A discrete-continuous-time stochastic framework for attention-deficit/hyperactivity disorder-related symptom modeling and pharmacological intervention via methylphenidate

Attention Deficit Hyperactivity Disorder (ADHD) is a highly prevalent neurodevelopmental condition; however, its neurobiological diagnosis remains challenging due to the lack of reliable imaging-based biomarkers, particularly anatomical markers. Structural MRI (sMRI) provides a non-invasive modality for investigating brain alterations associated with ADHD; nevertheless, most deep learning approaches function as black-box systems, limiting clinical trust and interpretability. In this work, we propose DuSCN-FusionNet, an interpretable sMRI-based framework for ADHD classification that leverages dual-channel Structural Covariance Networks (SCNs) to capture inter-regional morphological relationships. ROI-wise mean intensity and intra-regional variability descriptors are used to construct intensity-based and heterogeneity-based SCNs, which are processed through an SCN-CNN encoder. In parallel, auxiliary ROI-wise variability features and global statistical descriptors are integrated via late-stage fusion to enhance performance. The model is evaluated using stratified 10-fold cross-validation with a 5-seed ensemble strategy, achieving a mean balanced accuracy of 80.59% and an AUC of 0.778 on the Peking University site of the ADHD-200 dataset. DuSCN-FusionNet further achieves precision, recall, and F1-scores of 81.66%, 80.59%, and 80.27%, respectively. Moreover, Grad-CAM is adapted to the SCN domain to derive ROI-level importance scores, enabling the identification of structurally relevant brain regions as potential biomarkers.

Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder whose neuroimaging-based diagnosis remains challenging due to complex time-varying disruptions in brain connectivity. Functional MRI (fMRI) provides a powerful non-invasive modality for identifying functional alterations. Existing deep learning (DL) studies employ diverse neuroimaging features; however, static functional connectivity remains widely used, whereas dynamic connectivity modeling is comparatively underexplored. Moreover, many DL models lack interpretability. In this work, we propose D-GATNet, an interpretable temporal graph-based framework for automated ADHD classification using dynamic functional connectivity (dFC). Sliding-window Pearson correlation constructs sequences of functional brain graphs with regions of interest as nodes and connectivity strengths as edges. Spatial dependencies are learned via a multi-layer Graph Attention Network, while temporal dynamics are modeled using 1D convolution followed by temporal attention. Interpretability is achieved through graph attention weights revealing dominant ROI interactions, ROI importance scores identifying influential regions, and temporal attention emphasizing informative connectivity segments. Experiments on the Peking University site of the ADHD-200 dataset using stratified 10-fold cross-validation with a 5-seed ensemble achieved 85.18% +_5.64 balanced accuracy and 0.881 AUC, outperforming state-of-the-art methods. Attention analysis reveals cerebellar and default mode network disruptions, indicating potential neuroimaging biomarkers.

Motivated behaviour relies on the brain's capacity to evaluate effort and reward. Dysregulation within these processes contributes to a spectrum of conditions, from hyperactivity in attention-deficit/hyperactivity disorder (ADHD) to diminished goal-directed behaviour in apathy. This thesis investigates the neural mechanisms underlying ADHD using electroencephalography (EEG) and examines individual differences in effort and reward sensitivity using neuroimaging, applying machine learning approaches through three main studies. In Study 1, task-based and resting-state EEG were employed with machine learning models to classify adult individuals with ADHD and healthy controls. Machine learning classifiers trained on task-based EEG during a stop signal task outperformed those trained on resting-state EEG, with the strongest predictive features arising from gamma-band spectral power over fronto-central and parietal regions. In Study 2, diffusion MRI and whole-brain permutation-based analyses identified associations between white matter integrity and computationally modelled parameters reflecting effort and reward sensitivity, with SMA-connected tracts emerging as a central hub. In Study 3, grey matter volumes from structural T1-weighted MRI were used to examine correlates of effort sensitivity, reward sensitivity, and subclinical apathy, with machine learning confirming robust decoding of reward sensitivity and apathy levels. Across studies, fronto-parietal circuits emerged as central to effort valuation and reward processing. These findings may serve as neural biomarkers for improving diagnostic accuracy in ADHD and motivational impairments, and for guiding personalised neurotechnological interventions.