Culbreth A J, Schwartz E K, Frank M J, Brown E C, Xu Z, Chen S, Gold J M, Waltz J A
Department of Psychiatry, Maryland Psychiatric Research Center (MPRC), University of Maryland School of Medicine, Baltimore, MD, USA.
Signant Health, San Diego, CA, USA.
Psychol Med. 2023 Oct;53(14):6600-6610. doi: 10.1017/S0033291722003993. Epub 2023 Feb 8.
Prior evidence indicates that negative symptom severity and cognitive deficits, in people with schizophrenia (PSZ), relate to measures of reward-seeking and loss-avoidance behavior (implicating the ventral striatum/VS), as well as uncertainty-driven exploration (reliant on rostrolateral prefrontal cortex/rlPFC). While neural correlates of reward-seeking and loss-avoidance have been examined in PSZ, neural correlates of uncertainty-driven exploration have not. Understanding neural correlates of uncertainty-driven exploration is an important next step that could reveal insights to how this mechanism of cognitive and negative symptoms manifest at a neural level.
We acquired fMRI data from 29 PSZ and 36 controls performing the Temporal Utility Integration decision-making task. Computational analyses estimated parameters corresponding to learning rates for both positive and negative reward prediction errors (RPEs) and the degree to which participates relied on representations of relative uncertainty. Trial-wise estimates of expected value, certainty, and RPEs were generated to model fMRI data.
Behaviorally, PSZ demonstrated reduced reward-seeking behavior compared to controls, and negative symptoms were positively correlated with loss-avoidance behavior. This finding of a bias toward loss avoidance learning in PSZ is consistent with previous work. Surprisingly, neither behavioral measures of exploration nor neural correlates of uncertainty in the rlPFC differed significantly between groups. However, we showed that trial-wise estimates of relative uncertainty in the rlPFC distinguished participants who engaged in exploratory behavior from those who did not. rlPFC activation was positively associated with intellectual function.
These results further elucidate the nature of reinforcement learning and decision-making in PSZ and healthy volunteers.
先前的证据表明,精神分裂症患者(PSZ)的阴性症状严重程度和认知缺陷与寻求奖励和避免损失行为的测量指标(涉及腹侧纹状体/VS)以及不确定性驱动的探索(依赖于 rostrolateral 前额叶皮层/rlPFC)有关。虽然已经在 PSZ 中研究了寻求奖励和避免损失的神经相关性,但尚未研究不确定性驱动的探索的神经相关性。了解不确定性驱动的探索的神经相关性是重要的下一步,这可能揭示这种认知和阴性症状机制在神经层面如何表现的见解。
我们从 29 名 PSZ 患者和 36 名对照组中获取了 fMRI 数据,他们执行了时间效用整合决策任务。计算分析估计了与正性和负性奖励预测误差(RPE)的学习率相对应的参数,以及参与者依赖相对不确定性表征的程度。生成了每次试验的预期值、确定性和 RPE 的估计值,以对 fMRI 数据进行建模。
在行为上,与对照组相比,PSZ 表现出寻求奖励行为减少,并且阴性症状与避免损失行为呈正相关。PSZ 中这种偏向于避免损失学习的发现与先前的研究一致。令人惊讶的是,两组之间在探索的行为测量指标或 rlPFC 中的不确定性神经相关性方面均无显著差异。然而,我们表明,rlPFC 中相对不确定性的每次试验估计值区分了参与探索行为的参与者和未参与探索行为的参与者。rlPFC 激活与智力功能呈正相关。
这些结果进一步阐明了 PSZ 患者和健康志愿者中强化学习和决策的本质。