University of Ottawa Institute of Mental Health Research, Ottawa, Ontario, Canada; Department of Psychiatry, Massachusetts General Hospital, Charlestown, Massachusetts; Harvard Medical School, Boston, Massachusetts.
Department of Psychiatry, Massachusetts General Hospital, Charlestown, Massachusetts.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2021 Dec;6(12):1165-1175. doi: 10.1016/j.bpsc.2021.01.006. Epub 2021 Jan 29.
Associative learning and memory processes, including the generalization of previously learned associations, may be altered in schizophrenia. Deficits in schizophrenia in stimulus generalization, one of the simplest forms of memory, could interfere with the ability to efficiently categorize related, similar information, potentially leading to impairments in daily functioning.
To measure generalization in schizophrenia, 37 individuals with a nonaffective psychotic disorder and 32 demographically matched healthy control subjects underwent a Pavlovian fear conditioning and generalization procedure, which accounted for variation in perceptual ability across participants, while undergoing functional magnetic resonance imaging. Skin conductance and neural responses to conditioned (CS+), neutral (CS-), and generalization stimuli were measured. Explicit memory ratings reflecting successful generalization were also collected after the scanning, as well as measures of symptom severity.
Compared with healthy control subjects, individuals with nonaffective psychotic disorders showed significant deficits in fear generalization across multiple measurements, with impairments in memory ratings and reductions in activation and deactivation of the salience and default networks, respectively, during fear generalization. Moreover, in the psychotic disorder group, greater behavioral and neural abnormalities in generalization were associated with higher levels of negative symptoms.
Fear generalization is impaired in psychotic illness. Given that successful generalization relies on a dynamic balance between excitatory and inhibitory neurotransmission, these results reveal a potentially quantifiable mechanism linked to negative symptoms that can be investigated further in future human and experimental animal studies.
联想学习和记忆过程，包括先前学习的联想的泛化，可能在精神分裂症中发生改变。精神分裂症在刺激泛化方面的缺陷，这是最简单的记忆形式之一，可能会干扰有效分类相关、相似信息的能力，从而导致日常功能受损。
为了测量精神分裂症中的泛化，37 名非情感性精神病患者和 32 名在人口统计学上匹配的健康对照者接受了 Pavlovian 恐惧条件反射和泛化程序的测试，该程序考虑了参与者之间感知能力的变化，同时进行了功能磁共振成像。皮肤电导和对条件（CS+）、中性（CS-）和泛化刺激的神经反应也进行了测量。扫描后还收集了反映成功泛化的外显记忆评分，以及症状严重程度的测量。
与健康对照组相比，非情感性精神病患者在多种测量中表现出明显的恐惧泛化缺陷，在记忆评分中表现出缺陷，在恐惧泛化过程中，突显和默认网络的激活和失活分别减少。此外，在精神病障碍组中，泛化中更大的行为和神经异常与更高水平的阴性症状相关。
在精神病中，恐惧泛化受损。鉴于成功的泛化依赖于兴奋性和抑制性神经递质之间的动态平衡，这些结果揭示了与阴性症状相关的一种潜在可量化的机制，可以在未来的人类和实验动物研究中进一步研究。
