Abstract：
OBJECTIVE: Cerebello-cortical functional dysconnectivity plays a key role in the pathology of schizophrenia (SZ). We aimed to investigate the changes in cerebello-cortical directional connectivity in patients with SZ.
METHODS: A total of 180 drug-naïve patients with first-episode SZ (54 reassessed after 1 year of treatment) and 166 healthy controls (HCs) were included. Resting-state functional magnetic resonance imaging was used to perform Granger causal analysis, in which each of the nine cerebellar functional systems was defined as a seed. The observed effective connectivity (EC) alterations at baseline were further assessed at follow-up and were associated with changes in psychotic symptom.
RESULTS: We observed increased bottom-up EC in first-episode SZ from the cerebellum to the cerebrum (e.g. from the cerebellar attention and cingulo-opercular systems to the bilateral angular gyri, and from the cerebellar cingulo-opercular system to the right inferior frontal gyrus). In contrast, decreased top-down EC in the first-episode SZ was mainly from the cerebrum to the cerebellum (e.g. from the right inferior temporal gyrus, left middle temporal gyrus, left putamen, and right angular gyrus to the cerebellar language system). After 1 year of antipsychotic treatment, information projections from the cerebrum to the cerebellum were partly restored and positively related to symptom remission.
CONCLUSIONS: These findings suggest that decreased top-down EC during the acute phase of SZ may be a state-dependent alteration related to symptoms and medication. However, increased bottom-up EC may reflect a persistent pathological trait.
METHODS: A total of 180 drug-naïve patients with first-episode SZ (54 reassessed after 1 year of treatment) and 166 healthy controls (HCs) were included. Resting-state functional magnetic resonance imaging was used to perform Granger causal analysis, in which each of the nine cerebellar functional systems was defined as a seed. The observed effective connectivity (EC) alterations at baseline were further assessed at follow-up and were associated with changes in psychotic symptom.
RESULTS: We observed increased bottom-up EC in first-episode SZ from the cerebellum to the cerebrum (e.g. from the cerebellar attention and cingulo-opercular systems to the bilateral angular gyri, and from the cerebellar cingulo-opercular system to the right inferior frontal gyrus). In contrast, decreased top-down EC in the first-episode SZ was mainly from the cerebrum to the cerebellum (e.g. from the right inferior temporal gyrus, left middle temporal gyrus, left putamen, and right angular gyrus to the cerebellar language system). After 1 year of antipsychotic treatment, information projections from the cerebrum to the cerebellum were partly restored and positively related to symptom remission.
CONCLUSIONS: These findings suggest that decreased top-down EC during the acute phase of SZ may be a state-dependent alteration related to symptoms and medication. However, increased bottom-up EC may reflect a persistent pathological trait.
摘要：
目的：小脑-皮质功能连接障碍在精神分裂症（SZ）的病理过程中起关键作用。我们旨在研究SZ患者小脑-皮层定向连接的变化。
方法：共包括180例首次出现SZ的药物初治患者（54例治疗1年后重新评估）和166例健康对照（HC）。静息态功能磁共振成像用于进行Granger因果分析，其中九个小脑功能系统中的每一个都被定义为种子。基线时观察到的有效连接（EC）改变在随访中进一步评估，并与精神病症状的变化有关。
结果：我们观察到从小脑到大脑的首发SZ自下而上的EC增加（例如，从小脑注意力和扣带系统到双侧角回，从小脑扣带-手术系统到右额下回）。相比之下,在第一次发作的SZ中，自上而下的EC下降主要是从大脑到小脑（例如，从右颞下回，左颞中回,左壳核,和小脑语言系统的直角回)。抗精神病药物治疗1年后，从大脑到小脑的信息预测部分恢复，并与症状缓解呈正相关。
结论：这些研究结果表明，在SZ急性期自上而下的EC减少可能是与症状和药物治疗有关的状态依赖性改变。然而,自下而上的EC增加可能反映了持续的病理特征。
方法：共包括180例首次出现SZ的药物初治患者（54例治疗1年后重新评估）和166例健康对照（HC）。静息态功能磁共振成像用于进行Granger因果分析，其中九个小脑功能系统中的每一个都被定义为种子。基线时观察到的有效连接（EC）改变在随访中进一步评估，并与精神病症状的变化有关。
结果：我们观察到从小脑到大脑的首发SZ自下而上的EC增加（例如，从小脑注意力和扣带系统到双侧角回，从小脑扣带-手术系统到右额下回）。相比之下,在第一次发作的SZ中，自上而下的EC下降主要是从大脑到小脑（例如，从右颞下回，左颞中回,左壳核,和小脑语言系统的直角回)。抗精神病药物治疗1年后，从大脑到小脑的信息预测部分恢复，并与症状缓解呈正相关。
结论：这些研究结果表明，在SZ急性期自上而下的EC减少可能是与症状和药物治疗有关的状态依赖性改变。然而,自下而上的EC增加可能反映了持续的病理特征。
