Thölke et al.

To handle the scarcity and heterogeneity of electroencephalography (EEG) data for Brain-Computer Interface (BCI) tasks, and to harness the power of large publicly available data sets, we propose Neuro-GPT, a foundation model consisting of an EEG encoder and a GPT model. The foundation model is pre-trained on a large-scale data set using a self-supervised task that learns how to reconstruct masked EEG segments. We then fine-tune the model on a Motor Imagery Classification task to validate its performance in a low-data regime (9 subjects). Our experiments demonstrate that applying a foundation model can significantly improve classification performance compared to a model trained from scratch, which provides evidence for the generalizability of the foundation model and its ability to address challenges of data scarcity and heterogeneity in EEG. The code is publicly available at github.com/wenhui0206/NeuroGPT.

Rui Xu, Mahdi Soltanolkotabi, Justin P. Haldar et al.

This paper presents a new algorithm, Accelerated Wirtinger Flow (AWF), for ptychographic image reconstruction from phaseless diffraction pattern measurements. AWF is based on combining Nesterov's acceleration approach with Wirtinger gradient descent. Theoretical results enable prespecification of all AWF algorithm parameters, with no need for computationally-expensive line searches and no need for manual parameter tuning. AWF is evaluated in the context of simulated X-ray ptychography, where we demonstrate fast convergence and low per-iteration computational complexity. We also show examples where AWF reaches higher image quality with less computation than classical algorithms. AWF is also shown to have robustness to noise and probe misalignment.

Wenhui Cui, Haleh Akrami, Anand A. Joshi et al.

The amount of manually labeled data is limited in medical applications, so semi-supervised learning and automatic labeling strategies can be an asset for training deep neural networks. However, the quality of the automatically generated labels can be uneven and inferior to manual labels. In this paper, we suggest a semi-supervised training strategy for leveraging both manually labeled data and extra unlabeled data. In contrast to the existing approaches, we apply robust loss for the automated labeled data to automatically compensate for the uneven data quality using a teacher-student framework. First, we generate pseudo-labels for unlabeled data using a teacher model pre-trained on labeled data. These pseudo-labels are noisy, and using them along with labeled data for training a deep neural network can severely degrade learned feature representations and the generalization of the network. Here we mitigate the effect of these pseudo-labels by using robust loss functions. Specifically, we use three robust loss functions, namely beta cross-entropy, symmetric cross-entropy, and generalized cross-entropy. We show that our proposed strategy improves the model performance by compensating for the uneven quality of labels in image classification as well as segmentation applications.

Haleh Akrami, Wenhui Cui, Anand A Joshi et al.

Segmentation is one of the most important tasks in MRI medical image analysis and is often the first and the most critical step in many clinical applications. In brain MRI analysis, head segmentation is commonly used for measuring and visualizing the brain's anatomical structures and is also a necessary step for other applications such as current-source reconstruction in electroencephalography and magnetoencephalography (EEG/MEG). Here we propose a deep learning framework that can segment brain, skull, and extra-cranial tissue using only T1-weighted MRI as input. In addition, we describe a robust method for training the model in the presence of noisy labels.

Wenhui Cui, Haleh Akrami, Anand A. Joshi et al.

Despite the remarkable success achieved by graph convolutional networks for functional brain activity analysis, the heterogeneity of functional patterns and the scarcity of imaging data still pose challenges in many tasks. Transferring knowledge from a source domain with abundant training data to a target domain is effective for improving representation learning on scarce training data. However, traditional transfer learning methods often fail to generalize the pre-trained knowledge to the target task due to domain discrepancy. Self-supervised learning on graphs can increase the generalizability of graph features since self-supervision concentrates on inherent graph properties that are not limited to a particular supervised task. We propose a novel knowledge transfer strategy by integrating meta-learning with self-supervised learning to deal with the heterogeneity and scarcity of fMRI data. Specifically, we perform a self-supervised task on the source domain and apply meta-learning, which strongly improves the generalizability of the model using the bi-level optimization, to transfer the self-supervised knowledge to the target domain. Through experiments on a neurological disorder classification task, we demonstrate that the proposed strategy significantly improves target task performance by increasing the generalizability and transferability of graph-based knowledge.

