LLM4SBR: A Lightweight and Effective Framework for Integrating Large Language Models in Session-based Recommendation

Traditional session-based recommendation (SBR) utilizes session behavior sequences from anonymous users for recommendation. Although this strategy is highly efficient, it sacrifices the inherent semantic information of the items, making it difficult for the model to understand the true intent of the session and resulting in a lack of interpretability in the recommended results. Recently, large language models (LLMs) have flourished across various domains, offering a glimpse of hope in addressing the aforementioned challenges. Inspired by the impact of LLMs, research exploring the integration of LLMs with the Recommender system (RS) has surged like mushrooms after rain. However, constrained by high time and space costs, as well as the brief and anonymous nature of session data, the first LLM recommendation framework suitable for industrial deployment has yet to emerge in the field of SBR. To address the aforementioned challenges, we have proposed the LLM Integration Framework for SBR (LLM4SBR). Serving as a lightweight and plug-and-play framework, LLM4SBR adopts a two-step strategy. Firstly, we transform session data into a bimodal form of text and behavior. In the first step, leveraging the inferential capabilities of LLMs, we conduct inference on session text data from different perspectives and design the component for auxiliary enhancement. In the second step, the SBR model is trained on behavior data, aligning and averaging two modal session representations from different perspectives. Finally, we fuse session representations from different perspectives and modalities as the ultimate session representation for recommendation. We conducted experiments on two real-world datasets, and the results demonstrate that LLM4SBR significantly improves the performance of traditional SBR models and is highly lightweight and efficient, making it suitable for industrial deployment.

Dimensional Neuroimaging Endophenotypes: Neurobiological Representations of Disease Heterogeneity Through Machine Learning

Machine learning has been increasingly used to obtain individualized neuroimaging signatures for disease diagnosis, prognosis, and response to treatment in neuropsychiatric and neurodegenerative disorders. Therefore, it has contributed to a better understanding of disease heterogeneity by identifying disease subtypes that present significant differences in various brain phenotypic measures. In this review, we first present a systematic literature overview of studies using machine learning and multimodal MRI to unravel disease heterogeneity in various neuropsychiatric and neurodegenerative disorders, including Alzheimer disease, schizophrenia, major depressive disorder, autism spectrum disorder, multiple sclerosis, as well as their potential in transdiagnostic settings. Subsequently, we summarize relevant machine learning methodologies and discuss an emerging paradigm which we call dimensional neuroimaging endophenotype (DNE). DNE dissects the neurobiological heterogeneity of neuropsychiatric and neurodegenerative disorders into a low dimensional yet informative, quantitative brain phenotypic representation, serving as a robust intermediate phenotype (i.e., endophenotype) largely reflecting underlying genetics and etiology. Finally, we discuss the potential clinical implications of the current findings and envision future research avenues.

Gene-SGAN: a method for discovering disease subtypes with imaging and genetic signatures via multi-view weakly-supervised deep clustering

Disease heterogeneity has been a critical challenge for precision diagnosis and treatment, especially in neurologic and neuropsychiatric diseases. Many diseases can display multiple distinct brain phenotypes across individuals, potentially reflecting disease subtypes that can be captured using MRI and machine learning methods. However, biological interpretability and treatment relevance are limited if the derived subtypes are not associated with genetic drivers or susceptibility factors. Herein, we describe Gene-SGAN - a multi-view, weakly-supervised deep clustering method - which dissects disease heterogeneity by jointly considering phenotypic and genetic data, thereby conferring genetic correlations to the disease subtypes and associated endophenotypic signatures. We first validate the generalizability, interpretability, and robustness of Gene-SGAN in semi-synthetic experiments. We then demonstrate its application to real multi-site datasets from 28,858 individuals, deriving subtypes of Alzheimer's disease and brain endophenotypes associated with hypertension, from MRI and SNP data. Derived brain phenotypes displayed significant differences in neuroanatomical patterns, genetic determinants, biological and clinical biomarkers, indicating potentially distinct underlying neuropathologic processes, genetic drivers, and susceptibility factors. Overall, Gene-SGAN is broadly applicable to disease subtyping and endophenotype discovery, and is herein tested on disease-related, genetically-driven neuroimaging phenotypes.

