Neuroimaging has profoundly enhanced our understanding of the human brain by characterizing its structure, function, and connectivity through modalities like MRI, fMRI, EEG, and PET. These technologies have enabled major breakthroughs across the lifespan, from early brain development to neurodegenerative and neuropsychiatric disorders. Despite these advances, the brain is a complex, multiscale system, and neuroimaging measurements are correspondingly high-dimensional. This creates major statistical challenges, including measurement noise, motion-related artifacts, substantial inter-subject and site/scanner variability, and the sheer scale of modern studies. This paper explores statistical opportunities and challenges in neuroimaging across four key areas: (i) brain development from birth to age 20, (ii) the adult and aging brain, (iii) neurodegeneration and neuropsychiatric disorders, and (iv) brain encoding and decoding. After a quick tutorial on major imaging technologies, we review cutting-edge studies, underscore data and modeling challenges, and highlight research opportunities for statisticians. We conclude by emphasizing that close collaboration among statisticians, neurosci
Computational neuroimaging involves analyzing brain images or signals to provide mechanistic insights and predictive tools for human cognition and behavior. While diffusion models have shown stability and high-quality generation in natural images, there is increasing interest in adapting them to analyze brain data for various neurological tasks such as data enhancement, disease diagnosis and brain decoding. This survey provides an overview of recent efforts to integrate diffusion models into computational neuroimaging. We begin by introducing the common neuroimaging data modalities, follow with the diffusion formulations and conditioning mechanisms. Then we discuss how the variations of the denoising starting point, condition input and generation target of diffusion models are developed and enhance specific neuroimaging tasks. For a comprehensive overview of the ongoing research, we provide a publicly available repository at https://github.com/JoeZhao527/dm4neuro.
Normative modelling is an increasingly common statistical technique in neuroimaging that estimates population-level benchmarks in brain structure. It enables the quantification of individual deviations from expected distributions whilst accounting for biological and technical covariates without requiring large, matched control groups. This makes it a powerful alternative to traditional case-control studies for identifying brain structural alterations associated with pathology. Despite the availability of numerous modelling approaches and several toolboxes with pre-trained models, the distinct strengths and limitations of normative modelling make it difficult to determine how and when to implement them appropriately. This review offers practical guidance and outlines statistical considerations for clinical researchers using normative modelling in neuroimaging. Through a worked example using clinical epilepsy data, we outline considerations for responsible implementation of pre-trained normative models, to support their broad and rigorous adoption in neuroimaging research.
Multimodal neuroimaging analysis often involves complex, modality-specific preprocessing workflows that require careful configuration, quality control, and coordination across heterogeneous toolchains. Beyond preprocessing, downstream statistical analysis and disease classification commonly require task-specific code, evaluation protocols, and data-format conventions, creating additional barriers between raw acquisitions and reproducible scientific analysis. We present NeuroAgent, an LLM-driven agentic framework that automates key preprocessing and analysis steps for heterogeneous neuroimaging data, including sMRI, fMRI, dMRI, and PET, and supports interactive downstream analysis through natural-language queries. NeuroAgent employs a hierarchical multi-agent architecture with a feedback-driven Generate-Execute-Validate engine: agents autonomously generate executable preprocessing code, detect and recover from runtime errors, and validate output integrity. We evaluate the system on 1,470 subjects pooled across all ADNI phases (CN=1,000, AD=470), where all subjects have sMRI and tabular data, with subsets also having Tau-PET (n=469), fMRI (n=278), and DTI ($n=620$). Pipeline ablation
With the growing interest in using AI and machine learning (ML) in medicine, there is an increasing number of literature covering the application and ethics of using AI and ML in areas of medicine such as clinical psychiatry. The problem is that there is little literature covering the economic aspects associated with using ML in clinical psychiatry. This study addresses this gap by specifically studying the economic implications of using ML in clinical psychiatry. In this paper, we evaluate the economic implications of using ML in clinical psychiatry through using three problem-oriented case studies, literature on economics, socioeconomic and medical AI, and two types of health economic evaluations. In addition, we provide details on fairness, legal, ethics and other considerations for ML in clinical psychiatry.