Wenhui Cui, Nicholas Swingle, Anand A. Joshi et al.

Objective: Post-traumatic epilepsy (PTE) is a debilitating neurological disorder that develops after traumatic brain injury (TBI). Early prediction of PTE remains challenging due to heterogeneous clinical data, limited positive cases, and reliance on resource-intensive neuroimaging data. We investigate whether routinely collected acute clinical records alone can support early PTE prediction using language model-based approaches. Methods: Using a curated subset of the TRACK-TBI cohort, we developed an automated PTE prediction framework that implements pretrained large language models (LLMs) as fixed feature extractors to encode clinical records. Tabular features, LLM-generated embeddings, and hybrid feature representations were evaluated using gradient-boosted tree classifiers under stratified cross-validation. Results: LLM embeddings achieved performance improvements by capturing contextual clinical information compared to using tabular features alone. The best performance was achieved by a modality-aware feature fusion strategy combining tabular features and LLM embeddings, achieving an AUC-ROC of 0.892 and AUPRC of 0.798. Acute post-traumatic seizures, injury severity, neurosurgical intervention, and ICU stay are key contributors to the predictive performance. Significance: These findings demonstrate that routine acute clinical records contain information suitable for early PTE risk prediction using LLM embeddings in conjunction with gradient-boosted tree classifiers. This approach represents a promising complement to imaging-based prediction.

Wenhui Cui, Haleh Akrami, Anand A. Joshi et al.

Despite the impressive advances achieved using deep learning for functional brain activity analysis, the heterogeneity of functional patterns and the scarcity of imaging data still pose challenges in tasks such as identifying neurological disorders. For functional Magnetic Resonance Imaging (fMRI), while data may be abundantly available from healthy controls, clinical data is often scarce, especially for rare diseases, limiting the ability of models to identify clinically-relevant features. We overcome this limitation by introducing a novel representation learning strategy integrating meta-learning with self-supervised learning to improve the generalization from normal to clinical features. This approach enables generalization to challenging clinical tasks featuring scarce training data. We achieve this by leveraging self-supervised learning on the control dataset to focus on inherent features that are not limited to a particular supervised task and incorporating meta-learning to improve the generalization across domains. To explore the generalizability of the learned representations to unseen clinical applications, we apply the model to four distinct clinical datasets featuring scarce and heterogeneous data for neurological disorder classification. Results demonstrate the superiority of our representation learning strategy on diverse clinically-relevant tasks. Code is publicly available at https://github.com/wenhui0206/MeTSK/tree/main

Wenhui Cui, Haleh Akrami, Ganning Zhao et al.

Despite the impressive advancements achieved using deep-learning for functional brain activity analysis, the heterogeneity of functional patterns and scarcity of imaging data still pose challenges in tasks such as prediction of future onset of Post-Traumatic Epilepsy (PTE) from data acquired shortly after traumatic brain injury (TBI). Foundation models pre-trained on separate large-scale datasets can improve the performance from scarce and heterogeneous datasets. For functional Magnetic Resonance Imaging (fMRI), while data may be abundantly available from healthy controls, clinical data is often scarce, limiting the ability of foundation models to identify clinically-relevant features. We overcome this limitation by introducing a novel training strategy for our foundation model by integrating meta-learning with self-supervised learning to improve the generalization from normal to clinical features. In this way we enable generalization to other downstream clinical tasks, in our case prediction of PTE. To achieve this, we perform self-supervised training on the control dataset to focus on inherent features that are not limited to a particular supervised task while applying meta-learning, which strongly improves the model's generalizability using bi-level optimization. Through experiments on neurological disorder classification tasks, we demonstrate that the proposed strategy significantly improves task performance on small-scale clinical datasets. To explore the generalizability of the foundation model in downstream applications, we then apply the model to an unseen TBI dataset for prediction of PTE using zero-shot learning. Results further demonstrated the enhanced generalizability of our foundation model.

