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Context-dependent goal-directed control in psychosis: Prioritizing loss avoidance over reward pursuit

Omlor, W.; Cecere, G.; Misra, A. R.; Huang, G.-Y.; Homan, P.

2025-07-03 psychiatry and clinical psychology
10.1101/2025.07.02.25330758 medRxiv
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Background and HypothesisIndividuals with schizophrenia spectrum disorders (SSD) often show diminished reward pursuit, whereas loss avoidance is relatively preserved. The neural mechanisms of this dissociation and its relation to negative symptoms remain unclear. We hypothesized that in SSD, cognitive resources are preferentially directed toward avoiding losses rather than pursuing rewards, potentially limiting reward processing and contributing to negative symptoms. Study DesignUsing computational modeling of behavior during a two-stage decision task which distinguished between goal-directed (model-based) and habitual (model-free) strategies under reward and loss conditions, we studied 42 stable individuals with SSD and 48 healthy controls (HC) during functional magnetic resonance imaging. Study ResultsIn individuals with SSD, model-based control was shifted toward loss avoidance relative to HC, with corresponding changes in prefrontal circuitry. In anterior cingulate, orbitofrontal, and dorsolateral prefrontal regions, individuals with SSD showed increased activation during model-based control in the loss condition. Within this group, loss-biased activation in the right anterior cingulate region was associated with anhedonia. In 25 patients with available follow-up data, loss-biased activation in the right anterior cingulate region at baseline was prospectively related to worsening of motivation and social engagement over the subsequent year. ConclusionsOur findings suggest that, compared to HC, those with SSD allocate their limited cognitive resources more toward loss avoidance relative to reward pursuit. The association between loss-biased anterior cingulate engagement and anhedonia supports a neurocomputational account of diminished pleasure in psychotic disorders, with potential implications for developing motivation-targeted treatments and early prediction of negative-symptom worsening.

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