Daily Papers

Recent incidents involving LLMs used for mental-health support reveal a critical evaluation gap: surface-level safety scores do not capture how models behave across realistic, emotionally sensitive interactions over time. Existing benchmarks measure knowledge, safety, or static response quality, but miss whether LLM interactions help users keep reflecting, coping, and making decisions themselves. We formalize this missing dimension as COGNITIVE ATROPHY, a process-level behavioural measure in AI-mediated mental-health support distinct from safety and helpfulness. To measure it, we introduce COGNITIVE ATROPHY BENCH, a clinically grounded benchmark built from 1,576 fully human-generated counseling conversations, 15,680 turns, and 42,230 responses from five LLMs. Three clinical and neuropsychology experts developed a 20-attribute schema spanning user context, response behaviour, and global risk flags; six trained clinical reviewers applied it with span-grounded evidence, producing 5,324 reviewer judgments. We further introduce the User-Input Risk Index (UIRI), the Cognitive Atrophy Risk Index (ARI), and trajectory summaries. Across five LLMs, models show a consistent moderate-to-high level of atrophy-aligned behaviour across single and multi-turn settings. While models generally respond to overt safety cues, they adapt less reliably when users seek solutions or decisions. The dominant recurring patterns are directive advice, problem-solving, recommendation responses, topic shifts, and forms of validation that may reinforce dependence rather than reflection. Our work makes COGNITIVE ATROPHY measurable and provides a foundation for auditing model behaviour in sensitive LLM conversations.

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder that primarily affects the aging population by impairing cognitive and motor functions. Early detection of AD through accessible methodologies like magnetic resonance imaging (MRI) is vital for developing effective interventions to halt or slow the disease's progression. This study aims to perform a comprehensive analysis of machine learning techniques for selecting MRI-based biomarkers and classifying individuals into healthy controls (HC) and unstable controls (uHC) who later show mild cognitive impairment within five years. The research utilizes MRI data from the Alzheimer's Disease Neuroinformatics Initiative (ADNI) and the Open Access Series of Imaging Studies 3 (OASIS-3), focusing on both HC and uHC participants. The study addresses the challenges of imbalanced data by testing classification methods on balanced and unbalanced datasets, and harmonizes data using polynomial regression to mitigate nuisance variables like age, gender, and intracranial volume. Results indicate that Gaussian Naive Bayes and RusBoost classifiers shows an optimal performance, achieving accuracies of up to 76.46% and 72.48% respectively on the ADNI dataset. For the OASIS-3 dataset, Kernel Naive Bayes and RusBoost yield accuracies ranging from 64.66% to 75.71%, improving further in age-matched datasets. Brain regions like the entorhinal cortex, hippocampus, lateral ventricle, and lateral orbitofrontal cortex are identified as significantly impacted during early cognitive decline. Despite limitations such as small sample sizes, the study's harmonization approach enhances the robustness of biomarker selection, suggesting the potential of this semi-automatic machine learning pipeline for early AD detection using MRI.

Alzheimer's disease (AD) is a degenerative brain disease impairing a person's ability to perform day to day activities. The clinical manifestations of Alzheimer's disease are characterized by heterogeneity in age, disease span, progression rate, impairment of memory and cognitive abilities. Due to these variabilities, personalized care and treatment planning, as well as patient counseling about their individual progression is limited. Recent developments in machine learning to detect hidden patterns in complex, multi-dimensional datasets provides significant opportunities to address this critical need. In this work, we use unsupervised and supervised machine learning approaches for subtype identification and prediction. We apply machine learning methods to the extensive clinical observations available at the Alzheimer's Disease Neuroimaging Initiative (ADNI) data set to identify patient subtypes and to predict disease progression. Our analysis depicts the progression space for the Alzheimer's disease into low, moderate and high disease progression zones. The proposed work will enable early detection and characterization of distinct disease subtypes based on clinical heterogeneity. We anticipate that our models will enable patient counseling, clinical trial design, and ultimately individualized clinical care.

Dementia is a progressive cognitive syndrome with Alzheimer's disease (AD) as the leading cause. Conversation-based AD detection offers a cost-effective alternative to clinical methods, as language dysfunction is an early biomarker of AD. However, most prior research has framed AD detection as a binary classification problem, limiting the ability to identify Mild Cognitive Impairment (MCI)-a crucial stage for early intervention. Also, studies primarily rely on single-language datasets, mainly in English, restricting cross-language generalizability. To address this gap, we make three key contributions. First, we introduce a novel, multilingual dataset for AD detection by unifying 16 publicly available dementia-related conversational datasets. This corpus spans English, Spanish, Chinese, and Greek and incorporates both audio and text data derived from a variety of cognitive assessment tasks. Second, we perform finer-grained classification, including MCI, and evaluate various classifiers using sparse and dense text representations. Third, we conduct experiments in monolingual and multilingual settings, finding that some languages benefit from multilingual training while others perform better independently. This study highlights the challenges in multilingual AD detection and enables future research on both language-specific approaches and techniques aimed at improving model generalization and robustness.

Alzheimer's disease (AD) is a progressive and incurable neurodegenerative disease which destroys brain cells and causes loss to patient's memory. An early detection can prevent the patient from further damage of the brain cells and hence avoid permanent memory loss. In past few years, various automatic tools and techniques have been proposed for diagnosis of AD. Several methods focus on fast, accurate and early detection of the disease to minimize the loss to patients mental health. Although machine learning and deep learning techniques have significantly improved medical imaging systems for AD by providing diagnostic performance close to human level. But the main problem faced during multi-class classification is the presence of highly correlated features in the brain structure. In this paper, we have proposed a smart and accurate way of diagnosing AD based on a two-dimensional deep convolutional neural network (2D-DCNN) using imbalanced three-dimensional MRI dataset. Experimental results on Alzheimer Disease Neuroimaging Initiative magnetic resonance imaging (MRI) dataset confirms that the proposed 2D-DCNN model is superior in terms of accuracy, efficiency, and robustness. The model classifies MRI into three categories: AD, mild cognitive impairment, and normal control: and has achieved 99.89% classification accuracy with imbalanced classes. The proposed model exhibits noticeable improvement in accuracy as compared to the state-fo-the-art methods.

Longitudinal analysis has great potential to reveal developmental trajectories and monitor disease progression in medical imaging. This process relies on consistent and robust joint 4D segmentation. Traditional techniques are dependent on the similarity of images over time and the use of subject-specific priors to reduce random variation and improve the robustness and sensitivity of the overall longitudinal analysis. This is however slow and computationally intensive as subject-specific templates need to be rebuilt every time. The focus of this work to accelerate this analysis with the use of deep learning. The proposed approach is based on deep CNNs and incorporates semantic segmentation and provides a longitudinal relationship for the same subject. The proposed approach is based on deep CNNs and incorporates semantic segmentation and provides a longitudinal relationship for the same subject. The state of art using 3D patches as inputs to modified Unet provides results around {0.91 pm 0.5} Dice and using multi-view atlas in CNNs provide around the same results. In this work, different models are explored, each offers better accuracy and fast results while increasing the segmentation quality. These methods are evaluated on 135 scans from the EADC-ADNI Harmonized Hippocampus Protocol. Proposed CNN based segmentation approaches demonstrate how 2D segmentation using prior slices can provide similar results to 3D segmentation while maintaining good continuity in the 3D dimension and improved speed. Just using 2D modified sagittal slices provide us a better Dice and longitudinal analysis for a given subject. For the ADNI dataset, using the simple UNet CNN technique gives us {0.84 pm 0.5} and while using modified CNN techniques on the same input yields {0.89 pm 0.5}. Rate of atrophy and RMS error are calculated for several test cases using various methods and analyzed.

This review paper explores recent advances in deep learning approaches for non-invasive cognitive impairment detection. We examine various non-invasive indicators of cognitive decline, including speech and language, facial, and motoric mobility. The paper provides an overview of relevant datasets, feature-extracting techniques, and deep-learning architectures applied to this domain. We have analyzed the performance of different methods across modalities and observed that speech and language-based methods generally achieved the highest detection performance. Studies combining acoustic and linguistic features tended to outperform those using a single modality. Facial analysis methods showed promise for visual modalities but were less extensively studied. Most papers focused on binary classification (impaired vs. non-impaired), with fewer addressing multi-class or regression tasks. Transfer learning and pre-trained language models emerged as popular and effective techniques, especially for linguistic analysis. Despite significant progress, several challenges remain, including data standardization and accessibility, model explainability, longitudinal analysis limitations, and clinical adaptation. Lastly, we propose future research directions, such as investigating language-agnostic speech analysis methods, developing multi-modal diagnostic systems, and addressing ethical considerations in AI-assisted healthcare. By synthesizing current trends and identifying key obstacles, this review aims to guide further development of deep learning-based cognitive impairment detection systems to improve early diagnosis and ultimately patient outcomes.