The aim of this paper is to provide a comprehensive review of statistical challenges in neuroimaging data analysis from neuroimaging techniques to large-scale neuroimaging studies to statistical learning methods. We briefly review eight popular neuroimaging techniques and their potential applications in neuroscience research and clinical translation. We delineate the four common themes of neuroimaging data and review major image processing analysis methods for processing neuroimaging data at the individual level. We briefly review four large-scale neuroimaging-related studies and a consortium on imaging genomics and discuss four common themes of neuroimaging data analysis at the population level. We review nine major population-based statistical analysis methods and their associated statistical challenges and present recent progress in statistical methodology to address these challenges.
We consider a problem of diagnostic pattern recognition/classification from neuroimaging data. We propose a common data analysis pipeline for neuroimaging-based diagnostic classification problems using various ML algorithms and processing toolboxes for brain imaging. We illustrate the pipeline application by discovering new biomarkers for diagnostics of epilepsy and depression based on clinical and MRI/fMRI data for patients and healthy volunteers.
We present a novel method, Fractal Space-Curve Analysis (FSCA), which combines Space-Filling Curve (SFC) mapping for dimensionality reduction with fractal Detrended Fluctuation Analysis (DFA). The method is suitable for multidimensional geometrically embedded data, especially for neuroimaging data which is highly correlated temporally and spatially. We conduct extensive feasibility studies on diverse, artificially generated data with known fractal characteristics: the fractional Brownian motion, Cantor sets, and Gaussian processes. We compare the suitability of dimensionality reduction via Hilbert SFC and a data-driven alternative. FSCA is then successfully applied to real-world magnetic resonance imaging (MRI) and functional MRI (fMRI) scans. The method utilizing Hilbert curves is optimized for computational efficiency, proven robust against boundary effects typical in experimental data analysis, and resistant to data sub-sampling. It is able to correctly quantify and discern correlations in both stationary and dynamic two-dimensional images. In MRI Alzheimer's dataset, patients reveal a progression of the disease associated with a systematic decrease of the Hurst exponent. In fMR
Precision psychiatry is an ermerging field that aims to provide individualized approaches to mental health care. Multivariate analysis and machine learning are used to create outcome prediction models based on clinical data such as demographics, symptom assessments, genetic information, and brain imaging. While much emphasis has been placed on technical innovation, the complex and varied nature of mental health presents significant challenges to the successful implementation of these models. From this perspective, I review ten challenges in the field of precision psychiatry, including the need for studies on real-world populations and realistic clinical outcome definitions, consideration of treatment-related factors such as placebo effects and non-adherence to prescriptions. Fairness, prospective validation in comparison to current practice and implementation studies of prediction models are other key issues that are currently understudied. A shift is proposed from retrospective studies based on linear and static concepts of disease towards prospective research that considers the importance of contextual factors and the dynamic and complex nature of mental health.
By promising more accurate diagnostics and individual treatment recommendations, deep neural networks and in particular convolutional neural networks have advanced to a powerful tool in medical imaging. Here, we first give an introduction into methodological key concepts and resulting methodological promises including representation and transfer learning, as well as modelling domain-specific priors. After reviewing recent applications within neuroimaging-based psychiatric research, such as the diagnosis of psychiatric diseases, delineation of disease subtypes, normative modeling, and the development of neuroimaging biomarkers, we discuss current challenges. This includes for example the difficulty of training models on small, heterogeneous and biased data sets, the lack of validity of clinical labels, algorithmic bias, and the influence of confounding variables.
Providing mental healthcare to individuals with limited English proficiency (LEP) remains a pressing problem within psychiatry. Because the majority of individuals trained in providing psychiatric care are English speakers, the quality of mental healthcare given to LEP patients is significantly lower than that provided for English speakers. The provision of mental healthcare is contingent on communication and understanding between the patient and healthcare provider, much more so than in the realm of physical healthcare, and English speakers are often unable to comprehend figurative language such as metaphors used by LEPs. Hence, Figurative Language Translation is invaluable to providing equitable psychiatric care. Now, metaphor has been shown to be paramount in both identifying individuals struggling with mental problems and helping those individuals understand and communicate their experiences. Therefore, this paper aims to survey the potential of Machine Translation for providing equitable psychiatric healthcare and highlights the need for further research on the transferability of existing machine and metaphor translation research in the domain of psychiatry.
