Relationship of ventral striatum activation during effort discounting to clinical amotivation severity in schizophrenia.

Autor: Prettyman GE; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, 19104, USA. gpretty@pennmedicine.upenn.edu., Kable JW; Department of Psychology, University of Pennsylvania, Philadelphia, PA, 19104, USA., Didier P; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, 19104, USA., Shankar S; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, 19104, USA., Satterthwaite TD; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Penn Lifespan Informatics and Neuroimaging Center, University of Pennsylvania, Philadelphia, PA, 19104, USA., Davatzikos C; Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Department of Radiology, University of Pennsylvania, Philadelphia, PA, 19104, USA., Bilker WB; Department of Biostatistics, Epidemiology & Informatics, University of Pennsylvania, Philadelphia, PA, 19104, USA., Elliott MA; Department of Radiology, University of Pennsylvania, Philadelphia, PA, 19104, USA., Ruparel K; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, 19104, USA., Wolf DH; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, 19104, USA.; Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Jazyk: angličtina
Zdroj: NPJ schizophrenia [NPJ Schizophr] 2021 Oct 08; Vol. 7 (1), pp. 48. Date of Electronic Publication: 2021 Oct 08.
DOI: 10.1038/s41537-021-00178-9
Abstrakt: Motivational deficits play a central role in disability due to negative symptoms of schizophrenia (SZ), but limited pathophysiological understanding impedes critically needed therapeutic development. We applied an fMRI Effort Discounting Task (EDT) that quantifies motivation using a neuroeconomic decision-making approach, capturing the degree to which effort requirements produce reductions in the subjective value (SV) of monetary reward. An analyzed sample of 21 individuals with SZ and 23 group-matched controls performed the EDT during fMRI. We hypothesized that ventral striatum (VS) as well as extended brain motivation circuitry would encode SV, integrating reward and effort costs. We also hypothesized that VS hypoactivation during EDT decisions would demonstrate a dimensional relationship with clinical amotivation severity, reflecting greater suppression by effort costs. As hypothesized, VS as well as a broader cortico-limbic network were activated during the EDT and this activation correlated positively with SV. In SZ, activation to task decisions was reduced selectively in VS. Greater VS reductions correlated with more severe clinical amotivation in SZ and across all participants. However, these diagnosis and amotivation effects could not be explained by the response to parametric variation in reward, effort, or model-based SV. Our findings demonstrate that VS hypofunction in schizophrenia is manifested during effort-based decisions and reflects dimensional motivation impairment. Dysfunction of VS impacting effort-based decision-making can provide a target for biomarker development to guide novel efforts to assess and treat disabling amotivation.
(© 2021. The Author(s).)
Databáze: MEDLINE
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