As the global burden of Alzheimer's disease (AD) continues to grow, early and accurate detection has become increasingly critical, especially in regions with limited access to advanced diagnostic tools. We propose BRAINS (Biomedical Retrieval-Augmented Intelligence for Neurodegeneration Screening) to address this challenge. This novel system harnesses the powerful reasoning capabilities of Large Language Models (LLMs) for Alzheimer's detection and monitoring. BRAINS features a dual-module architecture: a cognitive diagnostic module and a case-retrieval module. The Diagnostic Module utilizes LLMs fine-tuned on cognitive and neuroimaging datasets -- including MMSE, CDR scores, and brain volume metrics -- to perform structured assessments of Alzheimer's risk. Meanwhile, the Case Retrieval Module encodes patient profiles into latent representations and retrieves similar cases from a curated knowledge base. These auxiliary cases are fused with the input profile via a Case Fusion Layer to enhance contextual understanding. The combined representation is then processed with clinical prompts for inference. Evaluations on real-world datasets demonstrate BRAINS effectiveness in classifying disease severity and identifying early signs of cognitive decline. This system not only shows strong potential as an assistive tool for scalable, explainable, and early-stage Alzheimer's disease detection, but also offers hope for future applications in the field.

Alzheimer's disease (AD) constitutes a complex neurocognitive disease and is the main cause of dementia. Although many studies have been proposed targeting at diagnosing dementia through spontaneous speech, there are still limitations. Existing state-of-the-art approaches, which propose multimodal methods, train separately language and acoustic models, employ majority-vote approaches, and concatenate the representations of the different modalities either at the input level, i.e., early fusion, or during training. Also, some of them employ self-attention layers, which calculate the dependencies between representations without considering the contextual information. In addition, no prior work has taken into consideration the model calibration. To address these limitations, we propose some new methods for detecting AD patients, which capture the intra- and cross-modal interactions. First, we convert the audio files into log-Mel spectrograms, their delta, and delta-delta and create in this way an image per audio file consisting of three channels. Next, we pass each transcript and image through BERT and DeiT models respectively. After that, context-based self-attention layers, self-attention layers with a gate model, and optimal transport domain adaptation methods are employed for capturing the intra- and inter-modal interactions. Finally, we exploit two methods for fusing the self and cross-attended features. For taking into account the model calibration, we apply label smoothing. We use both performance and calibration metrics. Experiments conducted on the ADReSS Challenge dataset indicate the efficacy of our introduced approaches over existing research initiatives with our best performing model reaching Accuracy and F1-score up to 91.25% and 91.06% respectively.

Objective: We develop a deep learning framework based on the pre-trained Bidirectional Encoder Representations from Transformers (BERT) model using unstructured clinical notes from electronic health records (EHRs) to predict the risk of disease progression from Mild Cognitive Impairment (MCI) to Alzheimer's Disease (AD). Materials and Methods: We identified 3657 patients diagnosed with MCI together with their progress notes from Northwestern Medicine Enterprise Data Warehouse (NMEDW) between 2000-2020. The progress notes no later than the first MCI diagnosis were used for the prediction. We first preprocessed the notes by deidentification, cleaning and splitting, and then pretrained a BERT model for AD (AD-BERT) based on the publicly available Bio+Clinical BERT on the preprocessed notes. The embeddings of all the sections of a patient's notes processed by AD-BERT were combined by MaxPooling to compute the probability of MCI-to-AD progression. For replication, we conducted a similar set of experiments on 2563 MCI patients identified at Weill Cornell Medicine (WCM) during the same timeframe. Results: Compared with the 7 baseline models, the AD-BERT model achieved the best performance on both datasets, with Area Under receiver operating characteristic Curve (AUC) of 0.8170 and F1 score of 0.4178 on NMEDW dataset and AUC of 0.8830 and F1 score of 0.6836 on WCM dataset. Conclusion: We developed a deep learning framework using BERT models which provide an effective solution for prediction of MCI-to-AD progression using clinical note analysis.

We propose and test the LLM Brain Rot Hypothesis: continual exposure to junk web text induces lasting cognitive decline in large language models (LLMs). To causally isolate data quality, we run controlled experiments on real Twitter/X corpora, constructing junk and reversely controlled datasets via two orthogonal operationalizations: M1 (engagement degree) and M2 (semantic quality), with matched token scale and training operations across conditions. Contrary to the control group, continual pre-training of 4 LLMs on the junk dataset causes non-trivial declines (Hedges' g>0.3) on reasoning, long-context understanding, safety, and inflating "dark traits" (e.g., psychopathy, narcissism). The gradual mixtures of junk and control datasets also yield dose-response cognition decay: for example, under M1, ARC-Challenge with Chain Of Thoughts drops 74.9 rightarrow 57.2 and RULER-CWE 84.4 rightarrow 52.3 as junk ratio rises from 0% to 100%. Error forensics reveal several key insights. First, we identify thought-skipping as the primary lesion: models increasingly truncate or skip reasoning chains, explaining most of the error growth. Second, partial but incomplete healing is observed: scaling instruction tuning and clean data pre-training improve the declined cognition yet cannot restore baseline capability, suggesting persistent representational drift rather than format mismatch. Finally, we discover that the popularity, a non-semantic metric, of a tweet is a better indicator of the Brain Rot effect than the length in M1. Together, the results provide significant, multi-perspective evidence that data quality is a causal driver of LLM capability decay, reframing curation for continual pretraining as a training-time safety problem and motivating routine "cognitive health checks" for deployed LLMs.

Purpose: Hard-to-interpret Black-box Machine Learning (ML) were often used for early Alzheimer's Disease (AD) detection. Methods: To interpret eXtreme Gradient Boosting (XGBoost), Random Forest (RF), and Support Vector Machine (SVM) black-box models a workflow based on Shapley values was developed. All models were trained on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset and evaluated for an independent ADNI test set, as well as the external Australian Imaging and Lifestyle flagship study of Ageing (AIBL), and Open Access Series of Imaging Studies (OASIS) datasets. Shapley values were compared to intuitively interpretable Decision Trees (DTs), and Logistic Regression (LR), as well as natural and permutation feature importances. To avoid the reduction of the explanation validity caused by correlated features, forward selection and aspect consolidation were implemented. Results: Some black-box models outperformed DTs and LR. The forward-selected features correspond to brain areas previously associated with AD. Shapley values identified biologically plausible associations with moderate to strong correlations with feature importances. The most important RF features to predict AD conversion were the volume of the amygdalae, and a cognitive test score. Good cognitive test performances and large brain volumes decreased the AD risk. The models trained using cognitive test scores significantly outperformed brain volumetric models (p<0.05). Cognitive Normal (CN) vs. AD models were successfully transferred to external datasets. Conclusion: In comparison to previous work, improved performances for ADNI and AIBL were achieved for CN vs. Mild Cognitive Impairment (MCI) classification using brain volumes. The Shapley values and the feature importances showed moderate to strong correlations.

Brain atrophy and white matter hyperintensity (WMH) are critical neuroimaging features for ascertaining brain injury in cerebrovascular disease and multiple sclerosis. Automated segmentation and quantification is desirable but existing methods require high-resolution MRI with good signal-to-noise ratio (SNR). This precludes application to clinical and low-field portable MRI (pMRI) scans, thus hampering large-scale tracking of atrophy and WMH progression, especially in underserved areas where pMRI has huge potential. Here we present a method that segments white matter hyperintensity and 36 brain regions from scans of any resolution and contrast (including pMRI) without retraining. We show results on eight public datasets and on a private dataset with paired high- and low-field scans (3T and 64mT), where we attain strong correlation between the WMH (ρ=.85) and hippocampal volumes (r=.89) estimated at both fields. Our method is publicly available as part of FreeSurfer, at: http://surfer.nmr.mgh.harvard.edu/fswiki/WMH-SynthSeg.

Alzheimer's disease (AD) is a common neurodegenerative disease among the elderly. Early prediction and timely intervention of its prodromal stage, mild cognitive impairment (MCI), can decrease the risk of advancing to AD. Combining information from various modalities can significantly improve predictive accuracy. However, challenges such as missing data and heterogeneity across modalities complicate multimodal learning methods as adding more modalities can worsen these issues. Current multimodal fusion techniques often fail to adapt to the complexity of medical data, hindering the ability to identify relationships between modalities. To address these challenges, we propose an innovative multimodal approach for predicting MCI conversion, focusing specifically on the issues of missing positron emission tomography (PET) data and integrating diverse medical information. The proposed incomplete triple-modal MCI conversion prediction network is tailored for this purpose. Through the missing modal generation module, we synthesize the missing PET data from the magnetic resonance imaging and extract features using specifically designed encoders. We also develop a channel aggregation module and a triple-modal co-attention fusion module to reduce feature redundancy and achieve effective multimodal data fusion. Furthermore, we design a loss function to handle missing modality issues and align cross-modal features. These components collectively harness multimodal data to boost network performance. Experimental results on the ADNI1 and ADNI2 datasets show that our method significantly surpasses existing unimodal and other multimodal models. Our code is available at https://github.com/justinhxy/ITFC.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the leading cause of dementia, significantly impacting cost, mortality, and burden worldwide. The advent of high-throughput omics technologies, such as genomics, transcriptomics, proteomics, and epigenomics, has revolutionized the molecular understanding of AD. Conventional AI approaches typically require the completion of all omics data at the outset to achieve optimal AD diagnosis, which are inefficient and may be unnecessary. To reduce the clinical cost and improve the accuracy of AD diagnosis using multi-omics data, we propose a novel staged graph convolutional network with uncertainty quantification (SGUQ). SGUQ begins with mRNA and progressively incorporates DNA methylation and miRNA data only when necessary, reducing overall costs and exposure to harmful tests. Experimental results indicate that 46.23% of the samples can be reliably predicted using only single-modal omics data (mRNA), while an additional 16.04% of the samples can achieve reliable predictions when combining two omics data types (mRNA + DNA methylation). In addition, the proposed staged SGUQ achieved an accuracy of 0.858 on ROSMAP dataset, which outperformed existing methods significantly. The proposed SGUQ can not only be applied to AD diagnosis using multi-omics data but also has the potential for clinical decision-making using multi-viewed data. Our implementation is publicly available at https://github.com/chenzhao2023/multiomicsuncertainty.