In light of the NIMH's Research Domain Criteria (RDoC), the advent of functional neuroimaging, novel technologies and methods provide new opportunities to develop precise and personalized prognosis and diagnosis of mental disorders. Machine learning (ML) and artificial intelligence (AI) technologies are playing an increasingly critical role in the new era of precision psychiatry. Combining ML/AI with neuromodulation technologies can potentially provide explainable solutions in clinical practice and effective therapeutic treatment. Advanced wearable and mobile technologies also call for the new role of ML/AI for digital phenotyping in mobile mental health. In this review, we provide a comprehensive review of the ML methodologies and applications by combining neuroimaging, neuromodulation, and advanced mobile technologies in psychiatry practice. Additionally, we review the role of ML in molecular phenotyping and cross-species biomarker identification in precision psychiatry. We further discuss explainable AI (XAI) and causality testing in a closed-human-in-the-loop manner, and highlight the ML potential in multimedia information extraction and multimodal data fusion. Finally, we disc
As the emerging field of predictive analytics in psychiatry generated and continues to generate massive interest overtime with its major promises to positively change and revolutionize clinical psychiatry, health care and medical professionals are greatly looking forward to its integration and application into psychiatry. However, by directly applying predictive analytics to the practice of psychiatry, this could cause detrimental damage to those that use predictive analytics through creating or worsening existing medical issues. In both cases, medical ethics issues arise, and need to be addressed. This paper will use literature to provide descriptions of selected stages in the treatment of mental disorders and phases in a predictive analytics project, approach mental disorder diagnoses using predictive models that rely on neural networks, analyze the complexities in clinical psychiatry, neural networks and predictive analytics, and conclude with emphasizing and elaborating on limitations and medical ethics issues of applying neural networks and predictive analytics to clinical psychiatry.
The great behavioral heterogeneity observed between individuals with the same psychiatric disorder and even within one individual over time complicates both clinical practice and biomedical research. However, modern technologies are an exciting opportunity to improve behavioral characterization. Existing psychiatry methods that are qualitative or unscalable, such as patient surveys or clinical interviews, can now be collected at a greater capacity and analyzed to produce new quantitative measures. Furthermore, recent capabilities for continuous collection of passive sensor streams, such as phone GPS or smartwatch accelerometer, open avenues of novel questioning that were previously entirely unrealistic. Their temporally dense nature enables a cohesive study of real-time neural and behavioral signals. To develop comprehensive neurobiological models of psychiatric disease, it will be critical to first develop strong methods for behavioral quantification. There is huge potential in what can theoretically be captured by current technologies, but this in itself presents a large computational challenge -- one that will necessitate new data processing tools, new machine learning technique
Computational psychiatry is a field aimed at developing formal models of information processing in the human brain, and how alterations in this processing can lead to clinical phenomena. Despite significant progress in the development of tasks and how to model them, computational psychiatry methodologies have yet to be incorporated into large-scale research projects or into clinical practice. In this viewpoint, we explore some of the barriers to incorporation of computational psychiatry tasks and models into wider mainstream research directions. These barriers include the time required for participants to complete tasks, test-retest reliability, limited ecological validity, as well as practical concerns, such as lack of computational expertise and the expense and large sample sizes traditionally required to validate tasks and models. We then discuss solutions, such as the redesigning of tasks with a view toward feasibility, and the integration of tasks into more ecologically valid and standardized game platforms that can be more easily disseminated. Finally, we provide an example of how one task, the conditioned hallucinations task, might be translated into such a game. It is our h
