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Cerebellar-Prefrontal Network Connectivity and Negative Symptoms in Schizophrenia.
American Journal of Psychiatry ( IF 17.7 ) Pub Date : 2019-01-30 , DOI: 10.1176/appi.ajp.2018.18040429
Roscoe O Brady 1 , Irene Gonsalvez 1 , Ivy Lee 1 , Dost Öngür 1 , Larry J Seidman 1 , Jeremy D Schmahmann 1 , Shaun M Eack 1 , Matcheri S Keshavan 1 , Alvaro Pascual-Leone 1 , Mark A Halko 1
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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.

中文翻译:

精神分裂症的小脑-额叶网络连接和阴性症状。

目的过度依赖相关关系会极大地限制精神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想象关系是否与疾病,功能补偿过程或纯粹的现象有关。负面症状(例如,狂躁不安,情绪低落和表达缺陷)对目前的药物而言是难治的,并且是精神分裂症致残的首要原因之一。作者使用了两步方法来识别并通过经验测试精神分裂症症状的大脑网络模型。方法在第一个队列(N = 44)中,使用数据驱动的静息状态功能连通性分析来识别网络,其连通性对应于不良症状严重程度。在第二组中(N = 11),通过每天两次的小脑中线每天两次经颅磁刺激(TMS)5天来调节此网络连接。结果在特定的背外侧前额叶皮层至小脑网络中的连通性破坏直接对应于阴性症状严重程度。使用TMS恢复网络连通性可以缓解负面症状,从而显示出响应于功能连通性变化的负面症状变化具有统计学上显着的强相关性。结论这些结果表明,小脑与右前外侧前额叶皮层之间的连通性下降与症状严重度降低相关,并且对该故障的纠正可以减轻症状的严重度,
更新日期:2019-07-01
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