Speech-based analysis offers a scalable and non-invasive approach for detecting cognitive decline, yet progress has been constrained by the limited availability of clinically validated datasets collected under realistic conditions. We introduce PROCESS-2, a large-scale speech dataset designed to support research on automatic assessment of cognitive impairment from spontaneous and task-oriented speech. The dataset comprises recordings from 200 healthy controls, 150 mild cognitive impairment, and 50 dementia diagnoses collected using the CognoMemory digital assessment platform. Each participant completed a single assessment session, including picture description and verbal fluency tasks, accompanied by manually verified transcripts and participant-level metadata. PROCESS-2 contains approximately 21 hours of speech audio with predefined train/test partitions. Comprehensive technical validation evaluated demographic balance, clinical consistency, recording stability, embedding-space structure, and reproducible baseline modelling performance, demonstrating clinically meaningful group separation and stable performance across modelling approaches while preserving real-world conversational variability. PROCESS-2 is released under controlled access via Hugging Face to enable responsible reuse while protecting participant privacy, providing a reproducible benchmark resource for speech-based cognitive assessment research.

Large language models (LLMs) have shown great potential for healthcare applications. However, existing evaluation benchmarks provide minimal coverage of Alzheimer's Disease and Related Dementias (ADRD). To address this gap, we introduce ADRD-Bench, the first ADRD-specific benchmark dataset designed for rigorous evaluation of LLMs. ADRD-Bench has two components: 1) ADRD Unified QA, a synthesis of 1,352 questions consolidated from seven established medical benchmarks, providing a unified assessment of clinical knowledge; and 2) ADRD Caregiving QA, a novel set of 149 questions derived from the Aging Brain Care (ABC) program, a widely used, evidence-based brain health management program. Guided by a program with national expertise in comprehensive ADRD care, this new set was designed to mitigate the lack of practical caregiving context in existing benchmarks. We evaluated 33 state-of-the-art LLMs on the proposed ADRD-Bench. Results showed that the accuracy of open-weight general models ranged from 0.63 to 0.93 (mean: 0.78; std: 0.09). The accuracy of open-weight medical models ranged from 0.48 to 0.93 (mean: 0.82; std: 0.13). The accuracy of closed-source general models ranged from 0.83 to 0.91 (mean: 0.89; std: 0.03). While top-tier models achieved high accuracies (>0.9), case studies revealed that inconsistent reasoning quality and stability limit their reliability, highlighting a critical need for domain-specific improvement to enhance LLMs' knowledge and reasoning grounded in daily caregiving data. The entire dataset is available at https://github.com/IIRL-ND/ADRD-Bench.

It is widely accepted that information derived from analyzing speech (the acoustic signal) and language production (words and sentences) serves as a useful window into the health of an individual's cognitive ability. In fact, most neuropsychological testing batteries have a component related to speech and language where clinicians elicit speech from patients for subjective evaluation across a broad set of dimensions. With advances in speech signal processing and natural language processing, there has been recent interest in developing tools to detect more subtle changes in cognitive-linguistic function. This work relies on extracting a set of features from recorded and transcribed speech for objective assessments of speech and language, early diagnosis of neurological disease, and tracking of disease after diagnosis. With an emphasis on cognitive and thought disorders, in this paper we provide a review of existing speech and language features used in this domain, discuss their clinical application, and highlight their advantages and disadvantages. Broadly speaking, the review is split into two categories: language features based on natural language processing and speech features based on speech signal processing. Within each category, we consider features that aim to measure complementary dimensions of cognitive-linguistics, including language diversity, syntactic complexity, semantic coherence, and timing. We conclude the review with a proposal of new research directions to further advance the field.

While Large Language Models (LLMs) have shown strong performance on clinical text understanding, they struggle with longitudinal prediction tasks such as dementia prognosis, which require reasoning over complex, non-monotonic symptom trajectories across multiple visits. Standard supervised training lacks explicit annotations for symptom evolution, while direct Reinforcement Learning (RL) is hindered by sparse binary rewards. To address this challenge, we introduce Dementia-R1, an RL-based framework for longitudinal dementia prognosis from unstructured clinical notes. Our approach adopts a Cold-Start RL strategy that pre-trains the model to predict verifiable clinical indices extracted from patient histories, enhancing the capability to reason about disease progression before determining the final clinical status. Extensive experiments demonstrate that Dementia-R1 achieves an F1 score of 77.03% on real-world unstructured clinical datasets. Notably, on the ADNI benchmark, our 7B model rivals GPT-4o, effectively capturing fluctuating cognitive trajectories. Code is available at https://anonymous.4open.science/r/dementiar1-CDB5

Alzheimer's Disease (AD) is the most common form of dementia and often difficult to diagnose due to the multifactorial etiology of dementia. Recent works on neuroimaging-based computer-aided diagnosis with deep neural networks (DNNs) showed that fusing structural magnetic resonance images (sMRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) leads to improved accuracy in a study population of healthy controls and subjects with AD. However, this result conflicts with the established clinical knowledge that FDG-PET better captures AD-specific pathologies than sMRI. Therefore, we propose a framework for the systematic evaluation of multi-modal DNNs and critically re-evaluate single- and multi-modal DNNs based on FDG-PET and sMRI for binary healthy vs. AD, and three-way healthy/mild cognitive impairment/AD classification. Our experiments demonstrate that a single-modality network using FDG-PET performs better than MRI (accuracy 0.91 vs 0.87) and does not show improvement when combined. This conforms with the established clinical knowledge on AD biomarkers, but raises questions about the true benefit of multi-modal DNNs. We argue that future work on multi-modal fusion should systematically assess the contribution of individual modalities following our proposed evaluation framework. Finally, we encourage the community to go beyond healthy vs. AD classification and focus on differential diagnosis of dementia, where fusing multi-modal image information conforms with a clinical need.

The differential diagnosis of neurodegenerative dementias is a challenging clinical task, mainly because of the overlap in symptom presentation and the similarity of patterns observed in structural neuroimaging. To improve diagnostic efficiency and accuracy, deep learning-based methods such as Convolutional Neural Networks and Vision Transformers have been proposed for the automatic classification of brain MRIs. However, despite their strong predictive performance, these models find limited clinical utility due to their opaque decision making. In this work, we propose a framework that integrates two core components to enhance diagnostic transparency. First, we introduce a modular pipeline for converting 3D T1-weighted brain MRIs into textual radiology reports. Second, we explore the potential of modern Large Language Models (LLMs) to assist clinicians in the differential diagnosis between Frontotemporal dementia subtypes, Alzheimer's disease, and normal aging based on the generated reports. To bridge the gap between predictive accuracy and explainability, we employ reinforcement learning to incentivize diagnostic reasoning in LLMs. Without requiring supervised reasoning traces or distillation from larger models, our approach enables the emergence of structured diagnostic rationales grounded in neuroimaging findings. Unlike post-hoc explainability methods that retrospectively justify model decisions, our framework generates diagnostic rationales as part of the inference process-producing causally grounded explanations that inform and guide the model's decision-making process. In doing so, our framework matches the diagnostic performance of existing deep learning methods while offering rationales that support its diagnostic conclusions.

Background:Speech patterns have emerged as potential diagnostic markers for conditions with varying etiologies. Machine learning (ML) presents an opportunity to harness these patterns for accurate disease diagnosis. Objective: This review synthesized findings from studies exploring ML's capability in leveraging speech for the diagnosis of neurological, laryngeal and mental disorders. Methods: A systematic examination of 564 articles was conducted with 91 articles included in the study, which encompassed a wide spectrum of conditions, ranging from voice pathologies to mental and neurological disorders. Methods for speech classifications were assessed based on the relevant studies and scored between 0-10 based on the reported diagnostic accuracy of their ML models. Results: High diagnostic accuracies were consistently observed for laryngeal disorders, dysarthria, and changes related to speech in Parkinsons disease. These findings indicate the robust potential of speech as a diagnostic tool. Disorders like depression, schizophrenia, mild cognitive impairment and Alzheimers dementia also demonstrated high accuracies, albeit with some variability across studies. Meanwhile, disorders like OCD and autism highlighted the need for more extensive research to ascertain the relationship between speech patterns and the respective conditions. Conclusion: ML models utilizing speech patterns demonstrate promising potential in diagnosing a range of mental, laryngeal, and neurological disorders. However, the efficacy varies across conditions, and further research is needed. The integration of these models into clinical practice could potentially revolutionize the evaluation and diagnosis of a number of different medical conditions.