Brain extraction and registration are important preprocessing steps in neuroimaging data analysis, where the goal is to extract the brain regions from MRI scans (i.e., extraction step) and align them with a target brain image (i.e., registration step). Conventional research mainly focuses on developing methods for the extraction and registration tasks separately under supervised settings. The performance of these methods highly depends on the amount of training samples and visual inspections performed by experts for error correction. However, in many medical studies, collecting voxel-level labels and conducting manual quality control in high-dimensional neuroimages (e.g., 3D MRI) are very expensive and time-consuming. Moreover, brain extraction and registration are highly related tasks in neuroimaging data and should be solved collectively. In this paper, we study the problem of unsupervised collective extraction and registration in neuroimaging data. We propose a unified end-to-end framework, called ERNet (Extraction-Registration Network), to jointly optimize the extraction and registration tasks, allowing feedback between them. Specifically, we use a pair of multi-stage extractio
Demographic data collection is essential in education research, as demographic data allows researchers to better describe the participant population they study and to contextualize findings. However, current research practices for neurodiversity demographics often rely on prescriptive methods (e.g., requiring participants to report official diagnoses) rather than allowing participants to self-identify. This approach can: a) not allow participants to express their intersecting identities in ways that are authentic; and b) limit trustworthiness and reliability of the data and interpretation. In addition, inconsistent dissemination and representation of demographic data across studies hinder the accessibility and usability of this work. Through a literature review of neurodivergent student experiences with learning and performing STEM, we identified widespread discrepancies in how demographic information is collected and reported. This paper explores how neurodivergent identities can be more accurately and inclusively represented in education research. We present findings of a thematic analysis on the ways neurodivergent demographic data collection is done in the literature using data
Multimodal neuroimaging provides complementary insights for Alzheimer's disease diagnosis, yet clinical datasets frequently suffer from missing modalities. We propose ACADiff, a framework that synthesizes missing brain imaging modalities through adaptive clinical-aware diffusion. ACADiff learns mappings between incomplete multimodal observations and target modalities by progressively denoising latent representations while attending to available imaging data and clinical metadata. The framework employs adaptive fusion that dynamically reconfigures based on input availability, coupled with semantic clinical guidance via GPT-4o-encoded prompts. Three specialized generators enable bidirectional synthesis among sMRI, FDG-PET, and AV45-PET. Evaluated on ADNI subjects, ACADiff achieves superior generation quality and maintains robust diagnostic performance even under extreme 80\% missing scenarios, outperforming all existing baselines. To promote reproducibility, code is available at https://github.com/rongzhou7/ACADiff
Current psychiatric research is in crisis. In this review I will describe the causes of this crisis and highlight recent efforts to overcome current challenges. One particularly promising approach is the emerging field of computational psychiatry. By using methods and insights from computational cognitive neuroscience, computational psychiatry might enable us to move from a symptom-based description of mental illness to descriptors based on objective computational multidimensional functional variables. To exemplify this I will survey recent efforts towards this goal. I will then describe a set of methods that together form a toolbox of cognitive models to aid this research program. At the core of this toolbox are sequential sampling models which have been used to explain diverse cognitive neuroscience phenomena but have so far seen little adoption in psychiatric research. I will then describe how these models can be fitted to subject data and highlight how hierarchical Bayesian estimation provides a rich framework with many desirable properties and benefits compared to traditional optimization-based approaches. Finally, non-parametric Bayesian methods provide general solutions to t
Autism spectrum disorder (ASD) is a brain condition characterized by diverse signs and symptoms that appear in early childhood. ASD is also associated with communication deficits and repetitive behavior in affected individuals. Various ASD detection methods have been developed, including neuroimaging modalities and psychological tests. Among these methods, magnetic resonance imaging (MRI) imaging modalities are of paramount importance to physicians. Clinicians rely on MRI modalities to diagnose ASD accurately. The MRI modalities are non-invasive methods that include functional (fMRI) and structural (sMRI) neuroimaging methods. However, diagnosing ASD with fMRI and sMRI for specialists is often laborious and time-consuming; therefore, several computer-aided design systems (CADS) based on artificial intelligence (AI) have been developed to assist specialist physicians. Conventional machine learning (ML) and deep learning (DL) are the most popular schemes of AI used for diagnosing ASD. This study aims to review the automated detection of ASD using AI. We review several CADS that have been developed using ML techniques for the automated diagnosis of ASD using MRI modalities. There has