Prettyman Greer E, Kable Joseph W, Didier Paige, Shankar Sheila, Satterthwaite Theodore D, Davatzikos Christos, Bilker Warren B, Elliott Mark A, Ruparel Kosha, Wolf Daniel H
Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Department of Psychology, University of Pennsylvania, Philadelphia, PA, 19104, USA.
NPJ Schizophr. 2021 Oct 8;7(1):48. doi: 10.1038/s41537-021-00178-9.
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.
动机缺陷在精神分裂症（SZ）阴性症状所致的残疾中起核心作用，但对其病理生理学的了解有限阻碍了急需的治疗进展。我们应用了功能磁共振成像努力折扣任务（EDT），该任务使用神经经济学决策方法量化动机，捕捉努力需求导致货币奖励主观价值（SV）降低的程度。21名精神分裂症患者和23名年龄匹配的对照组在功能磁共振成像期间执行了EDT。我们假设腹侧纹状体（VS）以及扩展的脑动机回路会对SV进行编码，整合奖励和努力成本。我们还假设在EDT决策过程中VS激活不足将与临床无动机严重程度呈现维度关系，反映出努力成本的更大抑制作用。正如所假设的，在EDT期间VS以及更广泛的皮质-边缘网络被激活，并且这种激活与SV呈正相关。在精神分裂症患者中，VS对任务决策的激活选择性降低。在精神分裂症患者以及所有参与者中，VS更大程度的降低与更严重的临床无动机相关。然而，这些诊断和无动机效应无法通过对奖励、努力或基于模型的SV的参数变化的反应来解释。我们的研究结果表明，精神分裂症中VS功能减退在基于努力的决策过程中表现出来，并反映了维度动机损害。VS功能障碍影响基于努力的决策可以为生物标志物开发提供一个靶点，以指导评估和治疗致残性无动机的新努力。