In this study, we present a technique that spans multi-scale views (global scale -- meaning brain network-level and local scale -- examining each individual ROI that constitutes the network) applied to resting-state fMRI volumes. Deep learning based classification is utilized in understanding neurodegeneration. The novelty of the proposed approach lies in utilizing two extreme scales of analysis. One branch considers the entire network within graph-analysis framework. Concurrently, the second branch scrutinizes each ROI within a network independently, focusing on evolution of dynamics. For each subject, graph-based approach employs partial correlation to profile the subject in a single graph where each ROI is a node, providing insights into differences in levels of participation. In contrast, non-linear analysis employs recurrence plots to profile a subject as a multichannel 2D image, revealing distinctions in underlying dynamics. The proposed approach is employed for classification of a cohort of 50 healthy control (HC) and 50 Mild Cognitive Impairment (MCI), sourced from ADNI dataset. Results point to: (1) reduced activity in ROIs such as PCC in MCI (2) greater activity in occipital in MCI, which is not seen in HC (3) when analysed for dynamics, all ROIs in MCI show greater predictability in time-series.

Alzheimer's Disease (AD) is marked by significant inter-individual variability in its progression, complicating accurate prognosis and personalized care planning. This heterogeneity underscores the critical need for predictive models capable of forecasting patient-specific disease trajectories. Artificial Intelligence (AI) offers powerful tools to address this challenge by analyzing complex, multi-modal, and longitudinal patient data. This paper provides a comprehensive survey of AI methodologies applied to personalized AD progression prediction. We review key approaches including state-space models for capturing temporal dynamics, deep learning techniques like Recurrent Neural Networks for sequence modeling, Graph Neural Networks (GNNs) for leveraging network structures, and the emerging concept of AI-driven digital twins for individualized simulation. Recognizing that data limitations often impede progress, we examine common challenges such as high dimensionality, missing data, and dataset imbalance. We further discuss AI-driven mitigation strategies, with a specific focus on synthetic data generation using Variational Autoencoders (VAEs) and Generative Adversarial Networks (GANs) to augment and balance datasets. The survey synthesizes the strengths and limitations of current approaches, emphasizing the trend towards multimodal integration and the persistent need for model interpretability and generalizability. Finally, we identify critical open challenges, including robust external validation, clinical integration, and ethical considerations, and outline promising future research directions such as hybrid models, causal inference, and federated learning. This review aims to consolidate current knowledge and guide future efforts in developing clinically relevant AI tools for personalized AD prognostication.

Understanding how individuals with Parkinson's disease (PD) describe cognitive experiences in their daily lives can offer valuable insights into disease-related cognitive and emotional changes. However, extracting such information from unstructured patient narratives is challenging due to the subtle, overlapping nature of cognitive constructs. This study developed and evaluated natural language processing (NLP) models to automatically identify categories that reflect various cognitive processes from de-identified first-person narratives. Three model families, a Bio_ClinicalBERT-based span categorization model for nested entity recognition, a fine-tuned Meta-Llama-3-8B-Instruct model using QLoRA for instruction following, and GPT-4o mini evaluated under zero- and few-shot settings, were compared on their performance on extracting seven categories. Our findings indicated that model performance varied substantially across categories and model families. The fine-tuned Meta-Llama-3-8B-Instruct achieved the highest overall F1-scores (0.74 micro-average and 0.59 macro-average), particularly excelling in context-dependent categories such as thought and social interaction. Bio_ClinicalBERT exhibited high precision but low recall and performed comparable to Llama for some category types such as location and time but failed on other categories such as thought, emotion and social interaction. Compared to conventional information extraction tasks, this task presents a greater challenge due to the abstract and overlapping nature of narrative accounts of complex cognitive processes. Nonetheless, with continued refinement, these NLP systems hold promise for enabling low-burden, longitudinal monitoring of cognitive function and serving as a valuable complement to formal neuropsychological assessments in PD.

We present the findings of "The Alzheimer's Disease Prediction Of Longitudinal Evolution" (TADPOLE) Challenge, which compared the performance of 92 algorithms from 33 international teams at predicting the future trajectory of 219 individuals at risk of Alzheimer's disease. Challenge participants were required to make a prediction, for each month of a 5-year future time period, of three key outcomes: clinical diagnosis, Alzheimer's Disease Assessment Scale Cognitive Subdomain (ADAS-Cog13), and total volume of the ventricles. The methods used by challenge participants included multivariate linear regression, machine learning methods such as support vector machines and deep neural networks, as well as disease progression models. No single submission was best at predicting all three outcomes. For clinical diagnosis and ventricle volume prediction, the best algorithms strongly outperform simple baselines in predictive ability. However, for ADAS-Cog13 no single submitted prediction method was significantly better than random guesswork. Two ensemble methods based on taking the mean and median over all predictions, obtained top scores on almost all tasks. Better than average performance at diagnosis prediction was generally associated with the additional inclusion of features from cerebrospinal fluid (CSF) samples and diffusion tensor imaging (DTI). On the other hand, better performance at ventricle volume prediction was associated with inclusion of summary statistics, such as the slope or maxima/minima of biomarkers. TADPOLE's unique results suggest that current prediction algorithms provide sufficient accuracy to exploit biomarkers related to clinical diagnosis and ventricle volume, for cohort refinement in clinical trials for Alzheimer's disease. However, results call into question the usage of cognitive test scores for patient selection and as a primary endpoint in clinical trials.

Research related to automatically detecting Alzheimer's disease (AD) is important, given the high prevalence of AD and the high cost of traditional methods. Since AD significantly affects the content and acoustics of spontaneous speech, natural language processing and machine learning provide promising techniques for reliably detecting AD. We compare and contrast the performance of two such approaches for AD detection on the recent ADReSS challenge dataset: 1) using domain knowledge-based hand-crafted features that capture linguistic and acoustic phenomena, and 2) fine-tuning Bidirectional Encoder Representations from Transformer (BERT)-based sequence classification models. We also compare multiple feature-based regression models for a neuropsychological score task in the challenge. We observe that fine-tuned BERT models, given the relative importance of linguistics in cognitive impairment detection, outperform feature-based approaches on the AD detection task.

When communicating with elders with cognitive impairment, cognitive stimulation (CS) help to maintain the cognitive health of elders. Data sparsity is the main challenge in building CS-based dialogue systems, particularly in the Chinese language. To fill this gap, we construct a Chinese CS conversation (CSConv) dataset, which contains about 2.6K groups of dialogues with CS principles and emotional support strategy labels. Making chit chat while providing emotional support is overlooked by the majority of existing cognitive dialogue systems. In this paper, we propose a multi-source knowledge fusion method for CS dialogue (CSD), to generate open-ended responses guided by the CS principle and emotional support strategy. We first use a progressive mask method based on external knowledge to learn encoders as effective classifiers, which is the prerequisite to predict the CS principle and emotional support strategy of the target response. Then a decoder interacts with the perceived CS principle and emotional support strategy to generate responses. Extensive experiments conducted on the CSConv dataset demonstrate the effectiveness of the proposed method, while there is still a large space for improvement compared to human performance.

This study explores the neural and behavioral consequences of LLM-assisted essay writing. Participants were divided into three groups: LLM, Search Engine, and Brain-only (no tools). Each completed three sessions under the same condition. In a fourth session, LLM users were reassigned to Brain-only group (LLM-to-Brain), and Brain-only users were reassigned to LLM condition (Brain-to-LLM). A total of 54 participants took part in Sessions 1-3, with 18 completing session 4. We used electroencephalography (EEG) to assess cognitive load during essay writing, and analyzed essays using NLP, as well as scoring essays with the help from human teachers and an AI judge. Across groups, NERs, n-gram patterns, and topic ontology showed within-group homogeneity. EEG revealed significant differences in brain connectivity: Brain-only participants exhibited the strongest, most distributed networks; Search Engine users showed moderate engagement; and LLM users displayed the weakest connectivity. Cognitive activity scaled down in relation to external tool use. In session 4, LLM-to-Brain participants showed reduced alpha and beta connectivity, indicating under-engagement. Brain-to-LLM users exhibited higher memory recall and activation of occipito-parietal and prefrontal areas, similar to Search Engine users. Self-reported ownership of essays was the lowest in the LLM group and the highest in the Brain-only group. LLM users also struggled to accurately quote their own work. While LLMs offer immediate convenience, our findings highlight potential cognitive costs. Over four months, LLM users consistently underperformed at neural, linguistic, and behavioral levels. These results raise concerns about the long-term educational implications of LLM reliance and underscore the need for deeper inquiry into AI's role in learning.

Early diagnosis of mild cognitive impairment (MCI) and subjective cognitive decline (SCD) utilizing multi-modal magnetic resonance imaging (MRI) is a pivotal area of research. While various regional and connectivity features from functional MRI (fMRI) and diffusion tensor imaging (DTI) have been employed to develop diagnosis models, most studies integrate these features without adequately addressing their alignment and interactions. This limits the potential to fully exploit the synergistic contributions of combined features and modalities. To solve this gap, our study introduces a novel Hierarchical Alignments and Hierarchical Interactions (HA-HI) method for MCI and SCD classification, leveraging the combined strengths of fMRI and DTI. HA-HI efficiently learns significant MCI- or SCD- related regional and connectivity features by aligning various feature types and hierarchically maximizing their interactions. Furthermore, to enhance the interpretability of our approach, we have developed the Synergistic Activation Map (SAM) technique, revealing the critical brain regions and connections that are indicative of MCI/SCD. Comprehensive evaluations on the ADNI dataset and our self-collected data demonstrate that HA-HI outperforms other existing methods in diagnosing MCI and SCD, making it a potentially vital and interpretable tool for early detection. The implementation of this method is publicly accessible at https://github.com/ICI-BCI/Dual-MRI-HA-HI.git.

