Distinct neural representations encode psychiatric states across multiple timescales

<jats:title>Abstract</jats:title> <jats:p>Psychiatric states manifest over multiple timescales, from transient fluctuations in disorder-related distress to long-term variations in disease severity, yet whether these expressions share common neural representations remains unknown. We addressed this question in obsessive-compulsive disorder (OCD) by comparing neural activity associated with momentary distress evoked by triggers versus that associated with clinically assessed chronic symptom severity. We analyzed more than 200 hours of intracranial recordings from the ventral capsule and orbitofrontal cortex throughout deep brain stimulation treatment, together with quantitative facial- and speech-derived measures. Neural signatures of OCD severity were dissociable from and stronger than signatures of momentary distress, indicating distinct underlying brain states. Integrating behavioral data into a predictive model improved neural decoding performance of both momentary distress and OCD severity. These findings demonstrate that clinically relevant psychiatric states across varying timescales are encoded by distinct neural processes. Future closed-loop neuromodulation strategies should consider these differences and choose neural signals associated with the appropriate target state.</jats:p>