Applications of Generative Adversarial Networks in Neuroimaging and Clinical Neuroscience

Generative adversarial networks (GANs) are one powerful type of deep learning models that have been successfully utilized in numerous fields. They belong to a broader family called generative methods, which generate new data with a probabilistic model by learning sample distribution from real examples. In the clinical context, GANs have shown enhanced capabilities in capturing spatially complex, nonlinear, and potentially subtle disease effects compared to traditional generative methods. This review appraises the existing literature on the applications of GANs in imaging studies of various neurological conditions, including Alzheimer's disease, brain tumors, brain aging, and multiple sclerosis. We provide an intuitive explanation of various GAN methods for each application and further discuss the main challenges, open questions, and promising future directions of leveraging GANs in neuroimaging. We aim to bridge the gap between advanced deep learning methods and neurology research by highlighting how GANs can be leveraged to support clinical decision making and contribute to a better understanding of the structural and functional patterns of brain diseases.

Surreal-GAN:Semi-Supervised Representation Learning via GAN for uncovering heterogeneous disease-related imaging patterns

A plethora of machine learning methods have been applied to imaging data, enabling the construction of clinically relevant imaging signatures of neurological and neuropsychiatric diseases. Oftentimes, such methods don't explicitly model the heterogeneity of disease effects, or approach it via nonlinear models that are not interpretable. Moreover, unsupervised methods may parse heterogeneity that is driven by nuisance confounding factors that affect brain structure or function, rather than heterogeneity relevant to a pathology of interest. On the other hand, semi-supervised clustering methods seek to derive a dichotomous subtype membership, ignoring the truth that disease heterogeneity spatially and temporally extends along a continuum. To address the aforementioned limitations, herein, we propose a novel method, termed Surreal-GAN (Semi-SUpeRvised ReprEsentAtion Learning via GAN). Using cross-sectional imaging data, Surreal-GAN dissects underlying disease-related heterogeneity under the principle of semi-supervised clustering (cluster mappings from normal control to patient), proposes a continuously dimensional representation, and infers the disease severity of patients at individual level along each dimension. The model first learns a transformation function from normal control (CN) domain to the patient (PT) domain with latent variables controlling transformation directions. An inverse mapping function together with regularization on function continuity, pattern orthogonality and monotonicity was also imposed to make sure that the transformation function captures necessarily meaningful imaging patterns with clinical significance. We first validated the model through extensive semi-synthetic experiments, and then demonstrate its potential in capturing biologically plausible imaging patterns in Alzheimer's disease (AD).

Subtyping brain diseases from imaging data

The imaging community has increasingly adopted machine learning (ML) methods to provide individualized imaging signatures related to disease diagnosis, prognosis, and response to treatment. Clinical neuroscience and cancer imaging have been two areas in which ML has offered particular promise. However, many neurologic and neuropsychiatric diseases, as well as cancer, are often heterogeneous in terms of their clinical manifestations, neuroanatomical patterns or genetic underpinnings. Therefore, in such cases, seeking a single disease signature might be ineffectual in delivering individualized precision diagnostics. The current chapter focuses on ML methods, especially semi-supervised clustering, that seek disease subtypes using imaging data. Work from Alzheimer Disease and its prodromal stages, psychosis, depression, autism, and brain cancer are discussed. Our goal is to provide the readers with a broad overview in terms of methodology and clinical applications.

Multidimensional representations in late-life depression: convergence in neuroimaging, cognition, clinical symptomatology and genetics

Late-life depression (LLD) is characterized by considerable heterogeneity in clinical manifestation. Unraveling such heterogeneity would aid in elucidating etiological mechanisms and pave the road to precision and individualized medicine. We sought to delineate, cross-sectionally and longitudinally, disease-related heterogeneity in LLD linked to neuroanatomy, cognitive functioning, clinical symptomatology, and genetic profiles. Multimodal data from a multicentre sample (N=996) were analyzed. A semi-supervised clustering method (HYDRA) was applied to regional grey matter (GM) brain volumes to derive dimensional representations. Two dimensions were identified, which accounted for the LLD-related heterogeneity in voxel-wise GM maps, white matter (WM) fractional anisotropy (FA), neurocognitive functioning, clinical phenotype, and genetics. Dimension one (Dim1) demonstrated relatively preserved brain anatomy without WM disruptions relative to healthy controls. In contrast, dimension two (Dim2) showed widespread brain atrophy and WM integrity disruptions, along with cognitive impairment and higher depression severity. Moreover, one de novo independent genetic variant (rs13120336) was significantly associated with Dim 1 but not with Dim 2. Notably, the two dimensions demonstrated significant SNP-based heritability of 18-27% within the general population (N=12,518 in UKBB). Lastly, in a subset of individuals having longitudinal measurements, Dim2 demonstrated a more rapid longitudinal decrease in GM and brain age, and was more likely to progress to Alzheimers disease, compared to Dim1 (N=1,413 participants and 7,225 scans from ADNI, BLSA, and BIOCARD datasets).