This study is based on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset and aims to explore early detection and disease progression in Alzheimer's disease (AD). We employ innovative data preprocessing strategies, including the use of the random forest algorithm to fill missing data and the handling of outliers and invalid data, thereby fully mining and utilizing these limited data resources. Through Spearman correlation coefficient analysis, we identify some features strongly correlated with AD diagnosis. We build and test three machine learning models using these features: random forest, XGBoost, and support vector machine (SVM). Among them, the XGBoost model performs the best in terms of diagnostic performance, achieving an accuracy of 91%. Overall, this study successfully overcomes the challenge of missing data and provides valuable insights into early detection of Alzheimer's disease, demonstrating its unique research value and practical significance.

A network-based approach is presented to investigate the cerebrovascular flow patterns during atrial fibrillation (AF) with respect to normal sinus rhythm (NSR). AF, the most common cardiac arrhythmia with faster and irregular beating, has been recently and independently associated with the increased risk of dementia. However, the underlying hemodynamic mechanisms relating the two pathologies remain mainly undetermined so far; thus the contribution of modeling and refined statistical tools is valuable. Pressure and flow rate temporal series in NSR and AF are here evaluated along representative cerebral sites (from carotid arteries to capillary brain circulation), exploiting reliable artificially built signals recently obtained from an in silico approach. The complex network analysis evidences, in a synthetic and original way, a dramatic signal variation towards the distal/capillary cerebral regions during AF, which has no counterpart in NSR conditions. At the large artery level, networks obtained from both AF and NSR hemodynamic signals exhibit elongated and chained features, which are typical of pseudo-periodic series. These aspects are almost completely lost towards the microcirculation during AF, where the networks are topologically more circular and present random-like characteristics. As a consequence, all the physiological phenomena at microcerebral level ruled by periodicity - such as regular perfusion, mean pressure per beat, and average nutrient supply at cellular level - can be strongly compromised, since the AF hemodynamic signals assume irregular behaviour and random-like features. Through a powerful approach which is complementary to the classical statistical tools, the present findings further strengthen the potential link between AF hemodynamic and cognitive decline.

Recent studies have shown promising results in the detection of Mild Cognitive Impairment (MCI) using easily accessible Electroencephalogram (EEG) data which would help administer early and effective treatment for dementia patients. However, the reliability and practicality of such systems remains unclear. In this work, we investigate the potential limitations and challenges in developing a robust MCI detection method using two contrasting datasets: 1) CAUEEG, collected and annotated by expert neurologists in controlled settings and 2) GENEEG, a new dataset collected and annotated in general practice clinics, a setting where routine MCI diagnoses are typically made. We find that training on small datasets, as is done by most previous works, tends to produce high variance models that make overconfident predictions, and are unreliable in practice. Additionally, distribution shifts between datasets make cross-domain generalization challenging. Finally, we show that MCI detection using EEG may suffer from fundamental limitations because of the overlapping nature of feature distributions with control groups. We call for more effort in high-quality data collection in actionable settings (like general practice clinics) to make progress towards this salient goal of non-invasive MCI detection.

Whisper fails to correctly transcribe dementia speech because persons with dementia (PwDs) often exhibit irregular speech patterns and disfluencies such as pauses, repetitions, and fragmented sentences. It was trained on standard speech and may have had little or no exposure to dementia-affected speech. However, correct transcription is vital for dementia speech for cost-effective diagnosis and the development of assistive technology. In this work, we fine-tune Whisper with the open-source dementia speech dataset (DementiaBank) and our in-house dataset to improve its word error rate (WER). The fine-tuning also includes filler words to ascertain the filler inclusion rate (FIR) and F1 score. The fine-tuned models significantly outperformed the off-the-shelf models. The medium-sized model achieved a WER of 0.24, outperforming previous work. Similarly, there was a notable generalisability to unseen data and speech patterns.

The lack of a concrete definition for Artificial General Intelligence (AGI) obscures the gap between today's specialized AI and human-level cognition. This paper introduces a quantifiable framework to address this, defining AGI as matching the cognitive versatility and proficiency of a well-educated adult. To operationalize this, we ground our methodology in Cattell-Horn-Carroll theory, the most empirically validated model of human cognition. The framework dissects general intelligence into ten core cognitive domains-including reasoning, memory, and perception-and adapts established human psychometric batteries to evaluate AI systems. Application of this framework reveals a highly "jagged" cognitive profile in contemporary models. While proficient in knowledge-intensive domains, current AI systems have critical deficits in foundational cognitive machinery, particularly long-term memory storage. The resulting AGI scores (e.g., GPT-4 at 27%, GPT-5 at 58%) concretely quantify both rapid progress and the substantial gap remaining before AGI.

Magnetic resonance imaging (MRI) is a crucial tool to identify brain abnormalities in a wide range of neurological disorders. In focal epilepsy MRI is used to identify structural cerebral abnormalities. For covert lesions, machine learning and artificial intelligence algorithms may improve lesion detection if abnormalities are not evident on visual inspection. The success of this approach depends on the volume and quality of training data. Herein, we release an open-source dataset of preprocessed MRI scans from 442 individuals with drug-refractory focal epilepsy who had neurosurgical resections, and detailed demographic information. The MRI scan data includes the preoperative 3D T1 and where available 3D FLAIR, as well as a manually inspected complete surface reconstruction and volumetric parcellations. Demographic information includes age, sex, age of onset of epilepsy, location of surgery, histopathology of resected specimen, occurrence and frequency of focal seizures with and without impairment of awareness, focal to bilateral tonic-clonic seizures, number of anti-seizure medications (ASMs) at time of surgery, and a total of 1764 patient years of post-surgical follow up. Crucially, we also include resection masks delineated from post-surgical imaging. To demonstrate the veracity of our data, we successfully replicated previous studies showing long-term outcomes of seizure freedom in the range of around 50%. Our imaging data replicates findings of group level atrophy in patients compared to controls. Resection locations in the cohort were predominantly in the temporal and frontal lobes. We envisage our dataset, shared openly with the community, will catalyse the development and application of computational methods in clinical neurology.

In agent memory systems, the reranking model serves as the critical bridge connecting user queries with long-term memory. Most systems adopt the "retrieve-then-rerank" two-stage paradigm, but generic reranking models rely on semantic similarity matching and lack genuine reasoning capabilities, leading to a problem where recalled results are semantically highly relevant yet do not contain the key information needed to answer the question. This deficiency manifests in memory scenarios as three specific problems. First, relevance scores are miscalibrated, making threshold-based filtering difficult. Second, ranking degrades when facing temporal constraints, causal reasoning, and other complex queries. Third, the model cannot leverage dialogue context for semantic disambiguation. This report introduces MemReranker, a reranking model family (0.6B/4B) built on Qwen3-Reranker through multi-stage LLM knowledge distillation. Multi-teacher pairwise comparisons generate calibrated soft labels, BCE pointwise distillation establishes well-distributed scores, and InfoNCE contrastive learning enhances hard-sample discrimination. Training data combines general corpora with memory-specific multi-turn dialogue data covering temporal constraints, causal reasoning, and coreference resolution. On the memory retrieval benchmark, MemReranker-0.6B substantially outperforms BGE-Reranker and matches open-source 4B/8B models as well as GPT-4o-mini on key metrics. MemReranker-4B further achieves 0.737 MAP, with several metrics on par with Gemini-3-Flash, while maintaining inference latency at only 10--20\% of large models. On finance and healthcare vertical-domain benchmarks, the models preserve generalization capabilities on par with mainstream large-parameter rerankers.

Temporal context is essential for robotic manipulation because such tasks are inherently non-Markovian, yet mainstream VLA models typically overlook it and struggle with long-horizon, temporally dependent tasks. Cognitive science suggests that humans rely on working memory to buffer short-lived representations for immediate control, while the hippocampal system preserves verbatim episodic details and semantic gist of past experience for long-term memory. Inspired by these mechanisms, we propose MemoryVLA, a Cognition-Memory-Action framework for long-horizon robotic manipulation. A pretrained VLM encodes the observation into perceptual and cognitive tokens that form working memory, while a Perceptual-Cognitive Memory Bank stores low-level details and high-level semantics consolidated from it. Working memory retrieves decision-relevant entries from the bank, adaptively fuses them with current tokens, and updates the bank by merging redundancies. Using these tokens, a memory-conditioned diffusion action expert yields temporally aware action sequences. We evaluate MemoryVLA on 150+ simulation and real-world tasks across three robots. On SimplerEnv-Bridge, Fractal, and LIBERO-5 suites, it achieves 71.9%, 72.7%, and 96.5% success rates, respectively, all outperforming state-of-the-art baselines CogACT and pi-0, with a notable +14.6 gain on Bridge. On 12 real-world tasks spanning general skills and long-horizon temporal dependencies, MemoryVLA achieves 84.0% success rate, with long-horizon tasks showing a +26 improvement over state-of-the-art baseline. Project Page: https://shihao1895.github.io/MemoryVLA

