Medical Physics,
AI and Neurotechnology

Music is a universal phenomenon that influences human experiences across cultures. We investigate whether music can be decoded from human brain activity measured with fMRI, by modeling mappings between neural data and latent representations of musical stimuli. Our approach integrates functional and anatomical alignment techniques to facilitate cross-subject decoding. Starting from the GTZan fMRI dataset, where five participants listened to 540 musical tracks from 10 genres, we used the CLAP model to extract latent representations of the musical stimuli and developed voxel-wise encoding models to identify brain regions responsive to these stimuli, by applying a threshold to the correlation between predicted and actual brain activity. Our decoding pipeline, primarily retrieval-based, employs a linear map to project back brain activity to the corresponding CLAP features. This enables us to retrieve the musical stimuli most similar to those that originated the fMRI data. Our results demonstrate state-of-the-art identification accuracy, outperforming existing approaches.

Thrombotic events (TEs) occur in up to 40% of patients with vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic (VEXAS) syndrome, but data on its clinical-genomics features and anticoagulation strategies are limited. To gain more insight into this, we conducted a two-step study evaluating the prevalence and outcome of TE in VEXAS. First, among 1086 patients followed for TEs, 198 were men aged >40 years with unprovoked thrombosis and no known thrombophilia; 21 also had at least one VEXAS-compatible feature and underwent UBA1 exon 3 testing. No UBA1 mutation was detected in these 21 patients. Next, we leveraged our Italian VEXAS network, and we accrued 87 molecularly confirmed Italian VEXAS cases (median age 70 years). Any history of TE was documented in 43/87 patients (49%), deep vein thrombosis being the most common (71%). Because follow-up varied, incident thrombosis was analyzed using a time-to-first-event framework from molecular VEXAS diagnosis, with death without prior TE treated as a competing event. Among 49 patients without prior/concomitant TE, five developed incident post-diagnosis TE; the 24-month cumulative incidence was 18.3%. Thrombophilia testing revealed a 15% co-occurrence, including heterozygous Factor V Leiden, Factor II G20210A, and anti-cardiolipin antibodies. Treatments comprised direct oral anticoagulants (DOACs) (51%), low molecular weight heparin (LMWH) (28%), Fondaparinux (14%), and vitamin K antagonists (AVKs) (7%). Notably, 27% experienced multiple TEs, of which 22% occurring despite anticoagulation during disease flares. Our findings provide an updated cartography of VEXAS-related TE, suggesting early screening for thrombophilia in these patients to inform both personalized anticoagulation and disease-control strategies.

BACKGROUND: Externalizing and internalizing disorders are common in youth but are often studied separately, preventing researchers from identifying shared (i.e., transdiagnostic) alterations in brain structure. Using data from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium, we conducted a mega-analysis to identify shared and distinct cortical and subcortical brain alterations across internalizing (anxiety disorders and depression) and externalizing (attention-deficit/hyperactivity disorder [ADHD] and conduct disorder [CD]) disorders in youth.

METHODS: 3D T1-weighted magnetic resonance imaging data from youths (age range 4-21 years) with anxiety disorders (n = 1044), depression (n = 504), ADHD (n = 1317), and CD (n = 1172) along with healthy control participants (n = 4743) were analyzed. We assessed group differences in regional cortical thickness, surface area (SA), and subcortical volume using linear models, adjusted for site, age, and sex, as well as total intracranial volume in the SA and subcortical volume models.

RESULTS: We observed transdiagnostic associations, with both internalizing and externalizing disorders characterized by lower SA in the insula, entorhinal cortex, and middle temporal gyrus and lower amygdala volume (Cohen's ds = -0.07 to -0.24) as well as total SA and intracranial volume (ds = -0.11 to -0.25). Externalizing-specific reductions in SA were observed in frontoparietal regions (ds = -0.08 to -0.13), but no internalizing-specific associations were identified. Disorder-specific alterations were identified for ADHD, CD, and anxiety disorders but not depression.

CONCLUSIONS: Both common and disorder-specific alterations were identified, with regions involved in salience attribution and emotion processing implicated across internalizing and externalizing disorders. These novel findings can guide future research targeting common biological processes across youth psychiatric disorders as well as features unique to individual disorders.