Cerebellar-Prefrontal Network Connectivity and Negative Symptoms in Schizophrenia
Cerebellar-Prefrontal Network Connectivity and Negative Symptoms in Schizophrenia
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DOI：
10.1176/appi.ajp.2018.18040429
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发表时间：
2019-07-01
影响因子：
17.7
通讯作者：
Halko, Mark A.
中科院分区：
文献类型：
--
作者：
Brady, Roscoe O., Jr.;Gonsalvez, Irene;Halko, Mark A.
目的：过度依赖相关关系严重限制了精神病学神经影像学结果的可解释性。纯粹的相关性研究不能单独确定行为成像关系是疾病的因果关系、功能代偿过程还是纯粹的副现象。阴性症状（如快感缺乏、动机和表达缺陷）对目前的药物难以治愈，是精神分裂症致残的主要原因之一。作者采用了两步方法来确定精神分裂症症状的大脑网络模型，然后对其进行实证测试。方法：在第一个队列（N = 44）中，采用数据驱动的静息状态功能连通性分析来识别与阴性症状严重程度相对应的网络连通性。在第二组（N = 11）中，通过对小脑中线进行为期5天的每日两次的经颅磁刺激（TMS）来调节这种网络连通性。结果：特定背外侧前额叶皮层-小脑网络连通性的破坏与负性症状的严重程度直接相关。经颅磁刺激后网络连通性的恢复与负性症状的改善相对应，负性症状变化对功能连通性变化的响应具有统计学意义的强相关性。结论：这些结果表明，小脑与右背外侧前额叶皮层之间的连通性中断与负性症状的严重程度有关，纠正这种连接中断可改善负性症状的严重程度，支持了药物难治性负性症状的新网络假说，并提示网络操作可能建立了网络标记物与临床现象之间的因果关系。
Objective: The interpretability of results in psychiatric neuroimaging is significantly limited by an overreliance on correlational relationships. Purely correlational studies cannot alone determine whether behavior-imaging relationships are causal to illness, functionally compensatory processes, or purely epiphenomena. Negative symptoms (e.g., anhedonia, amotivation, and expressive deficits) are refractory to current medications and are among the foremost causes of disability in schizophrenia. The authors used a two-step approach in identifying and then empirically testing a brain network model of schizophrenia symptoms.Methods: In the first cohort (N = 44), a data-driven resting-state functional connectivity analysis was used to identify a network with connectivity that corresponds to negative symptom severity. In the second cohort (N = 11), this network connectivity was modulated with 5 days of twice-daily transcranial magnetic stimulation (TMS) to the cerebellar midline.Results: A breakdown of connectivity in a specific dorsolateral prefrontal cortex-to-cerebellum network directly corresponded to negative symptom severity. Restoration of network connectivity with TMS corresponded to amelioration of negative symptoms, showing a statistically significant strong relationship of negative symptom change in response to functional connectivity change.Conclusions: These results demonstrate that a connectivity breakdown between the cerebellum and the right dorsolateral prefrontal cortex is associated with negative symptom severity and that correction of this breakdown ameliorates negative symptom severity, supporting a novel network hypothesis for medication-refractory negative symptoms and suggesting that network manipulation may establish causal relationships between network markers and clinical phenomena.