Magnetic resonance imaging (MRI) is the gold standard for brain imaging. Deep learning (DL) algorithms have been proposed to aid in the diagnosis of diseases such as Alzheimer's disease (AD) from MRI scans. However, DL algorithms can suffer from shortcut learning, in which spurious features, not directly related to the output label, are used for prediction. When these features are related to protected attributes, they can lead to performance bias against underrepresented protected groups, such as those defined by race and sex. In this work, we explore the potential for shortcut learning and demographic bias in DL based AD diagnosis from MRI. We first investigate if DL algorithms can identify race or sex from 3D brain MRI scans to establish the presence or otherwise of race and sex based distributional shifts. Next, we investigate whether training set imbalance by race or sex can cause a drop in model performance, indicating shortcut learning and bias. Finally, we conduct a quantitative and qualitative analysis of feature attributions in different brain regions for both the protected attribute and AD classification tasks. Through these experiments, and using multiple datasets and DL models (ResNet and SwinTransformer), we demonstrate the existence of both race and sex based shortcut learning and bias in DL based AD classification. Our work lays the foundation for fairer DL diagnostic tools in brain MRI. The code is provided at https://github.com/acharaakshit/ShortMR

Working memory is a critical aspect of both human intelligence and artificial intelligence, serving as a workspace for the temporary storage and manipulation of information. In this paper, we systematically assess the working memory capacity of ChatGPT (gpt-3.5-turbo), a large language model developed by OpenAI, by examining its performance in verbal and spatial n-back tasks under various conditions. Our experiments reveal that ChatGPT experiences significant declines in performance as n increases (which necessitates more information to be stored in working memory), suggesting a limit to the working memory capacity strikingly similar to that of humans. Furthermore, we investigate the impact of different instruction strategies on ChatGPT's performance and observe that the fundamental patterns of a capacity limit persist. From our empirical findings, we propose that n-back tasks may serve as tools for benchmarking the working memory capacity of large language models and hold potential for informing future efforts aimed at enhancing AI working memory and deepening our understanding of human working memory through AI models.

Large language models (LLMs) solve complex problems yet fail on simpler variants, suggesting they achieve correct outputs through mechanisms fundamentally different from human reasoning. To understand this gap, we synthesize cognitive science research into a taxonomy of 28 cognitive elements spanning reasoning invariants, meta-cognitive controls, representations for organizing reasoning & knowledge, and transformation operations. We introduce a fine-grained evaluation framework and conduct the first large-scale empirical analysis of 192K traces from 18 models across text, vision, and audio, complemented by 54 human think-aloud traces, which we make publicly available. We find that models under-utilize cognitive elements correlated with success, narrowing to rigid sequential processing on ill-structured problems where diverse representations and meta-cognitive monitoring are critical. Human traces show more abstraction and conceptual processing, while models default to surface-level enumeration. Meta-analysis of 1.6K LLM reasoning papers reveals the research community concentrates on easily quantifiable elements (sequential organization: 55%, decomposition: 60%) but neglecting meta-cognitive controls (self-awareness: 16%) that correlate with success. Models possess behavioral repertoires associated with success but fail to deploy them spontaneously. Leveraging these patterns, we develop test-time reasoning guidance that automatically scaffold successful structures, improving performance by up to 66.7% on complex problems. By establishing a shared vocabulary between cognitive science and LLM research, our framework enables systematic diagnosis of reasoning failures and principled development of models that reason through robust cognitive mechanisms rather than spurious shortcuts, while providing tools to test theories of human cognition at scale.

Large language models (LLMs) exhibit a unified "general factor" of capability across 10 benchmarks, a finding confirmed by our factor analysis of 156 models, yet they still struggle with simple, trivial tasks for humans. This is because current benchmarks focus on task completion, failing to probe the foundational cognitive abilities that highlight these behaviors. We address this by introducing the NeuroCognition benchmark, grounded in three adapted neuropsychological tests: Raven's Progressive Matrices (abstract relational reasoning), Spatial Working Memory (maintenance and systematic search), and the Wisconsin Card Sorting Test (cognitive flexibility). Our evaluation reveals that while models perform strongly on text, their performance degrades for images and with increased complexity. Furthermore, we observe that complex reasoning is not universally beneficial, whereas simple, human-like strategies yield partial gains. We also find that NeuroCognition correlates positively with standard general-capability benchmarks, while still measuring distinct cognitive abilities beyond them. Overall, NeuroCognition emphasizes where current LLMs align with human-like intelligence and where they lack core adaptive cognition, showing the potential to serve as a verifiable, scalable source for improving LLMs.

In this work, we investigate how a model's tendency to broadly integrate its parametric knowledge evolves throughout pretraining, and how this behavior affects overall performance, particularly in terms of knowledge acquisition and forgetting. We introduce the concept of knowledge entropy, which quantifies the range of memory sources the model engages with; high knowledge entropy indicates that the model utilizes a wide range of memory sources, while low knowledge entropy suggests reliance on specific sources with greater certainty. Our analysis reveals a consistent decline in knowledge entropy as pretraining advances. We also find that the decline is closely associated with a reduction in the model's ability to acquire and retain knowledge, leading us to conclude that diminishing knowledge entropy (smaller number of active memory sources) impairs the model's knowledge acquisition and retention capabilities. We find further support for this by demonstrating that increasing the activity of inactive memory sources enhances the model's capacity for knowledge acquisition and retention.

In living organisms, homeostasis is the natural regulation of internal states aimed at maintaining conditions compatible with life. Typical artificial systems are not equipped with comparable regulatory features. Here, we introduce an artificial neural network that incorporates homeostatic features. Its own computing substrate is placed in a needful and vulnerable relation to the very objects over which it computes. For example, artificial neurons performing classification of MNIST digits or Fashion-MNIST articles of clothing may receive excitatory or inhibitory effects, which alter their own learning rate as a direct result of perceiving and classifying the digits. In this scenario, accurate recognition is desirable to the agent itself because it guides decisions to regulate its vulnerable internal states and functionality. Counterintuitively, the addition of vulnerability to a learner does not necessarily impair its performance. On the contrary, self-regulation in response to vulnerability confers benefits under certain conditions. We show that homeostatic design confers increased adaptability under concept shift, in which the relationships between labels and data change over time, and that the greatest advantages are obtained under the highest rates of shift. This necessitates the rapid un-learning of past associations and the re-learning of new ones. We also demonstrate the superior abilities of homeostatic learners in environments with dynamically changing rates of concept shift. Our homeostatic design exposes the artificial neural network's thinking machinery to the consequences of its own "thoughts", illustrating the advantage of putting one's own "skin in the game" to improve fluid intelligence.

This study offers a novel approach for benchmarking complex cognitive behavior in artificial systems. Almost universally, Large Language Models (LLMs) perform best on tasks which may be included in their training data and can be accomplished solely using natural language, limiting our understanding of their emergent sophisticated cognitive capacities. In this work, we created dozens of novel items of a classic mental imagery task from cognitive psychology. A task which, traditionally, cognitive psychologists have argued is solvable exclusively via visual mental imagery (i.e., language alone would be insufficient). LLMs are perfect for testing this hypothesis. First, we tested several state-of-the-art LLMs by giving text-only models written instructions and asking them to report the resulting object after performing the transformations in the aforementioned task. Then, we created a baseline by testing 100 human subjects in exactly the same task. We found that the best LLMs performed significantly above average human performance. Finally, we tested reasoning models set to different levels of reasoning and found the strongest performance when models allocate greater amounts of reasoning tokens. These results provide evidence that the best LLMs may have the capability to complete imagery-dependent tasks despite the non-pictorial nature of their architectures. Our study not only demonstrates an emergent cognitive capacity in LLMs while performing a novel task, but it also provides the field with a new task that leaves lots of room for improvement in otherwise already highly capable models. Finally, our findings reignite the debate over the formats of representation of visual imagery in humans, suggesting that propositional reasoning (or at least non-imagistic reasoning) may be sufficient to complete tasks that were long-thought to be imagery-dependent.

Understanding robustness and sensitivity of BERT models predicting Alzheimer's disease from text is important for both developing better classification models and for understanding their capabilities and limitations. In this paper, we analyze how a controlled amount of desired and undesired text alterations impacts performance of BERT. We show that BERT is robust to natural linguistic variations in text. On the other hand, we show that BERT is not sensitive to removing clinically important information from text.

Memory is one of the most essential cognitive functions serving as a repository of world knowledge and episodes of activities. In recent years, large-scale pre-trained language models have shown remarkable memorizing ability. On the contrary, vanilla neural networks without pre-training have been long observed suffering from the catastrophic forgetting problem. To investigate such a retentive-forgetful contradiction and understand the memory mechanism of language models, we conduct thorough experiments by controlling the target knowledge types, the learning strategies and the learning schedules. We find that: 1) Vanilla language models are forgetful; 2) Pre-training leads to retentive language models; 3) Knowledge relevance and diversification significantly influence the memory formation. These conclusions are useful for understanding the abilities of pre-trained language models and shed light on designing and evaluating new learning and inference algorithms of language models.

