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1. Tensor Decomposition of Large-scale Clinical EEGs Reveals Interpretable Patterns of Brain Physiology

   https://doi.org/10.1109/NER52421.2023.10123800  

   Gupta, Teja; Wagh, Neeraj; Rawal, Samarth; Berry, Brent; Worrell, Gregory; Varatharajah, Yogatheesan (April 2023, 2023 11th International IEEE/EMBS Conference on Neural Engineering (NER))

   Identifying abnormal patterns in electroencephalography (EEG) remains the cornerstone of diagnosing several neurological diseases. The current clinical EEG review process relies heavily on expert visual review, which is unscalable and error-prone. In an effort to augment the expert review process, there is a significant interest in mining population-level EEG patterns using unsupervised approaches. Current approaches rely either on two-dimensional decompositions (e.g., principal and independent component analyses) or deep representation learning (e.g., auto-encoders, self-supervision). However, most approaches do not leverage the natural multi-dimensional structure of EEGs and lack interpretability. In this study, we propose a tensor decomposition approach using the canonical polyadic decomposition to discover a parsimonious set of population-level EEG patterns, retaining the natural multi-dimensional structure of EEG recordings (time×space×frequency) . We then validate their clinical value using a cohort of patients with varying stages of cognitive impairment. Our results show that the discovered patterns reflect physiologically meaningful features and accurately classify the stages of cognitive impairment (healthy vs mild cognitive impairment vs Alzheimer's dementia) with substantially fewer features compared to classical and deep learning-based baselines. We conclude that the decomposition of population-level EEG tensors recovers expert-interpretable EEG patterns that can aid in studying smaller specialized clinical cohorts. 

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2. Comprehensive Anatomical Staging Predicts Clinical Progression in Mild Cognitive Impairment: A Data-Driven Approach

   https://doi.org/10.3390/ijms26125514  

   Tandon, Raghav; Mei, Yajun; Lah, James J; Mitchell, Cassie S (June 2025, International Journal of Molecular Sciences)

   Alzheimer’s disease (AD) presents significant challenges in clinical practice due to its heterogeneous manifestation and variable progression rates. This work develops a comprehensive anatomical staging framework to predict progression from mild cognitive impairment (MCI) to AD. Using the ADNI database, the scalable Subtype and Stage Inference (s-SuStaIn) model was applied to 118 neuroanatomical features from cognitively normal (n = 504) and AD (n = 346) participants. The framework was validated on 808 MCI participants through associations with clinical progression, CSF and FDG-PET biomarkers, and neuropsychiatric measures, while adjusting for common confounders (age, gender, education, and APOE ε4 alleles). The framework demonstrated superior prognostic accuracy compared to traditional risk assessment (C-index = 0.73 vs. 0.62). Four distinct disease subtypes showed differential progression rates, biomarker profiles (FDG-PET and CSF Aβ42), and cognitive trajectories: Subtype 1, subcortical-first pattern; Subtype 2, executive–cortical pattern; Subtype 3, disconnection pattern; and Subtype 4, frontal–executive pattern. Stage-dependent changes revealed systematic deterioration across diverse cognitive domains, particularly in learning acquisition, visuospatial processing, and functional abilities. This data-driven approach captures clinically meaningful disease heterogeneity and improves prognostication in MCI, potentially enabling more personalized therapeutic strategies and clinical trial design. 

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3. Population-based spectral characteristics of normal interictal scalp EEG inform diagnosis and treatment planning in focal epilepsy

   https://doi.org/10.1038/s41598-025-08871-w  

   Wagh, Neeraj; Duque-Lopez, Andrea; Joseph, Boney; Berry, Brent; Jehi, Lara; Crepeau, Daniel; Barnard, Leland; Gogineni, Venkatsampath; Brinkmann, Benjamin H; Jones, David T; et al (December 2025, Scientific Reports)