Woojae Jeong, Aditya Kommineni, Kleanthis Avramidis et al.

Depression and suicidality affect cognitive and emotional processes, yet objective, task-evoked neural readouts of mental health remain limited. We investigated the spatiotemporal dynamics of affective semantic processing using multivariate decoding of time-resolved, 64-channel electroencephalography (EEG). Participants (N=137) performed a sentence-evaluation task with emotionally salient, self-referential statements. We identified robust neural signatures of semantic processing, with peak decoding accuracy between 300-600 ms -- a window associated with rapid, stimulus-driven semantic evaluation and conflict monitoring. Relative to healthy controls, individuals with depression and suicidal ideation showed earlier onset, longer duration, and greater amplitude decoding responses, along with broader cross-temporal generalization and enhanced contributions from frontocentral and parietotemporal components. These findings suggest altered sensitivity and impaired disengagement from emotionally salient content in the clinical groups, advancing our understanding of the neurocognitive basis of mental health and establishing a compact and interpretable EEG-based index of semantic-evaluation dynamics with potential diagnostic relevance.

Jihwan Lee, Parsa Razmara, Kevin Huang et al.

Speech production is a complex process spanning neural planning, motor control, muscle activation, and articulatory kinematics. While the acoustic speech signal is the most accessible product of the speech production act, it does not directly reveal its causal neurophysiological substrates. We present the first simultaneous acquisition of real-time (dynamic) MRI, EEG, and surface EMG, capturing several key aspects of the speech production chain: brain signals, muscle activations, and articulatory movements. This multimodal acquisition paradigm presents substantial technical challenges, including MRI-induced electromagnetic interference and myogenic artifacts. To mitigate these, we introduce an artifact suppression pipeline tailored to this tri-modal setting. Once fully developed, this framework is poised to offer an unprecedented window into speech neuroscience and insights leading to brain-computer interface advances.

Kleanthis Avramidis, Woojae Jeong, Aditya Kommineni et al.

Identifying physiological and behavioral markers for mental health conditions is a longstanding challenge in psychiatry. Depression and suicidal ideation, in particular, lack objective biomarkers, with screening and diagnosis primarily relying on self-reports and clinical interviews. Here, we investigate eye tracking as a potential marker modality for screening purposes. Eye movements are directly modulated by neuronal networks and have been associated with attentional and mood-related patterns; however, their predictive value for depression and suicidality remains unclear. We recorded eye-tracking sequences from 126 young adults as they read and responded to affective sentences, and subsequently developed a deep learning framework to predict their clinical status. The proposed model included separate branches for trials of positive and negative sentiment, and used 2D time-series representations to account for both intra-trial and inter-trial variations. We were able to identify depression and suicidal ideation with an area under the receiver operating curve (AUC) of 0.793 (95% CI: 0.765-0.819) against healthy controls, and suicidality specifically with 0.826 AUC (95% CI: 0.797-0.852). The model also exhibited moderate, yet significant, accuracy in differentiating depressed from suicidal participants, with 0.609 AUC (95% CI 0.571-0.646). Discriminative patterns emerge more strongly when assessing the data relative to response generation than relative to the onset time of the final word of the sentences. The most pronounced effects were observed for negative-sentiment sentences, that are congruent to depressed and suicidal participants. Our findings highlight eye tracking as an objective tool for mental health assessment and underscore the modulatory impact of emotional stimuli on cognitive processes affecting oculomotor control.

Anand A. Joshi, Soyoung Choi, Haleh Akrami et al.