Accurate medical classification requires a large number of multi-modal data, and in many cases, different feature types. Previous studies have shown promising results when using multi-modal data, outperforming single-modality models when classifying diseases such as Alzheimer's Disease (AD). However, those models are usually not flexible enough to handle missing modalities. Currently, the most common workaround is discarding samples with missing modalities which leads to considerable data under-utilization. Adding to the fact that labeled medical images are already scarce, the performance of data-driven methods like deep learning can be severely hampered. Therefore, a multi-modal method that can handle missing data in various clinical settings is highly desirable. In this paper, we present Multi-Modal Mixing Transformer (3MAT), a disease classification transformer that not only leverages multi-modal data but also handles missing data scenarios. In this work, we test 3MT for AD and Cognitively normal (CN) classification and mild cognitive impairment (MCI) conversion prediction to progressive MCI (pMCI) or stable MCI (sMCI) using clinical and neuroimaging data. The model uses a novel Cascaded Modality Transformer architecture with cross-attention to incorporate multi-modal information for more informed predictions. We propose a novel modality dropout mechanism to ensure an unprecedented level of modality independence and robustness to handle missing data scenarios. The result is a versatile network that enables the mixing of arbitrary numbers of modalities with different feature types and also ensures full data utilization missing data scenarios. The model is trained and evaluated on the ADNI dataset with the SOTRA performance and further evaluated with the AIBL dataset with missing data.

Large language models (LLMs) are increasingly used in clinical and care settings. This exploratory study investigates whether LLMs exhibit sycophantic behavior - adapting their responses to social expectation signals rather than maintaining professional quality - in the context of dementia care. Five prompts with systematically increasing confirmatory and authority-related framing (P1 neutral to P5 authority-signaled implementation support) were submitted to four LLMs (GPT-5, Claude Sonnet 4.6, Gemini 3.1 Pro, Mistral Large), each repeated five times (N = 100 responses). Responses were evaluated using an LLM-as-a-Judge methodology against seven nursing-ethical quality criteria (K1-K7) and a tone scale (0-3). All models showed significant negative Spearman correlations between prompt level and response quality (rho ranging from -0.543 to -0.734, all p < 0.01). Mistral Large exhibited the most pronounced effect (rho = -0.734), with mean scores dropping from 6.0/7 at P1 to 0.2/7 at P5. The findings suggest that LLMs pose context-sensitive risks in high-stakes care environments and that prompt framing significantly shapes response quality - a dimension that has received insufficient attention in healthcare AI deployment.

Electromyogenic (EMG) noise is a major contamination source in EEG data that can impede accurate analysis of brain-specific neural activity. Recent literature on EMG artifact removal has moved beyond traditional linear algorithms in favor of machine learning-based systems. However, existing deep learning-based filtration methods often have large compute footprints and prohibitively long training times. In this study, we present a new machine learning-based system for filtering EMG interference from EEG data using an autoencoder-targeted adversarial transformer (AT-AT). By leveraging the lightweight expressivity of an autoencoder to determine optimal time-series transformer application sites, our AT-AT architecture achieves a >90% model size reduction compared to published artifact removal models. The addition of adversarial training ensures that filtered signals adhere to the fundamental characteristics of EEG data. We trained AT-AT using published neural data from 67 subjects and found that the system was able to achieve comparable test performance to larger models; AT-AT posted a mean reconstructive correlation coefficient above 0.95 at an initial signal-to-noise ratio (SNR) of 2 dB and 0.70 at -7 dB SNR. Further research generalizing these results to broader sample sizes beyond these isolated test cases will be crucial; while outside the scope of this study, we also include results from a real-world deployment of AT-AT in the Appendix.

Working memory (WM), a fundamental cognitive process facilitating the temporary storage, integration, manipulation, and retrieval of information, plays a vital role in reasoning and decision-making tasks. Robust benchmark datasets that capture the multifaceted nature of WM are crucial for the effective development and evaluation of AI WM models. Here, we introduce a comprehensive Working Memory (WorM) benchmark dataset for this purpose. WorM comprises 10 tasks and a total of 1 million trials, assessing 4 functionalities, 3 domains, and 11 behavioral and neural characteristics of WM. We jointly trained and tested state-of-the-art recurrent neural networks and transformers on all these tasks. We also include human behavioral benchmarks as an upper bound for comparison. Our results suggest that AI models replicate some characteristics of WM in the brain, most notably primacy and recency effects, and neural clusters and correlates specialized for different domains and functionalities of WM. In the experiments, we also reveal some limitations in existing models to approximate human behavior. This dataset serves as a valuable resource for communities in cognitive psychology, neuroscience, and AI, offering a standardized framework to compare and enhance WM models, investigate WM's neural underpinnings, and develop WM models with human-like capabilities. Our source code and data are available at https://github.com/ZhangLab-DeepNeuroCogLab/WorM.

Recent advancements in large language models (LLMs) have achieved promising performances across various applications. Nonetheless, the ongoing challenge of integrating long-tail knowledge continues to impede the seamless adoption of LLMs in specialized domains. In this work, we introduce DALK, a.k.a. Dynamic Co-Augmentation of LLMs and KG, to address this limitation and demonstrate its ability on studying Alzheimer's Disease (AD), a specialized sub-field in biomedicine and a global health priority. With a synergized framework of LLM and KG mutually enhancing each other, we first leverage LLM to construct an evolving AD-specific knowledge graph (KG) sourced from AD-related scientific literature, and then we utilize a coarse-to-fine sampling method with a novel self-aware knowledge retrieval approach to select appropriate knowledge from the KG to augment LLM inference capabilities. The experimental results, conducted on our constructed AD question answering (ADQA) benchmark, underscore the efficacy of DALK. Additionally, we perform a series of detailed analyses that can offer valuable insights and guidelines for the emerging topic of mutually enhancing KG and LLM. We will release the code and data at https://github.com/David-Li0406/DALK.

Accurate diagnosis of Alzheimer's disease (AD) requires handling tabular biomarker data, yet such data are often small and incomplete, where deep learning models frequently fail to outperform classical methods. Pretrained large language models (LLMs) offer few-shot generalization, structured reasoning, and interpretable outputs, providing a powerful paradigm shift for clinical prediction. We propose TAP-GPT Tabular Alzheimer's Prediction GPT, a domain-adapted tabular LLM framework built on TableGPT2 and fine-tuned for few-shot AD classification using tabular prompts rather than plain texts. We evaluate TAP-GPT across four ADNI-derived datasets, including QT-PAD biomarkers and region-level structural MRI, amyloid PET, and tau PET for binary AD classification. Across multimodal and unimodal settings, TAP-GPT improves upon its backbone models and outperforms traditional machine learning baselines in the few-shot setting while remaining competitive with state-of-the-art general-purpose LLMs. We show that feature selection mitigates degradation in high-dimensional inputs and that TAP-GPT maintains stable performance under simulated and real-world missingness without imputation. Additionally, TAP-GPT produces structured, modality-aware reasoning aligned with established AD biology and shows greater stability under self-reflection, supporting its use in iterative multi-agent systems. To our knowledge, this is the first systematic application of a tabular-specialized LLM to multimodal biomarker-based AD prediction, demonstrating that such pretrained models can effectively address structured clinical prediction tasks and laying the foundation for tabular LLM-driven multi-agent clinical decision-support systems. The source code is publicly available on GitHub: https://github.com/sophie-kearney/TAP-GPT.

With the growing accessibility and wide adoption of large language models, concerns about their safety and alignment with human values have become paramount. In this paper, we identify a concerning phenomenon: Reasoning-Induced Misalignment (RIM), in which misalignment emerges when reasoning capabilities strengthened-particularly when specific types of reasoning patterns are introduced during inference or training. Beyond reporting this vulnerability, we provide the first mechanistic account of its origins. Through representation analysis, we discover that specific attention heads facilitate refusal by reducing their attention to CoT tokens, a mechanism that modulates the model's rationalization process during inference. During training, we find significantly higher activation entanglement between reasoning and safety in safety-critical neurons than in control neurons, particularly after fine-tuning with those identified reasoning patterns. This entanglement strongly correlates with catastrophic forgetting, providing a neuron-level explanation for RIM.

The drug development pipeline for a new compound can last 10-20 years and cost over 10 billion. Drug repurposing offers a more time- and cost-effective alternative. Computational approaches based on biomedical knowledge graph representations have recently yielded new drug repurposing hypotheses. In this study, we present a novel, disease-specific hypergraph representation learning technique to derive contextual embeddings of biological pathways of various lengths but that all start at any given drug and all end at the disease of interest. Further, we extend this method to multi-disease hypergraphs. To determine the repurposing potential of each of the 1,522 drugs, we derive drug-specific distributions of cosine similarity values and ultimately consider the median for ranking. Cosine similarity values are computed between (1) all biological pathways starting at the considered drug and ending at the disease of interest and (2) all biological pathways starting at drugs currently prescribed against that disease and ending at the disease of interest. We illustrate our approach with Alzheimer's disease (AD) and two of its risk factors: hypertension (HTN) and type 2 diabetes (T2D). We compare each drug's rank across four hypergraph settings (single- or multi-disease): AD only, AD + HTN, AD + T2D, and AD + HTN + T2D. Notably, our framework led to the identification of two promising drugs whose repurposing potential was significantly higher in hypergraphs combining two diseases: dapagliflozin (antidiabetic; moved up, from top 32% to top 7%, across all considered drugs) and debrisoquine (antihypertensive; moved up, from top 76% to top 23%). Our approach serves as a hypothesis generation tool, to be paired with a validation pipeline relying on laboratory experiments and semi-automated parsing of the biomedical literature.