   Normal routine electroencephalograms (EEGs) can cause delays in the diagnosis and treatment of epilepsy, especially in drug-resistant patients and those without structural abnormalities. There is a need for alternative quantitative approaches that can inform clinical decisions when traditional visual EEG review is inconclusive. We leverage a large population EEG database (N = 13,652 recordings, 12,134 unique patients) and an independent cohort of patients with focal epilepsy (N = 121) to investigate whether normal EEG segments could support the diagnosis of focal epilepsy. We decomposed expertly graded normal EEGs (N = 6,242) using unsupervised tensor decomposition to extract the dominant spatio-spectral patterns present in a clinical population. We then, using the independent cohort of patients with focal epilepsy, evaluated whether pattern loadings of normal interictal EEG segments could classify focal epilepsy, the epileptogenic lobe, presence of lesions, and drug response. We obtained six physiological patterns of EEG spectral power and connectivity with distinct spatio-spectral signatures. Both pattern types together effectively differentiated patients with focal epilepsy from non-epileptic controls (mean AUC 0.78) but failed to classify the epileptogenic lobe. Spectral power-based patterns best classified drug-resistant epilepsy (mean AUC 0.73) and lesional epilepsy (mean AUC 0.67), albeit with high variability across patients. Our findings support that visibly normal patient EEGs contain subtle quantitative differences of clinical relevance. Further development may yield normal EEG-based computational biomarkers that can augment traditional EEG review and epilepsy care. 

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4. Generalizable deep learning model for early Alzheimer’s disease detection from structural MRIs

   https://doi.org/10.1038/s41598-022-20674-x  

   Liu, Sheng; Masurkar, Arjun V.; Rusinek, Henry; Chen, Jingyun; Zhang, Ben; Zhu, Weicheng; Fernandez-Granda, Carlos; Razavian, Narges (December 2022, Scientific Reports)

   Abstract Early diagnosis of Alzheimer’s disease plays a pivotal role in patient care and clinical trials. In this study, we have developed a new approach based on 3D deep convolutional neural networks to accurately differentiate mild Alzheimer’s disease dementia from mild cognitive impairment and cognitively normal individuals using structural MRIs. For comparison, we have built a reference model based on the volumes and thickness of previously reported brain regions that are known to be implicated in disease progression. We validate both models on an internal held-out cohort from The Alzheimer's Disease Neuroimaging Initiative (ADNI) and on an external independent cohort from The National Alzheimer's Coordinating Center (NACC). The deep-learning model is accurate, achieved an area-under-the-curve (AUC) of 85.12 when distinguishing between cognitive normal subjects and subjects with either MCI or mild Alzheimer’s dementia. In the more challenging task of detecting MCI, it achieves an AUC of 62.45. It is also significantly faster than the volume/thickness model in which the volumes and thickness need to be extracted beforehand. The model can also be used to forecast progression: subjects with mild cognitive impairment misclassified as having mild Alzheimer’s disease dementia by the model were faster to progress to dementia over time. An analysis of the features learned by the proposed model shows that it relies on a wide range of regions associated with Alzheimer's disease. These findings suggest that deep neural networks can automatically learn to identify imaging biomarkers that are predictive of Alzheimer's disease, and leverage them to achieve accurate early detection of the disease. 

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5. Classifying Non-Dementia and Alzheimer’s Disease/Vascular Dementia Patients Using Kinematic, Time-Based, and Visuospatial Parameters: The Digital Clock Drawing Test

   https://doi.org/10.3233/JAD-201129  

   Davoudi, Anis; Dion, Catherine; Amini, Shawna; Tighe, Patrick J.; Price, Catherine C.; Libon, David J.; Rashidi, Parisa (June 2021, Journal of Alzheimer's Disease)

   Bondi, Mark (Ed.)

   Background: Advantages of digital clock drawing metrics for dementia subtype classification needs examination. Objective: To assess how well kinematic, time-based, and visuospatial features extracted from the digital Clock Drawing Test (dCDT) can classify a combined group of Alzheimer’s disease/Vascular Dementia patients versus healthy controls (HC), and classify dementia patients with Alzheimer’s disease (AD) versus vascular dementia (VaD). Methods: Healthy, community-dwelling control participants (n = 175), patients diagnosed clinically with Alzheimer’s disease (n = 29), and vascular dementia (n = 27) completed the dCDT to command and copy clock drawing conditions. Thirty-seven dCDT command and 37 copy dCDT features were extracted and used with Random Forest classification models. Results: When HC participants were compared to participants with dementia, optimal area under the curve was achieved using models that combined both command and copy dCDT features (AUC = 91.52%). Similarly, when AD versus VaD participants were compared, optimal area under the curve was, achieved with models that combined both command and copy features (AUC = 76.94%). Subsequent follow-up analyses of a corpus of 10 variables of interest determined using a Gini Index found that groups could be dissociated based on kinematic, time-based, and visuospatial features. Conclusion: The dCDT is able to operationally define graphomotor output that cannot be measured using traditional paper and pencil test administration in older health controls and participants with dementia. These data suggest that kinematic, time-based, and visuospatial behavior obtained using the dCDT may provide additional neurocognitive biomarkers that may be able to identify and tract dementia syndromes. 

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