Due to the spontaneous nature of resting-state fMRI (rs-fMRI) signals, cross-subject comparison and therefore, group studies of rs-fMRI are challenging. Most existing group comparison methods use features extracted from the fMRI time series, such as connectivity features, independent component analysis (ICA), and functional connectivity density (FCD) methods. However, in group studies, especially in the case of spectrum disorders, distances to a single atlas or a representative subject do not fully reflect the differences between subjects that may lie on a multi-dimensional spectrum. Moreover, there may not exist an individual subject or even an average atlas in such cases that is representative of all subjects. Here we describe an approach that measures pairwise distances between the synchronized rs-fMRI signals of pairs of subjects instead of to a single reference point. We also present a method for fMRI data comparison that leverages this generated pairwise feature to establish a radial basis function kernel matrix. This kernel matrix is used in turn to perform kernel regression of rs-fMRI to a clinical variable such as a cognitive or neurophysiological performance score of interest. This method opens a new pointwise analysis paradigm for fMRI data. We demonstrate the application of this method by performing a pointwise analysis on the cortical surface using rs-fMRI data to identify cortical regions associated with variability in ADHD index. While pointwise analysis methods are common in anatomical studies such as cortical thickness analysis and voxel- and tensor-based morphometry and its variants, such a method is lacking for rs-fMRI and could improve the utility of rs-fMRI for group studies. The method presented in this paper is aimed at filling this gap.

Haleh Akrami, Anand A. Joshi, Sergul Aydore et al.

Estimation of uncertainty in deep learning models is of vital importance, especially in medical imaging, where reliance on inference without taking into account uncertainty could lead to misdiagnosis. Recently, the probabilistic Variational AutoEncoder (VAE) has become a popular model for anomaly detection in applications such as lesion detection in medical images. The VAE is a generative graphical model that is used to learn the data distribution from samples and then generate new samples from this distribution. By training on normal samples, the VAE can be used to detect inputs that deviate from this learned distribution. The VAE models the output as a conditionally independent Gaussian characterized by means and variances for each output dimension. VAEs can therefore use reconstruction probability instead of reconstruction error for anomaly detection. Unfortunately, joint optimization of both mean and variance in the VAE leads to the well-known problem of shrinkage or underestimation of variance. We describe an alternative approach that avoids this variance shrinkage problem by using quantile regression. Using estimated quantiles to compute mean and variance under the Gaussian assumption, we compute reconstruction probability as a principled approach to outlier or anomaly detection. Results on simulated and Fashion MNIST data demonstrate the effectiveness of our approach. We also show how our approach can be used for principled heterogeneous thresholding for lesion detection in brain images.

Haleh Akrami, Sergul Aydore, Richard M. Leahy et al.

We propose a robust variational autoencoder with $β$ divergence for tabular data (RTVAE) with mixed categorical and continuous features. Variational autoencoders (VAE) and their variations are popular frameworks for anomaly detection problems. The primary assumption is that we can learn representations for normal patterns via VAEs and any deviation from that can indicate anomalies. However, the training data itself can contain outliers. The source of outliers in training data include the data collection process itself (random noise) or a malicious attacker (data poisoning) who may target to degrade the performance of the machine learning model. In either case, these outliers can disproportionately affect the training process of VAEs and may lead to wrong conclusions about what the normal behavior is. In this work, we derive a novel form of a variational autoencoder for tabular data sets with categorical and continuous features that is robust to outliers in training data. Our results on the anomaly detection application for network traffic datasets demonstrate the effectiveness of our approach.

Haleh Akrami, Anand A. Joshi, Jian Li et al.

Machine learning methods often need a large amount of labeled training data. Since the training data is assumed to be the ground truth, outliers can severely degrade learned representations and performance of trained models. Here we apply concepts from robust statistics to derive a novel variational autoencoder that is robust to outliers in the training data. Variational autoencoders (VAEs) extract a lower-dimensional encoded feature representation from which we can generate new data samples. Robustness of autoencoders to outliers is critical for generating a reliable representation of particular data types in the encoded space when using corrupted training data. Our robust VAE is based on beta-divergence rather than the standard Kullback-Leibler (KL) divergence. Our proposed lower bound lead to a RVAE model that has the same computational complexity as the VAE and contains a single tuning parameter to control the degree of robustness. We demonstrate the performance of our $β$-divergence based autoencoder for a range of image datasets, showing improved robustness to outliers both qualitatively and quantitatively. We also illustrate the use of our robust VAE for outlier detection.