Disentangling brain heterogeneity via semi-supervised deep-learning and MRI: dimensional representations of Alzheimer's Disease

Heterogeneity of brain diseases is a challenge for precision diagnosis/prognosis. We describe and validate Smile-GAN (SeMI-supervised cLustEring-Generative Adversarial Network), a novel semi-supervised deep-clustering method, which dissects neuroanatomical heterogeneity, enabling identification of disease subtypes via their imaging signatures relative to controls. When applied to MRIs (2 studies; 2,832 participants; 8,146 scans) including cognitively normal individuals and those with cognitive impairment and dementia, Smile-GAN identified 4 neurodegenerative patterns/axes: P1, normal anatomy and highest cognitive performance; P2, mild/diffuse atrophy and more prominent executive dysfunction; P3, focal medial temporal atrophy and relatively greater memory impairment; P4, advanced neurodegeneration. Further application to longitudinal data revealed two distinct progression pathways: P1$\rightarrow$P2$\rightarrow$P4 and P1$\rightarrow$P3$\rightarrow$P4. Baseline expression of these patterns predicted the pathway and rate of future neurodegeneration. Pattern expression offered better yet complementary performance in predicting clinical progression, compared to amyloid/tau. These deep-learning derived biomarkers offer promise for precision diagnostics and targeted clinical trial recruitment.

MAGIC: Multi-scale Heterogeneity Analysis and Clustering for Brain Diseases

There is a growing amount of clinical, anatomical and functional evidence for the heterogeneous presentation of neuropsychiatric and neurodegenerative diseases such as schizophrenia and Alzheimers Disease (AD). Elucidating distinct subtypes of diseases allows a better understanding of neuropathogenesis and enables the possibility of developing targeted treatment programs. Recent semi-supervised clustering techniques have provided a data-driven way to understand disease heterogeneity. However, existing methods do not take into account that subtypes of the disease might present themselves at different spatial scales across the brain. Here, we introduce a novel method, MAGIC, to uncover disease heterogeneity by leveraging multi-scale clustering. We first extract multi-scale patterns of structural covariance (PSCs) followed by a semi-supervised clustering with double cyclic block-wise optimization across different scales of PSCs. We validate MAGIC using simulated heterogeneous neuroanatomical data and demonstrate its clinical potential by exploring the heterogeneity of AD using T1 MRI scans of 228 cognitively normal (CN) and 191 patients. Our results indicate two main subtypes of AD with distinct atrophy patterns that consist of both fine-scale atrophy in the hippocampus as well as large-scale atrophy in cortical regions. The evidence for the heterogeneity is further corroborated by the clinical evaluation of two subtypes, which indicates that there is a subpopulation of AD patients that tend to be younger and decline faster in cognitive performance relative to the other subpopulation, which tends to be older and maintains a relatively steady decline in cognitive abilities.

Smile-GANs: Semi-supervised clustering via GANs for dissecting brain disease heterogeneity from medical images

Machine learning methods applied to complex biomedical data has enabled the construction of disease signatures of diagnostic/prognostic value. However, less attention has been given to understanding disease heterogeneity. Semi-supervised clustering methods can address this problem by estimating multiple transformations from a (e.g. healthy) control (CN) group to a patient (PT) group, seeking to capture the heterogeneity of underlying pathlogic processes. Herein, we propose a novel method, Smile-GANs (SeMi-supervIsed cLustEring via GANs), for semi-supervised clustering, and apply it to brain MRI scans. Smile-GANs first learns multiple distinct mappings by generating PT from CN, with each mapping characterizing one relatively distinct pathological pattern. Moreover, a clustering model is trained interactively with mapping functions to assign PT into corresponding subtype memberships. Using relaxed assumptions on PT/CN data distribution and imposing mapping non-linearity, Smile-GANs captures heterogeneous differences in distribution between the CN and PT domains. We first validate Smile-GANs using simulated data, subsequently on real data, by demonstrating its potential in characterizing heterogeneity in Alzheimer's Disease (AD) and its prodromal phases. The model was first trained using baseline MRIs from the ADNI2 database and then applied to longitudinal data from ADNI1 and BLSA. Four robust subtypes with distinct neuroanatomical patterns were discovered: 1) normal brain, 2) diffuse atrophy atypical of AD, 3) focal medial temporal lobe atrophy, 4) typical-AD. Further longitudinal analyses discover two distinct progressive pathways from prodromal to full AD: i) subtypes 1 - 2 - 4, and ii) subtypes 1 - 3 - 4. Although demonstrated on an important biomedical problem, Smile-GANs is general and can find application in many biomedical and other domains.