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

Abstract 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 neuroec...

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Autores principales:	Greer E. Prettyman, Joseph W. Kable, Paige Didier, Sheila Shankar, Theodore D. Satterthwaite, Christos Davatzikos, Warren B. Bilker, Mark A. Elliott, Kosha Ruparel, Daniel H. Wolf
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Psychiatry RC435-571
Acceso en línea:	https://doaj.org/article/a0155da9ab6d4263a3f7852965137986
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spelling	oai:doaj.org-article:a0155da9ab6d4263a3f78529651379862021-12-02T19:16:18ZRelationship of ventral striatum activation during effort discounting to clinical amotivation severity in schizophrenia10.1038/s41537-021-00178-92334-265Xhttps://doaj.org/article/a0155da9ab6d4263a3f78529651379862021-10-01T00:00:00Zhttps://doi.org/10.1038/s41537-021-00178-9https://doaj.org/toc/2334-265XAbstract 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.Greer E. PrettymanJoseph W. KablePaige DidierSheila ShankarTheodore D. SatterthwaiteChristos DavatzikosWarren B. BilkerMark A. ElliottKosha RuparelDaniel H. WolfNature PortfolioarticlePsychiatryRC435-571ENnpj Schizophrenia, Vol 7, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Psychiatry RC435-571
spellingShingle	Psychiatry RC435-571 Greer E. Prettyman Joseph W. Kable Paige Didier Sheila Shankar Theodore D. Satterthwaite Christos Davatzikos Warren B. Bilker Mark A. Elliott Kosha Ruparel Daniel H. Wolf Relationship of ventral striatum activation during effort discounting to clinical amotivation severity in schizophrenia
description	Abstract 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.
format	article
author	Greer E. Prettyman Joseph W. Kable Paige Didier Sheila Shankar Theodore D. Satterthwaite Christos Davatzikos Warren B. Bilker Mark A. Elliott Kosha Ruparel Daniel H. Wolf
author_facet	Greer E. Prettyman Joseph W. Kable Paige Didier Sheila Shankar Theodore D. Satterthwaite Christos Davatzikos Warren B. Bilker Mark A. Elliott Kosha Ruparel Daniel H. Wolf
author_sort	Greer E. Prettyman
title	Relationship of ventral striatum activation during effort discounting to clinical amotivation severity in schizophrenia
title_short	Relationship of ventral striatum activation during effort discounting to clinical amotivation severity in schizophrenia
title_full	Relationship of ventral striatum activation during effort discounting to clinical amotivation severity in schizophrenia
title_fullStr	Relationship of ventral striatum activation during effort discounting to clinical amotivation severity in schizophrenia
title_full_unstemmed	Relationship of ventral striatum activation during effort discounting to clinical amotivation severity in schizophrenia
title_sort	relationship of ventral striatum activation during effort discounting to clinical amotivation severity in schizophrenia
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a0155da9ab6d4263a3f7852965137986
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Relationship of ventral striatum activation during effort discounting to clinical amotivation severity in schizophrenia

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