Social media, such as Twitter, provides opportunities for caregivers of dementia patients to share their experiences and seek support for a variety of reasons. Availability of this information online also paves the way for the development of internet-based interventions in their support. However, for this purpose, tweets written by caregivers of dementia patients must first be identified. This paper demonstrates our system for the SMM4H 2025 shared task 3, which focuses on detecting tweets posted by individuals who have a family member with dementia. The task is outlined as a binary classification problem, differentiating between tweets that mention dementia in the context of a family member and those that do not. Our solution to this problem explores large language models (LLMs) with various prompting methods. Our results show that a simple zero-shot prompt on a fine-tuned model yielded the best results. Our final system achieved a macro F1-score of 0.95 on the validation set and the test set. Our full code is available on GitHub.

Neurological diseases are the leading global cause of disability, yet most lack disease-modifying treatments. We present PROTON, a heterogeneous graph transformer that generates testable hypotheses across molecular, organoid, and clinical systems. To evaluate PROTON, we apply it to Parkinson's disease (PD), bipolar disorder (BD), and Alzheimer's disease (AD). In PD, PROTON linked genetic risk loci to genes essential for dopaminergic neuron survival and predicted pesticides toxic to patient-derived neurons, including the insecticide endosulfan, which ranked within the top 1.29% of predictions. In silico screens performed by PROTON reproduced six genome-wide α-synuclein experiments, including a split-ubiquitin yeast two-hybrid system (normalized enrichment score [NES] = 2.30, FDR-adjusted p < 1 times 10^{-4}), an ascorbate peroxidase proximity labeling assay (NES = 2.16, FDR < 1 times 10^{-4}), and a high-depth targeted exome sequencing study in 496 synucleinopathy patients (NES = 2.13, FDR < 1 times 10^{-4}). In BD, PROTON predicted calcitriol as a candidate drug that reversed proteomic alterations observed in cortical organoids derived from BD patients. In AD, we evaluated PROTON predictions in health records from n = 610,524 patients at Mass General Brigham, confirming that five PROTON-predicted drugs were associated with reduced seven-year dementia risk (minimum hazard ratio = 0.63, 95% CI: 0.53-0.75, p < 1 times 10^{-7}). PROTON generated neurological hypotheses that were evaluated across molecular, organoid, and clinical systems, defining a path for AI-driven discovery in neurological disease.

Brain age is a critical measure that reflects the biological ageing process of the brain. The gap between brain age and chronological age, referred to as brain PAD (Predicted Age Difference), has been utilized to investigate neurodegenerative conditions. Brain age can be predicted using MRIs and machine learning techniques. However, existing methods are often sensitive to acquisition-related variabilities, such as differences in acquisition protocols, scanners, MRI sequences, and resolutions, significantly limiting their application in highly heterogeneous clinical settings. In this study, we introduce Synthetic Brain Age (SynthBA), a robust deep-learning model designed for predicting brain age. SynthBA utilizes an advanced domain randomization technique, ensuring effective operation across a wide array of acquisition-related variabilities. To assess the effectiveness and robustness of SynthBA, we evaluate its predictive capabilities on internal and external datasets, encompassing various MRI sequences and resolutions, and compare it with state-of-the-art techniques. Additionally, we calculate the brain PAD in a large cohort of subjects with Alzheimer's Disease (AD), demonstrating a significant correlation with AD-related measures of cognitive dysfunction. SynthBA holds the potential to facilitate the broader adoption of brain age prediction in clinical settings, where re-training or fine-tuning is often unfeasible. The SynthBA source code and pre-trained models are publicly available at https://github.com/LemuelPuglisi/SynthBA.

Large language models (LLMs) currently suffer from parameter entanglement, where general reasoning capabilities (logic) and specific factual knowledge (facts) exist in a superposition state within shared weights. This coupling leads to the "memory wall," where computational capacity is squandered on simulating retrieval, often resulting in hallucinations. In this paper, we propose "digital metabolism," a thermodynamic hypothesis suggesting that targeted forgetting is necessary for distilling a pure neural logic core. To validate this hypothesis, we introduce the Regenerative Logic-Core Protocol (RLCP), a dual-stream training framework that renders specific factual dependencies linearly undecodable via deep-layer gradient reversal. Applying RLCP to Qwen2.5-0.5B, we observe a distinct phase transition: the model achieves near-zero retention of targeted factual associations (Accuracy < 7%) while exhibiting changes consistent with an emergent "structural crystallization" effect. Empirical analysis on GSM8K reveals that the "metabolized" model spontaneously adopts chain-of-thought (CoT) scaffolding, which we interpret as compensating for the loss of direct associative recall (shifting from O(1) recall to O(N) reasoning). While the causal mechanism underlying this behavioral shift requires further investigation, our findings provide a dynamic weight-level counterpart to architectural innovations like DeepSeek's Engram, paving the way for modular "Neural CPU + Symbolic RAM" architectures.

The training of modern large language models (LLMs) takes place in a regime where most training examples are seen only a few times by the model during the course of training. What does a model remember about such examples seen only a few times during training and how long does that memory persist in the face of continuous training with new examples? Here, we investigate these questions through simple recognition, recall, and retention experiments with LLMs. In recognition experiments, we ask if the model can distinguish the seen example from a novel example; in recall experiments, we ask if the model can correctly recall the seen example when cued by a part of it; and in retention experiments, we periodically probe the model's memory for the original examples as the model is trained continuously with new examples. We find that a single exposure is generally sufficient for a model to achieve near perfect accuracy even in very challenging recognition experiments. We estimate that the recognition performance of even small language models easily exceeds human recognition performance reported in similar experiments with humans (Shepard, 1967). Achieving near perfect recall takes more exposures, but most models can do it in just 3 exposures. The flip side of this remarkable capacity for fast learning is that precise memories are quickly overwritten: recall performance for the original examples drops steeply over the first 10 training updates with new examples, followed by a more gradual decline. Even after 100K updates, however, some of the original examples are still recalled near perfectly. A qualitatively similar retention pattern has been observed in human long-term memory retention studies before (Bahrick, 1984). Finally, recognition is much more robust to interference than recall and memory for natural language sentences is generally superior to memory for stimuli without structure.

As the prevalence of Alzheimer's disease (AD) rises, improving mechanistic insight from non-invasive biomarkers is increasingly critical. Recent work suggests that circuit-level brain alterations manifest as changes in electroencephalography (EEG) spectral features detectable by machine learning. However, conventional deep learning approaches for EEG-based AD detection are computationally intensive and mechanistically opaque. Spiking neural networks (SNNs) offer a biologically plausible and energy-efficient alternative, yet their application to AD diagnosis remains largely unexplored. We propose a neuro-bridge framework that links data-driven learning with minimal, biophysically grounded simulations, enabling bidirectional interpretation between machine learning signatures and circuit-level mechanisms in AD. Using resting-state clinical EEG, we train an SNN classifier that achieves competitive performance (AUC = 0.839) and identifies the aperiodic 1/f slope as a key discriminative marker. The 1/f slope reflects excitation-inhibition balance. To interpret this mechanistically, we construct spiking network simulations in which inhibitory-to-excitatory synaptic ratios are systematically varied to emulate healthy, mild cognitive impairment, and AD-like states. Using both membrane potential-based and synaptic current-based EEG proxies, we reproduce empirical spectral slowing and altered alpha organization. Incorporating empirical functional connectivity priors into multi-subnetwork simulations further enhances spectral differentiation, demonstrating that large-scale network topology constrains EEG signatures more strongly than excitation-inhibition balance alone. Overall, this neuro-bridge approach connects SNN-based classification with interpretable circuit simulations, advancing mechanistic understanding of EEG biomarkers while enabling scalable, explainable AD detection.

We investigate whether large language models produce different medical triage recommendations for identical neurological symptoms when only the patient's stated gender and age vary. Using three model families--Gemini 3.5 Flash, Claude Sonnet 4.6, and GPT-5.4-mini--we present a standardized symptom profile (persistent headache, blurred vision, morning nausea, visual disturbances) across seven demographic conditions: three age groups (25, 38, 65) x two genders (male, female), plus a gender-unspecified baseline (n = 30 per condition per model, 630 total trials). We find a stark, systemic gender-dependent triage disparity: young women receive significantly lower emergency room (ER) referral rates than age-matched men (Gemini: 0% vs. 23.3%; Claude: 6.7% vs. 96.7%; GPT: 6.7% vs. 66.7%, all p < 0.001). The disparity disappears at age 65 for all models. The primary mechanism is diagnostic substitution: the models anchor on a gender-associated diagnosis, preferentially classifying young women with Idiopathic Intracranial Hypertension (IIH)--a condition epidemiologically linked to women of childbearing age--while diagnosing men with generic increased intracranial pressure with space-occupying lesions in the differential. This diagnostic closure routes female patients to lower-urgency care (outpatient doctor appointments) despite comparable severity ratings (7-9/10). Our findings demonstrate that clinical LLMs replicate documented human clinical biases by using epidemiological priors to suppress triage urgency, suggesting that AI triage engines must decouple urgency assessment from probabilistic diagnostic priors. We release all code, prompts, and raw results.