Back

An explainable AI latent space of brain dynamics reveals a cerebello-prefrontal signature of schizophrenia symptoms

Bonhoeffer, M.; Muratore, P.; Mathis, M. W.; Begue, I.

2026-08-28 neuroscience
10.64898/2026.08.25.746991 bioRxiv
Show abstract

Schizophrenia presents with several partially independent symptom dimensions, including positive symptoms, negative symptoms, and cognitive impairment; yet no neuroimaging framework has provided individual-level markers of symptom severity that remain anatomically interpretable. Here, we present an interpretable AI-based framework that addresses this gap by mapping high-dimensional resting-state rs-fMRI dynamics onto a low-dimensional latent manifold using self-supervised contrastive learning with a new attribution method to localize the highest decodable regions. Applied to two independent schizophrenia-spectrum cohorts, the label-free latent space supports individual-level prediction across clinical features of the disorder, including symptom severity and cognitive function. The attribution maps identify a disease-specific pathological footprint concentrated in prefrontal, posterior cerebellar and temporal areas that diverge from the manifold organization observed in healthy controls, which was dominated by auditory, limbic, and ventral-striatal circuits. These results establish an interpretable latent space framework for characterizing the distributed neural substrates of schizophrenia symptoms at the level of the individual patient, and provide an anatomically grounded route toward precision decoding of symptom severity.

Matching journals

The top 4 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.