Anticevic Alan, Cole Michael W, Repovs Grega, Murray John D, Brumbaugh Margaret S, Winkler Anderson M, Savic Aleksandar, Krystal John H, Pearlson Godfrey D, Glahn David C
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA NIAAA Center for the Translational Neuroscience of Alcoholism, New Haven, CT 06519, USA Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT 06519, USA.
Department of Psychology, Washington University in St. Louis, St. Louis, MO 63130, USA.
Cereb Cortex. 2014 Dec;24(12):3116-30. doi: 10.1093/cercor/bht165. Epub 2013 Jul 3.
Schizophrenia is a devastating neuropsychiatric syndrome associated with distributed brain dysconnectivity that may involve large-scale thalamo-cortical systems. Incomplete characterization of thalamic connectivity in schizophrenia limits our understanding of its relationship to symptoms and to diagnoses with shared clinical presentation, such as bipolar illness, which may exist on a spectrum. Using resting-state functional magnetic resonance imaging, we characterized thalamic connectivity in 90 schizophrenia patients versus 90 matched controls via: (1) Subject-specific anatomically defined thalamic seeds; (2) anatomical and data-driven clustering to assay within-thalamus dysconnectivity; and (3) machine learning to classify diagnostic membership via thalamic connectivity for schizophrenia and for 47 bipolar patients and 47 matched controls. Schizophrenia analyses revealed functionally related disturbances: Thalamic over-connectivity with bilateral sensory-motor cortices, which predicted symptoms, but thalamic under-connectivity with prefrontal-striatal-cerebellar regions relative to controls, possibly reflective of sensory gating and top-down control disturbances. Clustering revealed that this dysconnectivity was prominent for thalamic nuclei densely connected with the prefrontal cortex. Classification and cross-diagnostic results suggest that thalamic dysconnectivity may be a neural marker for disturbances across diagnoses. Present findings, using one of the largest schizophrenia and bipolar neuroimaging samples to date, inform basic understanding of large-scale thalamo-cortical systems and provide vital clues about the complex nature of its disturbances in severe mental illness.
精神分裂症是一种毁灭性的神经精神综合征，与可能涉及大规模丘脑 - 皮质系统的分布式脑连接障碍有关。精神分裂症中丘脑连接的不完全特征限制了我们对其与症状以及与具有共同临床表现的诊断（如可能存在于一个谱系上的双相情感障碍）之间关系的理解。使用静息态功能磁共振成像，我们通过以下方式对90名精神分裂症患者与90名匹配对照的丘脑连接进行了特征描述：（1）基于个体特异性解剖学定义的丘脑种子；（2）解剖学和数据驱动的聚类分析丘脑内连接障碍；（3）机器学习通过丘脑连接对精神分裂症、47名双相情感障碍患者及47名匹配对照进行诊断分类。对精神分裂症的分析揭示了功能上相关的紊乱：丘脑与双侧感觉运动皮质的过度连接，这可预测症状，但相对于对照，丘脑与前额叶 - 纹状体 - 小脑区域的连接不足，这可能反映了感觉门控和自上而下控制的紊乱。聚类分析表明，这种连接障碍在与前额叶皮质紧密连接的丘脑核中尤为突出。分类和交叉诊断结果表明，丘脑连接障碍可能是跨诊断紊乱的神经标志物。目前的研究结果，使用了迄今为止最大的精神分裂症和双相情感障碍神经影像学样本之一，为大规模丘脑 - 皮质系统的基本理解提供了信息，并为严重精神疾病中其紊乱的复杂性质提供了重要线索。
